The appearance of this tumor corresponds to what we have previously described as a Hodgkin's-like PTLD (Cancer, November 1993). The phenotype of the cells does not correspond precisely to those of Reed-Sternberg cells, but the pattern of growth and the morphologic appearance of these cells bears a striking resemblance to Reed-Sternberg and Hodgkin cells. The tumor also resembles the original late-appearing polymorphic lymphoma described by Frizzera, et al (Cancer Research, November, 1981). However, that term has since come to be used for earlier-arising lesions, which appear to be more closely related to infectious mononucleosis. The appearance is similar to the previous needle biopsy of the retroperitoneal lesion. Clinical correlation is required.
The common leukocyte antigen and epithelial membrane antigen immunoperoxidase stains are negative on the large atypical cells in Part 1. This pattern of staining is non-specific but can be seen in Reed-Sternberg cells, among other cell types. Occasional positive small lymphocytes are seen with the EBER in-situ hybridization, which is performed on a research basis on the renal tissue in Part 2. No evidence of lymphoproliferative disorder is seen in the kidney and these cells are interpreted as representative of the resting B-lymphocyte population, which is infected with EBV, likely in a latent form.
The term posttransplant lymphoproliferative disorder (PTLD) refers to a clinical syndrome which encompasses a wide range of hyperplastic and neoplastic disorders seen in the setting of iatrogenic immunodeficiency. Over 95% of cases are associated with the Epstein-Barr virus (EBV). The histopathologic appearance in some cases may be that of infectious mononucleosis. A second group shows a more diffuse and invasive growth of mononuclear cells with or without necrosis and/or occasional large atypical cells. The heterogeneity of cell sizes has led to the use of the term polymorphic to describe these lesions. A third category of EBV-positive lesions resembles non-Hodgkin's lymphoma. We originally proposed the term monomorphic PTLD to describe these latter lesions and to separate them from the polymorphic PTLDs. Cases such as the one presented above show that it is also possible to have EBV-positive tumors which resemble lymphomas but do not consist of sheets of uniform-appearing cells. The trend has been to label monomorphic PTLDs and lesions such as the current case as post transplant lymphomas and to reserve the term polymorphic PTLD for the second group of lesions described above.
The large atypical cell which represents the malignant population in this case raises fascinating questions in regard to its relationship with the Reed-Sternberg cell of Hodgkin's disease. It has long been known that occasional Reed-Sternberg-like cells could be seen in uncomplicated infectious mononucleosis. Also, the long-suspected relationship between EBV and Hodgkin's disease was documented in a subset of cases several years ago following the development of appropriate molecular and imunocytochemical reagents. Yet, surprisingly, there is no known increase in Hodgkin's disease in the immunosuppressed population, despite the fact that EBV is strongly associated with other lymphoid malignancies. Why? Could it be that the vast majority of infected lymphoid cells are at risk for autonomously growing as non-Hodgkin's lymphomas, whereas the few Reed-Sternberg-like cells of early EBV infection, which might otherwise be at risk for evolving into Hodgkin's disease, grow out as tumors such as seen in this case? This question must be left unanswered at present.
Therapy of these disorders is based on graded intervention, beginning with reduction of immunsuppression, antiviral therapy, and surgical support in many cases.
Contributed by Michael Nalesnik, MD and Charles A. Richert, MD