Multiple uncommon B-cell lymphomas each account for only a small percentage of non-Hodgkin lymphomas overall, but should be familiar to clinicians based on their unique clinical and pathologic features, natural histories, and approaches to therapy. These diseases reviewed in this chapter include Burkitt lymphoma, plasmablastic lymphoma, primary effusion lymphoma, lymphomatoid granulomatosis, hairy cell leukemia, and cutaneous B-cell lymphomas.
Burkitt's lymphoma is a highly aggressive mature B-cell lymphoma accounting for approximately 3% of new non-Hodgkin lymphoma (NHL) diagnoses annually in the United States. The disease has endemic, immunodeficiency-associated, and sporadic variants. Endemic Burkitt's lymphoma was the initial entity described as a rapidly progressive tumor most commonly occurring in the jaws of children in equatorial Africa, Brazil, and Papua New Guinea (1). This subtype occurs at a median age of 5–7, and is uniformly positive for Epstein–Barr virus (EBV). Immunodeficiency-associated Burkitt's lymphoma occurs most commonly in HIV-infected individuals, but may also be seen in patients following solid-organ transplantation or other immunodeficient states. These tumors express the EBV virus in approximately one-third of cases. Sporadic Burkitt's lymphoma occurs in healthy adults with a male predominance and a median age of 30–40 (2, 3). EBV is usually negative in immunocompetent patients.
DIAGNOSIS AND STAGING
Diagnosis should be made by excisional biopsy. Pathologically, Burkitt's lymphomas are characterized by a diffuse infiltrate of monomorphic medium-sized lymphoid cells with coarse chromatin, basophilic cytoplasm, frequent mitoses, and interspersed tingible-body-macrophages ingesting apoptotic debris and giving the tumor the classic "starry sky" appearance on low-power microscopy (Figure 36-1) (4). Immunohistochemical staining shows the cells to express pan B-cell markers (CD19, CD20, and CD79a) and markers of germinal center derivation (CD10 and BCL6). BCL-2 should be negative. Staining for Ki67 demonstrates a proliferation fraction that is usually approaching 100%. The genetic sine qua non is the rearrangement of the MYC proto-oncogene on chromosome 8, usually in the t(8;14), or occasionally the variant translocations t(2;8) or t(8:22) where the site of translocation of MYC is to the transcriptionally active immunoglobulin heavy-(chromosome 14) or light-chain genes (kappa on chromosome 2 or lambda on chromosome 22). In endemic Burkitt's lymphoma, the MYC breakpoint is usually upstream of the first coding exon and the immunoglobulin heavy chain breakpoint is in the joining (J) region. In sporadic and HIV-associated Burkitt's lymphoma, the MYC breakpoint is often between exons 1 and 2 and the heavy chain breakpoint is in the switch region. These distinct molecular changes are not always noted. The MYC translocation in Burkitt lymphoma typically occurs in the context of a simple karyotype. In settings of atypical morphologic, immunohistochemical, or genetic features, such as BCL-2 expression or a complex karyotype, those cases would generally not be classified as a Burkitt's lymphoma, but rather as B-cell lymphoma unclassifiable with intermediate features between diffuse large ...