Page 131 - AIDSBK23C

Page 131

like lymphomas (in the REAL classification), called intermediate grade and classified as small
noncleaved-cell (SNCLL) lymphomas (Burkitt or Burkitt-like lymphomas) in working
formulation classification, and called Burkitt lymphoma with or without plasmablastic
differentiation (in Kiel classification). They may also be called AIDS-related Burkitt
lymphomas. These NHL’s consist of cells having round nuclei with one or more prominent
nucleoli and scant cytoplasm. The cells comprise diffuse sheets that form a discrete mass or
irregularly intersect and infiltrate normal tissues without significant necrosis. Within the sheets
of lymphomatous cells, uniformly distributed macrophages containing phagocytized debris are
present, and occasional mitoses are seen. Plasmablastic features including eccentric nuclei and
well-defined Golgi zone may occur.[561,569]
Cytologic features of Burkitt ymphoma include monotonous, intermediate-sized
lymphocytes that lie singly. Their nuclei are similar or smaller than those of macrophages,
round-to-oval with well-defined nuclear borders, with coarse chromatin, and 2–5 small but
conspicuous nucleoli per nucleus. The Burkitt lymphoma cells contain scant to moderate
amounts of blue, vacuolated cytoplasm. The cytoplasmic vacuoles contain a neutral lipid best
seen with Romanowsky stain. Tingible body macrophages, mitotic figures, and apoptosis are
often seen. Aspirates of Burkitt lymphoma are usually cellular.[563]
The second broad category of non-Hodgkin lymphoma includes virtually all of primary
CNS lymphomas seen with AIDS and about 70% of systemic lymphomas in AIDS. This
category is composed of large cells that are best described as diffuse large B cell lymphoma (in
the REAL classification), which can be either large cell immunoblastic lymphomas in working
formulation classification (immunoblastic with or without plasmacytic differentiation in Kiel
classification) or large noncleaved-cell lymphomas in working formulation classification
(centroblastic diffuse in Kiel classification). The immunoblastic types consist of cells having
moderate to large amounts of cytoplasm with or without plasmacytic features of eccentric nuclei
and basophilic cytoplasm, large round to oval nuclei, and prominent single nucleoli. These large
cell types have less cytoplasm along with one or more peripheral nucleoli within a nucleus with
finely dispersed chromatin. Necrosis is often a prominent feature, and mitoses are
frequent.[561,569]
The molecular biology and biologic behavior of non-Hodgkin lymphomas with AIDS
shows some variation. The AIDS-related Burkitt lymphomas can occur when the CD4
lymphocyte count is low but sustained and can even be the initial manifestation of AIDS.
Virtually all of them demonstrate activation of the c-myc proto-oncogene. Mutations of the p53
tumor suppressor occur in 60% of them, while about 30% of these lymphomas demonstrate
Epstein-Barr virus (EBV). Though none demonstrate BCL-6 gene rearrangements, small
mutations in of the bcl-6 gene can be found in 60% of cases. These intermediate grade
lymphomas tend to occur at a younger age than the high-grade lymphomas.[561]
In contrast, the high grade AIDS-related diffuse large cell lymphomas typically occur
later in the course of AIDS, and the risk increases markedly as the immune system fails and the
CD4 count is low and declining. Infection with EBV can be demonstrated in 70 to 80% of cases.
Many have molecular alterations of the bcl-6 proto-oncogene, including mutations of the 5’
regulatory sequences. Rearrangements of the c-myc proto-oncogene may be seen in about 20%
of AIDS-related DLCL’s, when mutations of p53 are rarely seen.[561,567]
The 20% of NHL’s seen in the central nervous system are of the high-grade diffuse large
cell variety. They typically occur late in the course of AIDS when the CD4 count is low and
declining. Virtually all of them arise in the setting of EBV infection and they are essentially an