Search

Context.--Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma. Objective.--To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB protooncogene, transcription factor (MYB) loss in melanocytic neoplasms. Design.--One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard. Results.--ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth. Conclusions.--With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms. doi: 10.5858/arpa.2024-0027OA, Melanoma is an aggressive malignancy with a high rate of metastasis. It is the most common cause of death from skin cancer. (1,2) Early diagnosis and resection is often associated [...]

The entity commonly referred to as chondrolipoma is a rare and enigmatic breast lesion with unclear histogenesis and a complete lack of molecular characterization. It is uncertain whether it represents a hamartoma, choristoma, or a distinct neoplasm, including possibly a variant of mammary-type myofibroblastoma. We report two additional chondrolipomatous lesions of the breast. The lesions had varying histologic and immunohistochemical features similar to myofibroblastoma, including the loss of retinoblastoma (Rb) protein expression in one lesion. Molecular analysis by chromosomal microarray analysis performed on a second lesion did not demonstrate a loss of 13q14 or 16q typical of myofibroblastoma. Our findings further support the concept that at least a subset of breast lesions that historically have been classified as chondrolipoma are related to myofibroblastoma. However, the lack of myofibroblastoma-specific molecular alterations in one lesion suggests chondrolipomas may also have varying origins. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 46-year-old woman who presented with left retro-orbital headaches and other symptoms. Magnetic resonance imaging (MRI) revealed a 2.7 cm pituitary mass. Intraoperative and histological examinations showed a poorly differentiated neoplasm with high mitotic counts and loss of nuclear SMARCB1/INI1 staining. Chromosomal microarray analysis and next-generation sequencing detected copy neutral loss of heterozygosity (cnLOH) in chromosome 22 and a frameshift deletion in the SMARCB1 gene. The tumor was classified as an adult sellar atypical teratoid/rhabdoid tumor (AT/RT) and was found to be of the MYC subtype. The article emphasizes the rarity of adult sellar AT/RT and the importance of accurate diagnosis through molecular and cytogenetic analysis. [Extracted from the article]