KSHV- and EBV-associated germinotropic lymphoproliferative disorder: A rare lymphoproliferative disease of HIV patient with plasmablastic morphology, indolent course and favourable response to therapy

We describe a case of an unusual lymphoproliferative disease in a 60-year-old man. He presented at Hospital ‘‘Cardarelli’’ in March 2004 with fever, fatigue and weight loss. Physical examination and CT scan revealed a cervical lymphadenopaty, involving right laterocervical lymph node without enlargement of other lymph nodes. Laboratory serum tests for the common microrganisms and HIV were negative. A cervical lymph node biopsy was performed. Immediate post-operative follow-up with radiological studies and bilateral bone marrow biopsies did not reveal systemic involvement, nor evidence of monoclonal gammopathy found. No additional therapy was done. Later, the patient was dismissed for further evaluation. Today, after two years of diagnosis, there is no clinical evidence of relapse. For light microscopic examination, 4-mm-thick, formalin-fixed, paraffin-embedded tissue sections of case were stained with hematoxylin-eosin, periodic acid-Schiff and Giemsa. Consecutive sections were stained with antibodies to Ig heavy chains, light chains k, l, and CD10, CD20, CD19, CD22, CD21, CD30, CD79a, CD138, BCL2, BCL6, MUM1 and Ki67 (Dako, Glostrup, Denmark). For HHV-8 immunodetection was used in the monoclonal antibody for the latent nuclear antigen LNA-1 (clone 13B10, Cell Marque, Hot Springs, AR). Infection by EBV was investigated by in situ hybridization for EBV early RNA (EBER). For immunoglobulin gene rearrangements, we amplified DNA from whole paraffin sections of the CDRIII region of the rearranged IgVH gene using a mixture of seven framework 3 (FR3) family-specific primers and a consensus fluorescent primer for the JH gene. The surgical specimen consisted of a right cervical lymph node that measured 2.861.2 cm in diameter and had a fleshy cut surface. Histological examination showed the lymph node architecture partially effaced by a vaguely nodular infiltrate [Figure 1(a)] of atypical large cells resembling plasmablasts or immunoblasts, in small clusters or large sheets with involving the centre of lymphoid follicles [Figure 1(b)]. The ‘‘germinotropism’’ was confirmed by the presence of KSHV-positive cells within a meshwork of follicular dendritic cells CD21þ. Plasmablasts were also found in the mantle and interfollicular zones, often admixed with scattered individual large lymphoid cells and small aggregates of mature plasma cells [Figure 1(c)]. Residual atrophic lymphoid follicles were present. Immunohistochemical study showed that the plasmablasts were strongly positive for KSHV LNA-1 and co-expressed EBV as revealed by EBVencoded RNA (EBER) in situ hybridization