Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma. / La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en sarcoma pleomórfico dérmico.

BACKGROUND AND OBJECTIVE: Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. MATERIAL AND METHODS: Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. RESULTS: In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). CONCLUSIONS: PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness.

Impact of oxidative stress SNPs and dietary antioxidant quality score on prostate cancer.

Purpose: To analyse the relation between antioxidant genotypes and Dietary Antioxidant Quality score (DAQs) effect on prostate cancer (PCa) risk and aggressiveness in a Spanish population.Methods: Men (N = 155 patients and 152 controls) with PSA values >4 ng/ml were enrolled in the project. DAQs were used considering the daily recommended intake for Spanish people (DRI). Genotyping of 5 SNPs rs662 (PON1), rs10432782 (SOD1), rs4880 (SOD2), rs17650792 (GPX1) and rs1001179 (CAT) were included for the analysis.Results: rs17650792 was statistically significant between case and controls subjects. When comparing D´Amico risk, we found that rs662 (CC), rs10432782 (G allele) and rs17650792 (GG) confer a protection. When testing SNP-antioxidant nutrients interactions, we found an intake of vitamin A and rs100179 (T carriers) and selenium and rs17650792 (G carriers) confers a protection of being in low risk classification.Conclusions: We reported by the first time a correlation between rs662 (PON1) and PCa aggressiveness.

Familial seborrhoeic keratosis associated with multiple 'pure reticulated acanthomas' and infundibulocystic basal cell carcinomas.

BACKGROUND: A variety of genodermatoses with multiple cutaneous tumours and germline genetic alterations, such as PTCH1 mutations, have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis. OBJECTIVES: To describe the clinical, dermoscopic and histopathological features of multiple cutaneous lesions, mostly infundibulocystic basal cell carcinomas (ICBCCs) and pure reticulated acanthomas, present in a family affected by familial seborrhoeic keratosis. In addition, we tested for possible germline alterations in FGFR3 and PTCH1. METHODS: Ten members of one family were clinically examined and 92 skin biopsy specimens were evaluated. Blood samples from six individuals were analysed for FGFR3 and PTCH1 germline alterations. We reviewed the literature concerning genetic FGFR3 alterations in seborrhoeic keratosis. RESULTS: Individuals of all generations affected by familial seborrhoeic keratosis also presented other skin tumours that corresponded histologically to reticulated acanthomas without apocrine or sebaceous differentiation, as well as ICBCCs. In addition, two novel germline variants, p.Pro449Ser (c.1345C>T) in FGFR3 and p.Pro725Ser (c.2173C>T) in exon 14 of PTCH1 were identified in five participants. CONCLUSIONS: We characterize for the first time the clinical, dermoscopic and histopathological features of multiple reticulated acanthomas without apocrine or sebaceous differentiation, for which we propose the term 'pure reticulated acanthoma', and ICBCCs associated with familial seborrhoeic keratosis. We identified FGFR3 and PTCH1 germline polymorphisms whose influence in the development of reticulated acanthomas is unknown.

Clinically atypical spitzoid lesions: semi-quantitative histologic index correlation with dermoscopic scores (ABCD rule, 7-point checklist and pattern analysis).

BACKGROUND: The distinction of Spitz and Reed nevi with atypical features from melanoma may be a difficult task. In these cases, the dermoscopic scores could bring variable results and not always correlate with the histologic diagnosis. OBJECTIVE: The aim of this study was to compare the histopathologic and dermoscopic findings in a cohort of clinically atypical Spitz and Reed nevi. METHODS: We retrospectively reviewed 19 cases of atypical Spitz and Reed nevi from our files. We constructed a new semi-quantitative histologic index (HI) based on the reproducible microscopic features, and correlated it with two dermoscopic scores: ABCD and 7-point checklist, as well as with the predominant dermoscopic pattern. RESULTS: The HI values differs significantly when the multicomponent dermoscopic pattern was compared with the rest of patterns (U = 22.5, Z = 2.23, P = 0.01). The ABCD and the 7-point checklist scores did not show statistically significant correlation with the HI. CONCLUSION: To our knowledge, this is the first report in which a semi-quantitative histologic score is compared to different dermoscopic scores in clinically atypical spitzoid lesions. This score can be used to correlate in an objective way the entire histologic picture with the standardized dermoscopic scores. In our series we found a higher HI for those spitzoid lesions with multicomponent pattern.

