The Histopathologic Evaluation of Diagnostic Procedures in Nail Melanoma.

INTRODUCTION: The diagnostic delay in nail melanoma (NM) has been repeatedly emphasized. It may be related to both clinical misinterpretations and to errors in the bioptic procedure. OBJECTIVES: To assess the efficacy of histopathologic examination in different diagnostic biopsies in NM. METHODS: We retrospectively investigated the diagnostic procedures and histopathologic specimens referred to the Laboratory of Dermatopathology for the clinical suspicion of NM from January 2006 to January 2016. RESULTS: Eighty-six nail histopathologic specimens were analyzed consisting in 60 longitudinal, 23 punch and 3 tangential biopsies. A diagnosis of NM was performed in 20 cases, benign melanocytic activation in 51 cases and melanocytic nevi in 15 patients. Longitudinal and tangential biopsy were diagnostic in all cases, regardless of the clinical suspicion. Nail matrix punch biopsy instead was not diagnostic in most of the cases (13/23 specimens). CONCLUSIONS: In the presence of an NM clinical suspicion, longitudinal biopsy is recommended (lateral or median) because it provides exhaustive information on the characteristics of melanocytes morphology and distribution in all the components of the nail unit. Tangential biopsy, recently encouraged by expert authors due to the optimal surgical outcome, in our experience gives incomplete information on tumor extension. Punch matrix biopsy gives limited evidence in the diagnosis of NM.

Defining the Prognostic Role of MicroRNAs in Cutaneous Melanoma.

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.

Alopecia Areata Incognita and Diffuse Alopecia Areata: Clinical, Trichoscopic, Histopathological, and Therapeutic Features of a 5-Year Study.

BACKGROUND: Alopecia areata is a nonscarring hair loss that usually causes round patches of baldness, but alopecia areata incognita (AAI) and diffuse alopecia areata (DAA) can cause a diffuse and acute pattern of hair loss. OBJECTIVE: To analyze the clinical, trichoscopic, histological, and therapeutic features of AAI and DAA. METHODS: The study was designed to include data of patients with histological diagnosis of AAI and DAA enrolled in our Hair Disease Outpatient Consultations. RESULTS: DAA had a greater involvement of the parietal and anterior-temporal regions, while AAI manifested itself mainly in the occipital-parietal regions. The most frequent pattern was empty yellow dots, yellow dots with vellus hairs, and small hair in regrowth, but the presence of pigtail hair was found almost exclusively in those with AAI. In cases of DDA, the finding of dystrophic hair and black dots was more frequent. The most frequent trichoscopic sign in both diseases was the presence of empty yellow dots, which, however, were described in a higher percentage in cases of DAA. The diseases have a benign course and are responsive to topical steroid therapy. CONCLUSIONS: Trichoscopy is very important for the differential diagnosis between the 2 diseases and to select the best site for biopsy. In the presence of diffuse hair thinning, these entities must be considered.

Dermoscopic-Histopathological Correlation of Eccrine Poroma: An Observational Study.

BACKGROUND: Eccrine poroma (EP) is a benign adnexal neoplasm that can be pigmented in 17% of cases. Four histopathological variants of EP exist. Dermoscopically, EP can mimic many other skin neoplasms. OBJECTIVES: To provide a dermoscopic-histopathological correlation of EP, classifying the clinical and dermoscopic features of EPs on the basis of their histopathological subtype, in an attempt to better characterize these entities. PATIENTS AND METHODS: A single-center retrospective study was conducted. Clinical data were collected; patients were classified on the basis of the 4 histopathological variants of EPs. Dermoscopic images were reviewed. A dermoscopic-histopathological correlation was performed, and the results were compared with literature data. RESULTS: Twenty-six lesions were included, both pigmented and nonpigmented. Three of the 4 histopathological variants were identified. Different dermoscopic features were observed for each distinct histopathological subtype of EP. The lesions mimicked different types of other skin neoplasms, in particular: nonpigmented hidroacanthoma simplex resembled nonmelanoma skin cancer; pigmented hidroacanthoma simplex appeared like a seborrheic keratosis or a solar lentigo; EPs sensu stricto presented as pink nodules if nonpigmented and were similar to seborrheic keratosis if pigmented; dermal duct tumors appeared as pigmented nodular lesions. CONCLUSIONS: Distinct dermoscopic features appeared to be recurrent in each histopathological variant. Dermoscopy can provide important clues for the diagnosis of EP; the final diagnosis is allowed by histopathology. To achieve a correct diagnosis of EP, because of its clinical and dermoscopic variability, surgical excision is recommended.

