Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants: This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures: Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results: Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance: Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma.

Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven 'pure' Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52-89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.

The prevalence of Merkel cell polyomavirus in Japanese patients with Merkel cell carcinoma.

BACKGROUND: A novel polyomavirus, the Merkel cell polyomavirus (MCPyV) has been implicated in the pathogenesis of Merkel cell carcinoma (MCC); however, the prevalence of MCPyV in Japan has not been extensively investigated. OBJECTIVE: To clarify the prevalence of MCPyV in Japanese patients with MCC. METHODS: MCPyV DNA was examined by polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded (FFPE) or frozen tissue samples from 26 patients with MCC diagnosed in four medical centers in Japan. Immunohistochemistry was simultaneously performed using a monoclonal antibody against the viral large T (LT) antigen. FFPE samples from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were also analyzed as controls. RESULTS: Twenty-three out of 26 cases (88.5%) were positive for MCPyV DNA by PCR. The amplified products harbored 4 patterns of mutations. Phylogenetic analysis demonstrated that one of our strains was closely related to the other Japanese strains previously reported. The LT antigen was expressed in various degrees in 20 of 26 cases (76.9%) by immunohistochemistry. Histological type had little relation to CM2B4 positivity, whereas 3 of 5 trabecular-type tumors showed no staining. The immunoreactivity for CM2B4 did not correlate with the relative viral DNA load. In BCC and SCC, the LT antigen was immunohistochemically positive, but MCPyV DNA was not detected by PCR. The cells around some MCC and non-MCC tumors were stained with CM2B4 with a distribution similar to CD20- and CD45RO- (especially CD8-) positive lymphocytes. CONCLUSION: MCPyV was highly positive in Japanese patients with MCC. It is of note that the positive rate differs depending upon the detection method.

Immunohistochemistry for Merkel cell polyomavirus is highly specific but not sensitive for the diagnosis of Merkel cell carcinoma in the Australian population.

Recent studies have demonstrated a high frequency of detection of Merkel cell polyomavirus in Merkel cell carcinoma. However, most of these studies are from European or North American centers that have relatively low sun exposure and may have a higher incidence of virus-driven oncogenesis compared with the highly sun-exposed but predominantly fair-skinned Australian population. We performed immunohistochemistry for Merkel cell polyomavirus on 104 cases of Merkel cell carcinoma and 74 cases of noncutaneous small cell-undifferentiated carcinoma from 3 major Australian centers. Nineteen (18.3%) cases of Merkel cell carcinoma showed positive staining for Merkel cell polyomavirus versus 1 (1.3%) of small cell-undifferentiated carcinoma. All 15 cases (14.3%) of Merkel cell carcinoma with areas of mixed squamous differentiation showed negative staining. We found positive staining in only 3 (7.7%) of 39 Merkel cell carcinoma from the head and neck (the most sun-exposed area) versus 16 (24.6%) of 65 of tumors from other sites (P < .05). Our findings support the concept of a Merkel cell polyomavirus-driven and a non-Merkel cell polyomavirus-driven (primarily sun-dependent) pathway in Merkel cell carcinoma carcinogenesis, with the latter being significantly more frequent in Australia and in mixed squamous-Merkel cell carcinoma (which is also more frequent in Australia). Although immunohistochemistry for Merkel cell polyomavirus seems to be highly specific in all populations, the low incidence of Merkel cell polyomavirus-positive Merkel cell carcinoma in a highly sun-exposed population limits its diagnostic utility in this setting.

[Merkel cell carcinoma of the gingival mucosa in a black young adult]. / Carcinome à cellule de Merkel gingival chez un adulte jeune de race noire.

Merkel cell carcinoma (MCC) is a rare and aggressive primary neuroendocrine neoplasm of the skin with a poor prognosis. It occurs mainly in the skin of white elderly patients. Its occurrence in intraoral mucosal sites is rare. We report a rare case of MCC that arose in the gingival mucosa of young black adult.

Merkel cell tumor: two cases.

Merkel cell tumors are rare skin lesions that arise from the Merkel cell in the dermal layers. The two cases presented in this report are important in that they add more information to the literature than previously had been recognized. The first case discusses a collision tumor with a basal cell carcinoma. This is the first such report of this type of collision tumor. The second report is of a black female with a Merkel cell tumor of her finger. The case is unusual in that it is only the second time that a black female is reported to have this disease and the first time that it is reported on a digit. A review of the literature accompanies these case reports.

Neuroendocrine carcinoma of the skin (Merkel cell carcinoma) in a black.

Neuroendocrine carcinoma of the skin is an uncommon, small-cell neoplasm most commonly found on white, sun-exposed skin. Diagnosis by clinical and histologic means may be difficult. Immunohistochemical and ultrastructural analysis are often required. Because of the aggressive nature of neuroendocrine carcinoma of the skin, prompt diagnosis and treatment are essential. We present the rare occurrence of a neuroendocrine carcinoma of the skin on sun protected skin in a black. Clinical, histologic, immunohistochemical, and ultrastructural features are reviewed, and therapeutic options are discussed.