Intraoral Burkitt's lymphoma in an HIV positive patient.

Burkitt's lymphoma is an aggressive form of Non-Hodgkin's lymphoma composed of malignant cells of B lymphocyte origin. Burkitt's lymphoma is a rarity in the Indian subcontinent. Though intraoral Burkitt's lymphoma in HIV positive individuals is very uncommon, its importance lies in the fact that it is often the first sign of the underlying immunosuppression. We present a case of Burkitt's lymphoma in right maxillary region which was the first manifestation of HIV in the patient.

INTRODUCTION

Burkitt's lymphoma (BL) is a rare, extranodal malignancy of undifferentiated B lymphocytes commonly seen in children.[1] There are three clinical variants of BL: endemic BL, sporadic BL and HIV associated BL.[23] These clinical variants are similar histologically and identified partly by their geographic location.[2] Endemic BL is seen in children in Africa and Papua New Guinea as jaw or orbital masses; sporadic BL has no specific age or geographic predilection and occurs with abdominal or nodal involvement.[2] Immunodeficiency assocociated BL is seen in individuals with HIV.-[2] Intraoral presentation of HIV associated Burkitt's lymphoma has been rarely reported.[3] We present to you a case of Burkitts lymphoma of the posterior maxilla which was the first manifestation of HIV in the patient.

CASE REPORT

A 42-years-old male presented with a growth in the right maxillary molar region of 2 months duration. There was initial mobility of the tooth in that region for 3-4 months followed by exfoliation of the tooth. Subsequently, he noticed a growth emerging from the area of the exfoliated tooth which enlarged slowly and gradually. The medical and dental history of the patient was not significant. He was moderately built and nourished.

On extraoral examination, there was a diffuse swelling noticed over the right malar region which was non tender on palpation. Bilateral submandibular lymph nodes were palpable, mobile and non tender. There was no generalised lymphadenopathy.

On intraoral examination, there was a solitary, well defined, pedunculated growth in the right maxillary molar region which was predominantly blackish in appearance [Figure 1]. The growth was soft and friable in consistency. The buccal mucosa adjacent to the lesion was erythematous. Intraoral radiographs showed missing maxillary right second molar with bone loss extending beyond the tooth socket till the floor of the right maxillary sinus. Panoramic radiography showed soft tissue shadow distal to the right maxillary first molar with break in the continuity of the antral floor in the same region [Figure 2, area encircled in black]. Blood investigations detected leucopenia with a total count of 3,500/cmm. Further investigations revealed that he was HIV positive. Histopathological analysis of the lesion showed sheets of round cells with vesicular nuclei and indistinct cytoplasm interspersed with lymphocytes with condensed nuclei. Few macrophages were seen between the tumour cells [Figure 3]. These features were suggestive of Burkitt's lymphoma. Bone marrow aspirate was positive for malignant infiltrate. Unfortunately, due to certain logistical and financial reasons the patient did not report back to us and was subsequently lost to follow up.

Figure 1

Clinical image showing growth in right maxillary posterior region

Figure 2

Panoramic radiograph showing break in continuity of antral floor, ill defined radiolucency and soft tissue shadow ( encircled in black)

Figure 3

Photomicrograph (H and E, X 10 ) showing sheets of round cells with vesicular nuclei and indistinct cytoplasm interspersed with lymphocytes and macrophages

DISCUSSION

Human immunodeficiency virus (HIV) infection has been associated with a 60 fold increased risk of Non Hodgkin lymphoma (NHL).[4] NHL forms around one third of AIDS-related malignancies with Burkitt's Lymphoma accounting for 2.4-20% of HIV-associated NHL.[5]

Burkitt's Lymphoma (BL) was originally described by Dr Denis Burkitt in 1958 as a sarcoma of the jaw in children in endemic areas of equatorial East Africa.[1] Later on, sporadic cases were reported from Europe and America which were histologically and immunophenotypically identical and these were known as nonendemic or North American Burkitt's lymphoma.[1] The differences between the adult and pediatric variants are summarised in Table 1. The third type known as immunodeficiency associated BL, usually seen in association with human immunodeficiency virus (HIV) infection, is clinically similar to the sporadic cases but with higher incidence of lymph node and bone marrow involvement.[6] In an Indian series of solid malignant tumours, Burkitt's lymphoma had an incidence of 0.76%.[7] Burkitt's lymphoma has the highest proliferation rate of any human neoplasm, with a potential doubling time of 24 hours and a growth fraction of nearly 100%.[48]

Table 1

Differences in adult and pediatric presentation:[7910]

The pathogenesis of BL is due to the c-myc immunoglobulin (Ig) translocation and is thought to occur as a result of an error in activation induced cytidine deaminase (AID)-mediated Ig class switch recombination in germinal centers.[2] The most common translocation in BL is the t (8;14)in which there is fusion of cMYC to the immunoglobin (Ig)H locus.[6]

Jaw involvement is seen in approximately 60% of cases in endemic BL, while it occurs in only 15-18% of nonendemic BL.[1] The earliest clinical sign of intraoral BL is loosening and exfoliation of the teeth as the tumour enlarges.[7] We also observed similar features. In jaw lesions, the tumor can cause toothache, tooth mobility, tooth displacement, intraoral and extraoral swelling, and perioral paresthesia.[6]

The differential diagnosis usually includes the following conditions : p0 eriapical lesions, ameloblastoma, other non-Hodgkin's lymphomas, undifferentiated carci-nomas and sarcomas, and leukemia.[8]

Radiographic findings in Burkitt's lymphoma include radiolucent images of bone destruction with poorly defined and irregular margins.[78] In children, the tumor can cause generalized destruction of the tooth crypts with loss of lamina dura and loss of trabecular pattern in the mandible and maxilla.[1] In our case, there was ill defined radiolucency of the alveolar bone posterior to the first molar tooth.

Histologically, classic BL presents with monotonous, intermediate sized neoplastic cells with round nuclei and multiple peripheral nuclei with scant cytoplasm and clear vacuoles.[6] Mitotic figures are abundant with numerous interspersed tingible body macrophages phagocytosing abundant apoptotic debris, thus creating the starry-sky pattern.[46]

Burkitt's lymphoma is treated preferentially with intensive chemotherapy; 5-year survival rates range between 75 and 95%, depending on the stage of the lesion at the time of diagnosis.[8] New chemotherapeutic agents such as daunorubicine, arabinoside-C, tioguanide and hydroxyurea have been added to the classical treatment scheme.[9] Surgical debulking is of benefit in large localised jaw or abdominal tumours.[7]

Prognosis improves with younger age of diagnosis, minimal tumour burden and prompt initiation of chemotherapy.[8] Relapse occurs in two third cases, usually with advanced stages.[7]

Orofacial manifestation of BL in HIV-infected individuals is very uncommon. It has been highlighted that BL in an HIV-infected person may be one of the first clinical findings.[3] In our case also, the oral manifestation of BL was the first manifestation of HIV.

Thus, HIV positive patients present with a variety of clinical manifestations. The diagnosis of Burkitt's lymphoma in an otherwise healthy appearing individual should raise suspicion of underlying immunosuppression and appropriate investigations for HIV must be undertaken.