Background

Burkitt lymphoma (BL), or (small noncleaved cell lymphoma), is one of the highly aggressive Bcellnon-Hodgkin lymphomas (NHL) that is characterized by the translocation and deregulation of the c-myc gene on chromosome 8.[1] Malignant small noncleaved lymphoma, a historical term, was used to describe this disease in patients presenting with a solid tumor or nodal mass, whereas patients who had greater than 25% bone marrow involvement were considered to have French American British (FAB) L3 type acute lymphoblastic leukemia (L3 ALL). The World Health Organization (WHO) classification of lymphoid neoplasms identifies Burkitt lymphoma and Burkitt leukemia (L3 ALL) as 2 differentmanifestations of the same disease based on genetic and immunohistochemicalsimilarity.[2] The characteristic feature of this entity is the dysregulation and mutation of the c-myc oncogene. It often results from a translocation between chromosomes 8 and 14, t(8;14)(q34;q32). Other translocations are also reported to cause c-myc overexpression including t(2;8)(p12;q24) and t(8;22)(q24;q11). However, according to the WHO classification of lymphoid neoplasms, diagnosis of Burkitt lymphoma (BL) can still be made even in the absence of c-myc rearrangement, if other clinical, morphologic, and immunophenotypic findings support that diagnosis.[2] Three distinct forms of Burkitt lymphoma (BL) are identified: (1) endemic (African), (2) sporadic, and (3) immunodeficiency-associated subtypes. Although these forms differ in their clinical presentation and their epidemiology, they share the same aggressive clinical behavior and are histologically identical. Burkitt-like lymphoma (BLL) is considered to be a morphologic variant of Burkitt lymphoma (BL).[3] The sporadic variant (sBL) is present in North America and Western Europe, and the endemic variant (eBL) is observed in equatorial Africa. Immunodeficiency-associated Burkitt lymphoma (BL) occurs most commonly in patients with human immunodeficiency virus (HIV) infection, but it has also been reported in the posttransplantation setting[4] as well as in congenital immunodeficiency patients.[5] Immunodeficiency-associated Burkitt lymphoma (BL) accounts for about 30% of lymphomas in HIV patients.[6] Burkitt lymphoma (BL) was originally described in children, but this disease is also observed in adult patients. Burkitt lymphoma (BL) is one of the fastest growing malignancies in humans, with a growth fraction close to 100% and a doubling time of around 25 hours.[7] Burkitt and Burkitt-like lymphomas have a rapid and aggressive clinical course, commonly presenting in children and young adults, with frequent bone marrow and central nervous system (CNS) involvement. These are considered to be medical emergencies and require immediate diagnostic and therapeutic intervention. A computed tomography (CT) scan from a patient with small noncleaved cell non-Hodgkin lymphoma is provided below.

Computed tomography scan in a patient with a large, left-sided axillary mass from which a biopsy was obtained. Biopsy findings were consistent with small noncleaved cell non-Hodgkin lymphoma.

History and Physical Examination

Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma. All the symptoms are caused by rapid turnover of the mature B lymphocytes and the involvement of extranodal sites and invasion of contiguous organs. Because of the rapid growth of the Burkitt tumor, patients may quickly manifest significant metabolic derangement and renal function impairment. Less common presentations of Burkitt lymphoma (BL) include an epidural mass, skin nodules, central nervous system (CNS) symptoms, and bone marrow involvement.[6] Burkitt lymphoma (BL) can also present as acute lymphocytic leukemia (L3-ALL), with fever, anemia, bleeding, and adenopathy.

eBL, sBL, and immunodeficiency-associated BL

The 3 different clinical variants of Burkitt lymphoma (BL) described (endemic, sporadic, and immunodeficiency related) may have varied clinical presentations.[2, 7, 34] The endemic form of Burkitt lymphoma (eBL) is most commonly seen in patients in equatorial Africa, with jaw and facial bone (orbit) involvement occurring in more than 50% of cases. Patients most often present with swelling of the affected jaw or other facial bones, loosening of the teeth, and swelling of the lymph nodes, which are nontender and rapidly growing, in the neck or below the jaw. Other clinical presentations including abdominal masses (ileal, cecal, etc), as well as ovarian, gonadal, skeletal, and breast involvement have also been documented. The sporadic forms (sBL) most often present with abdominal tumors with bone marrow involvement. Patients most commonly present with abdominal tumors that cause swelling and pain in the affected area. Some patients present with symptoms of bowel obstruction secondary to an ileal-cecal intussusception caused by tumor growth. However, generalized lymphadenopathy is rare. Approximately 90% of patients with sBL and 50% of patients with eBL have abdominal masses upon presentation. Jaw tumors are very rare in sBL, but similar to the endemic variant, the ovaries, kidneys, and breasts can be involved. Cases of BL presenting as acute pancreatitis, cardiac masses, bilateral ovarian masses, and even skin lesions have been reported.[35, 36, 37, 38] Immunodeficiency-related Burkitt lymphoma (BL) cases usually present with nodal involvement with frequent bone marrow involvement. Waldeyer ring and mediastinal nodes are rarely involved.

Burkitt-like lymphoma
Patients with Burkitt-like lymphoma (BLL) may have a variable presentation compared with those with classic Burkitt lymphoma (BL). Patients with BLL usually present in their fourth or fifth decade of life. More than 50% of affected patients present with widespread (nodal and extranodal) disease with frequent bone marrow and peripheral blood involvement. Some patients have a leukemic presentation. After reviewing Southwest Oncology Group (SWOG) data, Braziel et al reported the following clinical features of Burkitt-like lymphoma (BLL)[39] : Median age was reported as 47 years (range, 28-69 y), and 70% of the patients presented with bulky advanced disease (stage II, III, or IV), with 60% of patients having 2 or more extranodal sites of lymphoma involvement.

Signs
Major signs of Burkitt lymphoma (BL) include a soft-tissue mass associated with the involvement of the jaw or other facial bones, rapidly enlarged cervical lymph nodes, abdominal masses, and ascites. The physical examination findings depend on the sites of extranodal involvement and may include the following:

Abdominal tenderness Ascites Abdominal mass Hepatosplenomegaly Palpable tumor of the mandibulomaxillary region Ecchymosis and/or petechiae (as a result of thrombocytopenia) Meningeal signs (from CNS disease) Painless lymphadenopathy

Summary of common BL symptoms/signs

Common findings and symptoms in patients with Burkitt lymphoma (BL) are summarized in this section. Abdominal masses, which can cause abdominal pain and distention andascites

Nausea and vomiting Loss of appetite, change in bowel habits, or both Gastrointestinal bleeding Signs and symptoms of acute abdomen Intestinal perforation Renal failure as a result of retroperitoneal disease and renal involvement or secondary to tumor lysis syndrome (TLS)

Mandibular or maxillary mass

Most common presentation in eBL Maxillary tumors are more common (may involve the orbit) Jaw involvement occurs much less frequently (15-20% of sBL cases)

CNS involvement

Meningeal infiltration, with or without cranial nerve (CN) involvement (frequently, CN III and CN VII); this is the most common mode of presentation with CNS disease Headaches, visual impairment, and paraplegia from spinal involvement; these may be the initial presenting features in some cases

"B" systemic symptoms

B systemic symptoms are uncommon but may be associated with other presenting symptoms, such as fever, weight loss, night sweats, fatigue.

Other

Bone marrow involvement is common in Burkitt lymphoma (BL) Lymphadenopathy is more common in affected adults than in children