Ecbse ch03 sonopathology

ECBSE General Sonopathology

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EFSUMB Course Book Student Edition Editors: Jan Tuma, Radu Badea, Christoph F. Dietrich

General Sonopathology (Signs of benign and malignant cystic and solid lesions) Dieter Nürnberg1, Vito Cantisani 2 1 2

Medizinisches Zentrum,Ruppiner Kliniken Charite Berlin, Germany University of Rome “La Sapienza”, Italy

Corresponding author: Dr. Vito Cantisani Department of Radiology,University of Rome "La Sapienza",Policlinico Umberto I, Viale Regina Elena 244, 00161, Rome,Italy Tel.: (39) 06-4455602 Fax.: (39) 06-490243 E mail: vito.cantisani@uniroma1.it

Acknowledgment: Mattia Di Segni, Hektor Grazhdani, Francesco Maria Drudi

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Content Introduction ..................................................................................................................... 2 Cystic lesions .................................................................................................................. 2 Criteria of normal cysts ............................................................................................... 2 Signs of pathological cysts ......................................................................................... 4 CEUS in differentiation of cystic lesions .................................................................. 10 Solid lesions .................................................................................................................. 11 Signs of pathological solid lesions............................................................................ 11 Ultrasound features indicating malignancy of solid lesion ....................................... 11 Stones ........................................................................................................................... 21 Free fluid and gas ......................................................................................................... 22 References/Recommended readings .......................................................................... 24

Introduction While ultrasound waves in liquids and therefore also in cysts are transmitted almost without hindrance and consequently with no echo, in solid structures, such as tumours, the waves encounter many structures with different densities compared to the surrounding tissue. This leads to a different echogenicity. Cysts are generally black or echo-free in an ultrasound image, while solid tumours have a range of densities leading to a range of echos, from hypoechoic, to isoechoic, to hyperechoic.

Cysts have typically features, which are explained in the following text.

Cystic lesions Criteria of normal cysts     

smooth wall (regular contour) round form echo free content posterior acoustic features (dorsal echo plus) tangential phenomenon / side shadowing

While ultrasound waves in liquid and therefore also cysts, are transmitted almost without hindrance and consequently without an echo, in solid structures such as tumours the waves encounter many structures with different densities compared to the surrounding tissue. This leads to a different echogenicity. Cysts are generally black or echo-free in an ultrasound image, while solid tumours have a range of densities leading to a range of echos, from hypoechoic, to isoechoic, to hyperechoic.

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Cysts have typical features, which are explained in the following text.

Figure 1 Cystic and solid lesion in liver. Cysts or encapsulated liquid structures can be very easily differentiated by ultrasound to circumscribed solid lesions. In figure 1 a ventral echo-free harmless cyst can be detected. Further dorsal a small hyperechoic solid lesion can be seen. The sonographical picture suggests a capillary haemangioma (see Liver Chapter). While the cyst, as a fluid-filled structure shows no echo or is almost echo-free, a solid tumorous structure shows a more or less homogenous echo.

Figure 2 Normal cyst. The image shows a round, echo-free structure with a smooth surface surrounded by homogenous liver tissue.

Theperipheral echo-free structures are vessel sections. The cyst shows the typical phenomenon of distal sound amplification, an echoincrease at the distal part of the cyst, visible as a light dorsal ray.

Laterally to the sound amplification, two hypoechoic, dark lines are visible, that originates from the lateral cusps of the cyst and delineatesthe amplification laterally. This is an artefact called the tangential phenomenon / side shadowing.

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Signs of pathological cysts Criteria of an abnormal cystic lesion    

irregular wall / irregular contour / calcifications not round form echogenic content and internal structures, solid parts no posterior acoustic features / no dorsal echo plus

Irregular wall: While normal cysts, without any pathological findings, have a smooth wall, an irregular wall [Figure 3a, 3b, 3c, 3d] and intramural calcifications are considered pathological signs. These can contribute information, e.g. to the origination of the cyst. Genuine cysts have a smooth configuration, secondary cysts show an irregular configuration, e.g. haemangioma, parasitic cysts, abscesses and pseudo-cysts.

