Vol. 90 No.

1 July 2000

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY CLINICOPATHOLOGIC CONFERENCE Dorsal tongue mass
Adi Yoskovitch, MD,a Michael P. Hier, MD,a Louis R. Bgin, MD,b Allan Okrainec, MD,a Dan Nachtigal, MD,a Michel A. Trudel, MD,b and Martin J. Black, MD,a Montreal, Quebec, Canada
MCGILL UNIVERSITY

Editor: John R. Kalmar

(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:5-8)

CASE REPORT
A 76-year-old white man had a 5-month history of an enlarging mass on the right dorsal surface of his tongue. The patient complained of worsening dysphagia and odynophagia, particularly over the previous month. The patients medical history was unremarkable, and he reported no systemic symptoms. In addition, he denied any history of tobacco or alcohol use. Clinical examination showed a firm, nontender, 3.5 4.0 2.0 cm submucosal mass on the right posterior aspect of the dorsal aspect of his tongue (Fig 1). No other pathologic findings were noted in the head and neck area, and a subsequent thorough physical examination also had negative results. Differential diagnosis The differential diagnosis for this mass included the broad categories of neoplastic and infectious disease. Although benign tumors are more common than their malignant counterparts, the clinical history and presentation were most suggestive of a malignant neoplasm. Squamous cell carcinoma (SCC) is the most common malignancy of the oral cavity.1 However, oral SCC usually appears with significant superficial mucosal involvement, including ulceration, and typically involves the lateral and ventral aspects of the tongue. In addition, SCC is frequently associated with a significant history of alcohol and tobacco use. A salivary gland malignancy, such as adenoid cystic carcinoma or mucoepidermoid carcinoma, was considered on the basis of clinical presentation. However, the tongue is an unusual site of involvement, representing less than 1% of all salivary gland tumors.2 Lymphoma can arise in the tongue, but it is usually associated
aDepartment of Otolaryngology, Head and Neck Surgery, Sir Mortimer B. DavisJewish General Hospital, McGill University, Montreal. bDepartment of Pathology, Sir Mortimer B. DavisJewish General Hospital, McGill University, Montreal. Received for publication Mar 23, 1999; accepted for publication Mar 8, 2000. Copyright 2000 by Mosby, Inc. 1079-2104/2000/$12.00 + 0 7/14/107153 doi:10.1067/moe.2000.107153

Fig 1. Mass of right, posterior dorsal tongue.

with systemic manifestations, such as hepatosplenomegaly and lymphadenopathy. In addition, although orofacial presentations of both Hodgkins and non-Hodgkins lymphoma have been associated with human immunodeficiency virus infection, the results of subsequent serologic studies were negative. Metastatic disease arising from an occult primary site, such as lungs, kidneys, gastrointestinal tract, or prostate, was considered. However, metastases to the oral and maxillofacial region are quite rare and preferentially involve bone rather than soft tissues. A variety of sarcomas, although also uncommon, can arise in the tongue. These include leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, synovial sarcoma, and extraskeletal osteogenic sarcoma.3,4 Despite the clinical features favoring a malignant process, the differential of possible benign neoplasms includes fibroma, peripheral nerve sheath tumor, benign salivary gland tumor, leiomyoma, and rhabdomyoma. Infectious processes, such as histoplasmosis, tuberculosis, and syphilis, were also considered, but were thought to be less likely on the basis of subsequent findings, including lack of pulmonary involvement and negative serologies.

6 Yoskovitch et al

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY July 2000

B
Fig 2. A, Diffuse infiltrate of small-to-mediumsized cells with interspersed macrophages containing ingested apoptotic debris (starry-sky pattern). B, Higher magnification demonstrating round-to-slightly-irregular nuclear outlines with small, often multiple nucleoli. Note mitoses (circles) and scattered macrophages with clear cytoplasm (arrows). (B5 fixation, hematoxylin-eosin, original magnification (A) 100; (B) 250).

