FOCAL INVOLVEMENT BY DIFFUSE LARGE B-CELL LYMPHOMA WITH PLASMABLASTIC FEATURES, HHV-8 POSITIVE.
The presence of HHV-8 in the lymphoma cells is unusual. It has previously been reported in patients with immunodeficiency. These reports include patients with multicentric Castleman's disease, some of which developed a plasmablastic variant of lymphoma similar to that seen in the current case. Although the lymph node in the current case does not have the classic features of Castleman's disease, it does display a significant reactive component with prominent interfollicular plasma cells and an unusual distribution of the lymphoma resembling that reported.
The plasmablastic variant of diffuse large B cell lymphoma typically presents in the oral cavity in the setting of HIV infection. In approximately 60% of cases the cells contain EBV. Although these lymphomas are indistinguishable from cases of immunoblastic lymphomas on morphologic grounds, only a few cells stain for CD20 and CD45 but many express plasma cell markers such as CD138 (1). Plasmablastic lymphoma has also been described in patients with multicentric Castleman's disease.
Castleman's disease was first described in 1956 (2). Microscopically there are two variants- the hyaline vascular or angiofollicular variant and the plasma cell variant. The former accounts for over 90% of the cases and is characterized by hyperplastic follicles that display marked vascular proliferation and hyalinization of their germinal centers. The interfollicular stroma is prominent with numerous hyperplastic vessels of the post capillary venule type and an admixture of plasma cells, eosinophils, immunoblasts and monocytes. The plasma cell variant accounts for less than 10% cases and is characterized by a diffuse plasma cell proliferation in the interfollicular tissue with the hyaline vascular changes in the follicles being inconspicuous or absent. From the clinical presentation point of view, Castleman's disease has been divided into solitary and multicentric forms. The plasma cell variant is frequently multicentric and is often associated with anemia and immunological abnormalities such as hypergammaglobulinemia and has a poorer prognosis. Furthermore patients with multicentric Castleman's disease (MCD) have been reported to develop secondary neoplasms such as Kaposi's sarcoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma and plasmacytoma. In one study 25% of patients with multicentric Castleman's disease developed non-Hodgkin's lymphoma and immunoblastic or plasmablastic B-cell lymphoma was the most frequent subtype described. MCD has also been described in human immunodeficiency virus (HIV) infected individuals (3, 4).
Human Herpes virus 8 (HHV-8)
HHV-8 is present in all epidemiological types of Kaposi's sarcoma (AIDS associated -KS, classic-KS, endemic-KS and post transplant KS). In addition, HHV-8 is also linked to multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). HHV-8 is present in the plasmablastic or immunoblastic cells in MCD and in plasmablastic lymphomas arising in a background of MCD (5).
Primary effusion lymphoma (PEL) is universally associated with HHV-8. It most often occurs in the setting of human immunodeficiency virus (HIV) infection. The disease also occurs in the absence of immunodeficiency in elderly males most often from areas with high prevalence for HHV-8 infection such as the Mediterranean areas. HIV positive PEL's appear to co harbor HHV-8 and EBV whereas HIV negative cases harbor only HHV-8 (6).
In one study of MCD (5) that included 8 HIV-1 positive and 12 HIV-1 negative patients, foci of plasmablasts that displayed lambda light chain restriction were seen in all 8 HIV positive cases and in 2/12 HIV negative patients. HHV-8 was identified in all these cases. These plasmablasts were not present in HHV-8 negative MCD or in the hyaline vascular type of Castleman's disease. All these cases were EBV negative. The authors suggested that confluent foci of HHV-8 positive plasmablasts could herald the development of plasmablastic lymphoma, which was seen in 3 of their cases.
In addition there are case reports of HHV-8 positivity in post transplant lymphoproliferative disorders (7,8).
This case highlights the use of immunohistochemistry in narrowing a wide differential and reaching a final diagnosis. Our patient was not documented to have any immunological abnormality but is currently being worked up.
Contributed by Uma Krishnamurti, MD, PhD and Fiona Craig, MD