RESUMEN
BACKGROUND: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. OBJECTIVES: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. METHODS: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. RESULTS: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. CONCLUSIONS: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.
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Melanoma , Enfermedades de la Uña , Neoplasias Cutáneas , Telomerasa , Humanos , Melanoma/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/diagnóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Regiones Promotoras Genéticas/genética , Mutación , Enfermedades de la Uña/genética , Análisis Mutacional de ADN , Telomerasa/genética , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genéticaRESUMEN
Merkel cell carcinoma (MCC) is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and immunosuppressed patients. Because a subset of MCC is closely related to UV radiation, MCC can develop concurrently with other tumors, most commonly, as a combined tumor with squamous cell carcinoma (SCC). These combined tumors appear to represent a distinct disease process from pure MCC, as they are mostly Merkel cell polyomavirus (MCPyV) negative, and show a more aggressive behavior. We present two additional cases of combined MCC and SCC with nodal metastases, one of which was MCPyV positive. Two different subtypes of MCC have been proposed based on their origin: a true neuroendocrine carcinoma, that is MCPyV positive and has a dermal origin, and a UV-related SCC with neuroendocrine differentiation. This theory could explain why MCC can develop concurrently with SCC, and why these combined cases are generally MCPyV negative. However, it fails to explain the minority of combined MCC and SCC tumors that are MCPyV positive. Because both our patients had a history of chronic UV exposure, we hypothesize that UV radiation probably played a major role in the pathogenesis of these tumors, while MCPyV integration probably acted as an additional trigger.
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Carcinoma de Células de Merkel , Carcinoma de Células Escamosas , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Neoplasias Cutáneas , Infecciones Tumorales por Virus , Humanos , Anciano , Carcinoma de Células de Merkel/patología , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/patología , Metástasis Linfática , Piel/patologíaRESUMEN
ABSTRACT: Trichoepithelioma is a benign adnexal neoplasm of follicular germinative cells, with bulbs, papillae, and sheaths of perifollicular connective tissue as signs of follicular differentiation. Accordingly, trichoepithelioma may arise in any hair-bearing location, mostly on the face. That is why trichoepithelioma cannot appear in glabrous skin, and, although the dorsum of the hands and feet are a hair-bearing area, acral location is exceptional. We report the first case of trichoepithelioma localized in the finger of a 79-year-old man. It was a brown-pink, firm, 7-mm diameter, solid papule on the dorsal aspect of his left index finger. The lesion was completely asymptomatic, and he remembered to have it for many years. We describe this case highlighting its rare anatomical location and correlate its dermoscopic features with the histopathological appearance.
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Enfermedades del Cabello , Neoplasias Cutáneas , Masculino , Humanos , Anciano , Neoplasias Cutáneas/patología , Enfermedades del Cabello/patología , Cabello/patología , Extremidad Superior/patología , Dedos/patologíaRESUMEN
BACKGROUND: Acral location of melanomas is associated with poor survival. It can be due, at least in part, to the fact that acral lentiginous melanoma, a distinct melanoma subtype, has a particular biological profile and a bad clinical behavior. However, since almost 50% of acral melanomas are not of acral lentiginous melanoma subtype, the worse clinical behavior could also be attributable to the intrinsic characteristics of the location. OBJECTIVE: This study aimed to investigate if melanomas of the lower limb excluding acral lentiginous melanoma differ by location. METHODS: This retrospective, observational study recruited patients from an oncology referral center in Spain. We included 285 patients with superficial spreading and nodular melanomas of the lower limb. We compare melanomas by site, clinical and pathological characteristics, and the differences by location of disease-free and melanoma-specific survival by the Kaplan-Meier method and Cox proportional hazard method. RESULTS: Patients with melanomas on the foot, compared to those on the rest of the limb, were older and reported having suffered less sunburns; the melanoma more frequently appeared in areas that had been rarely sun exposed, were more frequently of nodular type, presented thicker tumors, with more ulceration, less regression, and more advanced stage of the disease. Foot location increased the risk of relapse and decreased melanoma-specific survival. CONCLUSION: Melanoma development in foot is less related to sun exposure and is associated with pathological features that can account for the worse prognosis and poorer survival.
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Melanoma , Neoplasias Cutáneas , Humanos , Extremidad Inferior/patología , Melanoma/patología , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
ABSTRACT: Amyloidoma, otherwise known as tumoral amyloidosis, is a localized deposition of amyloid (AL-type or AA type) without systemic amyloidosis. It is the rarest form of tissue amyloid deposition, and up to 7% of amyloidomas develop systemic amyloidosis.Cutaneous AL-type amyloidoma is considered by many authors as an unusual variant of primary cutaneous marginal zone lymphoma. Although cutaneous amyloidoma can form calcifications, ossification is extremely unusual, with only 1 case previously published to date.We report the case of a 75-year-old woman with voluminous and strikingly ossifying AL-type amyloidoma in the left pretibial skin. Her medical history included excision of hepatic hydatidic cysts 25 years prior and diffuse large B-cell lymphoma of the left parotid gland 8 years prior treated with chemotherapy and radiotherapy with complete response. After the diagnosis of amyloidoma, an extension study with cervical, chest, abdominal, and pelvic TC was performed, with no additional lesions found. Serum and protein electrophoresis revealed elevations in kappa light chain and IgA immunoglobulin levels but did not reveal monoclonal bands. In situ hybridization for immunoglobulin light chains showed monotypic kappa expression in plasma cells infiltrating the amyloidoma.Extensive ossification in amyloidomas can make diagnosis difficult; therefore, we describe an interesting case of this histopathologically peculiar amyloidoma.