Assessment of regression in successive primary melanomas.

INTRODUCTION AND OBJECTIVES: It has been suggested that patients who have had a melanoma may develop increased immunity against certain antigens expressed by tumor-associated melanocytes. Thus our objective was to review the records of patients with successive primary melanomas to ascertain whether the pattern of regression might indicate the presence of an immunization effect arising from the first melanoma. MATERIAL AND METHODS: A review of all the cases recorded in the melanoma database of our dermatology department between 2000 and 2012 identified 19 patients who had multiple asynchronous melanomas (2.56% of all the cases recorded). We studied the presence or absence of regression in these melanomas and other clinical and histological characteristics. RESULTS: The presence of regression was significantly higher in successive melanomas than in the first tumors identified (42.10% vs 21.05%, P=.018). Regression of at least 1 melanoma was observed in 42.10% of the patients studied and regression of 2 melanomas was observed in 21.05%. In no case was regression observed in the first melanoma and not in the second; however, in 21.05% of the patients there was evidence of regression in the second tumor and none in the first. CONCLUSIONS: Our findings suggest the possibility that the first melanoma produces an immunization effect in some patients who develop multiple asynchronous melanomas.

Estimation of dietary folic acid intake in three generations of females in Southern Spain.

An adequate folic acid intake has been related to female fertility. The recommended intake of this vitamin was recently increased to 400µg/day, with an additional 200µg/day during pregnancy. The Mediterranean Diet includes sources of folate such as pulses, green-leaf vegetables, fruit, cereals, and dried fruits; other foods of interest are liver and blue fish. The objectives were to determine the foods that contribute most to folate intake and analyze the factors that influence their consumption by three generations in a female population (n=898; age, 10-75yrs) from Southern Spain: 230 adolescents (10-16yrs), 296 healthy pregnant women (19-45yrs), and 372 menopausal women (>45yrs). Participants completed a previously validated semi-quantitative food frequency questionnaire. Over 90% of their folate intake was supplied by cereals, fruit, natural juice, pulses, and cooked and raw vegetables. The mean (SD) daily intake of folate was 288.27(63.64) µg. A higher Mediterranean Diet Score (MDS) was significantly related to a greater folate intake. The daily folate intake was not significantly influenced by educational level, number of children, or place of residence (rural vs. urban). In logistic regression analysis, the factors related to an adequate folate intake (>2/3 of recommendations) were higher age, higher MDS, and lower BMI.

[Birt-Hogg-Dubé syndrome: an update]. / Actualización en el síndrome Birt-Hogg-Dubé

Birt-Hogg-Dubé syndrome is a rare autosomal dominant genodermatosis that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The most common histological types found in renal tumors from patients with the syndrome are oncocytoma-chromophobe carcinoma hybrids and pure forms of chromophobe carcinoma, oncocytic carcinoma, and clear cell or papillary cell carcinoma. The syndrome is linked to mutations in the FLCN gene, which encodes folliculin and is preferentially expressed in the skin, kidney, and lung. The syndrome can exhibit a high degree of clinical variability, and the skin lesions that are a warning sign for dermatologists may be absent in up to 70% of cases. Consequently, although skin lesions and mutations in FLCN are the main diagnostic criteria for Birt-Hogg-Dubé syndrome, a diagnosis can be made based on noncutaneous manifestations, with or without known family history of the syndrome, even in the absence of histological confirmation of fibrofolliculomas or trichodiscomas.

[Complete regression of melanocytic nevi: correlation between clinical, dermoscopic, and histopathologic findings in 13 patients]. / Regresión completa de nevos melanocíticos: correlación clínica, dermatoscópica e histológica de una serie de 13 casos.

