An unusual case of Burkitt's lymphoma presenting as a gingival enlargement.

Burkitt's lymphoma is an undifferentiated non-Hodgkin's B-cell lymphoma. Three clinical subtypes are recognized: African (endemic), American and other areas (sporadic) and human immunodeficiency virus (HIV) associated. Sporadic Burkitt's lymphoma is a rare malignancy among Asian population. This report describes a case of sporadic Burkitt's lymphoma presenting as generalized gingival enlargement with an alarmingly rapid spread. This type of rapid progression bespeaks the need for prompt recognition and life-saving referral by the dental practitioner. The purpose of this case report and review of the literature was to illustrate the fact that an inconspicuous and benign looking gingival enlargement may turn out to be an aggressive malignancy like Burkitt's lymphoma.

INTRODUCTION

Gingival enlargement, the currently accepted terminology for an increase in the size of the gingiva, is a common feature of gingival disease. This is strictly a clinical description of the condition and avoids the erroneous pathologic connotations of terms used in the past such as hypertrophic gingivitis, gingival hyperplasia or “gingival hypertrophy”. Gingival enlargement can be caused by a number of various stimuli, and treatment is based on an understanding of the cause and underlying pathologic changes. The etiological factors for gingival enlargements include inflammatory enlargement, drug-induced and those associated with systemic factors (pregnancy, puberty and Vitamin C deficiency, leukemia, granulomatous diseases, and neoplasms).[1]

Non-Hodgkin lymphoma commonly involves the oropharyngeal lymphoid tissue comprising Waldeyer's ring, and occasionally involves other oral tissues.[2] It accounts 3.5% of oral malignancies but rarely arises on the gingival; most of these being diffuse large B-cell lymphomas.[3] Burkitt's lymphoma is a malignant tumor of B-cell lymphocytic origin and is classified as a non-Hodgkin's lymphoma (NHL).

A tumor peculiar to the children of Tropical central Africa was reported by Denis Parsons Burkitt (1958–59), which later became named after him. Burkitt's lymphoma occurs endemically in parts of Africa and Papua, New Guinea and is restricted to areas with endemic malaria. It also occurs sporadically throughout the world. Three clinical variants are recognized: African (endemic), American (sporadic) and human immunodeficiency virus (HIV) associated.[4] Burkitt's lymphoma is probably the fastest growing malignant neoplasm to affect humans. It can double in size in 24 h with 80% of its cells undergoing mitosis at any point.[5]

Endemic Burkitt's lymphoma is usually diagnosed between the ages of 5 and 7 years and involves the jaws as well as other facial bones in 60–80% of cases. Less commonly, it involves the abdomen and bone marrow. In contrast, in sporadic type, abdomen is the most common site of presentation. About 25% of sporadic Burkitt's lymphoma cases involve the head and neck, most commonly in the form of cervical lymphadenopathy. Maxillofacial bony involvement occurs in fewer than 30% of cases.[6] The clinical features of Burkitt's lymphoma involving the jaws include severely mobile teeth, displaced teeth, and generalized regional lymphadenopathy.[7] Burkitt's lymphoma presenting as primary gingival enlargement has rarely been reported. The paper describes the rare case of sporadic Burkitt's lymphoma with gingival involvement.

CASE REPORT

A 38-year-old male patient reported to Department of Oral Pathology and Microbiology, YMT Dental College and PG Institute, Navi Mumbai with the chief complaint of swollen and bleeding gums since 6 months. A detailed history revealed that the swelling was present initially in the anterior maxillary region which gradually spread to adjacent areas involving the whole maxillary and mandibular gingiva with bleeding from gums while tooth brushing and during chewing food.

Clinical examination revealed generalized gingival enlargement, covering the middle third of the crown and also extended palatally and lingually [Figures 1–4]. The swelling was particularly prominent in the maxillary anterior (labial) and palatal regions. Gingival enlargement was fibrous; granular in some regions. Bleeding on probing was also present. Right submandibular lymph nodes appeared to be matted with size of approximately 2.5 cm. Cervical lymph nodes were enlarged, mobile and nontender. The patient had the habit of tobacco chewing along with lime since 7–8 years, 5–6 times a day and alcohol consumption occasionally. History of any other drug intake was ruled out.

Figure 1

Facial aspect: Gingival enlargement of maxillary anterior region

Figure 4

Gingival enlargement seen on lingual aspect of mandibular gingiva

Lateral view of maxillary anterior region

Palatal view of maxillary anterior region

The patient was referred to Department of Periodontics for oral prophylaxis. The swelling further increased in size 7 days after oral prophylaxis.

Incisional biopsy was performed from the anterior maxillary region after performing CBC and enzyme-linked immunosorbent assays (ELISA) for ruling out HIV.

Microscopically, H and E stained section showed a monotonous picture of darkly staining cells which appeared to be of lymphoid origin consistent with the diagnosis of lymphoma [Figures 5 and 6]. Typical starry sky pattern suggestive of Burkitt's lymphoma is seen [Figure 7]. A panel of antibodies was applied as a part of immunohistochemical investigations and finally the diagnosis of Burkitt's lymphoma was reached.

Figure 5

Basophilic staining cells (×4)

Figure 6

Lymphoid like aggregates seen (×10)

Figure 7

Starry sky pattern

DISCUSSION

The differential diagnosis of generalized gingival enlargements includes drug-induced gingival hyperplasia, HIV-induced gingival enlargement, leukemia, and lymphoma.[18] The absence of any relevant drug history and the negative ELISA test ruled out the first two entities.

