Autopsy & Case Reports by Editora Cubo

Autopsy and Case Reports 2012;2(1):1

Erratum

Gama AP, Santos IS, Olmos RD, Pinto LMO, Benseñor IJM, Lotufo PA. C-reactive protein as an inflammatory marker of acute infections outside intensive care settings: case report and evidence-based literature review. Autopsy Case Rep [Internet]. 2011;1(3):3-9. http://dx.doi.org/10.4322/acr.2011.011 On page 6, the Chart 1 was constructed incorrectly.

Chart 1 – How to calculate LR+, LR– and how to interpret test results. Adapted from Hatanaka.10 How to calculate LR+: Probability of positive test in individuals with disease Probability of positive test in individuals without disease How to calculate LR–: Probability of negative test in individuals with disease Probability of negative test in individuals without disease LR >10.0 or LR< 0.1 Very good test, almost always impacts on clinical judgement LR 5.0-10.0 or 0.1-0.2 Intermediate test value, can impact on clinical judgement LR 2.0-5.0 or 0.2-0.5 Weak test, seldom changes clinical judgement LR 0.5-2.0 Test is incapable of changing clinical judgement, it must not be performed’

The right presentation is as follows below:

Chart 1 – How to calculate LR+, LR– and how to interpret test results. Adapted from Hatanaka10 How to calculate LR+: Probability of positive test in individuals with disease Probability of positive test in individuals without disease How to calculate LR–: Probability of negative test in individuals with disease Probability of negative test in individuals without disease LR >10.0 or LR< 0.1 Very good test, almost always impacts on clinical judgement LR 5.0-10.0 or 0.1-0.2 Intermediate test value, can impact on clinical judgement LR 2.0-5.0 or 0.2-0.5 Weak test, seldom changes clinical judgement LR 0.5-2.0 Test is incapable of changing clinical judgement, it must not be performed

Autopsy and Case Reports 2012;2(1):3-5

Editorial

What does the future hold? Fernando Peixoto Ferraz de Camposa Campos FPF. What does the future hold? [editorial]. Autopsy Case Rep [Internet]. 2012;2(1):3-5. http://dx.doi.org/ 10.4322/acr.2012.001

Since ancient times the knowledge of the human body and physiologic theories were obtained secretly, against the laws of the Catholic Church, through exhumation followed by anatomic dissection of newly buried persons. From those times, the importance of post-mortem study for the advance of medical knowledge was noted. In this context, the nineteenth century saw the heyday of the autopsy. Since then, autopsy has been responsible for the progression of clinical medicine, medical education, epidemiology, and public health. From the 1950s up until 1990, 87 diseases were identified by autopsy. The discovery of severe acute respiratory syndrome (SARS) epidemic in 2003 and the avian flu epidemic in 2006 were through autopsy as well. Many researchers recognize the immeasurable value of autopsy for clinical, educational, epidemiological, and research purposes. Dr. Lundberg, a pathologist and former editor of JAMA, once said: “Medicine without the autopsy would not be worth being part of.” The information obtained from autopsies not only instructs and confirms diagnoses, but also serves as a pathway of study and a source of investigation, a necessary tool in elucidating the changing spectrum of diseases. Autopsies have, in the past, shed light on the mechanisms of diseases that cannot be elicited in the living being and they continue to do so to this day. Knowledge of diseases of the brain and the heart relies greatly on autopsies. Important examples include the recognition of variant Creutzfeldt-Jakob disease, delineation of Reye’s syndrome, WernickeKorsakoff syndrome and thiamine deficiency, and so on. As an instrument for teaching, by correlating pathology with clinical context, autopsy remains a

unrivalled. Teaching based on autopsies furnish valuable skills, some of which are not easily learnt elsewhere. Autopsies’ most powerful benefit is a quality assurance instrument. The continuous study of the clinico-pathological discrepancies may show the improvement of medical care in time. The discovery of these discrepancies in the autopsy room is a powerful tool for identifying faults in medical practice and shows the need for clinical audits. Autopsy results improve death certificate accuracy. They may also alleviate the grieving process by furnishing sensitive and reasonably full information concerning the death; they may even provide the disclosure of a genetic malady, which can be investigated among the close relatives. Infectious diseases may also be detected during the autopsy that could affect family members. Regardless of all these advantages, conversely, there is a gradual and progressive decline in the number of hospital autopsies undertaken. At present, anecdotal evidence suggests that the average non-coronial hospital autopsy rate of adult deceased is less than 10%. This decline extends overseas to the east, including China and Oceania. Several reasons are speculated to explain this process that has been occurring most notably in the last 40 years. One of the main contributing factors to this decline is that clinicians do not want autopsies done. Their reasons vary from distaste for the procedure to a belief that the accuracy of modern investigative techniques avoids the need of autopsy in elucidating nothing extra to the clinical picture. The self-confidence comes mainly from the improvement in the imaging techniques and laboratory resources. Their increasing clinical

Hospital Universitário - Universidade de São Paulo - São Paulo/SP – Brazil.

Copyright © 2012 Autopsy and Case Reports – This is an Open Access article distributed of terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any médium provided article is properly cited.

Autopsy and Case Reports 2012;2(1):3-5

confidence in the ante-mortem diagnoses supplants their need to request autopsies. This approach does not match the scientific basis, since several reports show persistent clinico-pathological discrepancies of 10–30%. These discrepancies may be higher in the context of HIV, elderly patients, critically-ill patients, as well as fetus and neonate autopsies. Paradoxically, community doctors generally show that they appreciate receiving autopsy reports and that, in a high proportion of cases, the findings are unexpected and could influence their future clinical practice. Fear of malpractice suits may also have a role in discouraging physicians to ask for post-mortem examinations. Moreover, in many instances, pathologists fail to give sufficient priority to autopsies, probably due to increasing workloads from surgical resections, biopsies, and cytology. The continuous changes in medical school curricula results in many students graduating without ever having seen an autopsy due to competing departmental demands, limited curriculum time, and an insufficient number of hospital autopsies. How can it be expected that these future doctors may believe in the benefits of the autopsy and request it in their routine practice? Other reasons for fewer autopsy requests include the doctor’s discomfort in asking for the family’s consent. Doctors are not trained for, nor even convinced of, the gain of going ahead with the procedure. It is common in many institutions for the clinician to have no contact with the family before the patient’s death. This makes it more difficult for a clinician to approach the family for an autopsy. We believe that obtaining consent from a family, in most cases, can be easier than expected. The family quite often feels relief with the autopsy information. In most cases the clear understanding of the disease and death process accompanied by the disclosure that nothing else could be done that would have altered the fatal evolution, promotes some comfort. In contrast, in the UK, an increased demand for alternative procedures for post-mortem examinations due to religious objections to autopsy, among the Jewish and Muslim communities has been noticed. Therefore, post-mortem imaging was introduced with minimally invasive alternatives. Many studies try to validate this approach to the diagnosis of the cause of death in coronial autopsies. In this case, computed tomography seems to be slightly superior than magnetic resonance image. Despite the fact that radiologists can provide a cause of death accepted by the Coroner without

Campos FPF.

autopsy in 90% of cases, other investigators doubt this accuracy. A major discrepancy existed in 30% of randomly selected cases between autopsy and imaging. Due to these limitations, in the context of the determination of the cause of death, we dare to consider imaging as an auxiliary instrument to improve autopsy accuracy—but it is far from a substitute method. Much effort and commitment is needed to reverse the declining number of autopsies trend. This reversion process involves the medical school’s graduation committee, those involved in teaching programs, the pathology department of the hospital, and the hospital administration. Also, the general community needs to be better informed about the value of autopsy. It is fundamental to discuss issues related to autopsies in a similar manner to organ donations. Pathologists and clinicians as a whole should engage in measures to enhance community knowledge of the autopsy and its value. Does modern medicine still need autopsy? The answer is affirmative. If clinical autopsy rates continue to decline, the future practice of medicine will be blind to many adverse consequences of clinical actions and omissions. We advocate close communication between pathologists and clinicians in the context of the results of autopsy findings. This relationship is a strong instrument in the perpetuation of autopsy for the excellence of clinical practice. In this regard, our institution promotes weekly autopsy meetings and publishes a scientific journal with autopsy reports. In the near future, we hope to extend these meetings to other institutions by video conferences. As teachers in a teaching hospital, we still face the challenge of ensuring that medical students and residents take part in these clinico-pathological debates and sessions focused on autopsies.

BIBLIOGRAPHY 1.

Roberts ISD, Benamore RE, Benbow EW, et al. Post-mortem imaging as an alternative to autopsy in the diagnosis of adult deaths: validation study. Lancet. 2012,379:136‑42. http://dx.doi.org/10.1016/S0140-6736(11)61483-9

Zhu MH, Yu DH. Fluctuations in the rate of autopsy in China. Chin Med J. 2011;124:3403-7.

Xiao J, Krueger GR, Buja LM, Covinsky M. The impact of declining clinical autopsy: need for revised healthcare policy. Am J Med Sci. 2009;337:41-6. PMid:19155753. http:// dx.doi.org/10.1097/MAJ.0b013e318184ce2b

What does the future hold? 4.

Ayoub T, Chow J. The conventional autopsy in modern medicine. J R Soc Med. 2008;101:177‑81. PMid:18387908. PMCid:2312379. http://dx.doi.org/10.1258/jrsm.2008.070479

The Royal College Of Pathologists of Australasia Autopsy Working Party. The decline of the hospital autopsy: a safety and quality issue for healthcare in Australia. Med J Aust. 2004;180:281-5. PMid:15012566.

O’Grady G. Death of the teaching autopsy. BMJ. 2003;327:802-3. PMid:14525883. PMCid:214120. http:// dx.doi.org/10.1136/bmj.327.7418.802

Autopsy and Case Reports 2012;2(1):3-5 7.

The Royal College Of Pathologists of Australasia. Autopsies and the use of tissues removed from autopsies. Document number 106581. Durham Hall; 2011 [cited 2012 Jan 10]. Available from: http://www.rcpa.edu.au/static/File/Assetlibrary/publicdocuments/PolicyManual/Policies/Autopsiesand theUseofTissuesRemovedfromAutopsies.pdf

Karunaratne S, Benbow EW. A survey of general practitioners’ views on autopsy reports. J Clin Pathol. 1997;50:548-52. PMid:9306932. PMCid:500046. http://dx.doi.org/10.1136/ jcp.50.7.548

Correspondence: Fernando Peixoto Ferraz de Campos Scientific Editor Autopsy and Case Reports Assistant Pphysician of Internal Medicine Division Hospital Universitário – Universidade de São Paulo, São Paulo/SP – Brazil E-mail: ffcampos@usp.br

Autopsy and Case Reports 2012;2(1):7-17

Article / Autopsy Case Report Artigo / Relato de Caso de Autópsia Schistosomiasis: a case of severe infection with fatal outcome Cristiane Rúbia Ferreiraa, Fernando Peixoto Ferraz de Camposb, João Gabriel Ramosc, João Augusto dos Santos Martinesd, Elizabeth Im Myung Kimb, Luciana Andréa Avena Smeilib Ferreira CR, Campos FPF, Ramos JG, Martines JAS, Kim EIM, Smeili LAA. Schistosomiasis: a case of severe infection with fatal outcome. Autopsy Case Rep [Internet]. 2012;2(1):7-17. http://dx.doi.org/10.4322/acr.2012.002

ABSTRACT Schistosomiasis is one of the most common parasitic diseases, still considered of public health significance. Acute schistosomiasis is of difficult diagnosis and therefore has been overlooked, misdiagnosed, underestimated and underreported in endemic areas. The delay between the exposure to contaminated water and the initial symptoms may explain this challenging diagnosis. Acute schistosomiasis is frequently reported in non-immune individuals while reinfection cases occurring in endemic areas is scarcely documented. The later usually shows a benign course but fatal cases do exist. The authors report a case of a young female patient, in the late puerperium, with a three-month history of weight loss, intermittent fever, cough, thoracic and abdominal pain and increased abdominal girth. Physical examination showed a tachycardia, tachypnea and hypotension. Laboratory tests showed a mild anemia, eosinophilia, and a slightly elevation of liver enzymes. Thorax and abdominal multidetector computed tomography evidenced a diffuse and bilateral pulmonary micronodules and peritoneal and intestinal wall thickening. The patient progressed rapidly to hepatic insufficiency, and death after respiratory insufficiency. An autopsy was performed and the findings were compatible with acute Schistosomiasis in a patient previously exposed to Schistosoma mansoni. Keywords: Schistosomiasis; Hepatic insufficiency; Respiratory insufficiency; Autopsy. CASE REPORT A 25-year-old female patient sought medical attention complaining of a three-month history of weight loss, intermittent fever, nonproductive cough, thoracic pain, abdominal pain and increased abdominal girth, nausea and vomiting. She presented syncope on the day she was admitted

in the hospital. Symptoms had begun two weeks after her third deliver. Her past obstetrics history comprised three gestations without pre natal care all of them were uneventful. She denied any other comorbidity, allergy, smoking, alcoholism, prior blood transfusion or similar cases in her family.

Anatomic Pathology Service - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. Department of Internal Medicine - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. c Department of Internal Medicine Hospital das Clínicas - Faculdade de Medicina - Universidade de São Paulo, São Paulo/SP – Brasil. d Department of Radiology - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. b

Autopsy and Case Reports 2012;2(1):7-17

Ferreira CR, Campos FPF, Ramos JG, Martines JAS, Kim EIM, Smeili LAA.

She lived in a Brazil’s northeastern state that is well known for high prevalence of schistosomiasis. Physical examination demonstrated tachycardia with pulse rate of 100 beats per minute, blood pressure of 90 × 60 mmHg, tachypnea with 25 respiratory movements per minute, temperature 37 °C, oxygen saturation of 96% at room air. Cardiac and pulmonary examinations were unremarkable while the abdominal exam showed signals of small ascites. Gynecological examination ruled out any abnormality and the transvaginal ultrasound was normal except for a presence of a small myoma. The initial laboratory tests are shown in Table 1. The multi detector computed tomography (CT) of thorax and abdomen are shown in Figures 1-3.

The patient progressed, on the day after admission, with worsening of the abdominal pain, nausea and vomiting and respiratory distress. Besides the stability of hemodynamic parameters, the cutaneous perfusion got worse and serum lactate level rose. Table 2 shows the liver enzymes and prothrombine time evolution. She was referred to the Intensive Care Unit because of her clinical instability and respiratory insufficiency, where she presented cardiac arrest after vomiting and probable aspiration of gastric content. Serologies for HIV and Hepatitis virus B and C were negative.

Table 1 – Laboratory tests 12,4/36,3%

Hemoglobin

10,4

12,3-15,3 g%

Hematocrit

36,0-45,0 %

Leucocytes

6100

Segmented

Potassium

4,1

3,5-5,0 mEq.L–1

Sodium

139

136-146 mEq.L–1

4,4-11,3 10 /mm

ALT

9-36 U.L–1

45-70 %

AST

10-31 U.L–1

Eosinophils

1-4 %

229

10-100 U.L–1

Basophils

0-2,5 %

γGT

1-24 U.L–1

Linfocytes

18-40 %

Total Bilirrubin

0,4

0,3-1,2 mg.dL–1

Monocytes

2-9 %

Albumin

2,8

3-5 g.dL–1

Platelets

314

150-400103/mm3

Globulin

5,1

3-4 g.dL–1

BUN

5-25 mg.dL–1

PT (INR)

1,93

Creatinine

0,6

0,4-1,3 mg.dL–1

Glucose

<99 mg.dL–1

CRP

Amilase

20-104 U.L–1

<5 mg.L

–1

AF = alkaline phosphatase, ALT = alanine aminotranspherase, AST = aspartate aminotranspharese, BUN = blood urea nitrogen CRP = C reactive protein, γGT = gama-glutamyltranspherase, INR = international normalized ratio, PT = Prothrombine time.

Figure 1 – MDCT of the thorax – axial images of the lung base (A and B), and the pulmonary apex (C). Note disseminated, bilateral non-calcified micro nodules with centro lobular distribution. The images B and C show wedge-shaped opacities with reversed halo sign, most evident in C compatible with pulmonary infarction.

Schistosomiasis: a case of severe infection with fatal outcome

Autopsy and Case Reports 2012;2(1):7-17

Figure 2 – MDCT of the abdomen, obtained after oral and intravenous contrast media. In A a reformatted coronal image showing an heterogeneous enhancement of the hepatic parenchyma mainly at the periphery of the hepatic right lobe. Note patent portal vein of normal caliber, and lack of hepatosplenomegaly. In B – axial image – note the thickening of the intestinal wall. Table 2 – Evolution of liver enzymes and coagulation test 2nd day

3rd day

ALT

436

811

9-36 U.L–1

AST

10096

1946

10-31 U.L–1

TP (INR)

2,86

3,07

ALT = alanine aminotranspherase, AST = aspartate aminotranspharese, INR = international normalized ratio, PT = Prothrombine time.

Figure 3 – MDCT of the abdomen, reformatted image, obtained after oral and intravenous contrast media. Note slightly enlarged mesenteric lymph nodes, thickening of the intestinal wall and presence of mild ascites. An autopsy was performed. The abdominal and thoracic cavities were opened, revealing a mild serous ascites and bowel distension. The visceral peritoneum showed a whitish diffuse thickening throughout the gastrointestinal tract from the stomach to the colon. (Figure 4).

The longitudinal sectioning of the small and large intestines showed some swollen and slightly congested patchy areas of the mucous membrane. The microscopic examination evidenced the presence of uncountable, embryonated and occasionally calcified eggs of Schistosoma mansoni within the wall (most prominent in the submucosal layer) and serosa of the gastrointestinal tract. Granulomatous reaction with eosinophilic infiltration surrounded the eggs. These granulomas, of miliary distribution, showed necrotic-exudative and productive patterns, but few of them showed an advanced fibrotic stage. There were also observed numerous viable and dead worms in the lumen of veins, especially in the subserosal layer and occasionally in the submucosa (Figures 5 and 6). On the distal submucosal layer of the esophagus it was found embryonated eggs. No evidence of esophageal varicose veins was depicted. The liver weighted 1547.0 g (reference value: 1100.0-1450.0 g). On sectioning it showed a winy appearance with thickening of the larger portal tracts, featuring the Symmers fibrosis.

Autopsy and Case Reports 2012;2(1):7-17

Ferreira CR, Campos FPF, Ramos JG, Martines JAS, Kim EIM, Smeili LAA.

