Marginal-zone B-cell lymphoma of the bony palate presenting as sinusitis.

Abstract

The diagnosis of low-grade B-cell lymphoma consistent with marginal-zone lymphoma has proven to be challenging when the disease involves the hard palate. The diagnosis is complicated by the nonspecific nature of the presenting symptoms and a difficult-to-differentiate histologic picture. We describe a case of low-grade B-cell lymphoma of the hard palate with a delayed presentation. We also compare the features of this case with the features of the small number of other such cases that have been reported in the literature. Finally, we review the etiology of low-grade B-cell lymphoma, we discuss its radiologic and pathologic features, and we briefly describe the treatment options.

Introduction

Marginal-zone B-cell lymphoma of the bony palate is uncommon. Its presentation can be confusing and misleading because of vague, nonspecific symptoms and nondiagnostic pathologic specimens. As a result of these diagnostic challenges, the initiation of treatment is often delayed.

We describe a new case of marginal-zone B-cell lymphoma of the bony palate in which these diagnostic challenges were encountered and overcome. By reporting this case, we hope to help physicians who might be faced with a similar circumstance to attain a diagnosis more quickly. To that end, we emphasize the need for obtaining sufficiently large tissue biopsies and focusing immediate attention on histologic evaluation, flow cytometry, and appropriate immunochemical studies. A rapid diagnosis not only facilitates the initiation of timely treatment, but it also prevents a situation in which a patient undergoes multiple nondiagnostic procedures. We also review the limited amount of information available on this type of lymphoma.

Case report

A 64-year-old black woman with chronic sinusitis presented to the otolaryngology office with a 10-year history of nasal pressure with occasional nasal obstruction and rhinitis. Her long history of symptoms also included tmilateral orbital pain, tinnitus, tightness in her scalp and frontal areas, and a productive cough. She added that during this 10-year period, her ill-fitting dentures had caused intermittent palatal pain.

The patient's medical history was also noteworthy for laryngopharyngeal reflux, hypertension, and a cerebrovascular accident with subsequent multiple episodes of transient ischemic attack. Her surgical history included a partial hysterectomy that had required a blood transfusion to manage extensive bleeding and bilateral partial mastectomies. Socially, the patient had a 40 pack-year cigarette history; she smoked marijuana daily, and she drank alcohol frequently.

On physical examination, the cranial nerves were intact. Nasal endoscopy revealed moderate chronic rhinitis without purulence or polyps. No buccal lesions were noted in the oral cavity, the tongue was mobile and in the midline, and the soft palate was elevated symmetrically. Underneath her dentures was a tender, nodular, submucosal lesion at the midbody of the hard palate. No erythema, drainage, or ulceration of the mucosa was noted, and no oroantral fistula was present. On palpation, the palate was soft, and no bone was felt along the midline.

Computed tomography (CT) of the sinuses identified a demarcated, lobular, soft-tissue mass of the hard and soft palates (figure 1). CT also revealed a nearly complete erosion of the bone of the hard palate and medial walls of the maxillary sinuses bilaterally. Soft-tissue invasion of the mass extended into the maxillary sinuses and bilaterally to the pterygopalatine fossae, skull base, and the right cavernous sinus.

[FIGURE 1 OMITTED]

Biopsy specimens were obtained from the palatal mucosa and deep submucosal tissues. Frozen-section analysis identified extensive lymphocytic infiltrate. Further staining, flow cytometry, and immunochemistry were all negative for lymphoma. No immunophenotypic evidence of abnormal cell populations was seen. Therefore, a second biopsy was recommended, and a larger tissue sample was obtained. The repeat biopsy led to a final pathologic diagnosis of a low-grade B-cell lymphoma consistent with marginal-zone lymphoma (figure 2). A polymerase chain reaction gene rearrangement study showed B-cell clonality.

The patient was referred to the oncology department for treatment planning. She was lost to follow-up.

Discussion

Marginal-zone B-cell lymphoma--which is known in the Revised European-American Lymphoma/World Health Organization (REAL/WHO) classification system as extranodal marginal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)--accounts for 7 to 8% of all non-Hodgkin's lymphomas. (1) It most frequently involves the lymphatics of the gastrointestinal tract, and it accounts for 1 to 4% of all malignancies that arise in the stomach, small intestine, and colon. (1)

Primary marginal-zone B-cell lymphomas of the head and neck are uncommon. (2) Such malignancies have been reported in the salivary glands, gingiva, floor of the mouth, palate, buccal vestibule, and bone of the maxilla and mandible. (2) Takahashi et al noted that most reported oral non-Hodgkin's lymphomas were B-cell lymphomas; cases of low-grade lymphoma of the palate outnumbered cases of extranodal lymphoma of the palate. (3) Because the features of the oral lymphoma that we reported were fairly consistent with documented trends of marginal-zone lymphoma, we presented this case in order to illustrate the difficulty of reaching this diagnosis.

