ABSTRACT
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma thought to arise via either viral (Merkel cell polyomavirus) or ultraviolet-associated pathways. Surgery and radiotherapy have historically been mainstays of management, and immunotherapy has improved outcomes for advanced disease. However, there remains a lack of effective therapy for those patients who fail to respond to these established approaches, underscoring a critical need to better understand MCC biology for more effective prognosis and treatment. Here, we review the fundamental aspects of MCC biology and the recent advances which have had profound impact on management. The first genetically-engineered mouse models for MCC tumorigenesis provide opportunities to understand the potential MCC cell of origin and may prove useful for preclinical investigation of novel therapeutics. The MCC cell of origin debate has also been advanced by recent observations of MCC arising in association with a clonally related hair follicle tumor or squamous cell carcinoma in situ. These studies also suggested a role for epigenetics in the origin of MCC, highlighting a potential utility for this therapeutic avenue in MCC. These and other therapeutic targets form the basis for a wealth of ongoing clinical trials to improve MCC management. Here, we review these recent advances in the context of the existing literature and implications for future investigations.
ABSTRACT
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with a high propensity for local invasion and recurrence. Although it is a rare event, the occurrence of multiple tumors in a single patient raises a diagnostic dilemma, as metastatic disease should be differentiated from multiple primary malignant events. In more than 90% of DFSP, a pathogenic t(17;22) translocation leads to the expression of COL1A1::PDGFB fusion transcripts. Karyotype analysis, fluorescence in situ hybridization, and RT-PCR can be useful ancillary studies in detecting this characteristic rearrangement, and sequencing of the fusion transcript can be used to support a clonal origin in metastatic and multifocal disease. However, previous reports have demonstrated variable sensitivity of these assays, in part due to the high sequence variability of the COL1A1::PDGFB fusion. Here, we report a patient who developed two distinct DFSP tumors over the course of 7 years. Chromosomal microarray analysis identified distinctive genomic alterations in the two tumors, supporting the occurrence of multiple primary malignant events.
Subject(s)
Dermatofibrosarcoma , Oncogene Proteins, Fusion , Skin Neoplasms , Humans , Male , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 22/genetics , Collagen Type I, alpha 1 Chain , Dermatofibrosarcoma/genetics , Dermatofibrosarcoma/pathology , Dermatofibrosarcoma/diagnosis , In Situ Hybridization, Fluorescence/methods , Microarray Analysis/methods , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Oncogene Proteins, Fusion/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Translocation, Genetic , Middle AgedABSTRACT
A 58-year-old woman was admitted for heart failure and concern for cardiogenic shock. The patient had been recently placed on colchicine and allopurinol, 4 months and 3 weeks, respectively, prior to admission. Upon admission, she had a cutaneous eruption that had started abruptly several days after allopurinol initiation. It included multiple erythematous papules with scant scale on the forearms and numerous erythematous papules on the legs. Because of the varied morphologic presentation, biopsies from both the thigh and forearm were performed for a suspected drug reaction. The specimen from the thigh showed a superficial-dermal, band-like lymphocytic infiltrate with dyskeratosis and numerous intraepidermal mitotic figures predominantly in metaphase. In addition, there were neutrophils with leukocytoclasia. The specimen from the forearm showed superficial perivascular lymphocytic inflammation and intraepidermal dyskeratosis with mitotic figures similar to the thigh biopsy specimen but without a dermal neutrophilic infiltrate. An unusual drug eruption with features of colchicine toxicity was favored. Colchicine toxicity is not a commonly encountered clinical scenario and cutaneous findings have only rarely been described. Herein we report an exceedingly rare case of an unusual drug reaction with "colchicine figures" (i.e., ring-shaped mitotic figures arrested in metaphase) consistent with colchicine toxicity.