BACKGROUND: The complete regression of melanocytic tumors, confirmed by histology, has rarely been reported in the literature. It is very difficult to determine the malignant or benign nature of a regressed tumor, and on occasions, the only indication of malignancy is the subsequent development of metastasis. MATERIAL AND METHODS: We performed a descriptive study of melanocytic nevi that had undergone complete, histologically confirmed regression prior to excision in the dermatology department of our hospital over a period of 3 years. We included only lesions in which dermoscopy performed prior to regression showed features that suggested benignity. We assessed various clinical, dermoscopic, histologic, and immunohistochemical features. RESULTS: The mean time to complete regression was 6.4 months. The main dermoscopic patterns observed were reticular and mixed reticular/globular. Unlike what is generally seen in melanomas, the main histologic finding was the presence of fine or lamellar fibrosis. In all cases, there was a predominance of CD8+ T cells. CONCLUSIONS: The clinical, dermoscopic, and histologic features of the melanocytic nevi studied suggest the existence of a highly characteristic form of tumor regression characterized by very rapid regression and the involvement of a cytotoxic mechanism.

[Role of chemokines in melanoma progression]. / Papel de las quimiocinas en la progresión del melanoma.

Metastasis is the main cause of death from melanoma. Chemokines are low molecular weight chemotactic cytokines that facilitate cellular migration. Thus, cells that express receptors for a given chemokine are attracted to the site of its production. As certain chemokines are found in abundance in organs that are common targets of metastasis and receptors for these chemokines are expressed by tumor cells, it was hypothesized that chemokine gradients might selectively facilitate metastasis to these organs. A later finding that these chemokines were produced by tumor cells, with evidence of autocrine effects, obliged the modification of that hypothesis. Many chemokines are also known to have opposing effects according to the type of cell they are acting on (tumor, inflammatory/immune, or endothelial cells), their functional status, or interactions with other molecules. The expression of chemokines and their receptors by melanoma cells enhances tumor progression by altering their microenvironment, stimulating angiogenesis, and inhibiting the immune response.

[Descriptive dermoscopic study of depigmentation in melanocytic nevi without a visible halo]. / Estudio descriptivo dermatoscópico de los nevos melanocíticos con despigmentación sin halo clínico.

BACKGROUND AND OBJECTIVES: There are few cases described in the literature in which depigmentation of melanocytic nevi occurs without the appearance of halos. The aim of this study was to analyze the correlation between clinical and dermoscopic findings and to assess the usefulness of dermoscopy to identify possible markers of complete regression in melanocytic lesions. MATERIALS AND METHODS: A prospective, observational, descriptive study of 77 melanocytic lesions in 52 patients was undertaken over a 5-year period. Melanocytic lesions from patients who underwent periodic follow-up in the digital dermoscopy unit were analyzed if they had exhibited partial or total, permanent depigmentation without a clinically apparent halo. RESULTS: We observed substantial variation in the time taken for pigmentation to disappear and the morphological characteristics of the nevi during the depigmentation process. Female sex and dermoscopic evidence of melanophage activity or of a halo were all associated with more rapid involution of pigmented lesions. The only variable which displayed a statistically significant association with complete depigmentation of melanocytic nevi was the presence of vascular proliferation. Fibrosis was the only variable that displayed a statistically significant association with heterogeneous depigmentation of melanocytic nevi. CONCLUSIONS: In this study, we have identified patterns of depigmentation in melanocytic lesions that differ from the classic halo nevus.

Protocol for the Histologic Diagnosis of Cutaneous Melanoma: Consensus Statement of the Spanish Society of Pathology and the Spanish Academy of Dermatology and Venereology (AEDV) for the National Cutaneous Melanoma Registry. / Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma.

This article describes a proposed protocol for the histologic diagnosis of cutaneous melanoma developed for the National Cutaneous Melanoma Registry managed by the Spanish Academy of Dermatology and Venereology (AEDV). Following a review of the literature, 36 variables relating to primary tumors, sentinel lymph nodes, and lymph node dissection were evaluated using the modified Delphi method by a panel of 8 specialists (including 7 pathologists). Consensus was reached on the 30 variables that should be included in all pathology reports for cutaneous melanoma and submitted to the Melanoma Registry. This list can also serve as a model to guide routine reporting in pathology departments.