Multiple whitish granules scattered randomly in the parenchyma were present, more evident in the left lobe (Figure 7). Microscopically, there were fibrous expansion of portal spaces in the pipe-stem pattern fibrosis with granulomatous reaction, at different stages of immunomodulation with eosinophilic infiltration, surrounding embryonated and occasionally calcified eggs in the conjunctive stroma or portal vessels, as well as in the hepatic lobule. In the hepatic lobule there were also extensive areas of sinusoidal congestion and hepatocyte necrosis, especially in zones 3 and 2, with areas of microvesicular steatosis (Figure 8). The pancreas weighted 193.0 g (reference value = 60.0-135.0 g) and presented a whitish thickening of the anterior surface. On sectioning it showed the usual lobulated parenchyma. On

microscopy, it was observed countless embryonated eggs entrapped in the pancreatic parenchyma, some of them surrounded by granulomatous reaction exhibiting a necrotic-exudative pattern with eosinophil (Figures 9 and 10). The spleen weighted 170.0 g (reference value = 112.0 g); the capsule was smooth and the parenchyma was homogeneous and winy, on sectioning. The microscopy showed white pulp reactive hyperplasia and red pulp congestion with no evidence of congestive spleen sclerosis (Figures 9 and 10). In the thoracic cavity effusions were not observed. Both lungs were enlarged, right lung weighted 610.0 g and left lung weighted 498.0 g (reference value RL = 360.0-57.0 g and LL = 325.0‑480.0 g) and showed countless whitish nodules measuring up to 0.2 cm scattered

Figure 4 – A- Panoramic picture of the abdominal cavity showing distended bowel segments covered by a whitish and thick serosa and mild ascites. B- Detail of small bowel surface serosa showing the whitish granular thickness.

Figure 5 – Photomicrography (HE-400x) - A and B- Viable adult S. mansoni worms within vessel lumen.

Schistosomiasis: a case of severe infection with fatal outcome

Autopsy and Case Reports 2012;2(1):7-17

throughout the lung parenchyma and pleural surface. In the left upper pulmonary lobe there was a cavitated lesion measuring 3.0 cm. In the base

of the right lung, a grayish triangular area of firm consistency was detected resembling a pulmonary infarction (Figure 11).

Figure 6 – Photomicrography - A- (HE-100x) Gastric wall presenting viable S. mansoni adult worms within a venous vessel of the submucosa and presence of numerous eggs in the lamina propria of the mucosal layer; B- (HE-400x) Presence of calcified eggs within the large intestine submucosal layer; C- (HE-200x) Scar fibrotic granuloma surrounding egg debris within the large intestine subserosa; D- (HE-200x) Necroticexudative pattern granuloma involving viable eggs within the large intestine subserosal layer.

Figure 7 – A- Gross examination of the liver showing winy hepatic parenchyma presenting multiple whitish micro nodules. Note the fibrous thickness of portal space; B- Detail of the whitish fibrous thickening of the portal space, characterizing the presence of Symmers fibrosis.

Autopsy and Case Reports 2012;2(1):7-17

Ferreira CR, Campos FPF, Ramos JG, Martines JAS, Kim EIM, Smeili LAA.

The microscopic examination showed a necrotic-exudative granulomatous reaction with eosinophil surrounding embryonated eggs of S. mansoni within peribronchial artery branches and adjacent alveolar parenchyma. There were

still observed the presence of numerous viable and dead worms within the vascular lumen, sometimes eliciting necrotic-exudative granulomatous reaction, eosinophilia, and ischemic necrosis of the adjacent parenchyma. It was also identified

Figure 8 – Photomicrography - A (HE-100x) Portal space presenting a necrotic exudative granuloma with eosinophils besides the presence of a calcified egg and Symmers fibrosis; B (HE-100x) Hepatic parenchyma presenting passive congestion with hepatocyte necrosis in zones 2 and 3; C (HE-400x) Presence of a scar granuloma with concentric fibrosis involving a calcified egg within the hepatic parenchyma; D (HE-400x) Presence of necrotic-exudative pattern granuloma surrounding a viable egg within the portal space. Note the presence of blackened schistosome pigment deposition in all these photomicrographies.

Figure 9 – A- Gross examination of the pancreas showing whitish thickening of the anterior surface, preserved parenchyma lobulation on sectioning and lack of steatonecrosis; B- Gross examination of the spleen showing a homogeneous winy parenchyma on sectioning surface.

Schistosomiasis: a case of severe infection with fatal outcome

Autopsy and Case Reports 2012;2(1):7-17

a dead worm within a segmental bronchus accompanied by the similar histologic feature of the acute Loeffler’s syndrome. On the wall of the left upper lobe cavity lesion it was identified the presence of countless embryonated eggs (Figure 12).

Lymphadenomegaly was found in the mesenteric, peripancreatic, along the curvature of the stomach, pulmonary hilum and peritracheal lymph node chains. Many of these lymph nodes entrapped schistosome eggs surrounded by granulomatous reaction.

Figure 10 – Photomicrography (HE-200x) – A- Numerous viable eggs of S. mansoni within the pancreatic parenchyma; B- Splenic parenchyma showing white pulp reactive lymphoid hyperplasia.

Figure 11 – A- Panoramic picture of the left lung showing a cavitary lesion in the apex of the superior lobe; B- Panoramic picture of right lung sectioning surface showing multiple whitish nodules and the presence of a triangular whitish area corresponding a inferior lobe infarction; C- Detail of the right inferior pulmonary lobe showing multiples tiny whitish nodules, measuring up to 0,1 cm and a triangular infarction area; D- Sectioning surface of the left superior pulmonary lobe showing an apical cavitary lesion.

Autopsy and Case Reports 2012;2(1):7-17

Ferreira CR, Campos FPF, Ramos JG, Martines JAS, Kim EIM, Smeili LAA.

No other significant gross or microscopic findings were detected.

DISCUSSION Schistosomiasis is one of the most common parasitic diseases, still considered of public health significance, affecting around 207 million people in tropical and subtropical areas of the globe.1,2 In Brazil, the disease ranks higher in prevalence than HIV/AIDS. The clinical manifestations can be divided into three major stages. The first stage occurs after skin penetration by the cercariae and manifests as a pruritic rash. The second stage usually occurs weeks after infection during maturation of the adult fluke and the third or chronic stage appears months to years after infection and results from granuloma formation around the schistosome eggs entrapped in many tissues. Acute schistosomiasis (AS) has been overlooked, misdiagnosed, underestimated and underreported in endemic areas. Among

the non-immune individuals, risk groups are well known, including military recruits, some religious congregations, rural tourists and recreational water sports practitioners.3 We report a fatal outcome case of postpartum young woman, coming from an endemic area for schistosomiasis, with signs of massive reinfection developing clinical symptoms of AS. AS or Katayama syndrome (KS) (formerly called Katayama fever) occurs as an early clinical manifestation of infection with Schistosoma species in non-immune individuals or after heavy reinfection with schistosome cercariae in endemic areas.3-5 The disease is usually acquired after the exposure to contaminated water. A contact as brief as 1-5 minutes may be enough to allow transcutaneous penetration by cercariae.6 KS caused by S. mansoni is rarely reported among chronically exposed population, probably because of in-utero sensitization or because an adaptive immune response protects from developing an acute toxemic condition7 or even because these

Figure 12 – Photomicrography - A (HE – 100X) Peribronchial arterial vessel showing endarteritis and granulomatous reaction surrounding viable eggs of S. mansoni; B (HE – 400X) Presence of dead worms, with coagulative necrosis, within the lumen of a small bronchus; C (HE – 100X) Lung parenchyma exhibiting the presence of necrotic-exudative granulomas surrounding viable eggs and alveolar edema; D (HE – 400X) Lung parenchyma exhibiting the presence of exudative granuloma with intense infiltration of eosinophils.

Schistosomiasis: a case of severe infection with fatal outcome

Autopsy and Case Reports 2012;2(1):7-17

cases simply go unrecognized.4,8 In Brazil, there were only two cases described in the literature.9-12

around the eggs. On gross examination the granulomas appear as tiny, whitish nodules, isolated or confluent, countless in the acute form of the disease, located mainly in the liver, small and large intestines and lungs. The number of the granulomas diminishes gradually with the chronicity of the disease.3,18 Protein antigens derived from eggs and adult worms induce immune response mediated by Th1 and Th2 lymphocytes alternatively, according to the stage of infection (acute, chronic or delayed).18

The KS occurs due to a systemic hypersensitivity reaction against the larvae (schistosomules), adult schistosome organisms and early oviposition by adult worms occurring within 14-60 days after the infection.3,5,13,14 In many cases, the acute phase of infection courses without symptoms.4 Incubation periods ranging from 1 to 12 weeks have been reported.6 The severity of symptoms varies according to the infecting species, the cercarial burden and immune response to the released parasites antigens. Rocha et al., showed a statistic significance correlation between the levels of IgE and IgG and the intensity of the infection estimated by the number of eggs in the feces.6,15 Disease onset is usually sudden, presenting high grade fever, chills, headache, fatigue, myalgia, malaise, facial and lower limbs edema, urticaria, non-productive cough (occasionally bronchospasm), eosinophilia and patchy pulmonary infiltrates on chest radiography. Abdominal symptoms may develop within a few weeks due to the migration of juvenile worms and oviposition by the mature ones. Most patients recover after 2-10 weeks, whereas some develop serious disease with weight loss, dyspnea, chest pain, diarrhea, diffuse abdominal pain, splenomegaly, hepatomegaly with elevation of hepatic enzymes, restrictive respiratory insufficiency and generalized rash.4,7,16 The central nervous system involvement of AS may occur as meningoencephalitis or myelitis.17 The clinical picture presented by our patient was very similar to the signs and symptoms described above. Advanced chronic schistosomiasis was not clinically identified, not even the computed tomography could show signs of hepatic fibrosis or portal hypertension.

The study of Jesus et al. showed that the Th1 response dominates the early phase of acute schistosomiasis when IFN-γ, IL-2 and TNF-α are detected in high levels. This proinflammatory reaction is down regulated by the secretion of a series of cytokines as: IL-4, IL-5, IL-10 and IL13, which are released when oviposition ensues. The Th2 cells produce protective eosinophil-rich granulomatous lesions around new deposited eggs, which in early phase show necrotic-exudative features. The absence of or inability to develop a Th2 response also contributes to maintaining the toxemic symptoms and a fatal outcome.3,7 Proinflammatory cytokines and TNF-α detected in the serum of these patients may explain constitutional symptoms.7 The granulomatous reaction is a dynamic process. Initialy, the granulomas are bulky, exhibits a necrotic-exudative pattern, with large numbers of macrophages, lymphocytes and eosinophils around the egg. This exudate progressively decreases, being replaced by fibrotic nodules.18 Granulomas of the acute phase of the disease are all synchronic and show the necrotic-exsudative pattern, featuring the first oviposition.3,19 The fibrotic granuloma appears from 150 days of the disease and as well as the calcified eggs characterizes the chronic phase of the disease. Another characteristic of chronic disease is the presence of non-synchronous granulomas indicating that the eggs appeared in successive periods.18,19

In the case reported here the hallmark pathological findings for the diagnosis of KS by reinfection of S. mansoni, on autopsy, were: the evolving pattern of granulomatous response, parasite load represented by the number of spread worms and eggs, the hepatic portal fibrosis with the typical pattern of Symmers fibrosis, and finally the absence of signs and findings of portal hypertension despite the hepatic portal fibrosis.

In the case reported here, it was observed a miliary spread of eggs with granulomas showing the necrotic-exudative pattern in all the affected organs. Fibrotic granulomas and calcified eggs were scarcely detected within the colon wall and the liver. The presence of Symmers fibrosis in the hepatic portal spaces also indicated the coexistence of the two forms of the disease simultaneously.

Regardless the anatomo clinical presentation of the disease, the most important lesion of schistosomiasis is the granulomatous inflammation

The Symmers fibrosis is described as the anatomopathologic hallmark of the chronic hepatosplenic form of schistosomiasis when portal

Autopsy and Case Reports 2012;2(1):7-17

Ferreira CR, Campos FPF, Ramos JG, Martines JAS, Kim EIM, Smeili LAA.

hypertension and its hemodynamic effects are present.18,19 Patients from endemic areas may show changes similar to those described in liver Symmers fibrosis, but without splenomegaly or other evidence of portal hypertension. It is suggested that these patients are able to adapt to minimize hemodynamic portal hypertension. Such cases could represent the advanced hepatointestinal or pre-hepatosplenic stage.19 Pulmonary involvement may occur at all stages of infection. During the acute stage, the pulmonary lesions are due to larval pneumonitis or by granulomatous reaction elicited by the eggs deposited around pulmonary vessels, what also occurs in chronic infection.20 The disproportion between the number of eggs and worms, the finding of granulomas and vascular lesions in different evolutive phases indicates that the eggs do not reach the lungs at the same time, but in successive periods during chronic infection.18 Interestingly, in this case, we observed an acute miliary spread of schistosome eggs and embolization of numerous worms alive or dead within the lungs, eliciting exudative-necrotic granulomatous reaction with dense eosinophilic infiltration. There were also dead worm pneumonitis, with areas of pulmonary infarction and cavitations, with histologic findings similar to Loeffler’s syndrome. Vascular lesions, such as vasculitis, endarteritis and necrosis secondary to embolized eggs and worms in small arteries and arterioles, were observed as well. Eggs and worms embolism into the pulmonary vessels elicit granulomatous and fibrous response that leads to pulmonary hypertension in patients with chronic infection who have liver disease with portal hypertension.20 The patient presented here did not present findings or signs of portal hypertension and the pulmonary pathological findings were more compatible with the acute phase of the disease. We assume that the pulmonary hypertension developed in this case was due to the extension of pulmonary vascular involvement, which associated to the cardiovascular collapse, resulted in passive congestion and hepatic necrosis with consequent hepatic failure. Pulmonary complications are correlated with scattered pulmonary nodules ranging in size from, 2 to 15 mm with ill-defined borders, observed on chest X-rays or computed tomography. Less common are the reticulonodular pattern. In some

cases the nodules are associated with a groundglass halo while diffuse ground-glass pattern is also reported. Labertucci et al reported a case in which the nodules seemed to coalesce in some areas, thus simulating pulmonary condensation. These radiographic abnormalities point to interstitial pneumonitis. Micronodules disseminated in both lung fields have also been described in acute or chronic schistosomiasis. The miliary distribution of eggs, known to occur in this phase, may be sufficient to explain this presentation.16,21 The radiographic abnormalities seem to be not correlated with respiratory symptoms, as they may be present even in the absence of the symptoms.6,22-25 Enormous effort has been made to control schistosomiasis in Brazil, but unfortunately it remains a public health problem. The recognition of acute schistosomiasis in populations from endemic and non-endemic areas with a prior infection history is still challenging. The AS has a wide spectrum of clinical manifestations, and may be fatal in severe forms.

ACKNOWLEDGEMENTS We are grateful to Rosa Maria C. Zanardi for the technical support on the visual work.

REFERENCES 1.

Beck L, Van-Lüme DSN, Souza JR, et al. Discriminating acute from chronic human schistosomiasis mansoni. Acta Tropica. 2008;108:229-33. PMid:18851939. http://dx.doi. org/10.1016/j.actatropica.2008.08.012

Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J. Schistosomiasis and water resources a review, metaanalysis and estimates of people at risk. Lancet Infect Dis. 2006;6:411‑25. http://dx.doi.org/10.1016/S1473-3099 (06)70521-7

Lambertucci JR. Acute schistosomiasis mansoni: revisited and reconsidered. Mem Inst Oswaldo Cruz. 2010; 105:422‑35. http://dx.doi.org/10.1590/S0074-02762010000400012

Ross AG, Vickers D, Olds GR, Shah SM, Mcmanus DP. Katayama syndrome. Lancet Infect Dis. 2007; 7:218-24. http://dx.doi.org/10.1016/S1473-3099(07)70053-1

Bottieau E, Clerinx J, de Vega MR, et al. Imported Katayama fever: clinical and biological features at presentation and during treatment. J Infect. 2006; 52:339-45. PMid:16169593. http://dx.doi.org/10.1016/j.jinf.2005.07.022

Schistosomiasis: a case of severe infection with fatal outcome

Autopsy and Case Reports 2012;2(1):7-17

Jauréguiberry S, Ansart S, Perez L, Danis M, Bricaire F, Caumes E. Acute neuroschistosomiasis: two cases associated with cerebral vasculitis. Am J Trop Med Hyg. 2007;76:964-6. PMid:17488923.

16. Lambertucci JR, Rayes AAM, Barata CH, Teixeira R, Gerspacher-Lara R. Acute Schistosomiasis: report on five singular cases. Mem Inst Oswaldo Cruz. 1997;92:631‑5. http://dx.doi.org/10.1590/S0074-02761997000500013

Jesus AR, Silva A, Santana LB. Clinical and immunologic evaluation of 31 patients with acute Schistosomiasis mansoni. J Infect Dis. 2002;185:98-105. PMid:11756987. http://dx.doi.org/10.1086/324668

King CL, Malhotra I, Mungai P, et al. B cell sensitization to helminthic infection develops in utero in humans. J Immunol. 1998;160:3578-84. PMid:9531321

17. Urban CA, Piovesan EJ, Almeida SM, Kowacs PA, Minguetti G, Werneck LC. Esquistossomose aguda com comprometimento cerebral. Arq Neuropsiquiatr 1996;54:677-82. Portuguese. PMid:9201353. http://dx.doi.org/10.1590/S0004-282X1996000400021

Neves J, Raso P. Estudo anátomo-clínico de um caso de forma toxêmica da esquistossomose mansoni que evoluiu para a forma hepatoesplênica em 130 dias (fibrose hepática de Symmers). Rev Inst Med Trop Sao Paulo. 1965;7:256-66. Portuguese. PMid:5854950.

10. Katz N, Bittencourt D. Sobre um provável caso de forma toxêmica no decurso da forma hepatoesplênica da esquistossomose mansônica. Hospital (Rio J). 1965;67:847‑58. Portuguese.

18. Raso P. Esquistossomose mansônica. In: Brasileiro Filho G, editor. Bogliolo patologia. 7a ed. Rio de Janeiro: Guanabara Koogan; 2006. p. 1337-59. Portuguese. 19. Freitas LAR, Reis MG, Freitas JR, et al. Esquistossomose mansônica. In: Brasileiro Filho G, editor. Bogliolo patologia. 8a ed. Rio de Janeiro: Guanabara Koogan; 2011. p. 1387-98. Portuguese. 20. Travis WD, Colby TV, Koss MN, et al. Lung infections. In: Travis WD, editor. Non-neoplastic disorders of the lower respiratory tract. Washington: Armed Forces Institute of Pathology; 2002. p. 696-9. Atlas of nontumor pathology.

