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Objectives: The extension of atypical melanocytes to the hair follicle, also termed melanoma folliculotropism, is poorly evaluated and its role is contradictory. We performed an observational study focusing on anatomical areas rich in follicles, such as the head and neck region. Methods: Primary head and neck melanomas diagnosed in the Melanoma Unit, Policlinic Sant'Orsola-Malpighi, University of Bologna were analyzed. Folliculotropism was evaluated with a quantitative and morphologic parameter. Statistical analyses were performed correlating patients' prognosis with folliculotropism and other clinical and histopathologic factors. Results: The study was carried out on a sample of 62 patients. The diffuse distribution (atypical melanocytes present in more than three contiguous follicular units) correlated with scalp localization, nodular subtype, higher Breslow thickness, and a poorer prognosis. Conclusions: We believe that folliculotropism should be further investigated and reported by pathologists during the histologic diagnosis of melanoma.

BACKGROUND: The incidence of cutaneous melanoma (cm) has increased in the last decades. germline mutations in the high-penetrance melanoma susceptibility gene CDKN2A (Cyclin-dependent kinase inhibitor 2a) are associated with a younger age at diagnosis and an increased risk to develop pancreatic cancer. METHODS: We retrospectively analyzed the data of patients with prior diagnosis of cm referring to our service from January 2005 to may 2017. the aim was to investigate the rate of multiple cms (mPm), assessing their clinical/pathological features. moreover, the genetic tests of patients who had undergone CDKN2A/CDKN2B, CDK4 and MITF screening were evaluated. RESULTS: One hundred fifteen patients (9.26%) were diagnosed with MPMs: 70 males (60.87%) and 45 women (39.13%). 75 patients (43 males and 32 females) underwent genetic screening for germline mutations. The screening revealed that 4/75 patients (5.33%) were carriers of the non-synonymous missense variation c.442g>a (p.ala148thr) in CDKN2A exon 2 in heterozygosis, 3 of whom had at least one in-situ melanoma. In 1 patient (1.33%) we detected the variation c.249C>A, p.His83Gln in CDKN2A exon 2 in heterozygosis and in 1 patient (1.33%) the mutation c.952g>a (p.glu318lys) in MITF gene was found. CONCLUSIONS: This study confirms the need for a full body skin examination and a prolonged surveillance in patients affected by cM, as MPMs were detected in up to 10% of total cases in our series and synchronous lesions in 1/5. Moreover, it reflects the great variability of cM high-susceptibility genes mutational status within the Italian territory. Patients carrying c.952g>a (p.glu318lys) MITF mutation have a higher risk to develop a nodular cm.

Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge.

Breslow thickness (BT) is the most important histopathologic factor for primary melanoma staging. BT determines the margins for wide local excision whether sentinel lymph node biopsy should be performed and subsequent melanoma staging, and patient management. The correct determination of a 0.8-mm cutoff in melanoma is important for pathologists because discrepancies leading to a change in stage can have significant clinical implications, including incorrect and/or inappropriate prognostic information, investigation, management, and follow-up. Difficulties in BT determination are mostly represented by the presence of regression or melanoma associated with a pre-existing nevus. This study aimed at investigating a molecular parameter, namely microRNA (miRNA) expression, in reference to BT assessment. Melanoma cell proliferation is influenced by miRNA dysregulation. Indeed, some miRNAs sustain and induce proliferative signals or repress growth-suppressive pathways, thereby promoting melanoma carcinogenesis. To identify the miRNAs correlating with BT, we analyzed our global miRNA expression data of 20 thin melanomas and identified two potential candidates, miR-21-5p and miR-146a-5p. We assessed the expression of these two specific miRNAs in 90 archive formalin-fixed and paraffin-embedded samples of superficially spreading melanomas (SSMs) and 25 nodular melanomas from two independent cohorts and correlated the individual and combined miRNA expression with BT and other tumor characteristics. The individually normalized expression of miR-21-5p and miR-146a-5p showed a highly significant and linear correlation with BT in SSM, and their combined expression value was more strongly correlated (Pearson’s r = 0.799, 95% CI = 0.71–0.86) than their individual expressions. This correlation was not significant in nodular melanoma. In SSM, we observed that the combined miRNA expression above or below 1.5 was significantly associated with overall survival and successfully identified all patients with relapsing SSM. We concluded that the combined assessment of miR-21-5p and miR-146a-5p expression in superficially spreading melanoma, in association with BT measurement, could aid pathologists in SSM staging.

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Antibodies directed against programmed death receptor 1 emerged as beneficial immune-checkpoint inhibitor therapy in many different types of cancer. However, programmed death receptor 1 is critical in promoting self-tolerance and the most common toxicities of checkpoint inhibitors are immune-related adverse events. We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital lichen sclerosus. To the best of our knowledge, this is the first reported case of extragenital lichen sclerosus on previous melanoma-associated leukoderma lesions related to nivolumab monotherapy. The increase in clinical experience with anti programmed death receptor 1 enhances the knowledge about adverse effects associated with these immunotherapies and allows to compare therapeutic strategies.

BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles. CONCLUSIONS: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.

A 58-year-old man was referred to our clinic with an 8-month history of red-brown nodules on the dorsal surface of his left hand. He reported that he collected fish in his home aquarium as a hobby. On this basis, a prior diagnosis of nontuberculous mycobacterial infection was made, but systemic clarithromycin was ineffective. The patient also reported a constant painful sensation, which worsened in the evening and after exposure to low temperatures. Dermatologic examination of the left hand revealed two large, tender, red-brown skin nodules on the extensor surfaces of the second and third metacarpophalangeal joint, one of which was partially covered by a hematic crust …

Norwegian scabies is a severe form of scabies infestation, which usually occurs in people who are immunosuppressed, severely physically incapacitated or elderly. Unlike classical scabies, it is characterized by a plethora of mites on the skin surface and also affects the scalp, face, back and the periungual folds. Moreover, pruritus is usually absent or moderate.