Do Primary Cutaneous Non-T Non-B CD4+CD56+ Lymphomas Belong to the Myelo-Monocytic Lineage?

Abstract

Primary cutaneous non-T non-B CD4+CD56+ tumors are extremely rare and peculiar neoplasms of unknown origin and of poor prognosis ( Petrella et al. 1999). They initially present as cutaneous nodules or tumors with histologic features of pleomorphic medium T cell lymphoma, but express a distinguishing phenotype. Indeed, tumor cells express CD4, CD56, and also CD45, CD43, and HLA-DR. All other T cell and B cell markers are negative, and cells lack T and B cell gene rearrangements. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, and lysozyme) are negative except for CD68, which was clearly positive in four cases and weakly expressed in two of the seven cases of Petrella ( Petrella et al. 1999). These tumors cannot be classified into T, natural killer, or myeloid malignancies as defined in the present classifications, such as the Revised European and American Lymphoma (REAL) ( Harris et al. 1994) or the EORTC cutaneous lymphoma classification (Willemze et al. 1997). This malignant disorder has initially a clear skin tropism, but secondary extra-cutaneous relapse, mainly occurring in bone marrow, is associated with a very bad prognosis. The CD56 antigen is an isoform of the human neuroneal cell adhesion molecule (N-CAM) that is expressed by cytotoxic cells and natural killer cells ( Griffin et al. 1983; Hercend et al. 1985). It has therefore been proposed that these tumors are derived from natural killer cells ( Bastian et al. 1998).