Answer: Immunosuppression-related lymphoproliferative disorder

Histology: Sections of terminal ileum are most notable for a dense and diffuse lymphoid infiltrate that extends from the mucosa to the serosal surface. Cytologically, the infiltrate comprises a polymorphous population of small, mature lymphocytes admixed with plasma cells, histiocytes, eosinophils, neutrophils and scattered large, atypical lymphoid cells. These latter cells,
which have irregular nuclear contours and prominent nucleoli, are morphologically consistent with Reed-Sternberg (RS) cells and RS variants. By immunohistochemistry, the RS cells are positive for CD30 and CD15 (see below), and are negative for CD20, CD3 and CD45 (not shown). In addition, these cells are positive for EBV-LMP and EBV-encoded mRNA (EBER). The small lymphocytes represent a mixture of CD3-positive T cells and CD20-positive B cells, and the plasma cells comprise a mixed population of kappa- and lambda-bearing cells.

Additionally, the ileal mucosa demonstrates features of active chronic inflammation, including crypt distortion, pyloric metaplasia and focal ulceration. There is no evidence of granulomas or ysplasia.

Discussion: This case represents a clonal lymphoproliferative disorder that developed in association with autoimmunity and chronic immunosuppressive therapy. Immunosuppression-related lymphoid proliferations (IRLPs) may resemble large B cell lymphoma, Hodgkin lymphoma, polymorphous post-transplant lymphoproliferative disorders, or less commonly, Burkitt lymphoma and peripheral
T cell lymphoma. Morphologically, the infiltrate in this case has all the earmarks of classical Hodgkin lymphoma. The neoplastic cells are large and have complex nuclear features; several are binucleated. Moreover, these cells are immunoreactive for CD30 and CD15, and lack reactivity for CD45 (CLA). As in many immunosuppression-related lymphoproliferations, the cells demonstrate EBV
expression.

The clinical, immunophenotypic and genetic features of IRLPs are similar in many ways to those lesions of similar histologic subtypes not associated with immunosuppression. An obvious exception, of course, is the increased incidence of active EBV infection in the immunosuppressed patients.
On whole, EBV positivity is noted in approximately half of the IRLPs, and is greatest in those resembling Hodgkin lymphoma (75%) and large B cell lymphoma (50%). Another relatively unique characteristic of IRLP is the occurrence of clinical regression after withdrawal of immunosuppressive therapy. Overall, about 60% of IRLP have shown at least partial regression, and the majority of responses have occurred in EBV-positive cases.