| Abstract|| |
Burkitt's lymphoma (BL) is the most common childhood cancer in Africa and is most prevalent in areas endemic for malaria. The disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumor of the jaw. It is however, a rarity in the Indian subcontinent. Through an extensive literary survey, it is seen that only a few cases of BL have been reported, accounting for only 0.76% of solid malignant tumors among Indian children. Here we present a case of BL of mandible extending to maxilla in a 13-year-old boy of Indian origin.
Keywords: Burkitt′s lymphoma, chemotherapy, jaws, non-Hodgkin′s, tumor
|How to cite this article:|
Vasudevan V, Mohandas U, Manjunath V. Burkitt's lymphoma in leukemic phase in an Indian boy. Indian J Dent Res 2011;22:340-4
Burkitt's lymphoma (BL) was first described in 1958 by Denis P Burkitt, a British surgeon working in Uganda, who noted a unique, rapidly growing jaw malignancy in children, which was especially common in low-altitude, high rainfall areas with a mean temperature over 16°C. 
|How to cite this URL:|
Vasudevan V, Mohandas U, Manjunath V. Burkitt's lymphoma in leukemic phase in an Indian boy. Indian J Dent Res [serial online] 2011 [cited 2013 Dec 19];22:340-4. Available from: http://www.ijdr.in/text.asp?2011/22/2/340/84315
BL/Burkitt cell leukemia is a B-cell neoplasm of an extranodal malignancy with distinct epidemiological, clinical, pathological, immunological, and molecular cytogenetic characteristics. The prognosis for Burkitt's lymphoma in the past was poor, with a median survival time of only 11 months. Besides the strong association with Epistein-Barr virus (EBV) and malaria, there is also higher frequency of BL in HIV infected patients. Most patients present with a swelling of the jaw, the gastrointestinal tract, kidneys, peritoneum and liver. EBV is associated with 90% of African patients with BL, but this percentage is considerably lower for BL seen in other parts of the world. The reason for the association between BL and EBV remains unknown. ,,
The clinical presentation of BL is characterized by rapid progression of symptoms with frequent multinodal involvement. Within the oral cavity, this tumor can progress very fast and appears as a facial swelling or exophytic mass involving the jaws; marked tooth mobility may be present because of aggressive destruction of the alveolar bone. ,,,,
The BL is highly aggressive and may double in size every 24 hours. ,
| Case Report|| |
A 13-year-old Indian male was referred to our Department of Oral Diagnosis for evaluation of a swelling on the left side of the face of 2 months duration. The patient reported that the swelling had rapidly increased in size. He also complained of high fever since 1 month, difficulty in chewing and bleeding from gums on brushing lower left teeth. He gave a history of extraction of a tooth in that region a month back. His medical history revealed no other past chronic disease; he appeared to be in poor health.
On physical examination, the patient had a pronounced asymmetry on the left side of the face. The swelling measured around 6×6 cm in size, extending superiorly to ala-tragal line, inferiorly crossing the lower border of mandible, posteriorly up to ramus of mandible and anteriorly to the midline. The surface of the swelling appeared smooth and stretched. On palpation, swelling was moderately tender, firm in consistency, non-fluctuant, non-compressible, non-reducible and fixed to underlying structures. There was local rise in temperature and there was no visible discharge. The left submandibular lymph nodes were enlarged, palpable, and tender, measuring about 1.5×2 cm in size, firm in consistency and fixed to the underlying structures. Nodes of other cervicofacial regions were not palpable [Figure 1], [Figure 2] and [Figure 3].
|Figure 1: Extra oral photographs showing diffuse swelling of the left lower third of the face with gross facial asymmetry|
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|Figure 2: Extra oral photographs showing diffuse swelling of the left lower third of the face with gross facial asymmetry|
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Intraoral examination revealed a well-defined, erythematous, tender, soft tissue swelling in mandibular left posterior region, measuring around 5×5 cm in diameter, extending anteroposteriorly from 31 to retromolar region of the same side. Obliteration of the buccal and lingual vestibules was noted. Surface of the swelling was irregular with a pressure indentation of teeth. On palpation, the mass was tender, hard in consistency, non-fluctuant, non-compressible, non-reducible and teeth were fairly loose. Patient's oral hygiene was poor [Figure 4].
