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Background: Reprogramming of energy metabolism to enhanced aerobic glycolysis has been defined as a hallmark of cancer., Objectives: To investigate the role of the mitochondrial proteins, β-subunit of the H + -ATP synthase (β-F1-ATPase), and heat-shock protein 60 (HSP60), and the glycolytic markers, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as the bioenergetic cellular (BEC) index, in melanoma progression., Materials and Methods: The expression of energy metabolism proteins was assessed on a set of different melanoma cells representing the natural biological history of the disease: primary cultures of melanocytes, radial (WM35) and vertical (WM278) growth phases, and poorly (C81-61-PA) and highly (C8161-HA) aggressive melanoma cells. Cohorts of 63 melanocytic naevi, 55 primary melanomas and 35 metastases were used; and 113 primary melanoma and 33 metastases were used for validation., Results: The BEC index was significantly reduced in melanoma cells and correlated with their aggressive characteristics. Overexpression of HSP60, GAPDH and PKM2 was detected in melanoma human samples compared with naevi, showing a gradient of increased expression from radial growth phase to metastatic melanoma. The BEC index was also significantly reduced in melanoma samples and correlated with worse overall and disease-free survival; the multivariate Cox analysis showed that the BEC index (hazard ratio 0·64; 95% confidence interval 0·4-1·2) is an independent predictor for overall survival., Conclusions: A profound alteration in the mitochondrial and glycolytic proteins and in the BEC index occurs in the progression of melanoma, which correlates with worse outcome, supporting that the alteration of the metabolic phenotype is crucial in melanoma transformation., (© 2018 British Association of Dermatologists.)

Background: Epidermal keratinization disorders comprise a heterogeneous group of skin diseases that share the common feature of abnormal epidermal maturation, often leading to a disturbed stratum corneum., Objective: To describe two cases of an unusual disorder of epidermal keratinization., Methods: The clinical features of two unrelated patients with a long-standing widespread cutaneous eruption are described. Histopathologic examination and immunohistochemical studies were performed on skin biopsy specimens., Results: The eruption was characterized by symmetric erythematous, flat, discrete papules with a polygonal shape and fine scaling. The papules covered most of the skin surface and, in some areas of the trunk, they were arranged along the lines of cleavage, parallel to the ribs. There was no facial, mucosal, nail, or palmoplantar involvement; the teeth and hair were normal. The first patient had a sister with an identical eruption, and a brother of the second patient was said to have similar skin lesions. Histopathology revealed well-demarcated areas of compact eosinophilic orthokeratotic hyperkeratosis overlying a slightly acanthotic epidermis. Lesional skin showed weaker immunoexpression for connexin 43 compared with normal skin., Limitations: Only two patients and one sibling were investigated., Conclusion: We propose the name "saurian papulosis" to describe this newly described clinicopathologic entity., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Alpha-1-antitrypsin deficiency is a congenital error of metabolism linked to pulmonary (emphysema) and liver (cirrhosis) disease. Since 1972, panniculitis has been associated with this deficiency, initially related to Weber-Christian syndrome and finally as a differentiated entity. Clinical manifestations typically consist of wide nodular lesions on the trunk and proximal extremities that evolve to ulceration and drainage. Histopathologically it presents as a mixed septal-lobular panniculitis pattern with some typical findings referred. Differential diagnosis from other types of panniculitis and neutrophilic dermatosis must be established. Different treatments, including tetracyclines, dapsone, and alpha-1-antitrypsin repositioning, have shown variable efficacy in controlling this disease.