Diagnosis An incisional biopsy was performed. On gross examination, the biopsy specimen consisted of fleshy, homogenous, whitish, soft tissue with a glistening surface. Microscopic examination showed a diffuse, infiltrative cellular process, composed of solid sheets of small-to-medium-sized cells with scant, amphophilic cytoplasm (Fig 2). The nuclei were roundto-ovoid, with finely granular chromatin and 1 to 4 nucleoli. Abundant mitotic and apoptotic figures were seen. An associ-

ated phagocytic reaction was present in many areas, creating a starry-sky appearance. Phenotypic characterization by immunohistochemistry and flow cytometry supported a B-cell lineage. Tumor cells exhibited strong membranous expression of CD45, CD20, and surface immunoglobulin with dominant light chain expression. HLA-DR and CD10 were positive, whereas CD5 was negative. Non-neoplastic T-lymphocytes and rare eosinophils were intermingled among the tumor cells. The diagnosis was American (sporadic) Burkitts

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 90, Number 1 lymphoma, as described in the Revised European American Lymphoma (REAL) classification.5 Management Thorough work-up, including abdominal computed tomography, produced no evidence of abdominal or other extraabdominal disease, and the patient was classified as Ziegler Stage A (Table I). Treatment consisted of a combined chemotherapeutic regimen that included vincristine, etoposide, mitoxantrone, and procytox. After therapy, the mass decreased in size, with improvement of the patients dysphagia and odynophagia. Several months later, a slight increase in tumor size was detected, and the patient was placed on a second course of chemotherapy. Eighteen months after initial presentation, no evidence of recurrent or metastatic disease could be identified.

Yoskovitch et al 7

Table I. Clinical staging of Burkitts lymphoma (Ziegler classification)

Stage A B C D AR Extent of disease Single extraabdominal site Multiple extraabdominal site Intraabdominal tumor Intraabdominal tumor with involvement of multiple extraabdominal sites Stage C disease with >90% of tumor removed surgically

DISCUSSION Burkitts lymphoma (BL) is a monoclonal, small, noncleaved B-cell lineage lymphoma. Although mentioned by Cook at the turn of the century,6 it was formally described by Burkitt in 1958.7 BL is the fastest growing neoplasm known to man, with a potential doubling time approaching 2 hours.8 There are 2 major subtypes: the endemic, African form (AFBL), and the sporadic, American form (AMBL). AFBL is endemic in central Africa, where it represents the most common malignancy between the ages of 3 and 15 years,9 accounting for between 50% and 70% of pediatric malignancies.10 Involvement of the head and neck, especially the jaws, occurs in approximately 60% of patients11 with a maxillary predilection (2:1) when compared with the mandible.12 Central nervous system manifestations, including paraplegia, may be seen among the presenting clinical features in approximately one third of cases. In contrast to the endemic form, AMBL appears sporadically, with an incidence of 1 case per 1 million per year. 13 First described by OConnor et al14 in 1965, AMBL is histologically identical to its African counterpart. Patients with AMBL are typically older than those with AFBL, with a mean age of 31 years11 and there is no reported racial predilection. AMBL often presents as an abdominal mass, usually involving the distal ileum, cecum, or mesentery. Presentations in the head and neck are uncommon, with involvement of the facial bones, jaw, and other extranodal sites reported in less than 10% of cases.13-16 Specific sites of head and neck involvement by AMBL include the nasopharynx, tonsil, ethmoid sinus, orbit, mandible, maxilla, cheek, hard palate, mastoid, and parapharyngeal space. Previous report of tongue involvement was not identified in a search of the English literature.11,12,17 Various classification systems have been proposed for staging of BL. One of the most commonly used was first described by Magrath et al18 and later modified by

Ziegler19 (Table I). Accurate staging requires the use of computed tomography to assess the presence of abdominal disease. Based on these stages, median survival rates range from 20 months (stage A) to 6 months (stage D).13 The treatment of choice for BL is combination chemotherapy, including agents such as cyclophosphamide, vincristine, etoposide, prednisone, and methotrexate.11 During the induction phase of chemotherapy, radiation therapy may be used to shrink tumor volume.11,20,21 However, radiation therapy alone does not appear to be effective. Although disease prognosis for adult patients has generally been less favorable than with pediatric cases, a recent report suggests that intensive chemotherapy may improve survival in adults to greater than 90%.22 Histologically, Burkitts lymphoma is characterized by a diffuse growth pattern of small-to-mediumsized cells having round-to-ovoid nuclei with coarse chromatin and several nucleoli.23 Mitoses are very numerous, and the presence of scattered, large, optically-clear macrophages that may contain apoptotic debris imparts the classic starry-sky appearance. From a histopathologic perspective, the differential diagnosis of BL includes high-grade B-cell lymphoma (Burkitt-like), lymphoblastic lymphoma, mantle cell lymphoma, (blastoid variant), myeloid (granulocytic) sarcoma, alveolar rhabdomyosarcoma, peripheral neuroectodermal tumor, undifferentiated carcinoma, and metastatic disease such as malignant melanoma. Distinction from high-grade B-cell lymphoma, Burkittlike, a provisional category in the REAL classification, can be especially difficult.5 Both cytomorphologic (nuclear size and uniformity) and phenotypic (CD10+) features of the current case were considered most consistent with the diagnosis of AMBL. Genetic studies of BL show that most tumors demonstrate a translocation from chromosome 8 to either the Ig-heavy chain region on chromosome 14 or one of the light chain loci on chromosome 2 or 22.24 The translocations are most often near or within the c-myc oncogene. In AFBL, the breakpoint on chromosome 14 involves the heavy chain joining region, whereas in AMBL, the translocation involves the heavy chain

