Diagnosis of Malignant Lymphoma in Effusions from Patients with AIDS by Gene Rearrangement

Abstract

Patients infected with human immunodeficiency virus are prone to a wide variety of lymphoproliferative disorders. In these patients the clinical presentation of malignant lymphoma often overlaps with that of benign lymphoid proliferations. Both may include lymphadenopathy, splenomegaly, blood and bone marrow dyscrasias, and lymphocyte-rich effusions. Because benign and malignant lymphocyte-rich effusions, as well as effusions from other malignancies, may contain large cells that resemble immunoblasts or Burkitt's cells, cytomorphologic characteristics alone are unreliable for definitive diagnosis of malignant lymphoma. Usual immunotyping panels using antibodies to B- and T-cell markers frequently fail to demonstrate cell lineage in lymphoma cells of patients with acquired immune deficiency syndrome (AIDS). The authors used gene rearrangement to confirm the diagnosis of malignant lymphoma in effusions from three patients with AIDS when routine cell marker studies failed to demonstrate cell lineage or clonality. Use of biotinylated probes eliminated the need for handling radioactive material and enabled performance of studies in a routine immunohistochemistry laboratory.

Role of Defective Oct-2 and OCA-B Expression in Immunoglobulin Production and Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation in Primary Effusion Lymphoma

“…Kaposi's sarcoma-associated herpesvirus (KSHV) is considered to be the etiologic agent responsible for PEL as well as for Kaposi's sarcoma and plasmablastic variants of multicentric Castleman's disease (11,13,62). The identification of clonal immunoglobulin (Ig) gene rearrangements and somatic hypermutation of Ig genes suggests that PEL arises from post-germinal-center B cells (2,9,11,19,27,32,35,43,48,70). Consistent with this notion is the expression of plasma cell markers such as CD138/Syndecan-1 and somatic hypermutation of the noncoding region of the BCL-6 gene (22,23).…”

“…Recently, analysis of PEL gene expression led to its classification as immunoplasmacytoid, since it showed features most similar to AIDS immunoblastic lymphoma and multiple myeloma (30,34). Despite the clear B-cell derivation, PEL cells lack expression of many B-cell markers, including CD19, CD20, and CD22 (2,11,27,32,35,48,70). Moreover, they lack surface Ig (sIg) expression despite having rearranged Ig genes without crippling mutations (2,11,27,32,35,48,70).…”

“…Despite the clear B-cell derivation, PEL cells lack expression of many B-cell markers, including CD19, CD20, and CD22 (2,11,27,32,35,48,70). Moreover, they lack surface Ig (sIg) expression despite having rearranged Ig genes without crippling mutations (2,11,27,32,35,48,70). Given their pre-plasma-cell derivation, PEL cells may express cytoplasmic Ig (cIg) rather than sIg.…”

Linfoma primário de cavidade pleural em paciente imunocompetente

“…(12) The cytological diagnosis of PEL in an elderly patient who was seronegative for human immunodeficiency virus, presented no clinical or radiological evidence of primary nodal or extranodal sites, and in whose tumor cells it was possible to demonstrate clonality and incorporation of the genetic material of human herpes virus type 8, was conclusive for the diagnosis of pleural PEL.…”

Recent insights into the pathogenesis of Kaposi's sarcoma

“…In view of the putative mode of transmission, body fluids and stools from AIDS-KS patients have been analysed. Semen samples were positive in 3/18 specimens (Ambroziak et al, 1995;Friedman-Kien, 1995 (Knowles et al, 1989;Walts et al, 1990;Green et al, 1995). All eight cases were positive for KSHV; the other 185 lymphoma specimens were negative.…”