Plasmablastic lymphoma (PBL), extramedullary plasmacytoma, diffuse large B-cell lymphoma, mantle cell lymphoma, lymphoblastic lymphoma/leukemia were considered as histopathological differential diagnoses.[89] PBL and plasmacytoma were excluded on morphological grounds.

Microscopically, the morphological picture was consistent with NHLs and high-grade undifferentiated carcinoma. Immunohistochemistry was performed using common leukocyte antigen which was diffusely positive [Figure 8] excluding the possibility of latter. Myeloperoxidase was negative which indicated the presence of cells of the lymphoid series. Terminal deoxynucleotidyl transferase was also negative which indicated the presence of mature cells and not blast cells. Then, the specimens were stained for detection of CD3, and were positive in scattered T-cells which revealed that the cells were not of T-cell lineage. CD20 was focally positive [Figure 9] which confirmed the presence of B-cells. CD10 was positive [Figure 10] and the expression Mib 1 was almost 100% [Figure 11], revealing increased nuclear deoxyribonucleic acid synthesis. These findings along with the histopathology picture confirmed the diagnosis of Burkitt's Lymphoma [Table 1].

Figure 8

Leukocyte antigen diffusely positive

Figure 9

CD20 Focally positive

Figure 10

CD10 Focally positive

Figure 11

Mib 1 100% positive

Table 1

Immunohistochemical expression of various markers

An important entity to be distinguished from Burkitt's lymphoma is PBLs as of all the NHLs involving the oral cavity, 66% belonged to the rare entity of PBL. Although morphological appearance of PBL is indistinguishable from immunoblast, it lacks the characteristic immunoblastic marker CD20 and expresses the plasma cell markers, that is, CD138.[9]

In diffuse large B cell lymphoma, there is a diffuse infiltrate of large atypical lymphoid cells but without a conspicuous starry sky pattern. The neoplastic cells are larger and more pleomorphic, with more vesicular nuclei than seen in Burkitt's lymphoma. There is a continuum of expression of immunohistochemical markers, with no distinct separation of the two groups, suggesting there may be a true biologic continuum between lymphomas classified as Burkitt's and diffuse large B-cell types.[8]

Other entities in the differential diagnosis of Burkitt's lymphoma include lymphoblastic lymphoma/leukemia and blastoid mantle cell lymphoma. Lymphoblasts are usually more variable in size and shape and have more finely dispersed chromatin and less cytoplasm. Mantle-cell lymphoma, blastoid variant, has cells that resemble lymphoblasts or medium- to large-sized cells more pleomorphic than those seen in Burkitt's or Burkitt-like lymphoma. The striking starry-sky pattern and very high mitotic rate of Burkitt's lymphoma would be very unusual in lymphoblastic neoplasms and mantle-cell lymphoma; immunophenotyping establishes a diagnosis in difficult cases.[8]

The diagnosis of Burkitt's lymphoma in an HIV + individual often represents the first AIDS-defining criterion. HIV-associated Burkitt's lymphoma shares some pathogenic features with endemic Burkitt's lymphoma. HIV infection, analogous to malaria, leads to polyclonal B-cell activation and permits poorly controlled proliferation of epstein barr virus EBV + B-cells. The genetic instability of the EBV±, aberrantly regulated B cells leads to a greater risk of c-myc rearrangement and then to lymphoma. HIV is not directly involved in lymphomagenesis but is indirectly involved via cytokine deregulation, chronic antigenic stimulation, and decreased immune surveillance. Lymphoma often involves lymph nodes, bone marrow, and extranodal sites, most often in the abdomen. Burkitt's lymphoma occurring in transplant recipients tends to occur after a relatively long interval posttransplant (mean, 4.5 years in one series). Most patients are solid organ recipients, but recipients of stem cells are rarely affected as well. EBV is commonly but not uniformly present.[8]

Burkitt's lymphoma is one of the first human malignancies shown to be curable by chemotherapy alone. A combination of cyclophosphamide, doxorubicin, vincristine, and prednisone is one example of a drug therapy. Radiotherapy is reserved for overt central nervous system disease that is resistant to chemotherapy and is reported to be useful in certain emergencies, such as airway obstruction. Bone marrow transplantation may be necessary after completion of chemotherapy cycles.[10]

The prognosis of Burkitt's lymphoma depends on the extent of the disease, the patient's age and the timing of diagnosis. It is excellent in children, where it approaches 100% disease-free survival in early stages and 75–85% of patients survive free of disease in later life. Adults are less fortunate, with a survival rate of 50–75%. Adults are almost always HIV-positive patients and may die of other causes.[10]

In our case, the patient's platelet count fell to 20,000/µL blood within 7 days and to 10,000/µL blood in the next week. After that, patient was lost to follow-up.

CONCLUSION

The role of the dentist in the early diagnosis and prompt referral of patients with Burkitt's lymphoma cannot be overemphasized. Dentist must be suspicious when faced with a patient with generalized gingival enlargement which continues to increase in size despite oral prophylaxis. Immediate action should be taken in such a case so that diagnosis is made at the earliest and patient treated correctly and at the right time.

Our report highlighted some unusual presentations of this tumor that should be kept in mind when compiling a differential diagnosis for similar presentations. Pathologic and immunohistochemical tests remain the only definitive methods of diagnosis.