[568] Comparison of an Expanded Immunohistochemical Panel To Distinguish High Grade Non-Merkel Cell Neuroendocrine Carcinomas from Merkel Cell Carcinoma.

Arline Faustin, Chandrakanth Annaiah, Deepti Dhall, Bonnie Balzer. Cedars Sinai Medical Center, Los Angeles, CA

Background: High grade neuroendocrine carcinoma (HGNEC), particularly when metastatic, can be a challenge to distinguish from primary or metastatic Merkel cell carcinoma (MCC). Although each diagnosis constitutes a high grade carcinoma, identifying the primary site still plays a role in therapeutic decision making. Currently there is no specific marker for either diagnosis, but a standard set of immunohistochemical (IHC) stains (CK20, Synaptophysin (SYN), Chromogranin (CHR), TTF-1) is often applied to each case. Their pattern of reactivity overlaps between MCC and non-MCC HGNEC, and frequently a definitive diagnosis is withheld in the absence of reliable clinical information. Fli-1, a Ewing Sarcoma marker; Tdt, a marker of immature B-cells; and C-kit have all been reported as variably positive in MCC; however, no study has tested these markers in non-MCC HGNEC to determine whether or not they have differentiating reactivity from MCC. Our study aims to address this question.
Design: A total of 10 cases of non-MCC HGNEC and 8 cases of MCC were retrieved from archival material and selected for study following confirmation of diagnoses by two practicing surgical pathologists. Sites of origin for HGNEC were bronchopulmonary (3), bladder (2), esophagus (2), liver (1), colon (1), cervix (1). All MCC were cutaneous and involved head and neck (4) and extremity (4). Sections from corresponding tissue blocks were immunohistochemically stained for pancytokeratin, TTF-1, SYN, CHR, CK20, C-kit, Fli-1, and TdT. Stains were scored as positive or negative with the following pattern qualifications: pancytokeratin, CHR, SYN, C-kit (cytoplasmic); TTF-1, Fli-1 and TdT (nuclear); CK20 (perinuclear dot-like).
Results: All MCC and non-MCC were appropriately positive for pancytokeratin, SYN, and CHR. The number of cases positive for the remaining stains is summarized in table 1.

Table 1

Conclusions: In cases for which HGNEC has been made, the most sensitive marker in discriminating MCC from non-MCC is TdT (100% vs. 0). Fli-1 and CK20 (8/8 MCC and 1/10 non-MCC) are also highly discriminatory in this setting. Although C-kit has been reported as a positive marker in MCC, it is non-specific in this setting and overlaps significantly with non-MCC HGNEC. We propose that in cases for which the differential diagnosis includes MCC and non-MCC HGNEC an expanded panel including CK20, TdT, and Fli-1 can be useful adjuncts in making this distinction.
Category: Endocrine

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 56, Tuesday Afternoon


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