Answer: Classical Hodgkin lymphoma

Histology: The marrow biopsy is markedly hypercellular and is most notable for several large atypical cells surrounded by numerous small, round lymphocytes. The large atypical cells, which are scattered in the marrow interstitium, have complex nuclear features and prominent nucleoli, and some have frankly anaplastic morphology. The surrounding small lymphocytes have regular nuclear contours and a mature chromatin pattern. Elements of trilineage hematopoiesis are present in the background and show normal maturation patterns.

Discussion: While most cases of Hodgkin lymphoma arise in peripheral lymph nodes, such as cervical, supraclavicular, axillary and even inguinal lymph nodes, primary abdominal Hodgkin lymphoma is particularly uncommon. Moreover, the inconspicuous nature of abdominal Hodgkin lymphoma in its earliest clinical stages often precludes timely diagnosis and optimal therapy. Computed tomography studies that were performed subsequent to the marrow biopsy in the present case revealed a 4 cm mesenteric mass in addition to multiple discrete lesions in the spleen and liver. The spread of Hodgkin disease is nonrandom with dissemination to contiguous lymph node groups including the spleen. Hence, paraaortic or celiac lymph node involvement is associated with a high probability of splenic involvement, and splenic involvement is commonly followed by involvement of the liver and bone marrow.

Of the various histologic subtypes of Hodgkin lymphoma, a higher percentage of the lymphocyte depleted subtype of Hodgkin lymphoma has been associated with primary abdominal presentation than the other subtypes, and the lymphocyte predominant subtype virtually never presents as primary abdominal disease. The histologic pattern of lymphoma at the site of dissemination may or may not recapitulate the histologic pattern in the primary tissue. Nonetheless, the immunophenotypic patterns at the two sites should be the same. The Reed-Sternberg cells in the present case were immunohistochemically (IHC) positive for CD15 and CD30, and were negative for CD45(CLA), CD20 and CD3. This IHC pattern is typical of any of the subtypes of classical Hodgkin lymphoma, which includes nodular sclerosis, mixed cellularity, lymphocyte depleted and lymphocyte rich classical Hodgkin lymphoma. Notably absent from the present biopsy is increased marrow fibrosis, a histologic feature that is commonly present in marrow that is involved by Hodgkin disease.

Dissemination to marrow constitutes clinical stage IV disease and generally impacts therapeutic strategies. Clinical stage and the presence of systemic symptoms (i.e., “B” symptoms) are the strongest predictors of survival in Hodgkin disease. Of note, the incidence of Hodgkin lymphoma is increased 8 fold in HIV-positive patients, and most cases correspond to either the mixed cellularity or lymphocyte depleted subtypes. Also, nearly all cases of HIV-related Hodgkin lymphoma are associated with EBV infection.