A review of the epidemiology and treatment of Merkel cell carcinoma

Merkel cell carcinoma is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Articles in English, French, Italian, Portuguese, and Spanish from the last 20 years were identified in MEDLINE and reviewed. The key word “Merkel” was used for the search, relevant articles were selected, and their references were examined. The most important articles related to epidemiology, genesis and treatment were reviewed. The incidence of Merkel cell carcinoma is increasing due to the advancing age of the population, higher rates of sun exposure and an increasing number of immunocompromised individuals. With regard to etiology, the recently described Merkel Cell polyomavirus is thought to play a role. Either local or regional surgical intervention remains the standard of care, but adjuvant radiotherapy or radiotherapy as a primary treatment have been discussed as reasonable therapeutic options. An update on this rare neoplasia is essential because of its increasing incidence and changing treatment options

Primary Cutaneous Melanoma: An 18-Year Study

BACKGROUND: Primary cutaneous melanoma still constitutes the main cause of skin cancer death in developed countries, and its incidence in recent years has been increasing in a steady, worrisome manner. OBJECTIVES: This study evaluated the clinical, epidemiological and demographic aspects of this disease, and correlated them with patient prognosis. METHODS: Using epidemiologic and clinical data, we analyzed 84 patients with mild to severe primary cutaneous melanoma treated between 1990 and 2007. Slides containing surgical specimens were analyzed, and new slides were made from archived paraffin sections when necessary. RESULTS: The melanoma incidence was higher in areas of sun exposure, with lesions commonly observed in the trunk for males, and lower limbs for females. In addition to Breslow's thickness and ulceration (p = 0.043 and p < 0.001, respectively), the mitotic rate per mm² also correlated with worse patient outcome (p = 0.0007). The sum of ulceration (0 when absent or 1 when present), the Breslow index (1 when <1 mm, 2 when >1 mm and <4 mm, 3 when >4 mm) and the mitotic index (0 when absent or 1 when >1 per mm²) allowed the establishment of a prognostic score: if the sum was equal to or over three, nearly all (91.7%) patients had systemic disease. The 5-year survival was approximately seventy percent. CONCLUSION: Because American Join Committee of Cancer Staging will update the classification of malignant tumors (TNM) staging in the near future, and introduce mitosis as a prognostic factor, our results show the importance of such a feature. Additional studies are necessary to confirm the importance of a prognostic score as proposed herein

Rejeição e efeitos da ciclosporina nos transplantes cutâneos alógenos microcirúrgicos em ratos

Os efeitos da rejeição e da imunossupressão com ciclosporina A em retalhos epigástricos utilizados como transplantes cutâneos alógenos microcirúrgicos, foram estudados em 58 ratos, distribuídos em três grupos: Wistar-Furth isogênicos doadores e receptores; e Brown-Norway doadores e Wistar-Furth receptores, imunossuprimidos com cicloporina A(10mg/kg/dia). Biópsias dos retalhos e da pele normal contralateral utilizadas como contrôle foram colhidas no terceiro, sétimo, 15º e 30º dias pós transplante. As biópsias foram preparadas em historesina, e coradas em azul de toluidina, para avaliação do infiltrado inflamatório local, permitindo estudo quantitativo dos linfócitos infiltrantes nos retalhos. O modelo revelou-se eficiente, obtendo-se sobrevivência dos transplantes por 30 dias, de 83,3% entre animais isogênicos, e de 60% nos alogênicos sob ação da ciclosporina A. Em ratos alogênicos não imunossuprimidos houve 100% de rejeição dos retalhos, até o nono dia pós-operatório. Nos transplantes desses animais, verificou-se aumento significativo do número de linfócitos infiltrantes no terceiro dia, quando comparados aos ratos isogênicos. A linfocitose observada antecedeu os achados macroscópicos da rejeição, verificados apenas no quinto ou sexto dias.The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1) Wistar Furth isogenic donors and receptors (control set); (2) Brown Norway donors and Wistar Furth receptors (rejection set); and (3) Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set). Cyclosporin A (10 mg/kg/d) treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control) on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy

