Submitting Author: Xian (2), Rena Ruiyu, MD
Institution: (1)The Johns Hopkins Hospital and (2) the Hospital of the University of Pennsylvania
Additional authors:Brittany Holmes M.D.(1), Michael J. Borowitz, M.D., Ph.D.(1), and Amy S. Duffield, M.D., Ph.D.(1)
Session: Extramedullary manifestations of myeloid neoplasms

The patient is a 67 year old man with a history of prostate cancer, diabetes and coronary artery disease, who presents in consultation to our hospital with a recent diagnosis of plasmablastic lymphoma in Turkey. Although CHOP-based chemotherapy was recommended, the patient opted for a second opinion prior to initiating treatment. Review of the patient’s CT scans demonstrated numerous enlarged cervical, axillary, mediastinal, and hilar lymph nodes, with the largest measuring 4.0 cm. Lymph nodes within the left common iliac and right inguinal regions also showed borderline enlargement. The spleen was slightly increased in size; however, no focal lesions were identified. Laboratory studies demonstrated a WBC of 7.52 thousand/ul, hemoglobin of 9.7 g/dL, hematocrit of 29.4%, and a platelet count of 298 thousand/ul. A ferritin was within normal limits at 1075 ng/mL. Viral studies were negative for HIV, HBV surface antigen, and anti-HCV antibody. Antibodies against HBV surface and core antigens were positive.

An excisional biopsy of a right parotid tail lymph node was submitted for consultation review (case # S12-41033). The gross specimen contained four lymph nodes, the largest of which had a diameter of 1.2 cm. The specimen was fixed prior to processing in an unknown fixative. H&E sections show that the lymph node architecture is intact. Scattered germinal centers appear expanded by irregular clusters of atypical medium-to-large cells, while other germinal centers appear atrophic. The atypical cells located within the expanded germinal centers resemble immunoblasts or plasmablasts. They have abundant eosinophilic cytoplasm, large round-to-oval nuclei with irregular nuclear borders, vesicular chromatin, and variably prominent nucleoli. Some of the nuclei are multilobed and have intranuclear inclusions. Frequent mitotic figures are also noted in these cells. Although occasional follicles are atretic and some areas of the paracortex show prominent vasculature, the node does not show well-developed features of Castleman disease.

Immunohistochemical stains performed at the outside institution reportedly showed that the atypical cells are weakly positive for CD38, and negative for CD15, CD30, CD34, CD56, CD68, CD117, CD138, HMB-45, myeloperoxidase, pankeratin and TdT. Additional immunohistochemical stains and an in situ hybridization performed at our hospital demonstrate that the atypical cells are positive for EBV (EBER-ISH), HHV-8 and MUM-1. These cells also weakly express CD20, CD38, and CD45. Ki-67 shows a high proliferative index (>90%) in the atypical cells. The large atypical cells are negative for Bcl-2, Bcl-6, CD10, CD30, CD43, CD138, kappa, lambda, CD3, AE1/AE3, Cam5.2 and S100.

IGH@ gene rearrangement studies were not performed.

Kaposi sarcoma-associated herpesvirus (HHV-8/KSHV) is associated with several distinct lymphproliferative disorders including primary effusion lymphoma (PEL), multicentric castleman disease (MCD), MCD-associated plasmablastic lymphoma (MCDPL), and HHV-8/KSHV-associated germinotropic lymphoproliferative disorder (GLPD). PEL typically occurs in HIV+ patients, while MCD and MCDPL can occur with or without underlying HIV infection. GLPD is a rare condition that typically arises in immunocompetent patients who present with lymphadenopathy. Lymph node histology in GLPD shows germinotropic plasmablastic aggregates that lack most B cell markers. These plasmablasts are highly proliferative, and are always co-infected with EBV and HHV-8. While the atypical cells can show monotypic expression of immunoglobulin light chains, several published cases of GLPD describe polyclonal or oligoclonal IGH gene rearrangements; thus, this lesion is best considered a lymphoproliferative disorder rather than a lymphoma. Clinical data also suggest that GLPD is not a true HHV-8-associated lymphoma given its indolent clinical behavior and good response to therapy, which is potentially related to intact immune surveillance in these patients.

Here we describe an illustrative case of GLPD that was mistakenly diagnosed as plasmablastic lymphoma. The patient is HIV-negative with no known immunodeficiency, and presented with lymphadenopathy. Histologic and immunophenotypic evaluation of a lymph node at our hospital reveals a population of proliferating immunoblasts/plasmablasts that show a distinctive germinal center distribution. The atypical cells are positive for EBV (by EBER-ISH), HHV-8 and MUM-1, and show only dim expression of many hematolymphoid antigens (CD20, CD38, and CD45). Although plasmablastic lymphoma is often EBV+ and can have a varied histologic appearance, the intact nodal architecture, germinal center distribution of the atypical cells, HHV-8 positivity, and failure to express many of the typical plasma cell-associated markers are all consistent with a diagnosis of GLPD. Moreover, the patient had no reported B symptoms, whereas HHV8/KSHV-associated lymphomas are often clinically aggressive. Our oncology colleagues have advised continued surveillance, but chemotherapy was not recommended.

HHV-8/KSHV and EBV-associated germinotropic lymphoproliferative disorder.

HHV-8/KSHV and EBV-associated germinotropic lymphoproliferative disorder

Case 262