11. Lambertucci JR. Acute Schistosomiasis: clinical, diagnosis and therapeutic features. Rev Inst Med Trop Sao Paulo.1993;35:399-404. http://dx.doi.org/10.1590/S003646651993000500003

21. Bogliolo L. Subsídios para o estudo da anatomia patológica da forma aguda toxêmica da esquistossomose mansônica. Gen. 1964;19:157-236. Portuguese.

12. Ross AG, Sleigh AC, Li Y, et al. Schistosomiasis in the People’s Republic of China: prospects and challenges for the 21st century. Clin Microbiol Rev. 2001;14:270-95. PMid:1129263. PMCid:88974. http://dx.doi.org/10.1128/ CMR.14.2.270-295.2001

22. Nguyen LQ, Estrella J, Jett EA, Grunvald EL, Nicholson L, Levin DL. Acute schistosomiasis in nonimmune travelers: chest CT findings in 10 patients. AJR Am J Roentgenol. 2006;186:1300-3. PMid:16632722. http://dx.doi. org/10.2214/AJR.05.0213

13. Ross AG, Bartley PB, Sleigh AC, et al. Schistosomiasis. N Engl J Med. 2002;346:1212-20. PMid:11961151. http:// dx.doi.org/10.1056/NEJMra012396

23. Lambertucci JR, Silva LCS, Queiroz LC. Pulmonary nodules and pleural effusion in the acute phase of schistosomiasis mansoni. Rev Soc Bras MedTrop. 2007;40:374‑5. PMid:17653482. http://dx.doi.org/10.1590/S0037-86822007000300027

14. Zuidema PJ. The Katayama syndrome: an outbreak in Dutch tourists to the Omo National Park, Ethiopia. Trop Geogr Med. 1981;33:30-5. PMid:7245338. 15. Rocha MOC, Pedroso ERP, Greco DB, et al. Pathogenetic factors of acute schistosomiasis mansoni: correlation of worm burden, IgE, blood eosinophilia and intensity of clinical manifestations. Trop Med Int Health 1996;1:213‑20. http://dx.doi.org/10.1111/j.1365-3156.1996.tb00029.x

24. Schwartz E. Pulmonary schistosomiasis. Clin Chest Med. 2002;23:433-43. http://dx.doi.org/10.1016/S02725231(01)00013-2 25. Waldman ADB, Day JH, Shaw P, Bryceson ADM. Subacute pulmonary granulomatous schistosomiasis: high resolution CT appearances: another cause of the halo sign. J Radiol. 2001;74:1052-5.

Conflict of interest: None Submitted on: 6th February 2012 Accept on: 28th February 2012 Correspondence: Serviço de Anatomia Patológica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária – São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9384 E-mail: crisrf@hu.usp.br

Autopsy and Case Reports 2012;2(1):19-23

Article / Autopsy Case Report Artigo / Relato de Caso de Autópsia “Nutrothorax” complicating a misplaced nasogastric feeding tube in a severely ill patient Aloísio Felipe-Silvaa, Fernando Peixoto Ferraz de Camposb Felipe-Silva A, Campos FPF. “Nutrothorax” complicating a misplaced nasogastric feeding tube in a severely ill patient. Autopsy Case Rep [Internet]. 2012;2(1):19-23. http://dx.doi.org/10.4322/acr.2012.003

ABSTRACT Introduction of nasogastric feeding tubes is usually blindly performed and is generally considered a safe procedure. However, the rate of complications of a blind insertion technique varies from 0.3 to 15%, and is usually related to inadvertent insertion of nasogastric tubes into the trachea and distal airways. The main predisposing factors related to tube malpositioning and complications are altered mental status with decreased cough or gag reflex, a preexisting endotracheal tube and severe illness. Complications include severe aspiration pneumonia, hydrothorax, hemothorax, empyema and pneumothorax. The mortality related to misplacement of a nasogastric tube is around 0.1-0.3% of the procedures. This 61-year old female had a history of poor appetite, weight loss, dyspnea and fever. A chest axial computerized tomography showed enlarged mediastinal lymph nodes. Laboratory showed hypercalcemia with normal PTH and hypokalemia. As the patient remained anorectic, a nasogastric feeding tube was placed, through which the administration of enteral diet, by continuous infusion pump, was started. After 12 hours the patient developed dyspnea, hypoxemia and hypotension. During orotracheal intubation, it was disclosed the presence of the nasogastric tube in the trachea as well as the infused diet within the respiratory tract. Autopsy revealed an unusual complication of a nasogastric tube misplacement, which led to a massive collection of enteral nutrition fluid into the pleural space – a “nutrothorax”. Additionally, an underlying stage IV anaplastic large cell lymphoma with interstitial lung and bronchial mucosa involvement was diagnosed. Keywords: Enteral Nutrition; Lymphoma, Non-Hodgkin; Pleural Effusion; Hydrothorax; Autopsy CASE REPORT A 61-year old female patient sought medical attention complaining of poor appetite and weight loss during the last 3 weeks. She referred malaise, a recent onset of dyspnea and fever during the last 5 days. She denied any other gastrointestinal, genitourinary or respiratory symptoms. The patient a b

has been paraplegic of unknown cause since the age of 32 and was a mild smoker. Physical examination upon admission revealed a drowsy, weakened, pale, lightly emaciated, dehydrated and feverish patient.

Anatomic Pathology Service - Hospital Universitário - Universidade de São Paulo - São Paulo/SP – Brazil. Department of Internal Medicine - Hospital Universitário - Universidade de São Paulo - São Paulo/SP – Brazil.

Autopsy and Case Reports 2012;2(1):19-23

Felipe-Silva A, Campos FPF.

Room air oxygen saturation reading was 86% and respiratory rate was 8 movements per minute. The pulse rate was 80 beats per minute and blood pressure was 90 × 60 mmHg. Mild edema was evidenced on the lower limbs. She had pressure ulcers in sacral, pelvic and trochanteric regions with apparent infection signs on the latter. Remainder physical and neurological examination was unremarkable. Capillary blood glucose was 147 mg.dL–1. The chest X-ray showed a small bilateral pleural effusion and the electrocardiogram was within the normal limits. Initial laboratory tests showed mild anemia, moderate leukocytosis, hypercalcemia and hypokalemia (Table 1). The chest axial computerized tomography showed enlarged mediastinal lymph nodes (greater than 2.4 cm in its longest axis) in the right para-aortic chain, hilar and carinal regions, as well as in the aortopulmonary window; moderate pleural effusion and associated restrictive bilateral atelectasis. The patient was admitted with diagnoses of hypercalcemia with normal PTH, hypokalemia and mediastinal lymphadenopathy. Fever was attributed to an underlying lymphadenopathy (suspected lymphoma) and possibly to a secondary infection of pressure ulcers. Hypercalcemia was initially treated

with intravenous saline hydration and furosemide, followed by pamidronate administration. On the third day of hospitalization, as the patient remained anorectic, a standard silastic nasogastric feeding tube was blindly placed, through which the administration of enteral diet was started by a continuous infusion pump. This kind of feeding tube has a covered metal stylet on the tip. Introduction of the feeding tube was blindly performed and uneventful. The verification of tube placement was clinically evaluated by auscultation of the epigastric area while insufflating air through the tube. After 12 hours of the diet administration the patient developed dyspnea, hypoxemia and hypotension, demanding mechanical ventilatory support. During orotracheal intubation, it was disclosed the presence of the nasogastric tube in the trachea as well as the infused diet within the respiratory tract. The patient progressed rapidly to cardiopulmonary arrest unresponsive to cardiopulmonary resuscitation. An autopsy was required.

Autopsy Findings A massive right sided, pinkish and milky pleural effusion (about 1000 mL) was noted (Figure 1), accompanied by right lung collapse and extensive exudative pleuritis. Right main bronchus

Table 1 – Laboratory tests RV

Hemoglobin

11.5

12.3-15.3 g%

iCa

2.4

1.1-1.4 mmol.L–1

Hematocrit

36.0-45.0%

tCa

14.5

8.6-10.0 mg.dL–1

MCV

80-96 fL

MCH

27.5-33.2pg

BUN

5-25 mg.dL–1

RDW

18.2

11-16%

Creatinine

1.1

0.4-1.3 mg.dL–1

Leukocytes

16600

4.4-11.3 103/mm3

Mielocytes

Sodium

143

136-146 mEq.L–1

Bands

1-5%

Potassium

2.7

3.5-5.0 mEq.L–1

Segmented

45-70%

Eosinophils

1-4%

ALT

9-36 U/L

Basophils

0-2.5%

AST

105

10-31 U/L

Linfocytes

18-40%

Albumin

2.16

3-5 g.dL–1

Monocytes

TSH

1.64

0.5-4.7 mcUI.L–1

Platelets

157.10

PTH

10-65 pg.mL–1

2-9% 3

150-400 10 /mm 3

ALT = alanine aminotransferase, AST = aspartate aminotransferase, BUN = blood urea nitrogen, iCa = ionized calcium, MCH = mean corpuscular hemoglobin, MCV = mean cospuscular volume, PTH = parathyroid hormone, RDW = red cell distribution width, tCa = total calcium, TSH = thyroid stimulating hormone, RV = reference value.

“Nutrothorax” complicating a misplaced nasogastric feeding tube in a severely ill patient

Autopsy and Case Reports 2012;2(1):19-23

detected in the para-aortic chain, hilar and carinal regions (Figure 2). Enlarged (up to 2.0 cm) and partially necrotic lymph nodes were also detected in abdominal para-aortic, peripancreatic and retroperitoneal regions. Microscopic examination revealed lymph node architecture effacement by solid sheets of pleomorphic cells with horse-shoe or kidney-shaped nuclei in a necrotic and inflammatory background (Figure 3A). Immunostaining was diffusely positive for CD3 (Figure 3C) and CD30 (Figure 3D) and focally positive for CD56, CD4 and CD5. Immunostains for ALK, EMA, CD20, CD8 and EBV were negative. Cell proliferation index by Ki67 was 90%. These findings were consistent with an ALKnegative anaplastic large cell lymphoma (ALCL).

Figure 1 – Autopsy posterior view of the thoracic cavity. Note the milky enteral nourishment fluid covering almost all pleural surfaces. Diaphragm is seen in the bottom.

Spleen and bone marrow were diffusely infiltrated by ALCL. There were also multiple microscopic foci of interstitial infiltration in the liver, lungs, bronchial mucosa (Figure 3B) and kidneys. Microscopic examination of the right lung showed edema, congestion and focal foreign body giant cell reaction. Left lung showed only moderate congestion.

DISCUSSION

Figure 2 – Autopsy posterior view of trachea and main bronchi (opened). Note puncture lesion at the right main bronchus (white arrow) and inflamed background mucosa and right lung pleuritis. Note enlarged carinal lymph node (black arrow). examination depicted a puncture lesion within an inflamed background mucosa (Figure 2). This was consistent with a lesion caused by the nasogastric feeding tube. Multiple enlarged (up to 3.0 cm), partially necrotic and confluent lymph nodes were

Introduction of nasogastric feeding tubes is usually blindly performed and is considered a very safe procedure in awake patients.1 The placement of a nasogastric tube is usually evaluated by aspirating fluid from the proximal port or insufflating air while auscultating the epigastric area. However, both these physical examination based techniques may fail to detect tube malpositioning. Radiological confirmation of tube positioning is considered the gold standard method.2 The rate of complications of a blind insertion technique varies from 0.3 to 15%.1 and is usually related to inadvertent insertion of nasogastric tubes into the trachea and distal airways. Severe aspiration pneumonia, hydrothorax, hemothorax, empyema and delayed pneumothorax have been described as complications of releasing chemicals into the lungs and pleural spaces.3-6 Rarely, there may be penetration into the pleural cavity, which is a potentially lethal complication. Actually, the mortality related to misplacement of a nasogastric tube is around 0.1-0.3%.1,7 Haas and colleagues have

Autopsy and Case Reports 2012;2(1):19-23

Felipe-Silva A, Campos FPF.

Figure 3 – Anaplastic large cell lymphoma (A) with bronchial mucosa infiltration (B) – Hematoxilin and Eosin (400×). Immunostaining were positive for CD3 (C) and CD30 (D) – (400×). coined the term “nutrothorax” to name the collection of enteral nutrition fluid in the pleural space.8 The main predisposing factors related to tube malpositioning and complications are altered mental status with decreased cough or gag reflex, a preexisting endotracheal tube and severe illness. The bore and rigidity of the nasoenteral feeding tube are also related to the incidence of complications. The placement of large-bore nasogastric tubes in patients under general anesthesia is less frequently associated with the overwhelming bronchopulmonary complications observed with small-bore tubes in critically ill patients.1In fact, in Odocha series of tracheopleuropulmonary injuries following enteral feeding tube insertion, 14% of the patients had advanced cancer or other terminal state.7 The peak incidence of ALK-negative ALCL is in adults, with a modest male predominance (1.5:1).9 Most patients present with advanced stage III or IV disease, with peripheral and/or abdominal lymphadenopathy and B symptoms, with an overall 5-year survival less than 45%.10

This patient had a stage IV ALCL with some interstitial lung and bronchial mucosa involvement. She also had an altered mental status (drowsiness), although consciousness level was preserved. Ishigami et al described an autopsy case in which the pleural misinsertion of a nasogastric feeding tube was attributed to an increased fragility in a lung with pneumonia. They also found multinucleated giant cells in pleural exudate and in lung parenchyma that most likely appeared because of a foreign body reaction against the nourishment material.11 No previous significant primary pleuropulmonary disease was seen at this autopsy. However, one could hypothesize that multifocal interstitial infiltration by ALCL could have increased mucosal and parenchymal fragility, thus predisposing to lung perforation by a misplaced feeding tube. In summary, this case illustrates an unusual and dramatic presentation of nasogastric tube misplacement complications in a severely ill patient. Clinical and nurse staff should keep alert with respect to the nasogastric tube position. A 2-step radiological confirmation approach is advised when placing small-bore nasoenteral tubes in critically ill

“Nutrothorax” complicating a misplaced nasogastric feeding tube in a severely ill patient

patients.1Simple bedside tests are unreliable in this setting and careful imaging confirmation should become the standard of care.

Sabga E, Dick A, Lertzman M, Tenenbein M. Direct administration of charcoal into the lung and pleural cavity. Ann Emerg Med. 1997;30(5):695-7. http://dx.doi.org/10.1016/ S0196-0644(97)70090-8

Kawati R, Rubertsson S. Malpositioning of fine bore feeding tube: a serious complication. Acta Anaesthesiol Scand. 2005;49(1):58-61. PMid:15675983. http://dx.doi. org/10.1111/j.1399-6576.2005.00508.x

Odocha O, Lowery RC, Mezghebe HM, Siram SM, Warner OG. Tracheopleuropulmonary injuries following enteral tube insertion. J Natl Med Assoc. 1989;81(3):275-81. PMid:2496234. PMCid:2571629.

Haas LE, Tjan DH, van Zanten AR. ‘Nutrothorax’ due to misplacement of a nasogastric feeding tube. Neth J Med. 2006;64(10):385-6. PMid:17122457.

Mason DY, Harris NL, Delsol G, et al. Mature T – and NKcell neoplasms. Anaplastic large cell lymphoma, ALK-negative. In: Swerlow SH, Campo E, Harris NL, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 317-9.

ACKNOWLEDGEMENTS We are grateful to Rosa Maria C. Zanardi for the technical support on the visual work.

REFERENCES 1.

Halloran O, Grecu B, Sinha A. Methods and complications of nasoenteral intubation. JPEN J Parenter Enteral Nutr. 2011;35(1):61-6. PMid:20978245. http://dx.doi. org/10.1177/0148607110370976 Marderstein EL, Simmons RL, Ochoa JB. Patient safety: effect of institutional protocols on adverse events related to feeding tube placement in the critically ill. J Am Coll Surg. 2004;199(1):39-47. PMid:15217627. http://dx.doi. org/10.1016/j.jamcollsurg.2004.03.011

Torrington KG, Bowman MA. Fatal hydrothorax and empyema complicating a malpositioned nasogastric tube. Chest. 1981;79(2):240-2. PMid:7460662. http://dx.doi. org/10.1378/chest.79.2.240

Miller KS, Tomlinson JR, Sahn SA. Pleuropulmonary complications of enteral tube feedings. Two reports, review of the literature, and recommendations. Chest. 1985;88(2):230-3. PMid:3926393. http://dx.doi. org/10.1378/chest.88.2.230

Autopsy and Case Reports 2012;2(1):19-23

10. ten Berge RL, de Bruin PC, Oudejans JJ, Ossenkoppele GJ, van der Valk P, Meijer CJ. ALK-negative anaplastic large-cell lymphoma demonstrates similar poor prognosis to peripheral T-cell lymphoma, unspecified. Histopathology. 2003;43(5):462-9. PMid:14636272. http://dx.doi. org/10.1046/j.1365-2559.2003.01726.x 11. Ishigami A, Kubo S, Tokunaga I, Gotohda T, Nishimura A. An autopsy case of severe pleuritis induced by misinsertion of a nasogastric nourishment tube: diagnostic significance of multinucleated giant cells. Leg Med (Tokyo). 2009;11(4):191-4. PMid:19362870. http://dx.doi. org/10.1016/j.legalmed.2009.02.065

Conflict of interest: None Submitted on: 16th February 2012 Accept on: 1st March 2012 Correspondence: Serviço de Anatomia Patológica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária - São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9379. E-mail: aloisiosilva@hu.usp.br

Autopsy and Case Reports 2012;2(1):25-28

Artigo / Relato de Caso Clínico Article / Clinical Case Reports Aortic dissection-induced acute flaccid paraplegia treated with cerebrospinal fluid drainage Eduardo Leal Adama, Henrique Lane Staniaka, Rodolfo Sharovskyb, Adriano Ferreira da Silvab, Cláudio Campi de Castrob, Márcio Sommer Bittencourta Adam EL, Staniak HL, Sharovsky R, Silva AF, Castro CC, Bittencourt MS. Aortic dissection-induced acute flaccid paraplegia treated with cerebrospinal fluid drainage. Autopsy Case Rep [Internet]. 2012;2(1):25-28. http://dx.doi.org/10.4322/acr.2012.004

ABSTRACT Acute aortic dissection is a life-threatening event in which prompt and correct diagnosis is associated with better outcomes. In most cases, there is chest or back pain. However, in rare cases, patients have little or no pain and other symptoms are more conspicuous at presentation. The autors reports the case of a 47-year-old female patient who sought medical attention for sudden-onset paraplegia. The physical examination was normal except for bilateral lower limb flaccid paralysis, with abolition of deep tendon reflexes and paraesthesia in both feet. Computed tomography showed aortic dissection, with partial thrombosis of the false lumen, starting after the emergence of the left subclavian artery and extending, toward the bifurcation of the aorta, to the left iliac artery. After cerebrospinal fluid drainage, the evolution was favorable. Keywords: Aortic diseases; Aneurysm, dissecting; Paraplegia; Cerebrospinal fluid. CASE REPORT A 47-year-old female patient presented to the emergency room (ER) complaining of sudden-onset paraplegia for the last 30 minutes, accompanied by discrete back pain. On initial physical examination, blood pressure was 140/90 mmHg in both arms, heart rate was 72 bpm, pulses were palpable and symmetrical. The neurologic examination showed bilateral lower limb flaccid paralysis, with abolition of deep tendon reflexes, accompanied by paresthesias in both feet. The remainder of the physical exam and the admission electrocardiogram were normal. Her medical history was unremarkable, except for having been a smoker. Although pain was not the most prominent feature at presentation, aortic dissection with neurological symptoms was suspected as a diagnostic possibility for acute flaccid paraplegia. a b

Contrast computed tomography (CT) showed a Stanford Type B aortic dissection with partial thrombosis of the false lumen, starting immediately after the emergence of the left subclavian artery, extending, in the direction the bifurcation of the aorta, to the left iliac artery. The supra-aortic and abdominal branches were not affected by the dissection (Figures 1-3). After the initial medical treatment with betablockers and oxygen, the patient was transferred to a tertiary care hospital, where the treatment adopted consisted in drainage of the cerebrospinal fluid (CSF) through the insertion of a lumbar catheter. The aortic dissection was treated conservatively due to the false lumen thrombosis. The patient

Department of Internal Medicine - Hospital Universitário, Universidade de São Paulo, São Paulo/SP - Brazil. Radiology Department - Hospital Universitário, Universidade de São Paulo, São Paulo/SP - Brazil.