Eyelid trichoadenoma: surgical treatment associated with aesthetic lepharoplasty

Trichoadenoma is a benign cutaneous tumor that is asymptomatic, rare, and slow growing. There are few cases reported in the literature, and we could only identify one description of trichoadenoma occurring in the eyelid area. We describe the case of a patient with trichoadenoma in the outer corner of the lower eyelid that we treated with surgical excision associated with blepharoplasty.O tricoadenoma é um tumor cutâneo benigno, assintomático, raro e de crescimento lento. Existem poucos casos relatados na literatura e identificamos apenas um descrito na região palpebral. Apresentamos o caso de uma paciente portadora de tricoadenoma no canto externo da pálpebra inferior direita, tratada com excisão cirúrgica associada a blefaroplastia.Universidade de São Paulo Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP)Universidade de UberabaUNIFESPSciEL

Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma - review article

Atypical Mole Syndrome is the most important phenotypic risk factor for developing cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Because the diagnosis of melanoma at an early stage is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers is essential, as well as the creation of recommended preventative measures that must be taken by these patients

IMP dehydrogenase rod/ring structures in acral melanomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p 4.0mm, compared with only 29% in the RR-low/negative (p = .039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy

UTILIDADE DA GRISEOFULVINA NO TRATAMENTO DO GRANULOMA ACTÍNICO DE O’BRIEN

Actinic granuloma of O’Brien, also called annular elastolytic giant cell granuloma is a rare condition. It shows clinically as papules lesions that converge in annular plaques lesions with an atrophic center. Histologically, it evidences elastophagocytosis and elastolysis. The case below describes a female patient, 53 years old, that had classical clinical and histopathological lesions of actinic granuloma that showed a significant improvement upon the introduction of adjunctive griseofulvin therapy.O granuloma actiníco de O’Brien, ou também chamado de granuloma anular elastolítico de células gigantes é uma afecção rara. Apresenta-se clinicamente como pápulas que se confluem formando lesões anulares com centro atrófico. Histologicamente, evidencia-se elastofagocitose e elastólise. O seguinte caso relata uma paciente com 53 anos, que apresentava lesões clínicas e histopatológicas clássicas de granuloma actínico que evoluiu com melhora importante no tratamento adjuvante com griseofulvina

Diagnostic line ratios in the IC 1805 optical gas complex

Large HII regions, with angular dimensions exceeding 10 pc, usually enclose numerous massive O-stars. Stellar winds from such stars are expected to play a sizeable role in the dynamical, morphological and chemical evolution of the targeted nebula. Kinematically, stellar winds remain hardly observable i.e., the typical expansion velocities of wind-blown bubbles being often confused with other dynamical processes also regularly found HII regions. However, supersonic shock waves, developed by stellar winds, should favor shock excitation and leave a well-defined spectral signature in the ionized nebular content. In this work, the presence of stellar winds, observed through shock excitation, is investigated in the brightest portions of the Galactic IC 1805 nebula, a giant HII region encompassing at least 10 O-stars from main-sequence O9 to giant and supergiant O4. The use of the imaging Fourier transform spectrometer SpIOMM enabled the simultaneous acquisition of the spectral information associated to the Halpha6563A, [NII]6548, 6584A, and [SII]6716, 6731A ionic lines. Diagnostic diagrams, first introduced by Sabbadin and collaborators, were used to circumscribe portions of the nebula likely subject to shock excitation from other areas dominated by photoionization. The gas compression, expected from supersonic shocks, is investigated by comparing the pre- and post-shocked material's densities computed from the [SII]/[SII] line ratio. The typical [NII]/[NII] line ratio slightly exceeds the theoretical value of 3 expected in low-density regimes. To explain such behavior, a scenario based on collisional de-excitations affecting the [NII]6548A line is proposed.Comment: 22 pages, 19 figures, 1 table, Accepted for publication by MNRAS on November 11th 201

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement

IMPORTANCE A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose. OBJECTIVE To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG). EVIDENCE REVIEW Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0. FINDINGS The new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma. CONCLUSIONS AND RELEVANCE The implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients