Merkel Cell Carcinoma Immunoreactivity with PAX-5 and TdT – A Potential Diagnostic Pitfall?
RB Kolhe, MD Reid-Nicholson, P Ramalingam. Medical College of Georgia, Augusta, GA
Background: Merkel cell carcinoma (MCC) is a high-grade neuroendocrine carcinoma of skin characterized by cells with a "blastic" appearance, scant cytoplasm, and fine, evenly distributed chromatin. It can sometimes be difficult to accurately diagnose MCC by conventional light microscopy due to its histologic similarity to other "small round blue cell tumors". Ancillary techniques particularly immunohistochemistry are usually required to make a definitive diagnosis. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in thymic T cells, lymphoblastic leukemia/lymphoma, and some cases of acute myeloid leukemia. PAX-5 is a B cell specific transcription factor crucial for B-cell ontogeny and has been detected in most human B-cell lymphomas. We recently encountered a case of MCC which expressed PAX-5 and TdT resulting in its initial misinterpretation as B-lymphoblastic leukemia/ lymphoma. The aim of our study was to evaluate the expression of PAX-5 and TdT, markers of B-lymphoblastic leukemia/lymphoma (B-ALL), in a cohort of patients with MCC and determine if their expression was a consistent finding in these tumors.
Design: We retrieved 7 cases with initial diagnosis of MCC from our institution. Archival blocks and slides were retrieved and reviewed and clinical information obtained from patient charts.The diagnosis of MCC was confirmed in all cases. These 7 cases were stained with PAX-5, TdT, cytokeratin, synaptophysin, chromogranin, CK20 and TTF1. Immunohistochemical staining was scored as: negative (-), weak (1+), moderate (2+) or strong (3+).
Results: Immunohistochemical positivity was as follows: PAX-5 (7/7), TdT (4/7, 57%), PAX-5 and TdT co-expression 4/7 (57%), Cytokeratin (7/7) (both membrane and perinuclear dot positivity), Synaptophysin (7/7), Chromogranin A (7/7), and TTF-1 (0/7). The PAX-5 staining was strong in 6/7 (86%) and weak in 1/7 (14%) cases. TdT staining was strong in 2/7 (29%), moderate in 1/7 (14%) weak in 1/7 (14%) and negative in 3/7 (43%) cases.
Conclusions: Co-expression of TdT and PAX-5 by MCC may result in its misdiagnosis as B-ALL particularly since the latter is often negative for CD45, a frequently used lymphoid marker. Pathologists should be aware of this diagnostic pitfall so as to avoid misinterpretation of immunohistochemical results as evidence of lymphoma, particularly in small biopsies. PAX-5 and TdT positivity in conjunction with neuroendocrine markers further support the diagnosis of MCC when evaluating cutaneous small round blue cell tumors.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 86, Wednesday Afternoon