Figure 3a Liver cyst with irregular wall. The wall of the cyst is only partially smooth. There is a calcification visible in the wall with the typical acoustical shadow.

The sonic waves cannot penetrate the calcification. Calcifications are more often in secondary liquid lesions following a hematoma.

Figure 3bCystic lesion with a very irregular wall and echogenic content. The wall of the cyst is very irregular and frayed. The relative homogenous content is a collection of pus. A large liver abscess is depicted here.

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Figure 3c Cyst with irregular wall of the pancreas- pancreatic pseudocyst.

The ventral wall of the cyst is very irregular in this case.This is not a genuine cyst, but a pseudo cyst emerging after anacute pancreatitis.The ventral wall of the cyst is multiple millimetres thick.

Such a cysthas to be differentiated from a cystic tumour through clinical signs,patient history and further imaging techniques.

Endosonography and contrast agent enhanced ultrasound play a significant role.

Figure 3d Cyst with irregular wall and internal structure of the kidney- atypical renal-cyst. Deviated atypical cyst of the kidney, which has to be differentiated from a partly cystic tumour or cystic wall tumour.

Imaging techniques are to be used, especially contrast enhanced ultrasound.

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Echogenic content and internal structures: Echogenic content and solid structures (septa) within the cyst are conspicuous signsthat should be pursued further. If the content is echogenic, it could be blood after a haemorrhage or pus in an infected cyst [Figure 4]. Pancreatic pseudocysts can accumulate detritus or partly solid tissue (sequestrum). Septs in a cyst (internal structures) are suggestive of a tumour, but occur also in parasitic cysts (e.g. ecchinococcus).

Figure 4a Big cyst of pancreas with internal structures. The internal structures showed a blood circulation in contrast enhanced ultrasound. This facilitated the indication to an operation which led to the diagnosis of a macro-cystic, serous pancreas tumour (benign cystoadenoma).

Figure 4b

Partial cystic tumour of pancreas. There solid partsare more numerous than the liquid parts in this mucinous cystic adenoma of the pancreas. This is a benign pancreas tumour that can normally be identified by endoscopic ultrasound.

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Figure 4c Big cyst of left kidney with internal structures – ecchinococcus cyst.

Normally, ecchinococcous cyst occur more frequent in the liver than in the kidney, as shown here. In this ecchinococcous cyst septs and even round cystic structures are visible within a large cyst. (“cysts within a cyst”). By courtesy of G.v. Klingräf

Figure 4d

Big cyst of liver with internal structures – haemorrhagic cyst. A primary echo-free cyst in the liver appears diffuse hyperechoic aftera painful event. It bled into the cyst. The bleeding stops spontaneously (self-tamponade). There is an increased risk of secondary infections.

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Figure 4e Big cystic lesion of spleen with internal structures – spleen hematoma. While under anticoagulation a minor accident occurredand led to the discovery of this large liquid structure in the spleen. The septs are caused by parenchyma bridges. Also a hematoma during organization can cause these septs. The rupture of the spleen exceeded more than 50% of the organ, leading to a splenectomy. By courtesy of H. Pannwitz

Figure 4f

Cystic lesion of pancreatic tail with echogenic content – infected pancreatic pseudo cyst. ¾ of the cyst are filled with echogeniccontent. During the examination of the spleen the tail of the pancreas is well visible. In case of an infection an intervention (puncture or drainage) must follow.

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Figure 4g Big cystic formation with hypoechic content and gas – paracolic abscess. The combination of liquid content (hypoechoic, fluctuating) and gas (marker) proves the diagnosis of an abscessor an infection, respectively.

There are very hypoechoic, mainly hypervascular solid tumours that almost appear echo-free. This also applies to hypoechoic enlarged lymph nodes. The typical dorsal acoustical shadow that would occur in cysts is missing [Figure 5]. The echogenicity of the lesion is often visible, if the signal is increased (increase the gain!).

Figure 5Very echopoor (nearly echofree!) lesions without dorsal acoustic features. Especially enlarged lymph nodes in malignant lymphomas or in an acute lymphadenitis can appear almost cystic in nature and be misinterpreted. The image above shows mesenteric lymph nodes in a patient with Non-Hodgkin Lymphoma.

