The Synergistic Role of 2D and 3D Imaging in Evaluating Tumors of the Jaws: A Case Report of Diffuse Large B-Cell Lymphoma of the Mandible

Mark Mintline, DDS; Jeffrey A. Elo, DDS, MS, FACS; Setareh Lavasani, DDS, MS; James Ywom, DDS, MS; Ashtin Alves, DMD; and Ho-Hyun (Brian) Sun, DMD, MS

ABSTRACT

Background: Oral complications are common in head and neck cancer patients. Poor oral health is associated with increasing incidence and severity of unwanted effects. Prevention and management of complications can not only improve quality of life but also aid in an uninterrupted continuation of the ideal cancer treatment.

Case description: An interprofessional approach is conducive to minimizing complications during all phases of cancer treatment. Dentists serve as experts in the prevention, diagnosis and management of cancer-related orofacial sequelae. Increasingly, the use of in-office 3D imaging of the face — especially cone beam computed tomography (CBCT) — affords dentists with an overall greater ease and accuracy in locating otherwise undetected oral manifestations of cancer. CBCT technologies offer an advanced point-of-care imaging modality that clinicians should use selectively as an adjunct to conventional 2D dental radiography. CBCT imaging provides clinicians several diagnostic benefits: It allows clinicians to more closely examine the size of lesions, provides an opportunity to more critically assess cortical changes and facilitates surgical treatment planning. We present a case of a diffuse large B-cell lymphoma of the mandible that was diagnosed via examination in a dental office setting and further characterized by CBCT imaging.

Practical implications: The case demonstrates the efficacy with which a well-trained dental team could aid in the detection of serious illnesses, including cancer. It highlights the role of the dental professional not only in the detection of oral cancers like squamous cell carcinoma, but in the symptoms management of even systemic cancers like lymphoma.

Keywords: Diffuse large B-cell lymphoma of mandible, multidisciplinary, dental oncology, oral complications, cancer treatment, 2D imaging, 3D imaging, tumors of the jaws

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AUTHORS

Mark Mintline, DDS, is an assistant professor of oral and maxillofacial pathology and the coordinator of the advanced oral diagnosis workgroup at the Western University of Health Sciences College of Dental Medicine in Pomona, California. Conflict of Interest Disclosure: None reported.

Jeffrey A. Elo, DDS, MS, is a professor of oral and maxillofacial surgery at the Western University of Health Sciences College of Dental Medicine in Pomona, California. He is a fellow in the American College of Surgeons. Conflict of Interest Disclosure: None reported.

Setareh Lavasani, DDS, MS, is an associate professor of oral and maxillofacial radiology at the Western University of Health Sciences College of Dental Medicine in Pomona, California. Conflict of Interest Disclosure: None reported.

James Ywom, DDS, MS, is an associate professor of prosthodontics at the Western University of Health Sciences College of Dental Medicine in Pomona, California. Conflict of Interest Disclosure: None reported.

Ashtin Alves, DMD, is a general dentist in private practice in Hanford, California. Conflict of Interest Disclosure: None reported.

Ho-Hyun (Brian) Sun, DMD, MS, is a clinical assistant professor of oral and maxillofacial surgery at the Western University of Health Sciences College of Dental Medicine in Pomona, California. Conflict of Interest Disclosure: None reported.

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Oral complications are common in head and neck cancer patients. Poor oral health is associated with increasing incidence and severity of unwanted effects. Prevention and management of complications can not only improve quality of life but also aid in an uninterrupted continuation of the ideal cancer treatment. An interprofessional approach was proven conducive to minimizing such complications during all phases of cancer treatment.

Within an interprofessional setting, dentists may serve as experts in the prevention, diagnosis and treatment of cancer-related orofacial sequelae. In addition, an increasing ubiquity of in-office 3D imagery of the face — especially cone beam computed tomography (CBCT) — affords dentists with an overall greater ease and accuracy in locating otherwise undetected oral manifestations of cancer. CBCT technologies offer an advanced point-of-care imaging modality that clinicians should use selectively as an adjunct to conventional 2D dental radiography. CBCT imaging provides clinicians several diagnostic benefits: It allows clinicians to more closely examine and delineate the size of lesions in three dimensions; provides clinicians an opportunity to more critically assess the presence of any cortical changes such as facial or lingual cortical expansions and/or perforations; and facilitates the planning of interventive surgical treatment (incision placement, design and length).

