CD45 (leukocyte common antigen) immunoreactivity in metastatic undifferentiated and neuroendocrine carcinoma: a potential diagnostic pitfall

Leukocyte common antigen (CD45/LCA) and keratin expression are generally mutually exclusive in diagnostic surgical pathology. CD45 reactivity is a reliable indicator of the hematolymphoid nature of a tumor, whereas keratin reactivity is typical of epithelial differentiation (carcinomas and some sarcomas). Some lymphomas, however, might lack detectable CD45 expression, whereas occasional ones might express keratins. CD45 immunoreactivity has been considered exquisitely specific for hematopoietic cells. We report three undifferentiated or neuroendocrine carcinomas that showed membrane-associated immunoreactivity for CD45 in addition to showing distinctive keratin cocktail (AE1/AE3) and epithelial membrane antigen reactivity (all cases); also, keratin 7 was demonstrated in one case and keratin 19 in another. Two cases were lymph node metastases of undifferentiated carcinomas, one of them from the lungs and the other of an unknown origin; the former case showed neuroendocrine features. The third case represented a pulmonary large-cell undifferentiated carcinoma. These cases were negative for lineage-specific leukocyte antigens and did not show clonal immunoglobulin heavy-chain gene rearrangements. Electron microscopic studies demonstrated desmosomes and keratin-like tonofilaments in all three cases, thus confirming the epithelial nature of these tumors. The exceptional membrane staining for CD45 seen in these undifferentiated carcinomas might be comparable to experimentally detected incorporation of leukocyte antigens into the cell membranes of nonleukocytic cells in a leukocyte-rich environment. This rare diagnostic pitfall should be considered in the diagnostic surgical pathology of undifferentiated tumors. It is best avoided by employing a panel of leukocyte and epithelial antigens and by use of electron microscopy, if possible.