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CEUS in differentiation of cystic lesions Figure 6 Contrast enhanced ultrasound helps to differentiate between a cyst and a tumour. If a conspicuous wall lesion or echogenic content is detected in B-mode (marker), that cannot be detected in contrast enhanced ultrasound (no enhancement), the material is amorphousand has no blood circulation. This way, the differentiation between pseudocysts and cystic tumours is possible e.g. in the pancreas.

Solid lesions Signs of pathological solid lesions Criteria of malignant solid lesions are:  

the invasion of surrounding structures irregular wall / irregular margins

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not round form, taller than wide lesion inhomogeneous echogenic content and internal structures posterior acoustic shadowing microcalcifications hypervascularity (elevated RI index) New signs: Hypoenhancement during the portal and late phases at contrast enhanced ultrasound Stiff lesions at US elastography

Ultrasound features indicating malignancy of solid lesions Any new mass found in any organ at ultrasound examination, should be viewed with suspicion and the bigger the mass and the more solid component in it, the more attention should be paid. If the mass presents with an irregular form, it is highly suspicious for an infiltrating malignancy. On the other hand, however, a regular, round or oval form does not warrant tranquility and good knowledge of pathology and ultrasound signs of malignancies in the particular organ are required for the operator [8].

As a rule of the thumb, suspicion for malignancies should always be kept high in a new found nodule or mass. Of course, a purely cystic mass is rarely malignant, but in certain organs like the ovaries, yearly follow up is required if the cyst is bigger than 3 cm in a postmenopausal woman and bigger than 5 cm in a woman in her reproductive age. A palpable and painful mass in the breast that alarms the woman, when found at ultrasound to be a simple cyst, should warrant the operator to calm the patient by saying that the mass is only liquid and to suggest follow-up.

Decompression aspiration of the cyst resolves the pain and also the anxiety of the subject. A cystic mass that presents thickened walls and internal septa is denominated a complex cyst and it should be evaluated with greater attention when found in the ovary, kidney or pancreas. The more solid the component in walls and septa, the more the mass is suspected for malignancy. In the ovary, signs of vascularity at color-Doppler in the solid component increase the suspicion. When a complex ovarian cyst is found, the operator should check the abdomen for free fluid or peritoneal nodularity, which are both, in this clinical situation, sure signs of malignant peritoneal spread of ovarian cancer (peritoneal carcinomatosis). In the kidney and pancreas, a complex cystic mass requires computed-tomography evaluation and eventual surgery.

In certain cases a cyst is not anechoic at ultrasound, but presents as hypoechoic and has to be differentiated from a solid nodule which must be evaluated with attention and followed with repeated examinations when in the breast or thyroid. A cyst is complicated when containing debris, haemorrhage or infection and in these cases presents as hypoechoic at ultrasound. Ballottement with the probe, i.e. pushing sharply and releasing, may help detecting a complicated cyst in the breast.

Ultrasound elastography shows a characteristic artifact in fluids and makes diagnosis of cysts, and on the other hand if the lesion is solid elastography would show the signs of a soft or hard solid tissue.

A solid mass or nodule with irregular shape, spiculated margins [see Figure 19] and heterogeneity is generally suspicious.

Malignancy is almost certain if the mass has interrupted the organ's capsule and invades adjacent tissues such as in the case of a prostate, thyroid or salivary gland

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nodule, or a renal or liver mass. Vascular invasion is also a sure sign of malignancy and is seen with hepatocellular carcinomas (HCC) that invade the portal vein, with pancreatic carcinomas that encase and invade the mesenteric artery and vein, and with renal carcinomas that form intravascular malignant thrombi in the renal vein. If an intravascular echoic image containing internal Doppler signal is present in an enlarged vein, it is qualified as a neoplastic thrombus [see Figure 11 and 12].

Furthermore, a solid mass or nodule that is associated with prominent and unusually large regional lymph nodes is highly suspicious for malignancy and the nodes are suspicious for lymphatic spread (N1).

