Kenneth B. Calder

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.

New Insights Into Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare aggressive cutaneous malignancy of the elderly and immunocompromised populations. The clinical presentation of MCC is nonspecific, with the majority of cases presenting as localized skin involvement. Histologically and immunophenotypically, MCC is defined by both neuroendocrine and epithelial differentiation. Recently, the Merkel cell polyomavirus has been implicated in the pathogenesis of MCC. In addition, there have been numerous studies evaluating the histologic and immunohistochemical characteristics of MCC as they relate to diagnosis and prognosis. The purpose of this paper is to review the most salient and clinically relevant updates in the pathogenesis and histologic features of MCC. Specific attention is given to the clinical and histologic predictors of prognosis, staging, and the controversies concerning sentinel lymph node biopsy and therapy.

Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma

Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun‐damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms.

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.

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.

Carcinogenetic Pathway of Malignant Melanoma

With an increasing incidence in the last decade, melanoma has become a significant public health concern worldwide. Melanoma is an aggressive disease that currently lacks effective treatment. The biology of melanoma is complex, with numerous different histologic subtypes, genetic predispositions, environmental factors, and clinical features though to play a role in carcinogenesis and outcome. The purpose of this chapter is to review the most recent advances in the tumorigenesis of melanoma focusing on photocarcinogenesis and the molecular pathways implicated in the development of this malignancy.

Cytopathology of Cutaneous Tumors

Cytopathology is the study of morphologic cellular features based upon microscopic anatomy. In addition, the cytologic findings of cells reflect functional differentiation (cytoplasm) and cellular activity (nuclear findings). Understanding the cellular details of neoplasms has significant diagnostic utility. The cytologic features of the most common skin tumors are presented in this chapter.