Autopsy and Case Reports 2012;2(1):25-28

Adam EL, Staniak HL, Sharovsky R, Silva AF, Castro CC, Bittencourt MS.

Figure 1 – Multidetector CT of the thorax and abdomen. Sagittal reformatted images. Reconstruction of the entire aorta showing the dissection and partial thrombus from the subclavian to the iliac artery.

Figure 3 – Multidetector CT of the abdomen. Sagittal reformatted images of the abdominal aorta, highlighting the predominance of the dissection in the posterior portion, where the spinal cord branches typically emerge. the puncture. A follow-up CT performed at one week after admission showed that the extent of the dissection remained unchanged. The patient was discharged to outpatient medical and physical therapy follow-up.

DISCUSSION

Figure 2 – Multidetector CT of the abdomen. Coronal reformatted images of the abdominal aorta, showing the narrowed lumen of the abdominal aorta.

presented progressive neurological improvement during the first few days after initiation of the proposed treatment, achieving and maintaining grade 4 muscular strength in the lower extremities. The lumbar catheter was removed three days after

Acute aortic dissection is a cardiovascular emergency defined as the development of a tear in the aortic intima, followed by the passage of blood through the aortic media, creating a false lumen.1 It is a life-threatening event in which it is extremely important that a prompt and accurate diagnosis be made in the ER. Although chest or back pain is present in most cases, some patients can have little or no pain and other symptoms can be more conspicuous at presentation. In up to 95% of cases, the clinical presentation is characterized by severe chest or back pain, depending on whether the ascending or descending aorta is involved. When severe pain is absent at the initial presentation, the diagnosis can be challenging, leading to poor outcomes compared with those observed in patients presenting with painful aortic dissections.2

Aortic dissection-induced acute flaccid paraplegia treated with cerebrospinal fluid drainage

The development of a false lumen from the subclavian artery to the iliac arteries can lead to limb ischemia, producing the classically described asymmetry of pulses and blood pressure. However, when there is involvement of the aortic branches responsible for the blood supply to the intrathoracic or abdominal viscera, the diagnosis can only be clinically suspected due to the consequences of end-organ hypoperfusion, such as renal failure, mesenteric ischemia, acute myocardial infarction, and spinal cord ischemia leading to paraplegia,3,4 as in the case described here. The differential diagnosis of paraplegia is wide, including infectious, degenerative, toxicmetabolic, and vascular disorders, as well as spinal cord injury and neoplasms.5 Although various myelopathies can have a sudden onset, this form of presentation suggests, and should always raise the diagnostic possibility of, an acute vascular event such as aortic dissection, epidural hematoma, arteriovenous malformation, embolism, and vasculitides.6 Paraplegia occurs in 2-8% of aortic dissections, sometimes without pain, thereby requiring a high level of suspicion for diagnosis. Once suspected, the diagnosis must be confirmed, whenever possible, by an imaging study. In the ER setting, CT is typically available and therefore frequently used. In the current guidelines, there are no specific recommendations regarding the treatment of spinal cord ischemia in acute aortic dissection.7,8 Drainage of the CSF via a lumbar catheter, although frequently performed during aortic surgery for patients at high risk for spinal cord ischemia, has not been widely studied as a treatment option for aortic dissection accompanied by paraplegia.9 Previously published case reports have shown a benefit of this procedure in such patients.10 The rationale for such an intervention would be the increase in spinal cord perfusion pressure (spinal cord arterial pressure, or CSF pressure) as a consequence of CSF drainage. Despite the lack of recommendations or randomized controlled trials regarding this approach, it proved useful in this case, leading to an impressive neurological improvement during follow-up. The case reported here highlights the importance of including aortic dissection in the differential diagnosis of acute paraplegia, even in the presence of an entirely normal cardiovascular examination. In addition, the outcome was favorable after CSF drainage, a procedure not routinely indicated in this scenario.

AutopsyandCaseReports 2012;2(1):25-28

REFERENCES 1.

Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA. 2000;283(7):897-903. http://dx.doi.org/10.1001/jama.283.7.897

Park SW, Hutchison S, Mehta RH, et al. Association of painless acute aortic dissection with increased mortality. Mayo Clin Proc. 2004;79(10):1252-7. PMid:15473405. http://dx.doi.org/10.4065/79.10.1252

Joo JB, Cummings AJ. Acute thoracoabdominal aortic dissection presenting as painless, transient paralysis of the lower extremities: a case report. J Emerg Med. 2000;19(4):333-7. http://dx.doi.org/10.1016/S0736-4679 (00)00264-X

Donovan EM, Seidel GK, Cohen A. Painless aortic dissection presenting as high paraplegia: a case report. Arch Phys Med Rehabil. 2000;81(10):1436-8. PMid:11030513. http://dx.doi.org/10.1053/apmr.2000.7158

Cheshire WP, Santos CC, Massey EW, Howard JF Jr. Spinal cord infarction: etiology and outcome. Neurology. 1996;47(2):321-30. PMid:8757000.

Wilmshurst JM, Walker MC, Pohl KR. Rapid onset transverse myelitis in adolescence: implications for pathogenesis and prognosis. Arch Dis Child. 1999;80(2):137-42. PMid:10325728. PMCid:1717819. http://dx.doi.org/10. 1136/adc.80.2.137

Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22(18):1642‑81. PMid:11511117. http://dx.doi.org/10.1053/euhj.2001.2782

Hiratzka LF, Bakris GL, Beckman JA, et al. Guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010;121(3):e266-e369. PMid:20233780. http://dx.doi.org/10.1161/CIR.0b013e3181d4739e

McGarvey ML, Cheung AT, Szeto W, Messe SR. Management of neurologic complications of thoracic aortic surgery. J Clin Neurophysiol. 2007;24(4):336-43. PMid:17938602.

10. Blacker DJ, Wijdicks EFM, Ramakrishna G. Resolution of severe paraplegia due to aortic dissection after CSF drainage. Neurology. 2003;61(1):142-3. PMid:12847182.

Autopsy and Case Reports 2012;2(1):25-28

Adam EL, Staniak HL, Sharovsky R, Silva AF, Castro CC, Bittencourt MS.

Conflict of interest: None Submitted on: 30th November 2011 Accept on: 12th January 2012 Correspondence: Divisão de Clínica Médica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária – São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9200 E-mail: msbittencourt@bol.com.br

Autopsy and Case Reports 2012;2(1):29-35

Article / Clinical Case Reports Artigo / Relato de Caso Clínico Chronic meningococcemia: a rare presentation of meningococcal disease: case report Antonio Adolfo Guerra Soares Brandãoa, Aleksander Snioka Prokopowitschb, Fernando Peixoto Ferraz de Camposb, Liz Andrea Kawabata Yoshiharab Brandão AAGS, Prokopowitsch AS, Campos FPF, Yoshihara LAK. Chronic meningococcemia: a rare presentation of meningococcal disease: case report. Autopsy Case Rep [Internet]. 2012;2(1):29-35. http://dx.doi.org/10.4322/acr.2012.005

ABSTRACT Chronic meningococcemia is a rare clinical presentation within the spectrum of infections due to Neisseria meningitidis, which was first described in 1902. It is defined as a chronic and benign meningococcal bacteremia without meningeal signs or symptoms with at least one week’s duration, characterized by intermittent or continuous fever, polymorphic cutaneous rash, and migratory arthropathy. The incidence is believed to be around 1:200,000 inhabitants. It affects predominantly young people and adults, and it is equally distributed between genders. Diagnosis may be challenging in the early stages of the disease because of the difficulty in isolating Neisseria meningitidis (it reaches 74% of positivity in advanced stages). Recently, the use of PCR for detecting Neisseria sp antigen in skin biopsies specimens has been considered for those culture-negative cases. The authors report a case of a 54-year-old female patient who sought medical attention for a five-day fever followed by arthralgia and skin lesions predominantly in the lower limbs. The patient progressed to a toxemic clinical status that improved after the administration of antibiotic therapy, which consisted of oxacillin and ceftriaxone. The diagnosis of chronic meningococcemia was performed after the isolation of Neisseria meningitidis in two different blood sample cultures. This is, to our knowledge, the first case of chronic meningococcemia described in Brazil (up to the writing of this report). Keywords: Meningococcal infections; Arthritis; Immune complex diseases; Purpura; Fever.

CASE REPORT A 54-year-old female patient sought medical attention complaining of sore throat and fever for five days. Concomitantly, she experienced painful swelling of both ankles and similar, but less intense, symptoms involving wrist and metacarpophalangeal joints, bilaterally. These complaints revealed progressive worsening. She had a history of a b

hypertension, diabetes mellitus, and dyslipidemia, and was taking captopril, atenolol, glibenclamide, simvastatin, and aspirin. She had a myomectomy 15 years ago and surgical treatment of lumbar herniated intervertebral discs four years ago. The patient was a moderate smoker and used to drink about 40 g of alcohol per week, but quit both

Department of Internal Medicine - Hospital das Clínicas - Faculdade de Medicina - Universidade de São Paulo, São Paulo/SP – Brazil. Department of Internal Medicine - Hospital Universitário - Universidade de São Paulo - São Paulo/SP – Brazil.

Autopsy and Case Reports 2012;2(1):29-35

Brandão AAGS, Prokopowitsch AS, Campos FPF, Yoshihara LAK.

more than 10 years ago. On initial examination, the patient showed good clinical status, and was ruddy and hydrated. Edema was detected on the lower limbs. Her respiratory rate = 22 respiratory movements per minute, pulse = 100 beats per minute, blood pressure = 112 × 84 mmHg, axillary temperature = 36.5 °C. The Glasgow coma scale was 15, and no nuchal rigidity was found. Physical examination of the lungs and heart was unremarkable, whereas percussion of the abdomen showed dullness over Traube’s semilunar space. The joint examination revealed signs of joint effusion in the right knee with limited range of motion and local heat, and swelling and heat in the dorsal region of the left hand. Her skin was free of lesions. Initial laboratory tests are shown in Table 1. Transthoracic echocardiography showed LVEF = 64%, aorta = 31 mm, AE = 33 mm, septum = 9 mm, posterior wall = 8 mm, normal right ventricle performance, and absence of vegetation or thrombi, confirmed by transesophageal echocardiogram. Ultrasonography of the abdomen revealed an enlarged liver and the presence of an oval image located in segment III, which was suggestive of hemangioma. On the first day of hospitalization, besides the persistence of fever, violaceous maculae suggestive of purpura lesions appeared over the swollen and hyperemic lower limbs. Oxacillin had

been started since the patient’s admission, followed by the association of ceftriaxone. Further laboratory investigation included determinations of serology for HIV, hepatitis B and C, and syphilis, which were negative. Vasculitis associated with rheumatic diseases were ruled out with the negative results for rheumatoid factor, ANF, anti-ds DNA, anti Ro, antiSm, and normal levels of C3 and C4. The clinical progression was characterized by the worsening of skin lesions, which became necrotic (Figures 1–2), and arthritis of the left knee and left ankle (Figure 3) ensued. The synovial effusion of the knee was punctured and its analysis showed an inflammatory pattern with negative culture. The gram stain also failed to demonstrate any bacterial presence. Because of the advanced necrotic stage of the skin lesions, it was decided not to perform a biopsy. On the fourth day of hospitalization, blood cultures from two different samples showed the growth of Gram negative bacillus further identified as Neisseria meningitides serogroup C. The patient was prescribed 14 days of Oxacillin and 15 days of ceftriaxone. Despite the antimicrobial regimen, fever persisted in the absence of identifiable infectious focci. Her clinical

Table 1 – Laboratory tests 12,4/36,3%

Hemoglobin

12.4

12.3-15.3 g%

BUN

110

5-25 mg.dL–1

Hematocrit

36.0-45.0%

Creatinine

3.7

0.4-1.3 mg.dL–1

Leucocytes

10100

4.4-11.3 103/mm3

Potassium

4.7

3.5-5.0 mEq.L–1

Mielocytes

Sodium

133

136-146 mEq.L–1

Metamyelocytes

ALT

9-36 U.L–1

Bands

1-5%

AST

10-31 U.L–1

Segmented

45-70%

170

10-100 U.L–1

Eosinophils

1-4%

γGT

302

1-24 U.L–1

Basophils

0-2.5%

Total bilirrubin

1.96

0,3-1,2 mg.dL–1

Linfocytes

18-40%

Direct bilirrubin

1.52

<0,3 mg.dL–1

Monocytes

2-9%

PT (INR)

1.28

Platelets

206 × 103

150-400 103/mm3

Albumin

3,6

3-5 g.dL–1

CRP

451

<5 mg.L–1

26-140 U.L–1

LDH

203

120-246 U.L–1

AF = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CK = creatine phosphokinase; CRP = C reactive protein; γGT = gamma-glutamyltransferase; INR = international normalized ratio; LDH = lactate dehydrogenase; PT = prothrombin time; RV = reference value.

Chronic meningococcemia: a rare presentation of meningococcal disease: case report

Autopsy and Case Reports 2012;2(1):29-35

Figure 1 – A – Violaceous maculae suggestive of purpura lesions (arrows) appeared over the swollen and hyperemic lower limbs. Note intense erythema over the knee; B – Necrotic lesions, in the early stage, close to the external malleolus.

Figure 2 – A – Necrotic lesions over the right calf; B – Note also lesions close to the malleolus and the increased volume of the right knee.

Figure 3 – A - Edema of the left ankle; B – Increased left knee volume.

status was favorable allowing corticotherapy with prednisone once the possibility of a post meningococcal reactional status was considered. The patient became afebrile on the eighteenth day of treatment, was discharged with normalization of laboratory tests (CRP = 15 mg/dL) and healed skin lesions and decreased joint swelling.

DISCUSSION Meningococci are diverse organisms and are usually commensal bacteria in humans. According

to some studies, 20–40% of the adult population is permanently or temporarily asymptomatic carriers.1 Only a minority of nasopharyngeal isolates cause invasive disease.2 Meningococci associated with invasive disease elaborate a capsule, which provides protection from desiccation during transmission and aids in the evasion of host immune mechanisms. The major factor of virulence of these organisms is the release of outer-membrane vesicles that consist of lipooligosaccharide (endotoxin), outer membrane proteins, phospholipids, and capsular polysaccharides, which are used as antigen for vaccine production.2,3

Autopsy and Case Reports 2012;2(1):29-35

Chronic meningococcemia is a rare clinical presentation within the spectrum of infections due to Neisseria meningitidis, presenting some particularities regarding the clinical presentation and the evolutive profile. It was first described in 1902 by Salomon.4 This infrequent disease is defined as a chronic or benign meningococcal bacteremia without meningeal signs or symptoms with at least one week’s duration, characterized by intermittent or continuous fever, polymorphic cutaneous rash, and migratory arthropathy.5,6 The incidence and prevalence of chronic meningococcemia are believed to be very low, 1:200,000.7 However, the incidence may be higher as patients are sometimes treated with antibiotics without a previous etiological diagnosis.8,9 By the year 2005 there were 200 cases reported in the literature6,10, with the largest case series involving four patients.11 Searching the scientific databases Scielo and Lilacs by keywords: chronic meningococcemia, meningococcal disease, meningococcal infections, meningococcal infection-epidemiology, meningococcemia, and meningococcic, and in the PubMed data base with the word “chronic meningococcal disease,” we found out that this is the first case reported in Brazil until the time of this manuscript submission. The disease is characterized by affecting predominantly young people and adults (the mean age is of 26.5 years); the distribution between men and women seems to show no difference.5 Only about 10% of reported patients were under 18 years of age.12 Fever and chills are presented in all reported cases and series, skin rash was observed in 93.2%, and joint involvement was present in 70.3%.5 Fever can be spiking, persisting, or relapsing. In the series of Benoit et al., the patients who presented intermitent fever had afebrile periods of 2–10 days, while those with continuous fever patterns generally had a septic course.5 The patient reported here presented a persistent fever, even after appropriate antibiotic therapy and after a thorough investigation for other infectious foci. Ruling out the possibility of infection, it was assumed that the fever persistence, as well as the cutaneous-articular involvement, was due to a hypersensitivity reaction type III (immune complexes). This immune reaction is more frequently observed in patients with severe meningococcal disease, but it is also observed either in the infection by meningococci serogroup C (the same of this case report) as in adolescents and adults patients.13

Brandão AAGS, Prokopowitsch AS, Campos FPF, Yoshihara LAK.

