Burkitt's lymphoma (BL) is a rare and aggressive germ cell-derived B-cell lymphoma, which typically involves extranodal sites. It is first described in children of Central Africa by Denis Burkitt in 1958. It has three main variants endemic BL, sporadic BL, and immunodeficiency-associated BL. It accounts for 40% of all childhood non-Hodgkin's lymphoma and only <5% of lymphoma cases in adults. The median age of onset is 8 years with a male predominance (M: F = 4:1). Most adult patients present with abdominal involvement which can most frequently manifest as single or multiple lymph nodal or involving organs like the small bowel at the ileocecal region. Rarely, stomach, appendix, spleen, liver, pancreas, genitourinary, thyroid, and central nervous system (CNS) involvement are seen.
Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) is commonly used to localize and assess the extent of disease, as in this case report of a female patient with BL and retrovirus positivity, showing multiorgan involvement
A 43-year-old female, known hypertensive, presented with a 1.5-month history of left submandibular swelling after tooth extraction, along with complaints of weight loss and intermittent fever episodes. Fine-needle aspiration cytology from the submandibular swelling revealed features suspicious of lymphoproliferative disorder, following which a biopsy was suggestive of a poorly differentiated malignancy. A routine viral marker examination showed a positive status for human immunodeficiency virus (HIV).
Subsequently, a whole-body F-18 FDG PET/CT was performed, which showed metabolically active hypodense lesions, one involving the distal body and tail of pancreas measuring 4.1 cm × 3.7 cm × 3.9 cm – primary pancreatic cancer or lymphoma. Metabolically active 3.5 cm × 4.1 cm lesions involving segment V of the right lobe of the liver were noted and metabolically active 6.8 cm × 6.6 cm × 7.8 cm conglomerate lymph nodal mass involving left level Ib, II lymph nodes along with peripancreatic, paraaortic, and aortocaval lymph nodes [Figure 1]. Further immunohistochemistry (IHC) examination revealed tumor cells that were positive for CD20, BCL 6, and CD10 with a Ki67 index of 90% suggestive of BL [Figure 2]. Later, the patient was treated with R-EPOCH regimen.
BL is defined by the updated World Health Organization classification as high-grade aggressive B-cell lymphoma with a doubling time of <24 h. Adult-onset BL is less common. HIV patients have a 10%–20% lifetime risk for the development of BL. The immunodeficient variant of BL has more nodal involvement than endemic BL. Immunodeficiency-associated BL, usually seen in association with HIV infection, is clinically similar to the sporadic cases but with a higher incidence of lymph node and bone marrow involvement and has more nodal involvement than endemic BL.[8,9] However, in our case report, the patient is HIV positive with lymph nodal involvement but no bone marrow involvement.
BL presents with B symptoms (fever, night sweats, and weight loss), tumor lysis syndrome, ascites, pleural effusion, bowel obstruction, intussusception, biliary obstruction, and CNS symptoms based on the site and extent of the disease. However, in our case report, the patient had only a few B-like symptoms such as loss of weight and fever.
In a case report by Ajila et al. and Kamat et al. showed that intraoral BL can be one of the initial manifestations of HIV infection and in such patients, the earliest sign is exfoliation of the tooth.[11,12] Similarly, in our case report, the patient with HIV infection initially presented with submandibular swelling after tooth extraction.
BL is diagnosed by histopathological examination and immunophenotyping using IHC with or without flow cytometry analysis. Histologically, BL shows a “starry sky” appearance due to tangible-body macrophages having cellular debris and benign histiocytes containing abundant, clear cytoplasm dispersed among the background of homogeneous and basophilic tumor cells. The typical immunophenotype of BL is sIg+, CD10+, CD19+, CD20+, CD22+, TdT-, and Ki67+ (>95%), i.e., nearing 100%, BCL2-, and BCL6+. Similarly, our case report showed CD20+, BCL6+, and CD10+ with a Ki67 index of 90%.
BL has characteristic MYC rearrangement t (8;14) due to the juxtaposition of the MYC gene on chromosome 8 with the immunoglobulin heavy chain variable region on chromosome 14 is seen in 80% of cases. Other variants, such as t (2;8), t (8:22), and Burkitt-like lymphoma with 11q aberration, are rarely seen. In a case report by Pinisetti etal. showed that patients with c-MYC positivity and HIV infection cause uncontrolled B-cell proliferation. Similarly, in our case report, the patient is HIV infection positive, and chromosomal analysis showed characteristic MYC rearrangement positivity.
Various imaging modalities play an important role in BL for initial detection, evaluation of treatment response, and potential complications. Ultrasonography (USG) is predominantly used in the pediatric population due to radiation concerns to evaluate intussusception or palpable masses or involvement of superficial sites such as lymph nodes, gonads, and thyroid. However, ultrasound is subjective. CT with intravenous contrast is used for soft tissue and bone evaluation, in case of pancreatic involvement it often mimics features of adenocarcinoma of the pancreas. However, poor renal function and allergy are the main contraindications.
Magnetic resonance imaging (MRI) has superior soft-tissue characterization, in assessing tumor extension and CNS involvement. Maccioni etal. demonstrated staging accuracy of 97% and 100% for CT and MRI, respectively. In the same study, sensitivity, specificity, and accuracy for the detection of lymph nodes were found to be 96.2%, 97.0%, and 96.7% for MRI and 83.7%, 96.2%, and 90.6% for CT, respectively.
Nuclear medicine molecular imaging techniques with thallium-201 single-photon emission computed tomography (SPECT) and gallium-67 citrate SPECT have been used for the diagnosis of lymphoma and yielded good results.[19,20] F-18 FDG PET/CT is a more commonly used modality where the combination of functional as well as anatomical information is provided where accurate staging, assessing the extent of disease, treatment response, and relapse can be monitored. In a retrospective study done by Carrillo-Cruz etal. in 48 patients found that PET/CT detected more extranodal sites as compared to CT and achieved a 100% negative predictive value in predicting treatment response as well as a 100% positive predictive value in predicting recurrence.
Kara etal. reported a case of BL with pancreatic and liver involvement which mimics pancreatic adenocarcinoma with liver metastases and it can be differentiated by biopsy and not by any radiological methods. Similarly, in our case, PET/CT showed pancreatic and liver involvement with extensive lymphadenopathy and was considered a primary pancreatic tumor which was later diagnosed as BL with pancreatic involvement in IHC.
Different treatment regimens are recommended based on age and risk stratification such as CODOX-M, R-EPOCH, and hyper-CVAD regimens. In an HIV-affected individual, CODOX-M/IVAC, DA-EPOCH-R, RICE, and RIVAC regimens are preferred. As the tumor is extremely chemoresponsive, an aggressive treatment regimen has shown to have a 50%–75% survival rate in adult patients. In our case report, the patient is treated with an R-EPOCH regimen.
Adult-onset BL in females occurs less commonly and accounts for 40% of lymphomas associated with HIV-associated lymphomas. The abdomen, particularly the ileocecal junction, is the common site but involvement of other solid organs, particularly the pancreas is rare. F-18 FDG PET/CT performed in this patient showed multiorgan involvement and provided accurate staging information, thus helping in risk stratification and treatment planning.
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