Background: The immunohistochemical (IHC) marker PReferentially expressed Antigen in MElanoma (PRAME) has shown promise in the diagnosis of melanocytic lesions. A few studies have investigated PRAME IHC expression in acral melanomas, but PRAME expression in subungual melanomas is largely unknown.We evaluated the utility of PRAME IHC expression in distinguishing subungual melanomas (SUM) and non-subungual acral melanomas (AM) from acral nevi (AN).Methods: Twenty-two SUM, 20 AM, and 14 AN were identified. IHC studies were performed using an anti-PRAME antibody. The percentage of lesional cells with PRAME expression was recorded and categorized as follows: 0%, 0; 1%-25%, 1+; 26%-50%, 2+; 51%-75%, 3+; and >75%, 4+. Patient demographics and other relevant clinicopathologic parameters were recorded.Results: Diffuse (4+) PRAME IHC expression was identified in 55% (12/22) SUM and 70% (14/20) AM, respectively. Any PRAME expression (1+ to 4+) was identified in 73% (16/22) SUMs and 95% (19/20) AM, respectively. One of 14 (7%) AN exhibited PRAME expression; interestingly, the pattern of expression was diffuse.Conclusions: In our study, PRAME IHC expression was useful in identifying AM, including SUM. However, there are exceptions of PRAME-negative melanomas and PRAME-positive nevi.

Context.— Distinction between Merkel cell carcinoma (MCC) and pulmonary small cell carcinoma (PSmCC) can be challenging, even with the aid of immunohistochemistry (IHC) analysis of CK20 and TTF1, as these tumors occasionally lack classic immunophenotypes (CK20+/TTF1− in MCC and CK20−/TTF1+ in PSmCC). Objective.— To evaluate the diagnostic utility of SOX11 and PAX5 IHC for distinguishing MCCs from PSmCCs and compare it with that of CK20 and TTF1 IHC. Design.— SOX11, PAX5, CK20, and TTF1 expression (pattern, intensity, and proportion of tumor cells expressing protein) was assessed in 31 primary and 16 metastatic MCCs and 20 primary and 9 metastatic PSmCCs. Results.— SOX11 expression was present in all MCCs and was predominantly strong and diffuse. Only 19% of primary and 38% of metastatic MCCs exhibited diffuse PAX5 expression; none exhibited strong immunoreactivity. Strong and diffuse SOX11 expression was seen in less than 25% of primary and metastatic PSmCCs. PAX5 expression was rare in PSmCCs and was mostly weak and focal/patchy. SOX11 expression in at least 26% of tumor cells, with at least moderate intensity, favored the diagnosis of MCC over PSmCC (P < .001). Furthermore, SOX11 expression was more likely than CK20 expression to be strong or diffuse in sentinel lymph node (SLN) metastases of MCC, indicating that SOX11 is superior to CK20 for detecting tumor deposits in SLNs in MCC. Conclusions.— Our findings indicate that SOX11 not only is a powerful marker for distinguishing MCCs from PSmCCs, especially when used in conjunction with CK20 and TTF1, but also has utility for screening SLNs in MCC.

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer–binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME was negative in most DPN (n = 10/10, n = 9/10, one case with discrepancy between readers) and all BN (n = 16/16), while the 2 melanomas included were positive (n = 2/2). All DPN were positive for LEF1 (n = 9/9) while only a subset of BN were positive (n = 6/16, P = 0.0028; n = 5/16, P = 0.001, per both readers). LEF1 seemed to be easier to interpret than β-catenin because of its nuclear pattern of expression. The expression of LEF1 in the regular nevus component of combined BN presents a potential pitfall in practice because it may lead to misinterpretation of LEF1 as positive in the BN component of the lesion. However, a subset (approximately one-third) of combined BN seemed to show true LEF1 expression. Taking into account pitfalls in interpretation, the combinatorial panel of PRAME and LEF1, in addition to conventional histopathological features, may be useful to distinguish CDPN from combined BN and other benign and malignant mimics.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that may occasionally present divergent histopathologic features. We present two cases of MCC demonstrating ductal differentiation, one on the lower lip of an 81-year-old man and another on the right forearm of a 67-year-old man. The histopathologic features included TTF1-negative, infiltrative, high-grade basaloid tumor with paranuclear punctate positivity for cytokeratin (CK) 20 and synaptophysin. Rare luminal structures lined by atypical epithelioid cells positive for CEA and CK19 were noted, confirming the presence of ductal differentiation. Although the ductal differentiation is unusual, other histopathologic features and the immunohistochemical profile supported the diagnosis of MCC. Like most divergent features, ductal differentiation is rare in MCC and typically constitutes a very small proportion of the tumor, and is therefore under-recognized. Although the clinical significance of this feature is unclear, recognition and documentation of ductal differentiation and distinguishing it from other mimics such as acantholysis within squamous nests and entrapped eccrine ducts is essential to determine its clinical significance. We also discuss the differential diagnoses of cutaneous basaloid neoplasms with ductal differentiation.

Merkel cell carcinoma (MCC) is an aggressive, highly metastatic, cutaneous neuroendocrine malignancy with poor prognosis. Here, we describe a MCC excision specimen with a rare case of tumor-associated amyloid deposition in the absence of residual tumor cells. A 72-year-old man presented with a lesion of 5-6 months' duration on his left elbow, clinically thought to be a ganglion cyst. The biopsy specimen revealed