Skin eruption is the second most frequent clinical sign.5 The lesions appear quickly and may present as maculopapular rash (47.6%), petechial lesions (11.9%), nodular lesions (13.1%), or, less frequently, ecchymotic and pustular lesions were noted5,6,14 — sometimes even necrotic.15 They are painful in 32% of the cases 10 and involve the trunk, limbs, and extremities, and may affect palms and soles. The evolution may be recurrent. Very different from the lesions of purpura fulminans, they are sterile in most of the cases. The histology shows a polymorphic perivascular infiltrate with erythrocyte extravasation14 and deposition of immunoglobulins and C3 in the vessels wall (also different from purpura fulminans where meningococcal septic emboli are found).5,6,10 Our patient developed the skin lesions during hospitalization, showing a reticulated pattern suggestive of purpura in some manner similar to the manifestation of purpura fulminans.16 The manifestation of joint involvement is usually seen around the first to the twelfth day after the initial symptoms; it is primarily arthralgia with a migratory nature occurring in all joints except the temporo mandibular. Some authors pointed out the great joints, especially the knee, as the most involved joints.17 In the series of Benoit et al., arthritis occurred in 31% and joint effusion was present in 3 of 148 patients of this series.5 In the case described herein, there was an exuberant joint involvement with massive joint effusion, which analysis, besides being inflammatory, did not yield the isolation of Neisseria meningitidis, neither on the Gram stain nor in culture media. This finding is consistent with the fact that arthritis in meningococcal disease is usually manifested by immune-mediated mechanisms. Our patient presented arthritis in the left knee and left ankle observed after eight days of the demand for medical service, following a generalized polyarthralgia. Table 2 summarizes the clinical features reported in the Benoit et al. review, which involved the data of 148 cases of chronic meningococcemia. The involvement of the meninges is a sign of poor prognosis.5 Totan et al. reported a case of a child patient with chronic meningococcemia who presented cholestatic hepatitis, which resolved after the infection treatment.18 Op de Coul reported a case of a 14-year-old with a history of fever of four months’ duration, rash and arthralgia, with blood sample culture positive to Neisseria meningitidis, suggesting that chronic meningococcemia should be considered in the differential diagnosis of fever of unknown origin.19

Chronic meningococcemia: a rare presentation of meningococcal disease: case report

Table 2 – Clinical features of chronic meningococcemia 5 Symptom

Occurrence (%)

Symptom

Occurrence (%)

Fever

100

Headache

61.5

Skin rash

93.2

Previous URT infection

37.2

Joint involvement

70.3

URT = upper respiratory tract.

The differential diagnosis of chronic meningococcemia includes disseminated gonococcal infection (DGI) as clinical features are quite similar in both diseases. The diagnosis of DGI is more challenging due to the difficulty of aethiological agent isolation, which is currently possible in about 50% of the cases. The skin lesions in DGI are typically few, are limited to the extremities, and start as papules, which then progress into hemorrhagic pustules, and the joint involvement is characterized by arthritis and tenosynovitis.20,21 Other differential diagnosis possibilities include infective endocarditis, Henoch-Schoenlein purpura, secondary syphilis, connective tissue disorders, drugs eruptions, and systemic vasculitis.6,22 Chronic meningococcemia may be selflimiting, but meningitis and death can occur as a late complication. Untreated, the illness may continue for several months and although it may be self-limiting, abrupt change with a fatal outcome is reported. In one series, meningitis occurred as a late complication, and carditis, when present, was responsible for death.6 Other complications reported in chronic meningococcemia are pericarditis, nephritis, endocarditis, and epididymitis. Benoit, in summarizing the data of 148 cases of chronic meningococcemia showed that 15 patients died and 59 had secondary complications.5 The diagnosis is usually made after isolation of Neisseria meningitidis in blood cultures which show 74% of positivity, being less frequent in the early stages of the disease. Repeated samplings are frequently required. In the case related herein, it lasted 10 days from the initial symptoms to the positivity of the blood culture. The serotypes isolated in chronic meningococcemia are the same of that in acute meningococcal disease, but the serotype B represents 60% of the cases.10 Besides, the skin lesions are mainly caused by immune mediated mechanisms and some reports show isolation of Neisseria meningitidis in the culture of the affected

Autopsy and Case Reports 2012;2(1):29-35

skin,23,24 as well as the presence of Neisseria antigens by PCR assay in the same material. Skin biopsies should ideally have both a microbiological examination in order to isolate the meningococcus in the skin, and histological examination in order to seek a leukocytoclastic vasculitis, which is found in 78% of the cases. Recently, the PCR technique specific for Neisseria meningitidis, commonly used on CSF or blood in acute infections, has been implemented conclusively to the diagnosis of chronic meningococcemia in skin biopsies, which encourages the realization of this technique in the case of negative blood cultures.10,25 The host-pathogen interaction in chronic meningococcemia may explain the relative benignity of the disease, when compared to other manifestations of meningococcal disease. Most patients with chronic meningococcemia do not exhibit an immune system disorder; however, there is an association of hypoimmunoglobulinemia, defects in the complement system (mainly related to the components of the membrane attack complex— C5, C6, C7, properdin)26,27 as well as IgA deficiency28, low levels of IgG and co-infection with HIV. On the other hand, it was observed that complement deficiency did not increase the frequency of chronic meningococcemia.29 Even in the absence of massvaccination, a majority of adults, after 25 years of age, are fully immunized against most serotypes of Neisseria meningitidis, leading to very few acute meningococcemia diseases in immunocompetent adults. Thus, the relatively moderate clinical signs of chronic meningococcemia may be explained by a preexistent immunity against Neisseria meningitidis.6 With respect to bacteria, a higher prevalence of serogroup B infection is reported. Some authors state that the relatively reduced virulence of serogroup B may partly explain the chronicity of clinical signs and the reduced inflammatory response. An important virulence factor of the meningococcus is the cell-wall component lipopolysaccharide (LPS). The membrane anchoring part of LPS, lipid A, determines how well the meningococcus is recognized by the immune system through a Toll-like receptor 4 (TLR4).30 The most active form of LPS contain six fatty acids in the lipid A moiety. Recently, it was described as mutants with penta-acylated lipid A due to a mutation in the lpxL1 gene.31 The mutated strains activate TRL4 less efficiently, leading to less cytokine production, which explains the protracted and benign clinical course in patients with CM.32

Autopsy and Case Reports 2012;2(1):29-35

Brandão AAGS, Prokopowitsch AS, Campos FPF, Yoshihara LAK.

Despite the five-days-history, this case fulfilled all the clinical and microbiological criteria for the diagnosis and course of chronic meningococcemia, as described in the literature. This case points to a rare differential diagnosis, whose incidence is decreasing probably due to abusive use of empirical antibiotics nowadays.33 Another relevant point is the number of diseases similar to chronic meningococcemia, imposing such a diagnosis in the differential hypothesis among a febrile cutaneous-articular syndrome.6

11. Bloom DS. Chronic meningococcemia: epidemiology, diagnosis and treatment. Calif Med.1965;103:87-90. PMid:14347980. PMCid:1515949.

REFERENCES

14. Grouteau E, Chaminade S, Karsenty C, Chaix Y, Prere MF, Carriere JP. Meningococcemie chronique: trois cas chez l’enfant immunocompetent. Arch Pediatr. 1998;5:1232-5. French. http://dx.doi.org/10.1016/ S0929-693X(98)81242-6

Yazdankhah SP, Caaugant DA. Neisseria meninitidis: an overview of the carriagestate. J Med Microbiol. 2004;53:821-32. PMid:15314188. http://dx.doi. org/10.1099/jmm.0.45529-0 Rosenstein NE, Perkins AB, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. N Engl J Med. 2001;344:1378-88. PMid:11333996. http://dx.doi. org/10.1056/NEJM200105033441807 Santos S, Baruque-Ramos J, Tanizaki MM, Lebrun I, Schenkman I PF. Production of outer membrane vesicles (OMV) in batch cultivation of Neisseria meningitidis serogroup B. Braz J Microbiol. 2006;37:488-93.

12. Ploysangan T, Sheth AP. Chronic meningococcemia in childhood: case reportand review of literature. Pediatr Dermatol. 1996;13:483-7. PMid:8987058. http://dx.doi. org/10.1111/j.1525-1470.1996.tb00729.x 13. Goedvolk CA, von Rosenstiel IA, Bos AP. Immune complex associated complications in the subacute phase of meningococcal disease: incidence and literature review. Arch Dis Child. 2003;88:927-30. PMid:14500317. PMCid:1719308. http://dx.doi.org/10.1136/adc.88.10.927

15. Kernéis S, Mahé E, Heym B, et al. Chronic meningococcemia in a 16-year-old boy: a case report. Cases J. 2009,2:7103. PMid:19829911. PMCid:2740133. http:// dx.doi.org/10.4076/1757-1626-2-7103 16. Lipsker D, Kara F. Retiform purpura. N Engl J Med. 2008;358:e1. PMid:18184954. http://dx.doi.org/10.1056/ NEJMicm073564 17. Bhavnagri S, Steele N, Massasso D, Benn R, Youssef P, Bleasel J. Meningococcal-associated arthritis: infection versus immune-mediated. Intern Med J. 2008;38:71‑3. PMid:18190423. http://dx.doi.org/10.1111/j.1445-5994.2007. 01560.x

Salomon H. Ueber Meningokokkenseptikaemie. Berl klin Wocheschr. 1902;39:1045.

Benoit FL. Chronic meningococcemia: case report and review of the literature. Am J Med. 1963;35:103-12. http:// dx.doi.org/10.1016/0002-9343(63)90167-0

Harwood CA, Stevens JC, Orton D, et al. Chronic meningococcaemia: a forgotten meningococcal disease. Br J Dermatol. 2005;153:664-99. PMid:16120166. http:// dx.doi.org/10.1111/j.1365-2133.2005.06771.x

19. Op de Coul ME, Kardos G. [An unusual cause of fever: chronic meningococcemia]. Ned Tijdschr Geneeskd. 1996;140:785-7. Dutch. PMid:8668266.

Goldbloom AA, Nickman EH, Seidmon EEP. Meningococcic infections in an Army staging area. Ann Int Med. 1946;24:589. PMid:21025277.

20. Ghosn SH, Kibbi AG. Cutaneous gonococcal infections. Clin Dermatol. 2004;22:476-80. PMid:15596318. http:// dx.doi.org/10.1016/j.clindermatol.2004.07.001

Rasmussen LH, Andersen PL. Kroniskmeningokokæmi ( chronic meningococcemia). Ugeskrift Laeger 1991;153:3613‑4. Danish. PMid:1776205.

Hansen L, Christensen JJ, Breu L. Chronic meningococcaemia. Scand J Infect Dis. 2003;35:418-9. PMid:12953960. http://dx.doi.org/10.1080/00365540310011074

21. Suzaki A, Hayashi K, Kosuge K, Soma M, Hayakawa S. Disseminated gonococcal infection in Japan: a case report and literature review. Intern Med. 2011;50:2039-43. PMid:21921393. http://dx.doi.org/10.2169/internalmedicine. 50.5586

10. Roux M, Sire S, Lalnde V, et al. Fiévre prolongée associée à une eruption cutanée diffuse révelant une meningococcemia chronique. Rev Med Interne. 2010;31:4458. French. PMid:20395022. http://dx.doi.org/10.1016/j. revmed.2009.11.010

18. Totan M, Yildiz G, Kalayci AG. An uncommon presentation: chronic meningococcaemia associated with cholestatic hepatitis in a Turkish child. J Trop Pediatr. 2004;50:372-4. PMid:15537727. http://dx.doi.org/10.1093/tropej/50.6.372

22. Martinez JV, Verbanaz SC, Jordan R, Enriquez N, Efron ED. Meningococcemia cronica. Medicina. 2008;68:298300. Spanish. 23. Shah N, Dadzie OE. Skin culture: another diagnostic tool in chronic meningococcemia. Br J Dermatol. 2010;163:2189. PMid:20331447.

Chronic meningococcemia: a rare presentation of meningococcal disease: case report 24. Texereau M, Roblot P, Dumars A, et al. The usefulness of skin culture in the diagnosis of chronic meningoccaemia. J Intern Med. 1997;242:519-20. http://dx.doi. org/10.1111/j.1365-2796.1997.tb00026.x 25. Parmentier L, Garzoni C, Antille C, Kaiser L, Ninet B, Borradori L. Value of a novel neisseria meningitidis: specificpolymerase chain reaction assay in skin biopsyspecimens as a diagnostic toolin chronic meningococcemia. Arch Dermatol. 2008;144:770-3. PMid:18559767. http://dx.doi.org/10.1001/archderm.144.6.770 26. Nielsen HE, Koch C, Mansa B, Magnussen P, Bergmann OJ. Complement and immunoglobulin studies in 15 cases of chronic meningococcemia: properdin deficiency and hypoimmunoglobulinemia. Scand J Infect Dis. 1990;22:31-6. PMid:2320962. http://dx.doi. org/10.3109/00365549009023116 27. Solé D, Leser PG, Arita FN, Naspitz CK. Deficiência do sistema complemento: apresentação de um caso. Rev Bras Alerg Imunol.1990;13:55-7. Portuguese. 28. Theulin A, Rondeau M, Kuhnert C, Boileau J, Weber JC. Chronic meningococcemia and immunoglobulin A deficiency. J Med Microbiol. 2010;59:1375-8. PMid:20651040. http://dx.doi.org/10.1099/jmm.0.021980-0

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29. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev. 1991;4:359e95. 30. Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003;3:169e76. 31. Fransen F, Heckenberg SG, Hamstra HJ, et al. Naturally occurring lipid A mutants in Neisseria meningitidis from patients with invasive meningococcal disease are associated with reduced coagulopathy. PLoS Pathog. 2009;5:e1000396. PMid:19390612. PMCid:2667671. http://dx.doi.org/10.1371/journal.ppat.1000396 32. Brouwer MC, Spanjaaard L, Prins JM, van der Ley P, van de Beek D, van der Ende A. Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide. J Infect. 2011;62:479‑83. PMid:21459106. http://dx.doi.org/10.1016/j.jinf.2011.03.010 33. Schaad UB. Arthritis in disease due to Neisseria meningitidis. Rev Infect Dis. 1980;2:880-7. http://dx.doi. org/10.1093/clinids/2.6.880

Conflict of interest: None Submitted on: 30th December 2011 Accepted on: 23th January 2012 Correspondence: Divisão de Clínica Médica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária, São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9200 E-mail: ffcampos@usp.br

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Article / Clinical Case Reports Artigo / Relato de Caso Clínico Descending necrotizing mediastinitis secondary to a dental infection Edson Martins de Oliveira Juniora, Raphael Teixeira Moreirab, Tayguara Cerqueira Cavalcantec Oliveira Junior EM, Moreira RT, Cavalcante TC. Descending necrotizing mediastinitis secondary to a dental infection. Autopsy Case Rep [Internet]. 2012;2(1):37-42. http://dx.doi.org/10.4322/acr.2012.006

ABSTRACT Descending necrotizing mediastinitis is a rare type of deep infection of the soft tissues of the face, originating from cervical and oral infections, typically dental infections. It is associated with high mortality, due to its high invasive potential and the fact that the diagnosis is often delayed. We report the case of a 42-year-old female patient presenting with severe trismus, fever, purulent intraoral drainage, dysphagia, and dysphonia, accompanied by edema and redness in the cervical region. She was diagnosed with necrotizing descending mediastinitis secondary to a dental infection after the extraction of a mandibular third molar. The patient underwent surgical drainage and intravenous antibiotic therapy. Despite the development of septicemia, the evolution was favorable and the patient was discharged on post-admission day 20. Early and accurate diagnosis, together with prompt treatment, is imperative for better outcomes in this rare condition. Keywords: Mediastinitis; Therapeutics. INTRODUCTION Mediastinitis is defined as an inflammation of the mediastinal tissue.1,2 It is unusual for mediastinitis to be caused by dental infections, given that the infection would have to traverse the superficial and deep fasciae of the face, as well as the cervical fascia.3 Mediastinitis is often caused by esophageal perforation or infection of the sternum after cardiac surgery. In rare cases, mediastinitis can arise after Ludwig’s angina or can be secondary to deep neck space infection, in general, due to the infection of the second or third inferior molar.4,5 Such cases are

classified as descending necrotizing mediastinitis, and the clinical picture can be severe.6 Descending necrotizing mediastinitis primarily affects young adults (mean age, 36 years), and 86% of the patients are men.7 It is polymicrobial in origin,8 the most common etiological agents being Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas sp. and Escherichia coli.9,10 Gram-positive bacilli, such as Eubacterium and Lactobacillus spp., can also be involved.11 Descending necrotizing mediastinitis is a serious condition, with mortality rates as high as 40%.8

Department of Dentistry - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. Department of Dentistry - Hospital Universitário Oswaldo Cruz, Universidade de Pernambuco, Recife/PE - Brazil. c Department of Dentistry - Hospital Obras Sociais da Irmã Dulce, Salvador/BA - Brazil. b

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The clinical evaluation of a suspected patient should include an analysis of the family history, the duration of symptoms, and any previous treatment. In assessing the local and regional extent of the infection, the following signs and symptoms should be taken into consideration: trismus, stiffness, fistula formation, abscess formation, airway involvement, and dysphagia. Descending necrotizing mediastinitis can be characterized through a variety of imaging techniques, including periapical radiography of the maxillofacial complex and panoramic radiography of the maxilla, as well as chest X-ray for the evaluation of pulmonary impairment and X-ray of the cervical region in order to identify edema of the neck, a condition that can, depending on the degree, compress the upper airways.11 Radiography can reveal an increase in the size of the mediastinum. The use of computed tomography (CT) is essential and has value not only as a means of confirming the diagnosis but also for informing decisions regarding the surgical strategy.12,13. Laboratory tests should be requested, because they provide an overview of the systemic involvement. White cell counts, red cell counts, and blood glucose should be evaluated, because they have a direct effect on the treatment. Diagnostic errors can allow the infection to spread to adjacent spaces, worsening the clinical course.14 Because it is a severe form of infection, descending necrotizing mediastinitis requires early diagnosis and surgical treatment to reduce mortality. The emergency treatment should be initiated as

Oliveira Junior EM, Moreira RT, Cavalcante TC.

early as possible and should consist of transcervical mediastinal drainage and administration of intravenous antibiotics.

