MONOCLONAL LYMPHOPLASMACYTIC PROLIFERATION CONSISTENT WITH PLASMA CELL-RICH POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER
The presence of a monoclonal plasma-cell rich proliferation in a post-transplant patient is best considered a Posttransplant Lymphoproliferative Disorder (PTLD). This diagnosis is further supported by the presence of a clonal EBV infection in this specimen.
The recognition that apparent lymphomas arising in the setting of post-transplant immunosuppression are frequently characterized by clonal EBV-infection and may regress following reduction or discontinuation of immunosuppression led to the classification of these lesions as post-transplant lymphoproliferative disorders. There is a wide spectrum of lesions which can be seen, and multiple lesions within a given patient may be distinct, and fall into different categories.
Four broad categories are recognized: 1) early lesions, most commonly plasmacytic hyperplasia, 2) polymorphic PTLD, 3) monomorphic PTLD and 4) other lesions not falling into these categories. The early lesions, often involving lymph nodes or the oropharynx rather than other extranodal sites, contain polytypic immunoglobulins both by immunophenotypic and molecular studies. Histologically, they may resemble plasmacytic hyperplasia or an infectious mononucleosis morphology. EBV infection is usually present, but not clonal by molecular analysis of the EBV terminal repeat region. A minor clonal or oligoclonal EBV infection may be present in some of these cases. Polymorphic PTLD is characterized by destructive growth either in extranodal sites or effacing architecture in lymph nodes. The cells exhibit the full range of B-cell maturation, often giving the impression of "mixed small and large cell lymphoma." Necrosis and cytologic atypia are present to varying degrees in these lesions. Immunophenotyping demonstrates monotypic or polytypic B-cells with admixed T-cells, but molecular studies are essentially always positive for clonal immunoglobulin gene rearrangements and clonal EBV infection.
The third category of PTLD is monomorphic PTLD. These are essentially lesions which demonstrate characteristics of high-grade lymphoma, with most or all of the cells present being high-grade, as opposed to the spectrum seen in polymorphic lesions. These may be of either B- or T-cell type, and they most often resemble the diffuse large B-cell, anaplastic large cell, or large-cell peripheral T-cell lymphomas of the REAL classification. These lesions additionally frequently show molecular lesions involving ras, p53, or c-myc genes, which is not true of the polymorphic lesions.
Additionally, there are rarer lesions which do not readily fit into one of the categories. One group of these are the plasmacytoma-like PTLD's, or plasma cell-rich PTLD, which this case represents. The presence of clonal EBV infection, combined with the post-solid-organ transplant setting, strongly supports this diagnosis. These lesions have been reported to be indolent in this setting, and not clinicopathologically typical of myeloma. Some cases of PTLD with histologic and clinical features of multiple myeloma have been reported, and are distinct from the case described here.
EBV negative PTLD's do occur, typically later than EBV+ cases, and some respond to decreased immunosuppression. The nature of these lesions has yet to be elucidated, but they are recommended to be classified like EBV+ PTLD's, but with their EBV negativity noted.