Background: Interferon therapy at the injection sites has been related to different cutaneous lesions including erythema and induration as the most frequent ones. While the glycoprotein induces fatigue, fever and is even believed to precipitate autoimmune disorders such as type I diabetes, thyroid disease and systemic lupus erythematosus, a lupus erythematosus-like histologic reaction at the interferon injection site has never been reported. To our knowledge, a microscopic self-resolving lesion mimicking lupus erythematosus at the injection site of interferon has not been described., Results: We report five cases of cutaneous lesions at the inoculation site of interferon with a histopathologic lupus erythematosus-like pattern. Three of them were receiving interferon alfa therapy because of a malignant melanoma and the other two patients were receiving interferon beta-1b for multiple sclerosis. Biopsy specimens taken from different lesions showed similar microscopic findings consisting of dermal mucin deposits and dense lymphocytic infiltrates along hair follicles with hydropic degeneration of follicular basal layer., Conclusions: Multiple cutaneous lesions related to interferon at the injection site have been reported, but none of them with a histologic lupus-like presentation. In this study we describe five cases in which interferon therapy has induced a resolutive cutaneous lesion mimicking lupus erythematous. This peculiar microscopic pattern has been previously described once before, but interpreted as cutaneous mucinosis.

Several types of cutaneous vascular proliferations have been described in areas of irradiated skin, including both benign lesions, such as benign lymphangiomatous papules, atypical vascular lesions, or benign lymphangioendothelioma, and malignant neoplasms such as high-grade angiosarcomas. This report describes the clinicopathologic features of 15 cases of different types of benign cutaneous vascular proliferations arisen within irradiated skin. All patients were female ranging in age from 33 to 72 years, and they had received postoperative external radiotherapy for treatment of breast carcinoma (14 cases) or ovarian carcinoma (one case). In those cases in which the latency interval period between radiotherapy and the development of the vascular lesion was known from the clinical records, the latency interval period elapsed between radiotherapy and diagnosis of the vascular lesion ranged from 3 to 20 years. The most common clinical presentation of the cutaneous lesions consisted of papules, small vesicles, or erythematous plaques on the irradiated field. Histopathologically, most lesions consisted of irregular dilated vascular spaces, with a branching and anastomosing pattern, thin walls, and lymphatic appearance involving the superficial dermis. A discontinuous single layer of endothelial cells with flattened nuclei lined these vascular channels, and numerous small stromal papillary formations also lined by endothelial cells projected into the lumina of the dilated lymphatic vessels. These cases were classified as benign lymphangiomatous papules or plaques. Two cases showed different histopathologic findings because they consisted of poorly circumscribed and focally infiltrating irregular jagged vascular spaces involving the entire dermis and lined by inconspicuous endothelial cells. In some areas these irregular slit-like vascular spaces dissected collagen bundles of the dermis. These cases were classified as atypical vascular proliferations mimicking benign lymphangioendothelioma or patch-stage Kaposi's sarcoma. All cases showed similar immunohistochemical findings and the endothelial cells lining the vascular spaces expressed immunoreactivity for CD31, but they stained only focally positive for CD34 or were negative for this marker. Immunohistochemical investigations for alpha-smooth muscle actin failed to demonstrate a complete peripheral ring of actin-positive pericytes in most of the neoformed vascular structures. This immunohistochemical profile also supported the lymphatic nature of these vascular proliferations developed in irradiated skin. Although some of these lesions may mimic histopathologically patch-stage Kaposi's sarcoma or well-differentiated angiosarcoma, the follow-up of the patients of this series demonstrated that the vascular proliferations arisen in irradiated skin invariably showed a benign biologic behavior.

Visceral leishmaniasis is a protozoan infection that may complicate the course of patients with human immunodeficiency virus (HIV). Dermatofibroma is a cutaneous fibrohistiocytic lesion considered neoplastic by some authors and inflammatory by others. Eruptive dermatofibromas have been described in patients with HIV infection or with other altered immunity situations. We present the case of a 32-year-old, HIV-positive man with visceral leishmaniasis who complained of the appearance of a cutaneous lesion in the leg formed by the coexistence of dermatofibroma and Leishmania parasitic colonization. As far as we know, this type of association has not been reported previously. We consider that the dermatofibroma could have developed as an unusual form of fibrohistiocytic reaction to leishmania. From a practical approach, we recommend the search of leishmaniasis in dermatofibroma in immunosuppressed patients.