CASE REPORT A 42-year-old White female sought treatment at the Maxillofacial Trauma Clinic of the Hospital de Pronto Socorro de Maceió – Alagoas (AL – Brazil), complaining of a 10-day history of difficulty in opening her mouth, which prevented her from eating, as well as pus in her mouth, fever, and headache. The patient reported that her third left inferior molar (tooth 38) had been extracted 13 days earlier. The initial clinical examination revealed severe trismus, limited side-to-side head movement, intense halitosis, as well as a large quantity of purulent secretion, accompanied by volumetric changes and skin redness of the lower third of the face, neck, and of the upper thorax (Figures 1 and 2). The patient said that she was using antibiotics (amoxicillin at admission, and that she had also previously used azithromycin and metronidazole, for less than 3 days in both cases. An emergency CT scan showed disseminated infection, originating in the left submandibular space and extending from the pretracheal fascia space to the mediastinum (Figure 3). On the basis of the clinical and CT findings, the patient was diagnosed with a dental infection that had spread to the neck and mediastinum. The patient underwent surgery (neck incision and drainage) under general anesthesia. During the nasotracheal intubation procedure, the patient

Figure 1 – Appearance of the patient during the initial treatment. Patient, without the prosthesis, with trismus while attempting to open her mouth.

Descending necrotizing mediastinitis secondary to a dental infection

aspirated pus from the oral cavity, progressing to asphyxiation, necessitating emergency tracheostomy, hampered by the large amount of pus in the cervical region. Drainage was performed by cervical bilateral extension of the incision to tracheostomy. The patient was admitted to the ICU and was treated intravenously for nine days with

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ceftriaxone (1 g every 12 hours), metronidazole (500 mg every 8 hours) and gentamicin (80 mg every 8 hours). After discharge from the ICU, the patient was hospitalized for two days in the infirmary until the removal of the tracheostomy tube, after which she was discharged to outpatient follow-up. Fifty-four days later, the patient underwent repair of

Figure 2 – Static physical examination (anterior and profile). Note the swelling and redness of the neck.

Figure 3 – Axial CT images in the craniocaudal dimension, suggestive of the presence of gas produced at the site of infection dissecting the right pterygoid space and the pretracheal fascia.

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Oliveira Junior EM, Moreira RT, Cavalcante TC.

Figure 4 – Patient on post-admission day 41. Mouth opening to a near-normal extent (34 mm). Note the repair of the tracheal fistula. the tracheal fistula (Figure 4) and was discharged on post-procedure day 7.

causes are known, among which are the extent of the head and neck infection.20,21 Dental infections are the most common of such infections.10,17,22

DISCUSSION

The diagnosis of a deep neck infection can be difficult to make on the basis of history-taking and physical examination alone, especially in patients who have previously used antibiotics. Local signs such as edema, fluctuation, hyperemia, and pain might not be evident. Physical examination can reveal fever and neck swelling. In addition, patients with a deep neck infection typically present with dehydration, sore throat, dysphagia, dysphonia (impaired glottal function), dyspnea and trismus.6 In the case under discussion here, the patient presented with fever, severe trismus, difficulty in swallowing, and difficulty in speaking, all of which are clear clinical signs of infection. The skin on the anterior neck was red and swollen.

In the past, severe cervical infections, such as mediastinitis, were conditions that carried a significant risk of death. With improvements in antibiotic therapy, diagnostic techniques, and early surgical intervention, mortality rates have fallen significantly. However, in the case of mediastinitis, the mortality rate remains at approximately 40%.8,15 Although the case reported here did not evolve to death, the patient developed septicemia and required 2 weeks of treatment in the ICU. In cases of descending necrotizing mediastinitis, the infection originates in the fasciae of the head and neck, infiltrating into the mediastinum via the cervical fasciae, facilitated by gravity, respiration, and negative intrathoracic pressure. The most common anatomical pathway by which the infection spreads is the lateral pharyngeal space to the retrovisceral space (retropharyngeal) (implicated in 70% of cases), thereby extending inferiorly to the mediastinum.15-17 In the case reported here, the mediastinal infection developed after the extraction of a third molar and rapidly progressed to the superficial and deep fasciae of the face, severely affecting the deep layers of the cervical fascia before arriving at the mediastinum. Most cases of descending necrotizing mediastinitis occur as a postoperative complication of cardiovascular surgery.18,19 However, other

The microbiology of descending necrotizing mediastinitis is complex, 88% of cultures containing more than two microorganisms; 94% containing anaerobic bacteria only; and 52% containing anaerobic and aerobic bacteria.23 Chief among such microorganisms are Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas sp. and E. coli.9,10 In the case presented here, culture and sensitivity testing were not performed at admission. Because bacterial agents other than the normal oral flora are rarely found in cases of dental infection, the recommended antibiotic therapy can be initiated before the result of the microbial culture is known.24 Imaging studies are essential for assessing the presence of pus, the neck spaces affected, and the potential complications, as well as for planning

Descending necrotizing mediastinitis secondary to a dental infection

the treatment strategy. The most widely used imaging technique is CT,12 because it accurately shows the early involvement of the mediastinum, allowing the ideal surgical site to be identified.15 The diagnostic criteria for descending necrotizing mediastinitis are as follows25 evidence of oropharyngeal infection; radiographic features characteristic of mediastinitis; documented infection in the intra-operative period or post-mortem evaluation; and communication between the oropharyngeal process and the mediastinum. The primary treatment for descending necrotizing mediastinitis is the combination of antibiotics and drainage. The use of intravenous broad-spectrum antibiotics is not effective without adequate cervical drainage, extensive debridement and excision of the necrotic tissue. In most cases, repeated cervical drainage is required due to persistent infection.6 In the case reported here, the patient was treated with a combination of antibiotic therapy comprising ceftriaxone (2 g every 12 hours), metronidazole (500 mg every 8 hours) and gentamicin (80 mg every 8 hours) and surgical drainage. Patients with descending necrotizing mediastinitis are typically treated with a broadspectrum antibiotic in order to target gram-positive, gram-negative, and anaerobic bacteria.26 The surgical approaches to cervical drainage vary according to the location, extent, and degree of the infection.6,26,27 In our case, the infection was located in the upper mediastinum and we opted for high transcervical mediastinal drainage. The prognosis of descending necrotizing mediastinitis is poor, the high mortality rate (40‑50%) having changed little over time. The results depend on the degree of infection and the presence of pre-existing systemic diseases, such as HIV and diabetes.28 The causes of death are various, including septic shock, respiratory failure, and gastrointestinal bleeding.29

CONCLUSION Mediastinal infection can originate from the extraction of a third molar, with rapid progression through the superficial and deep fasciae of the face, as well as into the deep layers of the cervical fascia. This very aggressive form of mediastinitis with a high mortality rate imposes a fast diagnostic approach and combined therapy with antibiotics and drainage.

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REFERENCES 1.

Macrí P, Jiménez MF, Novoa N, Varela GA. Descriptive of a series of patients diagnosed with acute mediastinitis. Arch Bronconeumol. 2003;39(9):428-30. PMid:12975075.

Souza VC, Freire ANM, Tavares-Neto, J. Mediastinite pósesternotomia longitudinal para cirurgia cardíaca: 10 anos de análise. Rev Bras Cir Cardiovasc. 2002;17(3):266-70. Portuguese. http://dx.doi.org/10.1590/S0102-763820020 00300012

Peterson JL, Ellis III E, Hupp JR, Tucker MR. Cirurgia oral e maxilo-facial contemporânea. 4th ed. Rio de Janeiro: Elsevier; 2005. Portuguese.

Brommelstroet M, Rosa JFT, Boscardim PCB, Schmidlin CA, Shibata S. Mediastinite descendente necrosante pós angina de Ludwig. J Pneumologia. 2001;27(5):269-71. Portuguese.

Conto F, Rettore C, Bertoli MM, Rohden RM. Mediastinite de origem odontogênica. Rev Bras Cir Buco-Maxilo-Facial. 2011;11(2):27-34. Portuguese.

Marty-Ané CH, Alauzen M, Alric P, Serres-Cousine O, Mary H. Descendig necrotizing mediastinitis. J Thorac Cardiovasc Surg. 1994;107(1):55-61. PMid:8283919.

Moriwaki Y, Sugiyama M, Matsuda G, et al. Approach for drainage of descending necrotizing mediastinitis on the basis of the extending progression from deep neck infection to mediastinitis. J Trauma. 2002;53(1):112-6. http:// dx.doi.org/10.1097/00005373-200207000-00023

Prado R, Salim M. Cirurgia bucomaxilofacial: diagnóstico e tratamento. Rio de Janeiro: Medsi; 2004. Portuguese.

Sampaio DT, Alves JCR, Silva AF, et al. Mediastinite em cirurgia cardíaca: tratamento com epíploon. Rev Bras Cir Cardiovasc. 2000;15(1):23-31. Portuguese.

10. Sancho LM, Minamoto H, Fernandez A, Sennes LU, Jatene FB. Descending necrotizing mediastinitis: a retrospective surgical experience. Eur J Cardiothorac Surg. 1999;16(2):200-5. http://dx.doi.org/10.1016/S10107940 (99)00168-2 11. Vasconcelos BCE, Cauás M, Albert DGM, Nascimento GFJ, Holanda GZ. Disseminação de infecção odontogênica atraves das fascias cervicais profundas. Rev Cir Traumat Buco-maxilo-facial. 2002;2(1):21-5. Portuguese. 12. Hueb MM, Borges LM, Oliveira LR. Angina de Ludwig: tratamento cirúrgico minimamente invasivo e guiado por ultra-sonografia cervical. Arq Int Otorrinolaringol. 2004;8(3):181‑7. Portuguese. 13. Kaga K, Hida Y, Hirano S. Descending necrotizing mediastinitis. Kyobu Geka. 2011;64(8):752-7. PMid:21916190.

Autopsy and Case Reports 2012;2(1):37-42 14. Pádua JM, Rocha LB, Lia RCC, Pietro RCLR, FuscoAlmeida AM. Disseminação de infecção purulenta envolvendo segundo e terceiro molares inferiores - relato de caso clínico. BCI. 2000;7(25):29-32. Portuguese. 15. Wheatley MJ, Stirling MC, Kirsh MM, Gago O, Orringer MB. Descending necrotizing mediastinitis: transcervical drainage is not enough. Ann Thorac Surg. 1990;49(5):780‑4. http://dx.doi.org/10.1016/0003-4975(90)90022-X 16. Takao M, Ido M, Hamaguchi K, Chikusa H, Namikawa S, Kusagawa M. Descending necrotizing mediastinitis secondary to a retropharyngeal abscess. Eur Respir J. 1994;7(9):1716-8. PMid:7995405. http://dx.doi.org/10.118 3/09031936.94.07091716 17. Suga A, Inoue Y, Takeichi H, Yamada S, Iwazaki M. A case of an elderly patient treated for descending necrotizing mediastinitis. Gen Thorac Cardiovasc Surg. 2011;59(9):623‑6. PMid:22231792. http://dx.doi.org/10.1007/s11748-010-07 41-5 18. El Oakley RM, Wright JE. Postoperative mediastinitis: classification and management.Ann Thorac Surg. 1996;61(3):1030‑6. http://dx.doi.org/10.1016/0003-4975(95)01035-1 19. Callister ME, Wall RA. Descending necrotizing mediastinitis caused by group A streptococcus (serotype M1T1). Scand J Infect Dis. 2001;33(10):771-2. PMid:11728046. http://dx.doi.org/10.1080/003655401317074608 20. Sato S, Kajiyama Y, Kuniyasu T, et al. Successfully treated case of cervical abscess and mediastinitis due to esophageal perforation after gastrointestinal endoscopy. Dis Esophagus. 2002;15(3):250-2. PMid:12445000. http://dx.doi. org/10.1046/j.1442-2050.2002.00253.x 21. Von Rahden BH, Feith M, Dittler HJ, Stein HJ. Cervical esophageal perforation with severe mediastinitis

Oliveira Junior EM, Moreira RT, Cavalcante TC. due to an impacted dental prosthesis. Dis Esophagus. 2002;15(4):340-4. PMid:12472485. http://dx.doi. org/10.1046/j.1442-2050.2002.00290.x 22. Mitjans MS, Sanchís JB, Padro XB, et al. Descending necrotizing mediastinitis. Int Surg. 2000;85(4):331-5. PMid:11589602. 23. Chow AW. Life threatening infections of the head and neck. Clin Infect Dis. 1992;14(5):991-1002. PMid:1600027. http://dx.doi.org/10.1093/clinids/14.5.991 24. Dembo JB. Emergência em odontologia. Rio de Janeiro: Medsi; 1998. Portuguese. 25. Estrera AS, Lanay MJ, Grisham JM. Descending necrotizing mediastinitis. Surg Gynecol Obstet. 1983;157(6):545‑52. PMid:6648776. 26. Fatureto MC, Neves-Junior MA, Santana TC. Mediastinite aguda: análise retrospectiva de 21 casos. J Bras Pneumol. 2005;31(4):307-11. Portuguese. http://dx.doi.org/10.1590/ S1806-37132005000400007 27. Brunelli A, Sabbatini A, Catalini G, Fianchini A. Descending necrotizing mediastinitis: cervicotomy or thoracotomy. J Thorac Cardiovasc Surg. 1996;111(2):485-6. http:// dx.doi.org/10.1016/S0022-5223(96)70460-9 28. Cirino LMI, Elias FM, Almeida JLJ. Descending mediastinitis: a review. São Paulo Med J. 2006;124(5):285‑90. PMid:17262162. http://dx.doi.org/10.1590/S1516-318020 06000500011 29. Novellas S, Kechabtia K, Chevallier P, Sedat J, Bruneton JN. Descending necrotizing mediastinitis: a rare pathology to keep in mind. Clin Imaging. 2005;29(2):138‑40. PMid:15752971. http://dx.doi.org/10.1016/j.clinimag.2004. 10.001

Conflict of interest: None Submitted on: 23th December 2011 Accept on: 30th January 2012 Correspondence: Divisão de Odontologia Av. Prof. Lineu Prestes, 2565 – Cidade Universitária – São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9290 E-mail: jr.odonto@gmail.com

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Article / Clinical Case Reports Artigo / Relato de Caso Clínico Nodular lymphocyte predominance Hodgkin lymphoma of the parotid gland: a case report Carlos Augusto Ferreira Alvesa, Marcia Maria de Gouveiaa, Adalmir Gonzaga dos Santos Queiroza, Mariana Aparecida Brozoskia, José Pinhata Otochb, Paulo Sérgio Martins de Alcântarab, Patrícia Picciarelli de Limac, Aloísio Felipe-Silvac Alves CAF, Gouveia MM, Queiroz AGS, et al. Nodular lymphocyte predominance Hodgkin lymphoma of the parotid gland: a case report. Autopsy Case Rep [Internet]. 2012;2(1):43-47. http://dx.doi.org/10.4322/acr.2012.007

ABSTRACT The parotid is the most frequent site of primary salivary gland tumors. Lymphomas represent 0.2 to 0.8% of all malignant parotid tumors. Primary Hodgkin lymphoma of the parotid gland is rare with few cases reported in literature. The nodular lymphocyte predominance Hodgkin lymphoma (HL) is considered a particular clinical and histopathological subtype of HL. It has never been reported in the parotid gland since its incorporation in the 2001 World Health Organization Classification. The authors describe a case of a 32-year-old male who sought medical attention because of a one-year history of right cheek enlargement. A parotid nodule was submitted to a fine needle aspiration biopsy which disclosed a suspected lymphoproliferative disorder. A surgical dissection of the parotid gland was performed and an enlarged intraparotid lymph node measuring 4cm in its longest axis was excised, preserving the parotid gland integrity as well as the facial nerve. The pathological examination disclosed the diagnosis of nodular lymphocyte predominance Hodgkin lymphoma in this lymph node within the parotid gland. The treatment was completed with local radiotherapy and the 5-year follow up was uneventful. Keywords: Parotid gland; Adult Hodgkin lymphoma surgery; Fine needle biopsy. CASE REPORT A 32-year-old caucasian male patient sought the Surgery department at the University Hospital of the University of São Paulo, complaining of right cheek swelling for about one year (Figure 1A). There were no other symptoms. On clinical examination there was a nodule in the right parotid gland region, with up to 3 cm in its longest axis, with well-defined limits. On

palpation it was painless and hard, suggesting a parotid pleomorphic adenoma as first diagnostic hypothesis. There were no other signals on physical examination. The ultrasonography revealed a 3.0 cm hypoechoic nodular structure inside the parotid gland. The patient was submitted to a fine needle aspiration (FNA) biopsy and the cytologic analysis

Department of Dentistry - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. Department of Surgery - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. c Anatomic Pathology Service - Hospital Universitário - Universidade de São Paulo, São Paulo/SP - Brazil. b

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revealed scarce cells with large multilobed and convoluted nuclei, with nuclear membrane irregularity and macronucleoli, highly suggestive of Hodgkin lymphoma (HL) diagnostic cells (Figure 2A). These cells were present in a background containing a large number of small polymorphic lymphocytes, frequent eosinophils (Figure 2B) and rare aggregates of histiocytes in an outline of granulomas. Typical findings of reactive lymphoid hyperplasia like lymph-histiocytic aggregates or tangible body macrophages were not detected. FNA findings were interpreted as suspicious for lymphoproliferative disorder demanding surgical excisional biopsy for precise diagnosis definition. The right parotid gland was operated on by trans-node excision in order to preserve the facial nerve (Figures 1B,C). The excisional biopsy of the intraparotid lymph node was performed and the whole material was sent for pathological analysis. Gross examination revealed a 4.0 × 3.0 × 2.5 cm nodular tumor covered by a smooth and translucent capsule. On sectioning surface the tissue showed a light brown color, smooth appearance and elastic consistency (Figure 1D).

Alves CAF, Gouveia MM, Queiroz AGS, et al.

The histological analysis showed a diffuse and vaguely multinodular lymphoid proliferation. Large cells with the same characteristics observed in the FNA were distributed in a nodular background composed of small lymphocytes and numerous reactive granulomas formed by epithelioid histiocytes (Figures 3A,B). Special stains for microorganisms were negative. On immunohistochemistry analysis, the large cells were CD20 positive (Figure 4A), CD15 negative, CD30 negative, CD10 negative, EMA negative and CD3 negative. These morphological and immunohistochemical findings were consistent with lymphocytic and histiocytic (L&H) diagnostic cells of a nodular lymphocyte predominance Hodgkin Lymphoma (NLPHL). Around these cells, there was a crown of reactive CD3+ and CD57+ T lymphocytes. Small lymphocytes without atypia in the background were mainly CD20+. The reactive histiocytes and granulomas were CD68+ (Figure 4B) and a network of expanded follicular dendritic cells within the nodules was demonstrated by the positivity for CD21. Altogether, these findings were consistent with a NLPHL of a lymph node within the parotid gland.

Figure 1 – A- Asymmetric enlargement of the right cheek; B and C- Surgical exeresis of the intraparotid lymph node; D- Sectioning surface of the lymph node.

