IMPORTANCE Little is known about survival after a diagnosis of a second or higher-order (multiple) primary melanoma, and no study has explored survival in a population-based sample that included patients with single primary melanomas (SPMs) and multiple primary melanomas (MPMs) of any stage. Because people with a first primary melanoma are known to have an increased risk of being diagnosed with another, evidence for prognosis is needed.

Background: Merkel cell carcinoma (MCC) is an aggressive tumor of cutaneous neuroendocrine cells with a reported 13-fold increased incidence in immunocompromised patients, raising the possibility that it is driven by an oncogenic virus. Additionally, Merkel cell hyperplasia is seen in the Epstein-Barr virus (EBV)-driven process oral hairy leukoplakia, and EBV is known to be involved in the pathogenesis of several other malignancies.Objective: We tested the hypothesis that EBV is involved in MCC.Methods: We employed EBV-encoded RNA in situ hybridization (ISH), lytic EBV ISH, latent membrane protein 1 immunohistochemistry, and BamH1Z leftward reading frame 1 immunohistochemistry to detect and localize EBV in paraffin sections of MCC from five patients as well as seven other cutaneous tumors and positive controls for EBV infection.Results: Positive controls reacted appropriately. However, there was no evidence of latent or lytic EBV in any of the MCC biopsies or other cutaneous tumors.Conclusion: Our findings suggest that EBV is not associated with MCC.

Thomas, N.; Alexander, A.; Edmiston, S.; Millikan, R.; Groben, P.; Hao, H.; Tolbert, D.; Berwick, M.; Busam, K.; Begg, C.; Hummer, A.; Mattingly, D.; Ollila, D.; Conway, K. Author Information

We provide documentation of the onset of 3 invasive superficial spreading melanomas arising from clinically normal skin and correlation with histologic lack of nevus association. Clinical, dermoscopic, and pathologic features of these “de novo” melanomas, which became invasive while small in diameter and had few clinical criteria for diagnosis, are reported.

The RAS/RAF/MAPK pathway likely mediates critical cell proliferation and survival signals in melanoma. BRAF mutations have been found in a high percentage of melanoma cell lines and metastases; however, only a few studies with a limited number of specimens have focused on primary melanomas. We examined BRAF exon 15 mutational status in 37 primary invasive melanomas of varying thicknesses, which had undergone a standardized pathology review. BRAF mutational status was determined using direct manual sequencing of PCR products, followed by resequencing separately amplified DNA aliquots to confirm each mutation. BRAF exon 15 mutations were found in 17 of 37 (46%) primary melanomas. Tumor-specific tandem mutations, encoding either V599K, V599R, or V599E, were found in 5 of 17 (29%) melanomas with BRAF exon 15 mutations. Cloning of BRAF double base-pair substitutions confirmed that both base changes were on the same allele and can result in a positive charge at codon 599. BRAF mutations, including tandem mutations, were frequently found in both thin and thick primary melanomas, implying that these mutations can occur early in the progression of melanoma. The finding of tandem mutations in thin melanomas makes it more likely that they arise as a simultaneous rather than sequential event.

Primary malignant urethral neoplasms are unusual in women. Those of mixed histologic type are so rare as to define adequate documentation. We report the case of an elderly black woman with an urethral carcinoma which had features of a transitional cell carcinoma as well as clear cell adenocarcinoma. The histologic and ultrastructural features are presented and the histogenesis is discussed. Although the patient had both high grade and high stage disease and failed initially after external beam radiation therapy, she is alive and well, without evidence of recurrent disease, 19 months after anterior exenteration.

Small cell carcinoma of the cervix is a term used to describe several entities including cervical carcinoid, "oat cell" carcinoma, reserve cell carcinoma, and poorly differentiated nonkeratinizing squamous cell carcinoma. The light microscopic, ultrastructural, and clinical features of seven small cell cervical carcinomas are presented in this report. Five tumors in our report were diagnosed as small cell anaplastic or oat cell carcinoma by light microscopy. This diagnosis was associated with a poor prognosis, and four of these patients were dead of disease within 24 months. The ultrastructural features of these tumors were similar, but neurosecretory granules were demonstrable in only three of the five cases. Evidence of glandular differentiation was present in one of the five cases, and dual differentiation, i.e., neuroendocrine and squamous, was noted in another. The similarities between pulmonary small cell carcinoma and these cervical lesions are discussed and the literature is reviewed. Also included in the study is a well-differentiated neuroendocrine lesion, a carcinoid that behaved in an aggressive fashion. The final case was a carcinoma putatively derived from reserve cells. The features that help make the diagnosis of reserve cell carcinoma and that distinguish this lesion from other small cell carcinomas are presented.