8 Yoskovitch et al switch region.25 Information concerning the relationship of specific molecular rearrangements to patient survival has yet to be clearly established. In summary, Burkitts lymphoma is a rapidly growing, high-grade B-cell lymphoma with 2 clinical subtypes, endemic (African, AFBL) and sporadic (American, AMBL). Although most cases of AFBL occur in childhood, AMBL is a disease of adults, and aggressive chemotherapy is the treatment of choice. To the best of our knowledge, this report represents the first case of BL of the tongue to appear in the English literature.
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Burkitts lymphoma of the head and neck. Arch Otolaryngol Head Neck Surg 1992;118:193-9. Bauer GP, Volk MS, Siddiqui SY, Brecher ML, Brodsky LS, Stanievich JF et al. Burkitts lymphoma of the parapharyngeal space. Arch Otolaryngol Head Neck Surg 1993;119:117-20. Levine PH, Kamaraju LS, Connolly RR, Berard CW, Dorfman RF, Magrath I, et al. The American Burkitts lymphoma registry: eight years experience. Cancer 1982;49:1016-22. OConor GT, Rappaport K, Smith E. Childhood lymphoma resembling Burkitts tumor in the United States. Cancer 1965;18:4117. Kemeny MM, Magrath IT, Brennan NW. The role of surgery in the management of American Burkitts lymphoma and its treatment. Ann Surg 1982;196:82-6. Ziegler JL. Burkitts lymphoma. N Eng J Med 1981;305:735-45. Kearns DB, Smith RJ, Pitcock JK. Burkitts lymphoma. Int J Pediatr Otorhinolaryngol 1986;12:73-84. Magrath IT, Lwanga S, Carswell W, Harrison N. Surgical reduction of tumor bulk in management of abdominal Burkitts lymphoma. Br Med J 1974;2:308-12. Ziegler JL. Burkitts lymphoma. Med Clin Am 1977;61:1073-82. Jacobs C, Weiss L, Hoppe RT. The management of extranodal head and neck lymphoma. Arch Otolaryngol Head Neck Surg 1986;112:654-8. Wallace C, Ramsay AD, Quiney RE. Non-Hodgkins extranodal lymphoma: a clinico-pathological study of 24 cases involving head and neck sites. J Laryngol Otol 1988;102:914-22. Adde M, Shad A, Verzon D, Arndt C, Gootenberg J, Neider M. Additional chemotherapy agents improve outcome for children and adults with advanced B-cell lymphomas. Sem Oncol 1998;25:33-9. Lymph nodes. In: Rosai J, editor. Ackermans surgical pathology. 8th ed. Volume 11. St Louis: Mosby; 1996. p. 1661-773. Knudson A Jr. Genetics of tumors of the head and neck. Arch Otolaryngol Head Neck Surg 1993:119:735-7. Pelici PG, Knowles DM, Magrath I, Dalla-Favera R. Chromosomal breakpoints and structural alterations of the cmyc locus differ in endemic and sporadic forms of Burkitt lymphoma. Proc Nad Acad Sci USA 1986;83:2984-8.

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Reprint requests: Michael P. Hier, MD Department of OtolaryngologyHead and Neck Surgery Sir Mortimer B. DavisJewish General Hospital McGill University 3755 Cte Sainte Catherine Road, Suite E-209 Montreal, Quebec H3T 1E2 Canada