The selection of CBCT for dental and maxillofacial imaging should be based on professional judgment in accordance with the best available scientific evidence, weighing potential patient benefits against the risks associated with the level of radiation dose. The practitioner who operates a CBCT unit, or requests a CBCT study, must examine the entire image dataset. This is predicated on a thorough knowledge of CT anatomy for the entire acquired image volume, anatomic variations and observation of abnormalities. It is imperative that all image data be systematically reviewed for disease.

We present a case of a diffuse large B-cell lymphoma (DLBCL) of the mandible that was discovered via examination in a dental office setting that was further characterized by CBCT imaging. The case demonstrates the efficacy with which a well-trained dental team can aid in the detection of serious illnesses, including cancer. It highlights the role of the dental professional not only in the detection of oral cancers like squamous cell carcinoma but in the symptom management of systemic cancers such as lymphoma.

Clinical Presentation

A 25-year-old Hispanic female presented to a large dental university clinic for a routine dental examination. The patient’s medical and surgical histories were noncontributory with no current medications or known allergies. She denied recent nausea, vomiting, fevers or chills as well as constitutional symptoms including night sweats, fatigue or sudden weight loss. The patient had never used alcohol, tobacco or recreational drugs.

Extraoral examination revealed facial symmetry with a mouth opening of approximately 43 mm. Her facial skin was intact without rashes or gross neurological deficits. Palpation of the face and neck did not reveal any erythema, fluctuance, edema or tenderness, and the cervical lymph nodes were unremarkable.

Intraoral examination revealed good oral hygiene with no tenderness, purulence or dental mobility. All teeth tested vital to cold and electric pulp testing. There was no appreciable erythema, leukoplakia, ulcerations or swelling of the mucosal surfaces.

Routine radiographs were obtained and interpreted by a board-certified oral and maxillofacial radiologist. A plain film series demonstrated a heterogenous, ill-defined radiolucent entity of the right anterior mandible immediately distal to the canine (tooth No. 27) and around the apex of the lateral incisor (tooth No. 26) (FIGURE 1). The periphery of the lesion showed a wide transition zone with no discernable cortication and very minimal apical root resorption of tooth No. 27.

A CBCT imaging study demonstrated a lesion associated with teeth Nos. 26 through 28 with irregular borders that lacked a discernible cortication (FIGURE 2A). Irregular loss of lamina dura on the distal aspect of tooth No. 27 was noted, as was an area of wide transition zone between the center of the lesion to the normal bone at the periphery. Three-dimensional imaging also revealed that the lesion extended further inferiorly compared to what was visualized in the initial periapical radiograph. An axial view of the CBCT volume (FIGURE 2B) demonstrated a localized area of interruption of the buccal cortical plate at the region of tooth No. 27. Localized areas of dot-sized permeative (moth-eaten appearance) bone destruction were noted on the buccal aspect of tooth No. 27 (FIGURE 2C). No expansion or periosteal reaction of either cortices was noted. The radiologist’s report described the noted 2D and 3D findings and recommended referral to a surgeon for further evaluation with biopsy.

Diagnosis and Management

An aspirational biopsy was performed first, but did not yield notable fluids or aspirates, suggesting the entity was not cystic or vascular in nature. During the subsequent open biopsy (FIGURES 3A and 3B), a bony window revealed soft, friable tissue that appeared inflammatory in consistency and was distinct from the surrounding bone. The lesion had created a resorptive tunneling effect within the bone but curetted out easily. Manipulation did not produce abnormal bleeding. The specimen was submitted to a laboratory for histopathologic examination and reviewed hr a board. certified oral and maxillofacial pathologist and a board-certified hematopathologist.

Histopathologic examination revealed sheets of atypical and large transformed lymphocytes (centroblasts), tangible body macrophages and collections of small lymphocytes (FIGURE 4). The large and atypical cells were immunoreactive for CD20, Pax-5, BCL6 and CD30; they were negative for CD3, CD5, CD10, MUM1, CD21, ALK and EBER CISH. Ki-67 had a proliferation index of approximately 95%. The tumor was diagnosed as DLBCL: not otherwise specified (NOS), CD30 positive. The DLBCL had germinal center B-cell like immunophenotype (CD10−, BCL6+ and MUM1−).