In the spectrum of nodule characteristics, on the opposite side of an irregular shape mass, with spiculated margins and internal heterogeneity, lies a nodule with homogeneous echotexture, regular margins, and oval or round shape. Such a nodule, however, is considered attentively in the context of the organ where it is presented; for example, in the testicle, pancreas and kidney it is a common presentation for malignancies, and it is therefore suspicious when found in the liver and salivary glands. Whereas such a nodule in the uterus is a benign leiomyoma and unless it is symptomatic (haemorrhage when prominent in the cavity with endometrial irritation), it requires no particular attention. A nodule of salivary gland cannot be differentiated as benign or malignant either by ultrasound or by any other imaging modality. Thus, in the absence of helpful ultrasound signs, evaluation with knowledge of the pathology of the specific organ is required in such cases.

In a newly found nodule, further imaging work-up is needed with computed tomography or magnetic resonance, as in the case of nodule in the kidney, pancreas or liver. Ultrasound is diagnostic in the case of a testicular nodule, but traditional ultrasound is not capable of distinguishing a benign from a malignant lesion in the liver. A solid nodule in the liver is always suspicious for metastases or a primitive neoplasm (HCC), especially in the appropriate clinical context. However, on the other hand, benign liver lesions can be found in healthy subjects (haemangioma, follicular nodular hyperplasia and adenoma). The recent developments in ultrasound, with contrast agent studies and elastography techniques, are currently being established as valid adjunct tools. The EFSUMB guidelines indicate for liver lesions at contrastenhanced ultrasound, that hypoenhancement in the late and post-vascular phases, corresponding to the wash out phenomenon, characterizes malignancies [Figure 7, 8]. Almost all metastases show this feature, regardless of their enhancement pattern in the arterial phase. Very few exceptions to this rule have been reported, mainly in atypical hepatocarcinoma.

Figure 7 On the left side at contrastenhanced ultrasound two hypoechoic lesions during the late phase are clearly presented; on the right the lesions at Baseline-ultrasound appeared markedly hypoechoic (hepatic metastases).

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Figure 8

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On the left side at contrastenhanced ultrasound one hypoechoic lesion during the late phase; and at the right side the lesion at Baseline-ultrasound appeared markedly heterogeneous with tiny hypoechoic capsule. (Hepatic adenocarcinoma, hepatocarcinoma).

Ultrasound is the primary imaging modality for the diagnosis of thyroid cancer. 5060% of the population developsthyroid nodules during the life span and only 5-7 % of them are malignant. In a thyroid nodule, if the presence of one suspicious sign is found, fine-needle aspiration cytology (FNAC) is required. These signs are: microcalcifications, interrupted thyroid capsule by the nodule invasion, suspicious loco-regional lymph nodes, marked hypoechogenicity, irregular form and irregularity in the margins with spiculations and / or microlobulations, deeper than wide shape in the transverse scan, vivid internal hypervascularity at color-Doppler, and interval growth greater than 20% in two dimensions of the nodule[Figure 9].

US elastography is a valuable additional tool in the evaluation of thyroid nodules aiding in the decision making: to proceed to FNAC or to simply follow up. The nodules are suspicious when they present as hard, with high stiffness at the various elastography methods: at real time elastography (RTE) the score 3 or even more at score 4 [Figure 10], at strain ratio elastography a value greater than 2 and at the

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recent quantitative elastography techniques, high measured elasticity values (at shear wave elastography SWE >35 – 66 kPa, at acoustic radiation force impulse ARFI > 2,6 m/sec).

Figure 9

On the left side (B-mode ultrasound) an hypoechoic, fairly marginatedthyroid lesion is visible; on the right side (ultrasoundStrain elastography) a completely stiff lesion was evidenced.

A breast lesion ultrasound assessment is always required after an abnormal mammography or a non diagnostic mammography. Suspicious ultrasound features of breast nodules are: hypoechogenicity, irregular shape and irregular margins (spiculation, angular margins, micro or macro lobulations, duct extension and branch pattern), microcalcifications, echogenic halo, oval form but taller than wide, posterior acoustic shadowing [Figure 10], internal vascularity.

Figure 10

A hypoechoic lesion with internal part of shadowing shown. In thecenter of the measured lesion there is a portion that limits the through transmission, as shown by the distal shadow.

