Contributed by Valerie A. Lyons, MDFINAL DIAGNOSIS: B-CELL LYMPHOMA
DISCUSSION: This case describes a previously healthy 62-year-old male who developed an acute fulminant clinical course resulting in multi-organ failure and death secondary to a newly diagnosed B-cell lymphoma. Of interest is the rapid clinical course and its possible association with the NK-cell population identified by cytometric immunophenotypic studies.
Involvement of the liver is common in low grade lymphomas and usually occurs as disseminated disease. Less common are primary liver lymphomas, of B-cell type and the recently described hepatosplenic Gamma/Delta T-cell lymphoma. Lymphoma diffusely involving the liver frequently is associated with splenic involvement and may present as hepatic dysfunction. These lymphomas have specific genotypic, immunophenotypic and clinical presentations. In contrast, this case describes a previously healthy, elderly male who presented with neither hepatosplenomegaly nor peripheral lymphadenopathy. Once clinical symptoms appeared, progression of disease was rapidly fatal before treatment could be implemented. Immunophenotypic studies discovered a diffuse, moderately enlarged B-cell lymphoma with a separate population of CD2 positive, CD3 negative NK-type cells.
The NK-cells may represent a reactive population of lymphocytes, a second neoplasm or these surveillance cells may play a role in tumor progression, explaining this patients rapidly deteriorating clinical course. Recent evidence appears to support a role of NK cells in the pathogenesis of invasion and metastasis of epithelial cancer cells and the aggressive nature of B-cell lymphomas.
Matrix metallo proteinases (MMP) have an important role in tumor progression, especially invasion and metastasis of cancer cells via their degrading activity against extracellular matrix proteins. NK cells play an important role in host defense. One mechanism proposed for their role in resistance of cancer survival is the release of tumor derived suppressor factors. Amino acid sequences homologous to the MMP have been shown to have a suppressive effect of NK cells, possibly contributing to the survival of cancer cells in vivo. The generation of these amino acid sequences by tumor cells have been shown to enhance the growth and invasiveness of tumor cells in mice. Kataoka, H., et. aol. have shown that over expression of MMP's enhance growth and aggressiveness of invasive behavior and lymph node metastasis of human pancreatic adenocarcinoma. The mechanism underlying the suppression of NK cytotoxicity is uncertain1. Recent reports have shown patients with aggressive B-cell lymphoma, both advanced and limited disease, appear to have an increased population of NK- cells2. Animal models have shown that stimulation of NK-cells may provide growth promoting lymphokines that are necessary for progressive growth of the lymphoid cells3.
Whether the population of NK cells is responsible for this patient's rapid clinical deterioration is speculative. Further investigation may prove to support the suppressive effects on host NK cytotoxic cells, and the production of lymphokines which may provide a significant growth advantage to hematopoietic malignancies.
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Contributed by Valerie A. Lyons, MD