Acral melanoma: correlating the clinical presentation to the mutational status.

Acral lentiginous melanoma (ALM) is the most common type of malignant melanoma (MM) in Asians, Afro-Americans and Middle-Easterners. It represents 1.5-10% of all MM cases, being the most common histological type of MM arising on palms, soles and nail apparatus, which is more generically defined as acral MM. To date no risk factors have been officially established, however a history of trauma may be involved in the pathogenesis of acral MM. This shows heterogeneous clinical features and frequently presents with advanced stage and aggressive behavior, often as a result of misdiagnosis or delayed identification. Dermoscopy is helpful for an early diagnosis of ALM: the most characteristic dermoscopic patterns are the parallel ridge and the irregular diffuse pigmentation. On histopathology ALM displays a lentiginous growth pattern, with melanocytes arranged as solitary units along the basilar epidermis, without notable pagetoid growth in the early stage. Not all acral MMs present a lentiginous pattern: superficial spreading melanoma and nodular melanoma patterns are also possible. Novel studies investigating the biologic characteristics of acral MM reported variable results: the overall mutational rates ranged respectively between 8.5% and 23% for KIT, between 3.6% and 33.3% for BRAF and between 3% and 47% for NRAS in ALMs. Increasing attention has been recently given to other genes, such as telomerase reverse transcriptase, platelet-derived growth factor receptor alfa and cyclin D1. Larger molecular investigations urge to describe the molecular profile of acral MM, to allow the development of specific targeted therapies.

An Ulcerated Reddish Nodule of the Chest: When You See, Think .

A 97-year-old man with a previous personal history of multiple nonmelanoma skin cancers presented with a fast-growing, ulcerated reddish nodule on his chest. The nodule was surgically removed, and hematoxylin and eosin stains of the specimen showed an asymmetrical, nonpigmented lesion with architectural and structural impairment, round cells with clear, whitish, foamy cytoplasm, multiple dermal mitoses and nuclear pleomorphism. Our first hypothesis was sebaceous carcinoma, a rare malignant neoplasm derived from epithelial cells showing sebaceous differentiation. A further histopathologic examination showed the presence of pigment in a few areas of the neoplasm. On immunohistochemical study, neoplastic cells were negative for wide-spectrum cytokeratin and diffusely positive for S-100, MART-1, and HMB-45 proteins. Our final diagnosis was nodular malignant melanoma (MM) with balloon epithelioid cells, a "bizarre" presentation of MM in vertical growth phase, mimicking metastatic and primary neoplasms of different lineage derivations.

Epidemiology of pyoderma gangrenosum: Results from an Italian prospective multicentre study.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterised by painful, necrotic ulcerations. PG is described as a rare disease: the world-wide incidence is estimated to be around 3 to 10 cases per million population per year. These estimations are based mostly on case reports and retrospective case series; there are no prospective, multicentre studies on the matter. The apparent rarity of PG is in contrast with our clinical perception as dermatologists: in our opinion, PG is not so uncommon. Therefore, we decide to investigate the epidemiology of PG in the Italian population and confirm our clinical suspicions that it is not an orphan disease. We enrolled all patients diagnosed with PG in 8 Italian Dermatological Departments from 1st October 2014 to 1st November 2015, and we recorded their features. Our data, collected from 64 patients, are in accordance with those of the published literature regarding the epidemiology and features of PG. In an Italian population of roughly 8 million inhabitants of 7 provinces, we found an incidence of 5.17 new cases per million population per year. Unlike our predictions before the study, we confirmed the world-wide incidence of PG. To our knowledge, this is the first observational, multicentre study on PG. We hope that it provides a stimulus for further researches on PG and for the creation of an Italian register.