Peripheral T-Cell lymphoma manifested as gingival enlargement in a patient with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults and is associated with increased risk of malignancy. T-cell lymphoma associated with CLL has never been reported. The case report presents a unique case of peripheral T-cell lymphoma on the gingiva of a patient with CLL. A 66-year-old man with a history of CLL was referred to the Mayo Clinic, Department of Dental Specialties, for evaluation of swelling in the upper left posterior sextant. An intraoral examination revealed a soft tissue swelling in the area of teeth number 13 and 15, including the present edentulous ridge between number 13 and 15. An incisional biopsy was performed on the palatal aspect of tooth No. 15 and submitted for histologic evaluation. The histopathology revealed proliferation of large atypical cells beneath the epithelium, positive for antigens CD2, CD3, Beta-F1, TIA-1, and Granzyme B consistent for a diagnosis of a peripheral T-cell lymphoma. A team approach including the hematologist, general dentist and periodontist resulted in timely referrals leading to an early diagnosis and early intervention and treatment.

INTRODUCTION

Leukemias are a group of diseases resulting from proliferation of abnormal white blood cells. They are classified based on the cell type involved such as myeloid or lymphoid and also based on the clinical course as acute and chronic. A wide variety of etiological factors have been linked with the leukemias ranging from radiation to viruses to chromosomal abnormalities.

Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5+ B lymphocytes in the peripheral blood, bone marrow and secondary lymphoid organs (lymph nodes and spleen).[12] It is also the most common form of leukemia in adults accounting for nearly 25% of all leukemias with an estimated annual age-adjusted incidence of 3 per 1,000,000 persons in the United States.[3] Prevalence of CLL is estimated to be around 30–50:100,000 based on the estimated incidence and the long median survival of the disease.[4] About 15,000 new cases are diagnosed in adults in the USA each year. Chronic lymphocytic leukemia is more common in men than women with a sex ratio of about 1.5–2:1.[2] Natural course of CLL is very heterogenous with survival ranging from months to decades with a median of about 7.5 years.[5]

Leukemias can result in gingival enlargement which can either be diffuse, marginal, localized or generalized. True leukemic enlargement is found commonly in acute cases but very rarely in chronic leukemia. Chronic lymphocytic leukemia is associated with increased risk of malignancy but the occurrence of T-cell lymphoma is rare. Hence this case report is unique, in this the gingival enlargement is not due to CLL but independently due to a peripheral T-cell lymphoma.

CASE REPORT

A 66-year-old man returned to his hematologist for further evaluation and follow-up for B-cell CLL and associated sinopulmonary problems. Initially he was treated for CLL in 2001 at which time he received rituximab, fludarabine and cyclophosphamide. He experienced an episode of autoimmune hemolytic anemia the same year that was successfully treated with prednisone. A year before, he had a relapse of his CLL and was treated with pentostatin, cyclophosphamide and rituximab. The patient developed cytopenias that resulted in discontinuation of therapy.

In June 2007, he was noted to have evidence of early relapse with involvement of bilateral cervical and axillary nodes and the spleen. A complete blood count included hemoglobin of 14.4 g/dL (13.5–17.5 g/dl), white blood cell count (WBC) of 39,400 (3,500–10,500) and differential WBC showed 11% neutrophils (42%–75%), 85% lymphocytes (16%–52%) and 4% monocytes (1%–11%) which is diagnostic for CLL.

One month prior to visiting the hematologist for follow-up, the patient noted that tooth number 27 which was a terminal abutment for a 3 unit fixed partial denture was sensitive. His local dentist noted a soft tissue swelling in the area of the maxillary left posterior region in relation to teeth number 25 and 27 including the present edentulous ridge between teeth number 25 and 27. The local dentist removed the fixed partial denture and temporized the crowns on teeth Nos. 25 and 27.

Approximately one week later, the patient was referred to the periodontics section of Mayo Clinic, Department of Dental Specialties, for evaluation of the swelling in the maxillary left posterior sextant, specifically area number 25 through 27.

The patient was asymptomatic; however, a large soft tissue swelling was noted on the buccal and palatal of teeth Nos. 25 and 27 and the including edentulous ridge between 25 and 27 [Figure 1]. The gingival mass was firm but asymptomatic upon palpation. An area of ulceration was noted in the edentulous ridge of area number 26 that was yellow-gray in color. Panoramic and periapical radiographs were taken of the maxillary posterior sextant. Radiographic analysis of the Panorex and the periapical were negative for any periapical radiolucencies; however, moderate bone loss was evident on tooth No. 27.

Figure 1

Gingival enlargement noted on the buccal and palatal of teeth nos. 25 & 27 and included the edentulous ridge between 25 & 27

An incisional biopsy was performed on the palatal aspect of tooth No. 27. The specimen was placed in formalin and sent for histologic evaluation.

PATHOLOGY REPORT

Hematoxylin and Eosin staining of the biopsied tissue showed a diffuse infiltrate of large, pleomorphic tumor cells [Figures 2 and 3]. Immunoperoxidase studies were performed on paraffin sections of the biopsied tissue using antibodies directed against the following antigens: CD20, CD3, PAX5, CD2, CD4, CD5, CD8, CD30, TIA-1, Granzyme B, Beta-F1, and CD56. In addition, in situ hybridization was performed on paraffin-embedded sections of biopsied tissue.

Figure 2

Hematoxylin and eosin stain of biopsied tissue showing diffuse infiltrate of large, pleomorphic tumor cells at low magnification (×40)

Figure 3

Hematoxylin and eosin stain of biopsied tissue showing diffuse infiltrate of large, pleomorphic tumor cells at higher magnification (×100)

A proliferation of large atypical cells beneath the epithelium positive for CD2, CD3, Beta-F1, TIA-1, and Granzyme B was detected [Figure 4]. All other markers and Epstein–Barr virus were negative.

Figure 4

Immunohistochemical stain of the biopsied tissue showing the tumor cells being positive for the T-cell marker CD3 (brown reaction product) (×40)

The findings support the diagnosis of peripheral T-cell lymphoma, unspecified, with a cytotoxic phenotype.

Follow-up

Subsequently, a positron emission tomography (PET) scan showed diffuse spotty and extremely intensive uptake at multiple bony sites. The patient also presented with bilateral cervical and axillary lymphadenopathy. An MRI suggested involvement of face. A lesion adjacent to the C1 arch was also found, in addition to a lesion at the right C2 neuroforamen. In October 2007, the patient received three cycles of infusion with bolus carboplatin and etoposide chemotherapy. He responded very well and both the peripheral T-cell lymphoma and CLL appeared to be in remission. The patient was last seen on January 8, 2008.

DISCUSSION

There is no literature available reporting the occurrence of T-cell lymphoma occurring on the gingiva of patients with CLL. This appears to be the first case reported of a peripheral T-cell lymphoma occurring in the oral cavity of a patient previously diagnosed with CLL. T and B cell lymphomas have only rarely been reported associated with CLL.[67] Further studies have shown that T-cell lymphomas have been very rarely reported in patients with CLL.[86910]

A team approach including the hematologist, general dentist and periodontist provided an invaluable service to this patient. The timely referral by the general dentist and periodontist's decision to biopsy for a suspicious lesion provided an early diagnosis and early intervention with chemotherapy reducing this patient's morbidity.