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Ultrasound lymph node assessment is often requested by the clinician and furthermore a patient may present for a first examination with a mass that is found at ultrasound to be a metastatic lymph node or a primary or secondary lymphoma. A lymph node that presents as big, hypoechoic with a round or irregular shape, is evidently malignant. However, in many common cases, differentiating the normal reactive lymph nodes from the malignant ones is often a challenging task. Suspicious signs are short axis dimensions greater than 1 cm as a general rule, the absence of the hyperechoic fibro-fatty vascular medullary sinus, heterogeneity in internal texture, shape that is tending toward round and away from oval, and cortical vascularity at color-Doppler (normally the vascularity is only hilar with internal branching). A ratio short axis to long axis (in transverse scan) major than 0,5 is suspicious, showing a lymph node that is becoming round. Various authors report measured dimensions that serve as reliable cut-off values, as for example malignancy is suggestive by the following: in the lateral neck short axis greater than 5 mm, in the submandibular region short axis >8 mm, in axillary cavity lymph nodes with a focal cortical thickening greater than 3 mm, Cystic and calcific changes of any kind in a lymph node are signs of malignancies as they represent degenerative necrosis of malignant tissue.

Keeping in mind the general picture of the clinical condition of the patient is indispensable when evaluating a solid nodule or mass. If the patient has a primary neoplasm or has been treated for it, the suspicionsare always high despite few and slight ultrasound signs. Any new lesion in the liver is a metastasis, a minimally enlarged lymph node is suspicious and subcutaneous nodes are skin metastatic spread in such cases.

The main feature indicating malignancy is the invasion of surrounding structures:  vessels (e.g portal branches for hepatocarcinoma, mesenteric vessels for pancreatic neoplasms, renal vein for renal carcinoma); the presence of an intravascular echoic image [Figure 11] with internal Doppler signal is qualified as neoplastic thrombus or the evidence of direct invasion of a mass with echogenicity similar to the primary tumour is indicating as infiltrating neoplastic lesions [Figure 12]; Figure 11

At baseline ultrasound a renal lesion invading the ipsilateral vein is seen.

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Figure 12 A neoplastic thrombus (some colour-flow signals are evident) is detected within inferior vena cava.



organ capsule (e.g. prostate cancer or thyroid nodules), seen as a subtle extension over it or infiltration of adjacent structures, with associated limitations of physiologic movements in adrenal malignancies [Figure 13].

Figure 13

Ultrasound shows an heterogenous, mainly hypoechoic, with an antero-posterior diameter longer than the transverse, with irregular margins in the left thyroid lobe and infiltrates the capsule.

Lymph node metastases, another highly valuable feature, is surely best indicated by hypoechoic round or inhomogeneously echotextured [Figure 14] nodes with extensively altered vascularization and loss of the fatty hilum or with presence of focal hypoechoic areas; anyway, the most precocious feature – though non specific for lymph node metastases is the enlargement of lymph nodes located on the typical lymphatic drainage pathways for the organ.

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Figure 14

Baseline ultrasound shows an heterogeneous thyroid lesion (Thyroid Carcinoma) with adjacent hetereogeneous, hypoechoic Lymph node (metastasis).

Figure 15

Baseline ultrasound shows an hyperechoic lymph node with a peripheral hypoechoic area (metastasis).

Figure 16

Baseline ultrasound shows an heterogeneous, hypoechoic lymph node with tiny and irregular hylum.

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Figure 17

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At power-Doppler the lymph node appears hypervascular.

Echogenicity is rarely considered as a feature indicative of the nature of the nodules in organs other than the thyroid – where it must be associated to solid echotexture.

The possible exceptions that can be considered are liver hemangiomas and renal angiomyolipomas.

Echotexture, when inhomogeneous, is not a direct sign of malignancy – rather meaning the overgrowth compared to the feeding ability of the vascular background [Figure 18].

Figure 18

An inhomogeous, hypo-hyperechoic lesion at lower pole of the kidney is detected

Ill defined margins– applied when more than 50% of lesion borders are not well demarcated is a common descriptor. In thyroid lesions it was reported to have a sensitivity ranging between 53-89% and a specificity ranging 15-59%.

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Margins irregularity – appearing as jagged lesion border image – is also considered a sign of malignancy in many lesions.

Figure 19

At baseline ultrasound the hypoechoic lesion, presented irregular margins.