Preliminary radiological investigations were carried out, in which orthopantomogram (OPG) showed multiple expansile lytic lesions with thinning of the cortical rim inferiorly, and destruction of mandible on the left side [Figure 5]. Conventional lateral oblique radiography showed a destructive bone lesion of left mandibular body and ramus area giving "tooth floating in air appearance" [Figure 6].
|Figure 5: Panoramic radiograph showing thinning of the cortical rim and gross mandibular destruction|
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|Figure 6: Left lateral oblique view of mandible showing "tooth floating in air appearance"|
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Subsequently, the patient was subjected to a maxillofacial computed tomography (CT) to assess the lesion and its relationship to the adjacent soft and bone tissues. The CT soft window image demonstrated a homogenous soft tissue density mass. The axial CT showed a hypodense lytic aspect in the left anterior maxillary wall, with a wide destruction of the left mandibular body area [Figure 7].
|Figure 7: CT images showing left maxillary wall and mandibular destruction|
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On account of these findings, a provisional diagnosis of malignant lesion in relation to left side of the mandible was made. The differential diagnosis of the jaw swelling included osteosarcoma, Ewing's sarcoma, BL and non-Hodgkin's lymphoma.
Routine blood and biochemical examinations were conducted; Peripheral smear revealed decreased erythropoiesis, decreased leukopoiesis, 100% blast lymphoid cells, decreased megakaryocytes and plasma cells. Nucleus and cytoplasm showed vacuoles in all blast cells. Cytochemistry revealed the following: peroxidase negative, Sudan Black negative, chloroacetate esterase negative, and PAS positive. Peripheral smear showed presence of blast cells [Figure 8].
A complimentary Bone marrow aspiration (BMA) culture was performed, which showed clonal abnormalities, and karyotyping showed 46, XY dir (1) (q21-q24); t (8; 14) (q24; q32) [Figure 9]. Based on all these above findings, a final diagnosis of BL in leukemic phase was made. The patient was referred to the regional oncology center, where he was treated with one cycle of chemotherapy. Unfortunately, the patient could not undergo further cycles of chemotherapy, as he could not afford the treatment. The patient later succumbed to disease.
| Discussion|| |
BL is the most common childhood cancer in Africa and is most prevalent in areas where malaria is endemic. Occurrence of infection is also often dependent upon prevailing living conditions and is commonest in very low socioeconomic group, living in a crowded and unhygienic environment as in the developing nations. 
When it was first characterized in 1950s, the lymphoma was thought to spread by some infectious agents. But in 1964, the EBV was identified in cultured cell lines of the tumor,  and its consistent presence in African BL implicated a virus in the etiology of a human cancer for the first time.  BL is of greatest importance in sub-Saharan Africa, where it is the most common childhood cancer, accounting for up to 36% of childhood cancers and 70% of childhood lymphomas.  It is endemic in children in these areas; it also occurs sporadically throughout the world and in all age groups.
In 1987, Choudry et al. conducted a retrospective analysis of BL occurring in Indian population and showed the involvement of jaws,  which was consistent with features in the present case.
In India, a series of studies on solid tumors in children was conducted by Pramanik et al., who studied 263 cases over a 10-year period and found only two cases of BL.  Hence, we can consider BL as a rarity in Indian children.
The World Health Organization classification recognizes several variants of BL; all are highly malignant B-cell lymphomas. These are: BL (sporadic), BL (endemic) and BL associated with AIDS. The World Health Organization classification also includes an "atypical or pleomorphic" variant of BL. 
Two forms of BL are commonly distinguished: the "endemic" or African form, found in equatorial Africa and Papua New Guinea, and the "sporadic" form, found in areas such as North America, Northern and Eastern Europe and the Far East. An "intermediate" form may also be distinguished, and this occurs in areas such as Southern Europe, the Middle East and parts of South America.