The medical oncology team imaged and staged the tumor as DLBCL, NOS, CD30 positive: stage I AE with a National Comprehensive Cancer Network International Prognostic Index (NCCN- IPI) score of 0. Serology testing for human immunodeficiency (HIV), hepatitis A and hepatitis B was negative. The complete blood count, lactate dehydrogenase, beta-human chorionic gonadotropin and uric acid levels were normal. Renal, hepatic and cardiac function were normal. The first-line treatment consisted of chemoimmunotherapy and involved-site radiation therapy (ISRT) of the mandible.

The chemoimmunotherapy consisted of four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) plus two additional applications of rituximab ([4 x R-CHOP] + [2 x R]). 9 The tumor had a complete response to R-CHOP (FIGURES 5A and 5B). A standard radiation dose of 3600 cGy of intensity-modulation radiation therapy (IMRT) was then delivered: 20 fractions (180 cGy/day) of 6 MV photons over an elapsed 28 days.

Oral health education as well as adjunctive dental care and support were delivered for the patient before, during and after cancer treatment. One month prior to chemoimmunotherapy and radiation therapy, she underwent a thorough dental evaluation and had all potential sources of oral infection treated. Oral hygiene instruction was delivered as was education on the oral complications of cancer treatment. The patient was provided with a soft nylon-bristled toothbrush and a nonmint-flavored dentifrice with fluoride. She was instructed to brush three times per day using the Bass sulcular scrub method, floss once daily and use water if toothpaste became too painful. Custom fluoride gel applicators and 1.1% neutral pH sodium fluoride gel were prescribed prior to radiation therapy. A custom tonguedisplacing (CTD) stent using a novel cup-shaped “saddle” design was promptly fabricated from alginate impressions for the patient to wear during IMRT. The saddle design is an alternative to the teardropshaped “paddle” design 10 and offers a compartment for the tongue to rest during head and neck radiotherapy (FIGURE 6).

During the patient’s cancer treatment, she developed oral mucositis, dysgeusia and trismus. During the second week of radiation therapy, she developed Grade 2 (moderate) radiation mucositis according to the World Health Organization (WHO) scale. The patient tolerated a solid diet, but exhibited oral soreness, erythema and an ulceration of the right retromolar pad (FIGURES 7A and 7B). The oral mucositis was controlled with a combination of diphenhydramine oral solution, 2% lidocaine viscous solution, 0.12% chlorhexidine gluconate oral rinse and ice chips. The patient’s dysgeusia was managed with zinc supplementation (zinc sulfate 220 mg twice daily), and the patient’s taste acuity returned two months after radiation therapy. The patient was also instructed on post-radiation jaw physical therapy, which consisted of repeated passive TMJ opening to a tolerable limit three sets a day, 20 repetitions per set. Her maximum incisal opening returned to normal (42 mm) two weeks after radiation therapy.

After chemotherapy and radiation therapy concluded, optimal dental care resumed and has remained. The patient is now in remission 22 months later. A positron emission tomography (PET)/ CT scan and dental radiograph show no evidence of disease (FIGURE 8).

Conclusion

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma in the U.S. 11 and is fatal if left untreated. 12 Prompt diagnosis and immediate treatment is critical to patient survival. The dental team plays a vital role as part of a multidisciplinary oncology team to prevent and control oral complications related to cancer treatment. General dentists, dental specialists and dental hygienists help manage the oral cavity of the patient with cancer before, during and after cancer treatment. The dental team also plays a key role in the detection of tumors that may present in the 2D radiographs and 3D CBCT images of the jaws. In this case, the dental team helped detect, image, biopsy, diagnose, refer and manage a DLBCL of the mandible. This case was complex and required the collaboration of numerous dental specialists and medical providers in family medicine, hematopathology, oncology and radiation oncology. This case report also documents the first use of a CTD stent for an intraosseous non-Hodgkin lymphoma of the jaws. Additional studies are needed to determine the efficacy of CTD stents in the radiation therapy of tumors and hematologic malignancies of the jaws.