Calcifications are readily detected with ultrasound presenting as echogenic (sound absorption) with posterior acoustic shadow. The diagnostic significance of calcifications is variable depending on the organ where they are found.

Microcalcifications:Being small do not cast acoustic shadow [Figure 19 and 20] and they are a sign of malignancy in a thyroid nodule and in a breast lesion. Micro or macro calcification in a neck lymph node is a sign of metastatic spread.

Figure 20

At baseline ultrasound the hypoechoic lesion, presented multiple microcalcifications.

Vascularity and blood flow features: Doppler evaluation employs both qualitative features, i.e the presence and distribution of blood flow; hypervascularity is a finding to be taken in account since it is suggestive in majority of cases of malignancy.

Figure 21

The lesion presented some internal vascular flow signal.

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Quantitative features deriving from spectral analysis: 

Resistance Index, the ratio between the difference between systolic and diastolic velocities and the systolic velocity; high-RI is suggestive of malignancy

Figure 22

At color-Doppler the lesion presented RI >0.70

Stones Ultrasound is the primary modality and the most sensitive one, for the detection of biliary stones (gallstones) and the first line for the diagnosis of renal calculi.

Calcification absorbs the sound waves and the classical appearance of stones is that of an echogenic structure which casts posterior acoustic shadow. [Figure 23 and 24]

Figure 23

At baseline ultrasound an hyperechoic focus with posterior acoustic shadow is clearly visualized within the gall bladder.

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Figure 24

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At baseline ultrasound an hyperechoic focus with posterior acoustic shadow is clearly visualized at middle pole of the kidney.

In some small renal stone without clear acoustic shadow, twinkle artifact at colorDoppler (ring-down artifact) is a helpful sign [Figure 25].

Figure 25

At color-Doppler ultrasound an hyperechoic focus with posterior acoustic shadow twinkle artifact is clearly visualized within the ureteral distal part.

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Salivary duct stones and eventual accompanying sialadenitis are promptly diagnosed with ultrasound.

Free fluid and gas Free fluid in the abdomen or in thorax is echo free. Normally we see the fluid only in vessels, bile system, urinary system or gastrointestinal tract. In the situation of pathological effusion the fluid is in abnormal locations like around the liver or between the bowel.

In the situation of free gas we find the typical artefact of reverberation in atypical (or wrong) places.

Figure 26a Echo free ascites surround the liver – transudate in situation of decompensation of liver cirrhosis.

Figure 26b Echoic ascites with fibrin structures in the abdomen in situation of necrotizing pancreatitis.

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Figure 27aNo organs are visible because of a curtain of gas or reverberations.

Free perforation caused by stomach ulcer.

Figure 27b Two big air bubbles between abdominal wall and liver are also signs of perforation.

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References/Recommended reading    

Schmidt G., Greiner L., Nürnberg D. Differential Sonography. Thieme. 2013.

Dietrich CF. EFSUMB - European Course Book. 2012.

Nuernberg D et al. Ultrasound in gastroenterology--liver and spleen.

Z.Gastroenterol. 44 (9):991-1000, 2006.

Will U et al. Interventional ultrasound-guided procedures in pancreatic pseudocysts, abscesses and infected necroses - treatment algorithm in a large single-center study. Ultraschall Med. 32 (2):176-183, 2011.

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Dietrich CF, Nuernberg D. Interventional Ultrasound. Stuttgart:Thieme, 2013.

Rumack C M, Wilson S R, Charboneau J W, Levine D. Diagnostic Ultrasound, Mosby, New Jork, 4 edition, January 2011.

Claudon M, Dietrich CF, Choi BI et al. Guidelines and good clinical practice recommendations for Contrast Enhanced Ultrasound (CEUS) in the liver - update 2012: A WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol. 2013 Feb;39(2):187-210. doi: 10.1016/j.ultrasmedbio.2012.09.002. Epub 2012 Nov 5.

Cooper D. et al 2009: Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer.

Thyroid, 1911:1167-214.

Cantisani V, Lodise P, Grazhdani H, et al. Ultrasound elastography in the evaluation of thyroid pathology. Current status. Eur J Radiol. 2013 Jun 11.