'Endemic' form has a peak incidence in children between 3 and 8 years of age and the male to female ratio is 2:1. Common site of disease presentation is the face, with multiple facial bone involvement, usually maxilla and mandible.
'Sporadic' form affects the older individuals, with mean age of 11 years, and has no gender predilection. It is more likely to have leukemic or bone marrow involvement, and less likely to have jaw involvement. Common site of involvement is abdomen.
The distinction between different types is generally based on geographic location, association with EBV, clinical presentation, incidence, age at presentation and sex ratio. BL in India could be a variation between sporadic and endemic types in its clinical presentation. Its association with EBV varies from 25 to 80%.
The present case too could be classified as a sporadic form with variable presentation, exhibiting features of both endemic and sporadic forms. The features in favor of endemic BL are site of involvement and presence of mild pain. The features in favor of sporadic BL are age of patient, enlarged lymph nodes, and its association with acute lymphoblastic leukemia.
Diagnosis of Burkitt's lymphoma, especially when the sole presentation is in the maxillofacial region, is very difficult. The clinical presentation of the disease may mimic a wide variety of disorders more commonly found within the jaws. Because primary presentation of the disease is often in the mouth and jaws, a high index of suspicion is required from the dental professional in order to assure early diagnosis and a better prognosis of the disease. Clinical differential diagnosis of BL should include acute dentoalveolar abscess, osteomyelitis, rhabdomyosarcoma, periapical lesions, ameloblastoma, eosinophilic granuloma, multiple myeloma, leukemia, and other fibro-osseous lesions.
The radiographic features in this case are consistent with a malignant process and include a radiolucent destruction of the bone with ragged, ill-defined margins and "tooth floating in air" appearance. This process may begin at several sites, which eventually enlarge and coalesce. Loss of the lamina dura has been mentioned as an early sign of BL.
BL has become a model for the exploration of chromosomal aberrations in cancer pathogenesis. After identification of the EBV in this disease, Kohn et al.,  observed abnormalities of C-group chromosomes in their cytogenetic analyses of BL cell lines. In 1972, Manolov and Manolova  reported a marker band at the end of chromosome 14. Zech et al.  were the first to suggest that a translocation event occurred between the telomeric end of the long arm of chromosome 14 and the telomeric end of the long arm of chromosome 8. This was consistent in the present case. Variants in translocations toward 2p and 22q were described in BL cell lines in 1979. , The molecular targets of these translocations were discovered to be MYC (at 8q24), , and gene coding for the immunoglobulin heavy chain (IGH at 14q32), 10 kappa light chain (IGK at 2p12) and lambda light chain (IGL at 22q11). All translocations juxtapose the MYC gene to one of the IG enhancers, which results in constitutive deregulation of MYC expression. Although it is considered to be the hallmark of BL, translocation of MYC is not specific, as it is also seen in other types of lymphomas. ,, The reciprocal translocation t (8;14) occurs in approximately 80% of tumors. These findings were consistent with our case.
BL lesions have a dramatic response to chemotherapy, particularly cyclophosphamide. The tumor also has been shown to be sensitive to methotrexate, vincristine, and cytarabine. Combinations of drugs have achieved remissions in more than 90% of patients. Unfortunately, most of the cases recur and patients ultimately succumb to the disease. The prognosis for BL in the past was poor, with a median survival time of only 11 months. More recent clinical trials with intensive, multiagent chemotherapeutic protocols have shown a fair remission rate. 
According to our experience, dental professionals should evaluate patients with aggressive facial swelling, oral and gingival enlargement, and radiological findings of alveolar bone loss. They should suspect BL, considering the rapid growth rate. Despite a fairly good prognosis for the disease in general, survival may be very poor in developing countries because of factors that include the high cost of treatment, late presentation and limited access to health care. BL, therefore, remains an important health issue in some countries. Primary prevention depends on knowledge of etiology and thorough clinical knowledge.
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Department of Oral Medicine and Radiology, Krishnadevaraya College of Dental Sciences and Hospital, Bangalore, Karnataka
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]