Nodular lymphocyte predominance Hodgkin lymphoma of the parotid gland: a case report

Surgical treatment was complemented by adjuvant radiotherapy. The patient is in remission in

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a current 5-year follow-up with periodic clinical and imaging controls.

Figure 2 – Photomicrography – Cytologic examination of the intraparotid lymph node aspirate. A- (Papanicolau stain, 400X) large cells (black arrow) with irregular enlarged nuclei and macronucleoli; B- (Dry panotic stain, 1000X) Large atypical cell in a background of small lymphocytes and eosinophils (white arrow).

Figure 3 – Photomicrography – Histologic examination of the intraparotid lymph node. (hematoxilin & eosin) A- Panoramic view (100X) Diffuse, imprecise multinodular lymphoid proliferation, with reactive granulomas (arrow); B- (400X) Large atypical cells (arrow) in a background rich in small lymphocytes.

Figure 4 – Photomicrography – Immunohistochemistry. A- (400X) positivity for CD20 in the L&H cell (arrow); B- CD68+ reactive granulomas.

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DISCUSSION Hodgkin’s lymphoma is a malignant lymphoproliferative disorder defined in terms of histology and immunophenotype. It usually affects the lymph nodes of the cervical region of young adults in most cases.1 Lymphomas within the parotid gland are rare. Their incidence accounts for 0.2 to 0.8% of all malignant parotid tumors.2 The parotid gland is more commonly affected when compared to the submandibular and sublingual glands. Salivary glands lymphomas occur most frequently in women with Sjögren’s syndrome.3 In the parotid gland, the most common type of lymphoma is non-Hodgkin lymphoma.2,4 The NLPHL is considered a particular (nonclassical) clinical and histopathological subtype of HL.1 The classic form of HL comprises the other four histopathological categories: nodular sclerosis, mixed cellularity, lymphocyte depletion and the lymphocyte-rich classic HL.1 Approximately 3 to 5% of head and neck tumors are lymphomas, which can be classified as HL or non-Hodgkin lymphomas.5,6 HL is responsible for about 14% of all lymphomas.5 NLPHL corresponds to 5-10% of all HL. When compared to classic HL, NLPHL is more frequent in males (70%) with the involvement of peripheral lymph nodes. Symptoms such as fever, weight loss and night sweats (B symptoms) are observed in less than 20% of the affected patients. Additionally, the clinical course is usually indolent, with late relapses.1 NLPHL is distinguished from the classical HL by histological, genetic and immunophenotypic features. The scarce malignant cells in NLPHL are of the lymphocytic and histiocytic (L&H) type, morphologically different from the ReedStenberg cell of the classic HL. L&H cells are arranged in a reactive background of small B and T lymphocytes. They express B-lymphocytes markers (CD20, CD79a) and epithelial membrane antigen (EMA), but not CD30 or CD15, in contrast to the classic HL.1,7 Clinical presentation in the head and neck may vary from nodal and/or extranodal sites.8 Primary HL in the parotid gland is a rare entity with very few cases reported in the literature.9,10 In

Alves CAF, Gouveia MM, Queiroz AGS, et al.

fact, in order to be considered a primary parotid tumor, gland involvement must be the first clinical manifestation of lymphoma. HL is usually not suspected in the conventional approach of a parotid tumor. In a review of primary lymphomas of the parotid gland, Yencha et al. (2002) described the “lymphocyte predominance subtype” (classic HL) as the most common, accounting for 40% of cases.10 However, as the NLPHL entered the WHO classification only in 2001, possibly some of the previous cases described as lymphocyte-rich/ lymphocyte predominance classical HL would be now reclassified as NLPHL. In fact, in Yencha et al. series, immunophenotypic profiles of HL cases were not shown. We did not find any report in the literature of NLPHL located in the parotid gland. Although NLPHL was first described in the 1980’s, it was only incorporated into the WHO classification in 2001. It is likely that at least a few cases previously classified as primary lymphocyte-rich/lymphocyte predominance classic HL of the parotid gland would be reclassified as NLPHL nowadays. The access of major salivary glands is relatively easy, and therefore these glands are excellent targets for FNA biopsy.11This procedure is often indicated in the preoperative evaluation of parotid masses11,12 since it can furnish the diagnosis, preparing both the surgeon and the patient in the surgical planning. The cytological characteristics in this case were suggestive of Hodgkin lymphoma (HL). Specific cytological descriptions of NLPHL subtype are limited in the literature.13 The surgical procedure adopted in the present case permitted the separation of the superficial and deep lobes of the parotid gland from the origin of the facial nerve in order to preserve it. The non-occurrence of salivary fistula neither facial nerve injury showed the appropriate surgical technical option. Intraoperative evidence of exclusive involvement of intraparotid lymph node led to end the surgical procedure with its complete excision and preserving the parotid gland. The most common treatment for localized NLPHL is the total excision of involved lymph nodes followed by radiotherapy.14 None of the most frequent complications after the parotid gland manipulation like facial palsy, Frey’s syndrome, salivary fistula, and loss of sensation in the area of the parotid gland occurred in this case.15

Nodular lymphocyte predominance Hodgkin lymphoma of the parotid gland: a case report

In conclusion, lymphoproliferative disorders are usually not considered in the initial management of a parotid gland mass and are rarely suspected before biopsies or surgical removal. We describe a rare case of nodal NLPHL in the parotid gland, treated with lymph node excision and local radiotherapy with uneventful 5-year follow up.

ACKNOWLEDGEMENTS We are grateful to Rosa Maria C. Zanardi for the technical support on the visual work.

REFERENCES 1.

Swerdlow SH, Campo E, Harris NL, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Agency of Research in Cancer; 2008. v. 2, 439 p.

Von Stritzky M, Wereldsma JC, Pegels JG. Parotid mass as first symptom of a maligmant lymphoma. J Surg Oncol. 1998;67:25-7. http://dx.doi.org/10.1002/(SICI)1096-90 98(199801)67:1%3C25::AID-JSO5%3E3.0.CO;2-O

Rosai J. Major and minor salivary gland. In: Rosai J, editor. Rosai and Ackerman’s surgical pathology. 9th ed. Edinburg: Mosby; 2004. p. 896-7. Dispenza F, Cicero G, Mortellaro G, Marchese D, Kulamarva G, Dispenza C. Primary Non-Hodgkins lymphoma of the parotid gland. Braz J Otorhinolaryngol [Internet]. 2011 [cited 2012 Feb 29]; 77:639-64. Available from: http:// www.scielo.br/scielo.php?script=sci_arttext&pid=S180886942011000500017&lng=en&nrm=iso http://dx.doi.org/ 10.1590/S1808-86942011000500017. Boring CC, Squires TS, Tong T. Cancer statistics. CA Cancer J Clin. 1993;43:7-26. http://dx.doi.org/10.3322/canjclin.43.1.7

Autopsy and Case Reports 2012;2(1):43-47

Yuen A, Jacobs C. Lymphomas of the head and neck. Semin Oncol. 1999;26:338-45. PMid:10375090.

Sohani AR, Jaffe ES, Harris NL, Ferry JA, Pittaluga S, Hasserjian RP. Nodular lymphocyte-predominant hodgkin lymphoma with atypical T cells: a morphologic variant mimicking peripheral T-cell lymphoma. Am J Surg Pathol. 2011;35:1666-78. PMid:21997687. http://dx.doi. org/10.1097/PAS.0b013e31822832de

Lee AI, LaCasce AS. Nodular lymphocyte predominant Hodgkin lymphoma. Oncologist. 2009;14:739-51. PMid:19605845. http://dx.doi.org/10.1634/theoncologist.2009-0099

Masuda M, Segawa Y, Joe AK, Hirakawa N, Komune S. A case of primary Hodgkin’s lymphoma of the parotid gland. Auris Nasus Larynx. 2008;35:440-42. PMid:17983719. http://dx.doi.org/10.1016/j.anl.2007.09.008

10. Yencha MW. Primary parotid gland Hodgkin’s lymphoma. Ann Otol Rhinol. 2002;11:338-42. 11. Zapanta PE, Truelson JM, Rosen CA, Meyers AD. Fineneedle aspiration of salivary glands [Internet]. [place unknown]: WebMed Professional, c1994-2012 [updated 2011 May 4; cited 2012 Mar 8]. Available from: http:// emedicine.medscape.com/article/882291-overview 12. Zbären P, Schär C, Hotz MA, Loosli H. Value of fineneedle aspiration cytology of parotid gland masses. Laryngoscope. 2001;111:1989-92. PMid:11801984. http://dx.doi. org/10.1097/00005537-200111000-00023 13. Subhawong AP, Ali SZ, Tatsas AD. Nodular lymphocytepredominant Hodgkin lymphoma: Cytopathologic correlates on fine-needle aspiration. Cancer Cytopathol. 2012 Feb 24 [Epub ahead pf print]. http://dx.doi.org/10.1002/ cncy.21186 14. Spector N. Abordagem atual dos pacientes com doença de Hodgkin. Rev Bras Hematol Hemoter. 2004;26:35-42. Portuguese. 15. Kligerman J, Lima RA, Dias FL, Barbosa MM, Freitas EQ, Matos de Sá G. Complicações das cirurgias dos tumores das glândulas salivares. Rev Bras Cir Cabeça Pescoço. 2003;(31):55-60. Portuguese.

Conflict of interest: None Submitted on: 5th February 2012 Accept on: 25th February 2012 Correspondence: Serviço de Anatomia Patológica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária - São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9384 E-mail: patpicciarelli@yahoo.com.br

Autopsy and Case Reports 2012;2(1):49-53

Article / Clinical Case Reports Artigo / Relato de Caso Clínico Pyopericarditis and tropical pyomyositis: unusual concomitance Pedro Henrique Magalhães Craveiro de Meloa, Henrique Lane Staniaka, Aloísio Felipe-Silvab, Itamar Souza Santosa, Márcio Sommer Bittencourta Melo PHMC, Staniak HL, Felipe-Silva A, Santos IS, Bittencourt MS. Pyopericarditis and tropical pyomyositis: unusual concomitance. Autopsy Case Rep [Internet]. 2012;2(1):49-53. http://dx.doi.org/10.4322/acr.2012.008

ABSTRACT The authors report a case of a 19-year-old male who presented to the emergency room complaining of chest pain. His physical examination was unremarkable, but the EKG showed PR deviation and ST segment elevation. The patient was diagnosed as probable viral pericarditis and was prescribed oral anti-inflammatories. After 3 days he returned, complaining of chest pain worsening, generalized muscle pain and fever. Laboratory examinations showed creatine kinase isoenzyme MB (CK-MB) = 89.5 ng.mL–1 and C-Reactive Protein (CRP) = 391 mg.L–1. Echocardiogram showed pericardial thickening but no pericardial effusion was present. During admission the patient evolved with cardiac tamponade. Empirical ceftriaxone and oxacillin were started and the patient underwent pericardial surgical drainage. Staphylococcus aureus was isolated from the pericardial effusion. After 7 days the patient started complaining of leg pain, and fever recurred. Computed tomography of the lower limbs identified large muscle commitment compatible with the presence abscesses. These findings were suggestive of staphylococcal tropical myositis. The patient was treated with abscesses drainage and oxacillin. He was discharged after 18 days to complete oral antibiotic therapy. Keywords: Pericarditis; Chest pain; Tropical myositis; Staphylococcus aureus. CASE REPORT A 19-year-old male patient, previously healthy, sought the emergency medical service complaining of a one-day chest pain of sudden onset. He referred worsening of the symptom with breath movements and supine position. He had a history of upper airway infection one week prior to hospital presentation. Physical examination on admission was normal. The electrocardiogram revealed the presence of sinus tachycardia, PR segment deviation and upsloping ST segment a b

elevation (Figure 1). The echocardiogram, serum determination of troponin and CK-MB were normal. White blood cell count was 11200/mm3 (reference value = 4400 – 11300/mm3) and CRP = 24 mg.L–1 (RV <5). He was discharged after 24 hours of observation with complete relief of pain, with the presumptive diagnosis of uncomplicated viral pericarditis and was prescribed non-steroidal antiinflammatory for seven days.

Department of Internal Medicine - Hospital Universitário - Universidade de São Paulo, São Paulo/SP – Brazil. Anatomic Pathology Service - Hospital Universitário - Universidade de São Paulo, São Paulo/SP – Brazil.

Autopsy and Case Reports 2012;2(1):49-53

Melo PHMC, Staniak HL, Felipe-Silva A, Santos IS, Bittencourt MS.

Figure 1 – EKG showing sinus rhythm, heart rate= 136 bpm, PR interval 0,10 ms, SÂP axis +60°, SÂQRS axis +60°, diffuse upsloping ST segment elevation seen best here in leads I, II, aVF, and V2 to V6, There is also subtle PR segment deviation (positive in aVR, negative in I, II, III, aVF and V3 to V6). The patient returned to the hospital after 72 hours, complaining of worsening symptoms, fever and generalized myalgia. On physical examination he was acutely ill looking, wasted, and febrile. His hemodynamic parameters were stable and the heart and lung examination were normal. Laboratory tests on readmission revealed white blood cell count = 22.000/mm3 with a shift to the left, CK-MB = 89.5 ng.mL–1 (RV <5 ng.mL–1), CRP = 391 mg.L–1 (RV <5 mg.L–1), erythrocyte sedimentation rate (ESR) = 44 mm (RV <15 mm) in the first hour, the echocardiogram was repeated and showed the presence of pericardial thickening with no effusion nor signs of cardiac tamponade. On the second day of readmission, the patient was septic and presented clinical signs of pericardial tamponade, which was treated by pericardial surgical drainage and biopsy. The procedure resulted in 250 milliliters output of pus. He was transferred to the ICU with clinical signs of septic shock demanding ventilatory and hemodynamic support and was prescribed ceftriaxone and oxacillin. Further tests were carried out and the results were negative for HIV and EBV serologies, ANA and anti ds-DNA, determination of C3 and C4 were normal. The pericardial fluid analysis revealed the presence

of Gram-positive spherical bacteria. The search for fungus and acid fast bacilli (AFB) was negative and the culture isolated Staphylococcus aureus oxacillin sensitive. The pathological report was consistent with acute fibrinous pericarditis (Figure 2). On the seventh day of hospitalization, the patient complained of pain and swelling in the right thigh and fever persisted. Computed axial tomography of the lower limbs identified multiple hypoatenuating images compatible with abscesses involving the muscles: gluteus maximus, gluteus medius (Figure 3) as well as the muscles: biceps femoris, sartorius, rectus femuris, vastus lateralis, vastus medialis some of them bilaterally (Figure 4). The puncture of theses lesions disclosed the presence of purulent secretion. Staphylococcus aureus was also isolated from this site of infection leading to the diagnosis of staphylococcal pyomyositis. After surgical drainage of the abscesses and maintenance of antibiotic therapy the patient presented no further fever. A new transthoracic echocardiography demonstrated improvement of the pericardial lesion as well as no additional valvar lesions.

Pyopericarditis and tropical pyomyositis: unusual concomitance

He was discharged on the eighteenth day of hospitalization with the prescription of prolonged oral antibiotic.

Autopsy and Case Reports 2012;2(1):49-53

DISCUSSION Viral pericarditis accounts for most cases of acute pericarditis, occurring predominantly in young individuals, usually preceded by upper respiratory infection. It is characterized by a benign course and usually the treatment consists in the use of nonsteroidal anti-inflammatories. Although less frequent, infection by other agents such as: bacteria, fungi, tuberculosis bacillus; autoimmune, systemic diseases and cancer have to be considered in the differential diagnosis of acute pericarditis.

Figure 2 – Photomicrography (HE 400X) - fragment of pericardial tissue – presence of acute exudate with fibrin, polymorphonuclear leukocytes and reactive mesothelial hyperplasia - Acute fibrinous pericarditis.

Figure 3 – Axial computed tomography of the pelvis showing increased volume of the gluteus muscles due to edema and hypoatenuating lesions compatible with abscess.

The bacterial pericarditis is an uncommon condition in the current medical practice, usually associated with predisposing factors as immunosuppression and infection of the bloodstream. Nowadays, the purulent pericarditis is an uncommon diagnosis. Pyogenic pericarditis accounts for 0.7 to 1.0% of all cases of acute pericarditis. In a retrospective Spanish study of acute pericarditis there were found 33 cases of pyogenic pericarditis in a period of 19 years of study among a population of 593,600 people.1 In the antibiotics era bacterial pericarditis are associated with predisposing factors or diseases such as collagenosis, uremia and malignancies in 78%. The development of bacterial pericarditis may occur by: hematogenous dissemination, contiguity with infectious foci on chest or sub diaphragmatic space, direct trauma or thoracic surgery and by continuity of a myocardium abscess.2

Figure 4 – Computed Tomography of the lower limbs – coronal plane. A – image compatible with abscess in the right muscle biceps femoris; B – involvement of the muscles rectus femoris and vastus lateralis (mainly on the right side); C and D – involvement of muscles: vastus medialis and vastus lateralis bilaterally.

Autopsy and Case Reports 2012;2(1):49-53

Among the non-specific bacteriological etiologies Staphylococcus aureus is the most common etiological agent of purulent pericarditis, accounting for 22-31% of cases according to some series.2 Fungal infection is present in 19% of cases. Tuberculosis is another common cause however; the clinical presentation shows a subacute or chronic pattern.3 The initial evaluation of patients with suspected pericarditis should include the clinical history, physical examination focusing the search for signs of tamponade (jugular venous distention, muffled heart sounds, hypotension, and pulses paradoxus, pericardial rub), electrocardiogram, chest radiography and echocardiography.4 The electrocardiogram is the most frequently used test in the evaluation of suspected cases. The most common signs of pericarditis are diffuse ST segment elevation (typically concave up) and PR segment deviation, what means an elevation of the PR segment in lead aVR and depression of the PR segment in other limb leads and in the left chest leads V5 and V6.5 The normal echocardiogram does not exclude the diagnosis of pericarditis however, it must be requested in all cases with high suspicion of pericarditis and associated pericardial effusion, as well as signs of tamponade.6 The inflammatory process involved in the pericardium may extend to the underneath myocardium with increases in serum biomarkers of myocardial injury such as cardiac troponin and CK-MB. The high levels of these markers allow the classification of the disease as myopericarditis. The association between pyomyositis and pyopericarditis is scarcely reported. Reports suggest that pyomyositis may be associated with pericarditis and cardiac tamponade in some cases.7 Musa et al.8 reported two cases of pyomyositis associated with pyopericarditis caused by Staphylococcus aureus and Salmonella tiphy. The clinical manifestations of pyomyositis are fever and muscle pain, usually comprising the lower limbs. Multiple muscle groups involvement occur in in 20% of cases.9 In tropical countries, Staphylococcus aureus is implicated as the etiological agent in 90% of the cases.10 Treatment consists of antibiotic therapy plus multiple and repeated abscess drainage.

Melo PHMC, Staniak HL, Felipe-Silva A, Santos IS, Bittencourt MS.

Bacterial infections are common cause of excess mortality following influenza infection, well recognized in pandemic years. Superinfections from Staphylococcus aureus following influenza are of increasing concern. This association is well established for staphylococcal pneumonia specially caused by methicillin-resistant strains.11 The patient in this report had a prior history of a viral upper airway respiratory infection with pericardial involvement. We dare assume that this viral infection could facilitate the staphylococcal infection although this association was not proved. In the case reported here the pericardial involvement was present since the beginning of the history as well as the generalized myalgia. We assume that a staphylococcia happened after the suspected upper respiratory infection. The staphylococcal infection installed within the pericardium sac as in the striated muscle concomitantly. The pericardium involvement took the major role of the clinical picture due to the tamponade and the consequent hemodynamic collapse. When the pericardium infection seamed to be resolved the clinical picture of the pyomyositis arose. This case highlights an atypical presentation of pyopericarditis following an upper respiratory tract infection and associated with pyomyositis. The association of bacterial pericarditis with pyomyositis is rare, whether concomitantly or in addition.

REFERENCES 1.

Sagristà-Sauleda J, Barrabés JA, Permanyer-Miralda G, Soler-Soler J. Purulent pericarditis: review of a 20year experience in a general hospital. J Am Coll Cardiol. 1993;22:1661-5. http://dx.doi.org/10.1016/07351097(93)90592-O

Klacsmann PG, Bulkley BH, Hutchins GM. The changed spectrum of purulent pericarditis: an 86 year autopsy experience in 200 patients. Am J Med. 1977;63:666-73. http://dx.doi.org/10.1016/0002-9343(77)90150-4

Cegielski P, Dukes CS. Pericardial effusion in AIDS. Circulation. 1997;96:2080-1. PMid:14966036.

Permanyer-Miralda G. Acute pericardial disease: approach to the etiologic diagnosis. Heart. 2004;90:252-4. PMCid:1768141. http://dx.doi.org/10.1136/hrt.2003.024802

Imazio M, Demichelis B, Parrini I, et al. Day-hospital treatment of acute pericarditis: a management program for outpatient therapy. J Am Coll Cardiol. 2004;43:1042-6. PMid:15028364. http://dx.doi.org/10.1016/j.jacc.2003.09.055

Pyopericarditis and tropical pyomyositis: unusual concomitance 6.

Cheitlin MD, Alpert JS, Armstrong WF, et al. ACC/AHA Guidelines for the Clinical Application of Echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 1997; 95:1686-744. PMid:9118558. Andy JJ, Ekpo EB. Cardiovascular complications of tropical pyomiositis. Trop Geogr Med. 1987;39:260-4. PMid:3433341. Musa AA, Salami BA, Tade AO. Purulent pericarditis complicating septicaemia; report of two cases. East Afr Med J. 2003;80:331-3. PMid:12953744.

Autopsy and Case Reports 2012;2(1):49-53 9.

Crum NF. Bacterial pyomyosits in the united states. Am J Med. 2004;117:420-8. PMid:15380499. http://dx.doi. org/10.1016/j.amjmed.2004.03.031

10. Christin, L, Sarosi, GA. Pyomyositis in North America: case reports and review. Clin Infect Dis. 1992;15:668-77. PMid:1420680. http://dx.doi.org/10.1093/clind/15.4.668 11. Lee MH, Arrecubieta C, Martin FJ, Prince A, Borczuk AC, Lowy FD. A postinfluenza modelo f Staphylococcus aureus Pneumonia. J Infect Dis. 2010;201:508-15. PMid:20078212. http://dx.doi.org/10.1086/650204

Conflict of interest: None Submitted on: 7th February 2012 Accept on: 17th February 2012 Correspondence: Divisão de Clínica Médica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária, São Paulo/SP – Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9200 E-mail: msbittencourt@bol.com.br

Autopsy and Case Reports 2012;2(1):55-61

Article / Clinical Case Reports Artigo / Relato de Caso Clínico Spindle-cell carcinoma of the prostate Carlos Hirokatsu Watanabe Silvaa, Oliver Rojas Clarosa, Isaac Amselemb, Newton Soares Sá Filhob, Oscar Eduardo Hidetoshi Fugitaa,b Silva CHW, Rojas Claros O, Amselem I, Sá Filho NS, Fugita OEH. Spindle-cell carcinoma of the prostate. Autopsy Case Rep [Internet]. 2012;2(1):55-61. http://dx.doi.org/10.4322/acr.2012.009

ABSTRACT Sarcoma of the prostate and sarcomatoid carcinoma of the prostate are rare conditions, both characterized by a poor prognosis. Sarcomatoid carcinoma of the prostate typically arises from the evolution of an underlying adenocarcinoma, occasionally featuring heterologous elements, bulky disease being possible but rare. In contrast, sarcoma of the prostate derives from non-epithelial mesenchymal components of the prostatic stroma, shows rapid growth, and frequently presents as massive pelvic tumors obstructing the urinary tract at the time of diagnosis. We report the case of a 55-year-old patient with a two-month history of symptoms of urinary obstruction. The patient presented with an extremely enlarged heterogeneous prostate, although his prostatespecific antigen level was low. The lack of a history of prostatic neoplasia led us to suspect sarcoma, and a transrectal prostate biopsy was carried out. An immunohistochemical study of the biopsy specimen did not confirm the clinical suspicion. However, in view of the clinical features, we believe that sarcoma of the prostate was the most likely diagnosis. The patient received neoadjuvant chemotherapy followed by radiation therapy. At this writing, surgical resection had yet to be scheduled. Keywords: Prostate; Sarcoma; Carcinoma. CASE REPORT We report a case of a 55-year-old male patient who sought treatment in the Surgery Department Hospital. His primary complaint was acute urinary retention. He had a two-month history of symptoms of urinary obstruction. Physical examination revealed hard, lobulated enlargement of the prostate. Computed tomography (CT) scans of the abdomen and pelvis (Figures 1 and 2) showed an extremely enlarged heterogeneous prostate (estimated a b

volume, 300 cc) without evidence of adjacent tissue invasion. At diagnosis, his serum prostatespecific antigen (PSA) level was 0.7 ng.mL–1 (reference range, 0-4 ng.mL–1). Despite urinary catheterization, the patient developed renal failure. Another CT scan performed on postadmission day 10 showed rapid tumor growth, the volume of the prostate having increased to 700 cc.

Department of Surgery - Hospital Universitário - Universidade de São Paulo - São Paulo/SP – Brazil Department of Urology - Hospital São Camilo - Santana - São Paulo/SP – Brazil.

Autopsy and Case Reports 2012;2(1):55-61

Silva CHW, Rojas Claros O, Amselem I, Sá Filho NS, Fugita OEH.

Figure 1 – Axial computed tomography of the pelvis showing a massive tumor, with well-defined borders, in the topography of the prostate. In A, note the compression of the rectum and the bladder by the tumor. Pt: prostate; Bl: bladder.

DISCUSSION In the case reported here, the patient presented symptoms of urinary obstruction, an extremely enlarged prostate, and a low serum PSA level. In such cases, it is not uncommon for the patient to be misdiagnosed with prostatic hyperplasia. Despite the rarity of the condition, it is always advisable to include adenocarcinoma in the differential diagnosis of benign prostatic hyperplasia.

Figure 2 – Multidetector computed tomography of the abdomen and pelvis. Reformatted sagittal image showing a massive tumor occupying virtually all of the pelvic space. Note the heterogeneous distribution of the contrast medium. The patient was submitted to transrectal prostate biopsy. Examination of the biopsy specimen revealed undifferentiated malignant neoplasia. The results of an immunohistochemical panel (Table 1) were consistent with malignant neoplasia, the pleomorphic and spindle cell characteristics of which were suggestive of high-grade sarcoma or sarcomatoid carcinoma. Considering both diagnostic possibilities, the poor prognosis of both conditions, and the lack of any evidence-based treatment protocols, neoadjuvant chemotherapy and radiation therapy were initiated, with the objective of preparing the patient for subsequent surgical resection.

As in the case reported here, prostate biopsy specimens do not easily permit the differentiation between stromal tumors with spindle-cell morphology and poorly differentiated adenocarcinomas with a sarcomatoid component.1 A lack of awareness of this differential often delays the diagnosis, thereby compromising the treatment success and consequently worsening the prognosis.2-5 In the last two decades, numerous cases of rare carcinoma variants and stromal prostate cancer have been reported.2,3 We conducted a PubMed search using the search terms “prostate” and “sarcoma” and limited to studies published in English within the last 20 years and involving adults. We found twenty-five publications involving <3 patients,6-31 two involving 3-10 patients,2,4 and four involving >10 patients.1,3,32-34 The studies involving ≥5 patients or more were considered representative and are summarized in Table 2. A second search, with the same limiters, was conducted using the search terms “prostate” and “sarcomatoid carcinoma”. Twenty-seven papers were retrieved, only three of which involved ≥5 patients.10,11,35 Sarcoma of the prostate in adults is a rare disease that derives from non-epithelial mesenchymal components of the prostatic stroma.

Spindle-cell carcinoma of the prostate

Autopsy and Case Reports 2012;2(1):55-61

Table 1 – Immunohistochemical panel of the prostate biopsy specimen Antibody

Clone

Interpretation

SMA

1A4

Positive

HMB45

HMB-45

Negative

AE1-AE3

Negative

Desmine

D33

Negative

Vimentine

Positive

S-100

Polyclonal

Negative

34 beta E12

Negative

EMA

E29

Positive

Calponine

Calp1

Negative

CD34

QBEnd-10

Negative

Ki-67

MIB01

Positive in 25% of cells

PSA

Calp1

Negative

SMA = smooth muscle actin, EMA = epithelial membrane antigen, PSA = prostatic specific antigen.

Sarcomas account for <5% of all genitourinary tumors and for only 0.01-0.02% of all prostate tumors.2,4 Sarcomas can be classified by histological subtype, cell differentiation, and tumor size.3 In cases of sarcoma of the prostate, the most common histological subtype is rhabdomyosarcoma followed by leiomyosarcoma, the latter being the most common subtype in adults.34,36 Sarcoma of the prostate grows rapidly, presenting as extensive pelvic tumors, leading to urinary tract obstruction, and typically has a poor prognosis.2-5 In the case reported here, the clinical presentation consisted of symptoms of urinary obstruction and an initial CT scan of the topography of the prostate showed a massive heterogeneous mass that grew rapidly, despite the fact that the patient had a normal serum PSA level. In the largest known study of sarcoma of the prostate, involving 21 patients, Sexton et al.2 found that 16 (76%) had obstructive symptoms, 10 (48%) had pelvic or perineal pain, and 7 (33%) had irritative urinary symptoms. They also found that 5 (24%) had a history of urinary retention.2 In patients with sarcoma of the prostate, the serum PSA level is almost always normal, because of the non-epithelial origin of the sarcoma.2,5 At diagnosis, the majority of such patients have symptoms of urinary obstruction, which, together with the normal PSA level, often result in a misdiagnosis of prostatic hyperplasia,

which can lead to transurethral resection of the prostate, thus delaying the diagnosis of sarcoma.5,11 The largest series on sarcoma of the prostate retrieves data from 21 patients retrospectively reviewed along 3 decades. In the Sexton et al. study, the one-, three-, and five-year survival rates were 81%, 43%, and 38%, respectively.2 Longterm survival was mainly related to tumor-free surgical margins and the absence of metastatic disease at diagnosis.2 Neither tumor size nor grade (cell differentiation) have been shown to affect the prognosis, and there are conflicting data regarding the impact that the histological subtype has on the outcome.2,3 However, delayed diagnosis and advanced stage at the time of diagnosis have been shown to worsen the prognosis.4,37 Although there is as yet no consensus regarding the best treatment for sarcoma of the prostate, there is increasing evidence that a combined multimodal approach increases survival.2 Radical cystoprostatectomy is the recommended surgical procedure. Most studies suggest that the success rates are higher for the surgical approach than for other types of treatment used in isolation.2,37 Complete resection with tumor-free margins provides the best prognosis—five-year survival of 67%, compared with 0% when the surgical margins are invaded by tumor.1 These findings are similar to those obtained by Dotan et al.,32 who studied cases of sarcoma of the genitourinary tract. The authors demonstrated a disease-specific five-year survival rate of 65% when complete resection was performed, compared with 21% for partial resection.32 Despite the lack of published evidence regarding adjuvant and neoadjuvant therapy, as well as that of prospective trials evaluating the impact of those therapies, it seems logical and understandable that a multimodal approach would improve outcomes.32 Sarcomatoid carcinoma of the prostate is even rarer than is sarcoma of the prostate and combines high-grade epithelial and sarcomatoid histological components. Although controversial, the epithelial and sarcomatoid components are currently thought to originate from a single cell.38 It is possible that sarcomatoid carcinoma represents the evolution of an underlying adenocarcinoma into a lesion with associated sarcomatoid features and, in some cases, heterologous elements, resembling osteosarcoma, chondrosarcoma, and rhabdomyosarcoma36. Fewer than 100 cases have been reported, and there have been only three studies involving more than 10 patients.35,36,39 The

Autopsy and Case Reports 2012;2(1):55-61

Silva CHW, Rojas Claros O, Amselem I, Sá Filho NS, Fugita OEH.

Table 2 – Data from the last 20 years on sarcoma of the prostate: studies involving ≥5 patients Year, author

Histology

1992, Russo et al.34

Total

Surgery

ChT

5-year survival

Follow up

1+ 5*

Rhabdomyosarcoma

Leiomyosarcoma

1995, Cheville et al.33

Leiomyosarcoma

Varied: usually multimodal

17%

30% died from the tumor in 3-72 months

2000, Sexton et al.2

Total

38%

8 patients survived to 81.5 months

Leiomyosarcoma

16%

75% died from the disease. One lost to follow-up

Rhabdomyosarcoma

75%

No patients died, one lost to follow-up

Malignant fibrous histiocytoma

Unclassified sarcoma

100%

Total

29%

Leiomyosarcoma

Rhabdomyosarcoma

Other

Total

1†

Leiomyosarcoma

Rhabdomyosarcoma

Total

Rhabdomyosarcoma

50%

18.5 months

Leiomyosarcoma

100%

6 months

High grade

100%

15.5 months

2006, Dotan et al.32

2008, Ren et al.5

2009, Janet et al.3

Mean age, years

RT: radiation therapy; ChT: chemotherapy; NA: not available. *Multimodal therapy (surgery + ChT + RT); †ChT + RT.

largest of those involved 42 patients.36 In that study, there was a history of prostate adenocarcinoma in 66% of the patients for whom clinical data were available and many patients were diagnosed with sarcomatoid carcinoma many years after having been diagnosed with acinar adenocarcinoma. Half of the patients showed a high Gleason score at diagnosis.36 Although some reports have raised the possibility that prior radiation or hormone therapy influences the development of sarcomatoid carcinoma, there is no consistent evidence of a correlation between treatment modality and disease progression.36 In fact, no clinical or pathological data have proven useful in stratifying cases of sarcomatoid carcinoma by prognosis.1,36

Sarcomatoid carcinoma of the prostate is an aggressive tumor with a poor prognosis. Similar to those of sarcoma of the prostate, the clinical manifestations of sarcomatoid carcinoma include filling and voiding defects.38 Progressive tumor enlargement can lead to bladder outlet obstruction and often requires multiple resections of the prostate in order to relieve the symptoms.1 For sarcomatoid carcinoma, there is no serum tumor marker, and patients with the condition present with PSA levels that are lower than would be expected, given the considerable size of the tumor. The low PSA levels might be due to the mesenchymal component.38 On palpation, the prostate is typically enlarged, nodular, and hard. Transrectal needle biopsy is usually

Spindle-cell carcinoma of the prostate

diagnostic, and the differential diagnosis should include other conditions that combine malignant spindle-cell elements with epithelial components. In some cases, only sarcomatoid elements are seen. In such cases, the differential diagnosis should include pure sarcoma and pseudosarcoma.38 It should also be borne in mind that it is difficult to distinguish poorly differentiated adenocarcinoma with a sarcomatoid component from a primary mesenchymal tumor or benign prostatic hypertrophy.38 Regardless of the prostate tumor histology, CT and magnetic resonance imaging (MRI) are useful for showing the local extent of the disease and can inform the surgical planning.5,37 One recent study showed that sarcoma typically presents as a large, hypervascularized cystic tumor with heterogeneous soft-tissue enhancement in radiological studies (MRI and CT). The main MRI feature is a marked increase in the choline:citrate ratio, to a level higher than that observed in normal prostate tissue.5 The rarity of both types of prostate tumors discussed here might justify the difficulty in obtaining larger patient samples. Consequently, reliable data regarding treatment options and prognosis are scarce.2,4,36 The histological heterogeneity of and lack of a standardized staging system for such tumors make it difficult to draw comparisons across studies.2,4,32,37 Apparently, outcomes are worse for sarcomatoid carcinoma than for sarcoma. Although surgical resection is an option for localized tumors, only a few cases are operable at the time of presentation. After a diagnosis of sarcomatoid carcinoma of the prostate, the risk of death during the first year is 20%.1,36 Although the results of the immunohistochemical study of the case reported here did not allow us to differentiate between sarcomatoid carcinoma and high-grade sarcoma, we considered the latter diagnosis more suitable because of the clinical features (rapid growth of prostate, sudden onset of obstructive symptoms and very low PSA levels) and the lack of a history of prostate disease. In the Surgery Department of the University of São Paulo University Hospital, 2,322 procedures involving the prostate, including biopsies and resections, were performed between 1990 and 2009. The present case was the only one identified as sarcoma of the prostate.

Autopsy and Case Reports 2012;2(1):55-61

Sarcoma of the prostate is a major differential diagnosis in patients presenting with rapid prostate growth or extremely large prostate volume, accompanied by normal PSA values. A high level of suspicion is needed in order to avoid delaying the diagnosis and treatment.

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Conflict of interest: None Submitted on: 27th February 2012 Accept on: 3rd March 2012 Correspondence: Divisão de Clínica Cirúrgica Av. Prof. Lineu Prestes, 2565 – Cidade Universitária - São Paulo/SP –Brazil CEP: 05508-000 – Phone: +55 (11) 3091-9291; 3091-9489 E-mail: oscareh@hu.usp.br