An initial battery of immunohistochemical studies showed no expression of cytokeratins, but there was weak expression of estrogen receptor, and moderate expression of progesterone receptor (image 3).
The differential diagnosis includes poorly differentiated carcinoma and lymphoma. With a limited number of unstained slides, the decision was made to repeat pan-cytokeratin, which remained negative with good internal controls. Immunohistochemical studies for lymphoid markers CD43, CD20, and CD3 (images 4, 5, and 6, respectively) highlighted the small lymphocytes but not the larger cells. A final study using antibodies to PAX5 is shown as image 7; there is nuclear expression by the large malignant lymphoid cells, confirming B-cell lineage.
Final Diagnosis: Large B-cell lymphoma
Discussion: The histologic features of this malignant neoplasm strongly favor a malignant lymphoma, and the ultimate demonstration of nuclear PAX5 expression supports that diagnosis. It would be very unlikely for a carcinoma to be so undifferentiated that it did not show some cytokeratin expression, and yet retained expression of estrogen and progesterone receptors. I could not find any reports of hormone receptor expression by lymphoma, however it is intriguing to consider that the expression of the protein encoded by the proto-oncogene Bcl-2 (commonly associated with hematolymphoid malignancies) may be influenced by hormone regulation*.
*Am J Pathol 1994, September; 145(3): 535-540.