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Spitz tumours comprise a spectrum of melanocytic proliferations that share a set of distinct cytological features and molecular pathways. They include benign naevi, intermediate or indeterminate tumours and rare melanomas. Spitz tumours are notorious for the difficulty of distinguishing benign neoplasms with atypical features from melanomas and the related diagnostic uncertainty. Advances in the knowledge of the molecular pathways and genomic aberrations associated with these neoplasms have permitted opportunities for a reduction in the number of uncertain diagnoses and a more objective distinction between Spitz tumours from Spitz‐like neoplasms. The presence of a Spitz molecular pathway, such as Harvey rat sarcoma viral oncogene homologue (HRAS) aberrations or kinase fusions, distinguishes a bona fide Spitz neoplasm from Spitz‐like naevi or melanomas with conventional driver mutations. Spitz neoplasms with benign histopathological features and, if such testing is performed, benign cytogenetic and molecular findings, are termed Spitz naevi. Spitz neoplasms with frankly malignant histopathological findings or ambiguous microscopic findings associated with genetic or genomic aberrations most in keeping with melanoma are designated as Spitz melanoma. Tumours with microscopic features and genetic/genomic aberrations in between naevi and melanomas are classified as Spitz melanocytoma. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma in situ (SCCIS) of the nail unit is a complex malignancy; with little understanding of rate of upstaging or occult invasion in these patients. We sought to evaluate the rate of upstaging in nail unit SCCIS after Mohs micrographic surgery (MMS). Retrospective review of 346 patients who referred for and underwent MMS for biopsy proven SCCIS on the hands and feet between January 1, 2000 and December 30, 2019. Only cases in the nail unit were included. Clinical, surgical details, histopathological features, HPV status, and rate of upstaging were recorded. Thirty-one cases met the inclusion criteria and were analyzed. Twenty-four patients were males (77.4%). The mean age was 55 years (SD 17.26, range 27–84). The mean clinical size was 9.9 mm; 19 cases tested for HPV, 15/19 were positive (78.9%), and 8/19 (42.1%) were associated with high-risk HPV. Three patients (9.7%) were upstaged to invasive on either MMS margins or tumor debulking. Limitations included a relatively small sample size and retrospective in nature. The rate of upstaging of SCCIS in the nail unit is not frequent, and when upstaging occurred it was focal, superficial, and with no PNI or bone invasion. [ABSTRACT FROM AUTHOR]

NUT carcinomas are genetically defined epithelial neoplasms. Most tumors harbor fusions of NUTM1 with BRD4 or BRD3. Their histopathologic features have been predominantly reported as undifferentiated or poorly differentiated squamous cell carcinoma, and clinically they tend to be aggressive cancers. However, recent studies have revealed a broader spectrum of NUTM1‐rearranged neoplasms with several new fusion partners and associated variable histopathologic phenotypes and clinical behaviors, including benign and malignant cutaneous poroid tumors. We report herein a primary invasive carcinoma of skin adnexal origin with a previously undescribed fusion between BRD3 and NUTM2B. The tumor occurred on the shoulder of a 7‐year‐old girl and was excised with negative margins. A sentinel lymph node was positive. After follow‐up of 23 months, and without systemic treatment, the child remains free of tumor. This case expands the spectrum of NUT carcinomas by including a skin adnexal variant with follicular infundibular differentiation, a novel genomic aberration, and preliminary evidence of a less aggressive clinical course. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional hazards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p < 0.05) with presence of mitoses and melanomaspecific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted. [ABSTRACT FROM AUTHOR]

Fibroepithelioma of Pinkus (FEP) is a subtype of basal cell carcinoma (BCC) that can clinically resemble intradermal nevi (IDN) and fibromas. We performed a retrospective review of consecutively biopsied lesions confirmed to be FEP on histopathology diagnosed from January 1, 2008 to April 8, 2019. Clinical (n = 48), contact non-polarized dermoscopy (NPD) (n = 44), and contact polarized dermoscopy (PD) (n = 22) images from 36 patients were reviewed. Mean age was 64.5 years (SD 15.1 years, range 24–86 years) at diagnosis of first FEP lesion. Most lesions were located on the torso (n = 28, 58.3%), followed by the lower extremity (n = 9, 18.8%). The most common differential diagnoses at the time of biopsy included BCC (n = 40) and nevus (other than IDN, n = 5). Clinically, FEP were pink (95.8%), scaly (66.7%) papules (77.1%) displaying disrupted skin markings (62.5%) and absence of hair follicles (87.5%). NPD revealed serpentine (97.7%), dotted (81.8%), or polymorphous vessels (86.4%), and hypopigmented to pink lines intersecting at acute angles (HPLA) (52.3%). PD demonstrated serpentine (95.5%), dotted (86.4%), or polymorphous vessels (81.8%), shiny white lines (50.0%), and HPLA (59.1%). Classic features of BCC such as arborizing vessels (n = 2), ulceration (n = 1), shiny white blotches and strands (n = 1), blue-gray ovoid nest (n = 1), and leaf-like areas (n = 1) were uncommon. FEP often presents as scaly, erythematous papules with disrupted skin markings and absence of hair follicles. Dermoscopy reveals polymorphous vessels with shiny white lines and HPLA. [ABSTRACT FROM AUTHOR]

Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused 'precision biopsy' technique that correlates clinical–dermoscopy–RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy–RCM–histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22–91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for 'feature correlation' of structures on dermoscopy or RCM, and five (20.8%) for 'correlation of new/unknown' RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction. [ABSTRACT FROM AUTHOR]