Scott Schlauder

A case series and immunophenotypic analysis of CK20−/CK7+ primary neuroendocrine carcinoma of the skin

Background:  The diagnosis of Merkel cell carcinoma (MCC) can be rather challenging; therefore, the immunohistochemical profile is important in confirming the microscopic diagnosis. Characteristic of the neuroendocrine and epithelial differentiation of MCC, antibodies to cytokeratin (CK) 20, CK7, epithelial membrane antigen, and neuron‐specific enolase among others, are used in confirming the diagnosis. As reported in the literature, the majority of MCC express CK20 and are CK7 negative. Herein, we present a case series of seven patients with CK20−/CK7+ primary cutaneous neuroendocrine carcinoma.

CD117 immunoreactivity in atypical fibroxanthoma.

Atypical fibroxanthoma (AFX) is a spindle cell neoplasm of the skin seen typically on sun-damaged skin of the elderly. Though described as a benign entity, local recurrence and distant metastasis have been reported. This study aims to investigate the potential pathogenic role of CD117, the c-kit receptor in AFX. CD117 was detected in 15 of the 16 cases (94%). The percentage of positive cells for CD117 expression among all tumors was approximately 30%. CD117 proved to be a very sensitive marker of AFX. This antibody may be a useful diagnostic adjunct in AFX.

Malignant perivascular epithelioid cell tumor (‘PEComa’): a case report and literature review of cutaneous/subcutaneous presentations

Perivascular epithelioid cell (PEC) tumors, also called ‘PEComas,’ are distinct tumors showing PEC differentiation with characteristic histologic and immunophenotypic features. PEComas are rare tumors documented in the literature presenting in numerous anatomic sites including the thorax, abdomen, pelvis, soft tissue and skin. Criteria for malignancy does not exist for the subset of PEComas that pursue an aggressive clinical course. Herein, we present an unusual case of a malignant PEC tumor presenting as a scalp nodule in a patient with a prior diagnosis of ‘melanoma’ based upon the immunophenotypic profile of an excised enlarged cervical lymph node. The purpose of this case presentation is to further describe the rare clinical manifestations of a subcutaneous PEC tumor, emphasize the malignant potential of this entity, and review the literature focusing upon clinicopathologic features of cutaneous/subcutaneous PEComas.

Immunohistochemical expression of survivin in cutaneous sebaceous lesions.

Background:Survivin is a member of the inhibitor of apoptosis family of proteins implicated in the inhibition of apoptosis and cell cycle control, both crucial in the progression to malignancy. Survivin overexpression has been demonstrated in numerous malignancies including cutaneous squamous cell carcinoma and melanoma. To date, there are no studies evaluating the expression of survivin in sebaceous neoplasms. Methods:Immunohistochemical expression of survivin was evaluated in a total of 20 extraocular sebaceous neoplasms: sebaceous hyperplasia (SH, 8), sebaceous adenoma (SA, 8), and sebaceous carcinoma (SC, 4). All the results were independently evaluated by a single dermatopathologist. Results:Nuclear expression of survivin was present in 1.4% of lesional SH cells, 8.2% of SA cells, and 12.5% of SC cells. A significant difference in survivin expression with the Student t test was noted between SH and SA (P = 0.01), SA and SC (P = 0.05), and SH and SC (P = 0.001). Conclusions:There is a statistically significant difference in survivin expression among SH, SA, and SC. These findings demonstrate the potential diagnostic utility of survivin, further assisting in the microscopic differentiation of benign and malignant sebaceous neoplasms. However, larger studies are needed to determine the significance of survivin expression as it relates to recurrence, metastatic potential, and outcome.

ASSESSMENT OF MUSCARINIC AND NICOTINIC ACETYLCHOLINE RECEPTOR EXPRESSION IN PRIMITIVE NEUROECTODERMAL TUMOR/EWING FAMILY OF TUMOR AND DESMOPLASTIC SMALL ROUND CELL TUMOR: AN IMMUNOHISTOCHEMICAL AND WESTERN BLOT STUDY OF TISSUE MICROARRAY AND CELL LINES

The primitive neuroectodermal tumor (PNET)/Ewing family of tumors (EFT) and desmoplastic small round cell tumor (DSRCT) portend a grave prognosis. Ongoing research in similar neurocrest-derived neoplasms has implicated both the muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) in the pathogenesis of these neoplasms. Acetylcholine has been reported to impart a modulatory effect on chemotaxis and proliferation, an effect ameliorated by anticholinergic drugs. The aim of our study is to characterize the pattern of expression of mAChR and nAChR in PNET/EFT and DSRCT, in hopes of discovering a potential target for therapeutic improvements. We examined 34 cases of PNET/EFT and 2 DSRCT retrospectively by immunohistochemical studies. We found that AChRs are overexpressed in a significant number of PNET/EFT and DSRCT. The Western blot analysis of 3 human Ewing sarcoma cell lines confirms the presence of AChRs. Future studies are planned to confirm these results as well as to investigate their potential therapeutic implications.

AROMATASE MAY PLAY A CRITICAL ROLE IN THE PATHOGENESIS OF JUVENILE NASOPHARYNGEAL ANGIOFIBROMA

The pathophysiology of juvenile nasopharyngeal angiofibroma (JNA) has yet to be fully elucidated, but the influence of steroid hormones in their growth has been suggested. This neoplasm is known to afflict adolescent males. However, only a minority of the neoplastic cells express androgen receptors. The expression of estrogen receptor beta by the tumor cells recently has been demonstrated. Aromatase (P450) is an enzyme which is responsible for converting androgens to estrogens. However, the rule of aromatase in the pathogenesis of JNA is unknown. In this study we attempt to explain the hormone-induced growth theory by characterizing the aromatase (P450) in JNA. We examined five sinonasal JNA from adolescent males, all of which stained positive for aromatase. We propose that this enzyme is responsible for the local conversion of androgens into estrogens, which subsequently bind to the estrogen receptors leading to the growth of these tumors.

Expression of α-methylacyl-CoA racemase (P504S) in sebaceous neoplasms

Background:α‐Methylacyl‐CoA racemase (AMACR), also known as P504S, is a protein that plays an important role in mitochondrial and peroxisomal β‐oxidation of branched‐chain fatty acid and bile acid intermediates. AMACR has been established as a valuable diagnostic marker for prostate cancer and has recently been shown to be useful in the diagnosis of colorectal carcinoma. Despite the importance of lipid metabolism in sebum production by sebaceous glands of the skin, there are no studies evaluating the expression of AMACR in sebaceous neoplasms.

Bif-1 and Bax expression in cutaneous Merkel cell carcinoma

Background:  Bax‐interacting factor‐1 (Bif‐1) binds to Bax, which in turn activates this proapoptotic protein. In the absence of Bif‐1, the ability to induce apoptosis through the intrinsic pathway is greatly reduced. Merkel cell carcinoma (MCC) classically shows an aggressive behavior and lack of response to chemotherapy, which remains unexplained. Previous studies have documented the presence of Bax in MCC, but Bif‐1 expression has not been evaluated. Herein, the expression of Bif‐1 and Bax in cutaneous MCC is examined.