Etiology. The etiology of marginal-zone B-cell lymphoma remains unclear. Many patients have a history of autoimmune disease, such as Sjogren's syndrome (commonly involving the parotid gland) or Hashimoto's thyroiditis. In addition, some patients have a history of hepatitis C virus infection. Helicobacter pylori gastritis is most often seen in MALT lymphoma of the gastrointestinal tract. Researchers have used proinflammatory and immunoregulatory cytokines, neutrophil infiltration, specific T- and B-cell responses, and gastric lymphoid follicles to study the mechanisms leading to the development of MALT lymphoma. (4) Other factors associated with this type of lymphoma include Epstein-Barr virus infection, human immunodeficiency virus infection, blood transfusions, and marijuana and cocaine use. (5-9) Our patient had a history of both frequent marijuana use and blood transfusions.

Although this patient's lymphoma did not involve the gastrointestinal tract, her laryngopharyngeal reflux had suggested a possibility of Hpylori-associated lymphoma. Further research is needed to determine whether H pylori is associated with marginal-zone B-cell lymphoma of the proximal alimentary tract and, if so, whether the association influences the development of palatal lymphoma of this type.

Diagnosis. The diagnosis of low-grade B-cell lymphoma consistent with marginal-zone lymphoma has proven to be difficult when it occurs in the palate. Patients often present with ambiguous symptoms that span a wide spectrum of possible otolaryngologic entities. As a result of the nonspecific nature of the symptoms, diagnosis and treatment can be significantly delayed. Our patient presented with symptoms of chronic rhinosinusitis, laryngopharyngeal reflux, and otologic complaints.

Kuhlberg reported a case in which a patient later diagnosed with palatal lymphoma had presented with complaints of facial numbness and a sharp, burning facial pain, especially with chewing. (10) Fagel reported another case in which the patient presented with progressive diplopia. (11) In our case, the patient's vague complaints concealed the advanced stage of her disease at the time of diagnosis. Only after a complete physical examination and radiographic studies was the extensive bony erosion noted. However, prior to the tissue diagnosis, the CT evidence suggested an even more ominous diagnosis--possibly adenoid cystic carcinoma or mucoepidermoid carcinoma.

[FIGURE 2 OMITTED]

Another factor that makes this lymphoma so challenging is that a pathologic diagnosis is difficult to obtain. In all of the cases (10-13) reviewed in this article, the initial pathology reports were nondiagnostic. These unclear biopsy results necessitated repeat biopsies for a conclusive diagnosis. Repeat biopsies should be considered if the original biopsy shows nonspecific inflammatory changes, if the amount of the specimen is insufficient, or if crush artifact interferes with a diagnosis of a neoplastic process. (10,12) In Fagel's single case report, numerous biopsies obtained on different occasions were nondiagnostic. (11)

Treatment. Treatment should be individualized. Surgery, chemotherapy, and radiation therapy--alone and in various combinations--have been successful, even in patients who present with stage IV nongastric MALT lymphoma. Zucca et al reported a 5-year survival rate of 90%; one-quarter of those patients had stage IV disease. (2) Adjunctive antibiotic treatment aimed at eradicating H pylori has also been proven beneficial. (14,15)

Acknowledgment

The authors extend special thanks to Xiaoli Chen, MD, and Shuko Harada, MD, of the Department of Pathology and Laboratory Medicine at the Drexel University College of Medicine in Philadelphia for their help with the pathologic images.

References

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(13.) Nadimi H, Toto PD. Large cell, multilobulated, B-cell lymphoma of the palate. A case report. Int J Oral Maxillofac Surg 1991;20(6): 325-7.

(14.) Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacterpylori. Lancet 1993;342(8871):575-7.

(15.) Weber DM, Dimopoulos MA, Anandu DR et al. Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacterpylori. Gastroenterology 1994; 107(6): 1835-8.

Lisa Skultety Ayers, DO; Jacqueline Oxenberg, DO; Seth Zwillenberg, MD; Mahmoud Ghaderi, DO

From the Department of Otorhinolaryngology, Facial Plastic Surgery, and Head/Neck Surgery, Philadelphia College of Osteopathic Medicine.

Corresponding author: Lisa Skultety Ayers, DO, Department of Otorhinolaryngology, Facial Plastic Surgery, and Head/Neck Surgery, Philadelphia College of Osteopathic Medicine, 4170 City Ave., Philadelphia, PA 19131. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

The information in this article was originally presented at the 90th annual clinical assembly of the American Osteopathic Colleges of Ophthalmology and Otolaryngology-Head and Neck Surgery; May 3-7, 2006; Orlando, Fla.