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Amiloidosis , Neoplasias de los Tejidos Blandos , Anciano , Amiloide/análisis , Amiloidosis/patología , Femenino , Humanos , Inmunoglobulina A , Cadenas Ligeras de Inmunoglobulina , OsteogénesisRESUMEN
BACKGROUND: The incidence of cutaneous melanoma, an important global public health problem, has been increasing over the last several decades. OBJECTIVES: In order to decrease melanoma-related mortality, ways to communicate and implement the correct methods for conducting primary and secondary prevention measures (such as early detection via self-examination) should be investigated. MATERIALS AND METHODS: An observational, cross-sectional, retrospective study consisting of 409 patients diagnosed with cutaneous melanoma was conducted. An online questionnaire was created to evaluate knowledge levels, attitudes, and adherence to primary preventive measures and to skin self-examination practices. RESULTS: The results revealed that even when 43% of the patients perform cutaneous self-examinations, only half of them fully followed the recommendations. Patients aged <45 years, female, with a I-II phototype, with an intermediate/high level of education, and with a history of NMSC were more likely to have an adequate degree of knowledge. Moreover, patients aged <45 years and with an adequate degree of knowledge more frequently showed an adequate adherence to the primary prevention measures. Finally, patients aged 45-60 years and with an adequate degree of knowledge presented a good adherence to the self-skin examination measures. LIMITATIONS: Possible limitations of this study were memory bias through the influence of age within the study population, and bias due to a greater proportion of subjects with a high education level. CONCLUSION: Within the population of patients with melanoma, a high percentage of patients do not rigorously follow the recommended prevention measures. Our study highlights the need to implement awareness in this population to improve the prevention of cutaneous cancer.
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Conocimientos, Actitudes y Práctica en Salud , Melanoma/prevención & control , Cooperación del Paciente , Prevención Primaria , Autoexamen , Neoplasias Cutáneas/prevención & control , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/psicología , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/psicologíaRESUMEN
BACKGROUND: Small series of ultrasound findings in dermatofibrosarcoma protuberans (DFSP) have been published, but the usefulness of this technique as a preoperative planning tool for tumor resection has not been studied. MATERIALS AND METHODS: We retrospectively reviewed patients with DFSP at our hospital that underwent ultrasound examination. Depth of invasion was evaluated by ultrasound and histopathology. Accuracy of ultrasound for assessing depth of tumor invasion was estimated. RESULTS: Thirty histopathologically confirmed DFSPs were studied. Classic finger-like projections were observed in 73.3% of cases. A posterior hyperechoic area extending deep into the subcutaneous tissue correlated with the honeycomb DFSP pattern and was observed in 53.3% of patients. Concordance between ultrasound and histopathologic depth measurements was excellent. Lateral tumor extension and Doppler activity were not evaluated in our series. CONCLUSION: Ultrasound showed excellent prediction of depth of invasion. Further studies are required to define the usefulness of ultrasound for determining lateral tumor extension.
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Dermatofibrosarcoma , Neoplasias Cutáneas , Dermatofibrosarcoma/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Tejido Subcutáneo , UltrasonografíaRESUMEN
Locoregional lymph node recurrences of primary trunk melanoma can occur in basins not identified during sentinel lymph node biopsy. However, the factors associated with recurrences in non-sentinel lymph node basins are unknown. To evaluate these factors, this observational retrospective study examined the patterns of first lymph node recurrence and the factors associated with recurrence in non-sentinel lymph node basins. A total of 305 patients with primary trunk melanoma who had undergone sentinel lymph node biopsy from 2000 to 2015 were evaluated. Twenty-three patients presented locoregional lymph node recurrence; 8 of which (34.8%) were in non-sentinel lymph node basins. Non-sentinel lymph node recurrences were more frequent in patients with positive sentinel lymph nodes and in those patients whose number of tumour-involved nodes was > 3. These results suggest that clinical examination and ultrasound surveillance should be performed on all potential lymph node drainage basins of trunk melanomas.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Metástasis Linfática , Melanoma/cirugía , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/cirugíaRESUMEN
Solid carcinoma, probably the solid variant of microcystic adnexal carcinoma, is an apocrine adnexal tumor first described in 1998. The authors report an additional new case of the tumor at an unusual localization. A 78-year-old man presented with an asymptomatic firm plaque on his right thigh that had been present for 15 years. A biopsy was taken, and then, the lesion was removed. A pathological study showed a huge number of islands made up of aggregations of neoplastic epithelial cells. The epithelial islands showed variable sizes and shapes at scanning magnification, arranged columns, cords, and strands at the basis of the tumor. The neoplastic cells were embedded within a fibrotic stroma. Ductal differentiation, cystic structures, and neurotropism were also observed. Immunohistochemically, the neoplastic cells expressed high-molecular-weight keratin (cytokeratin 5/6), broad-spectrum keratin (AE1/AE3), p40, and p63. No immunoreactivity was found for BerEP4, cytokeratin 7, cytokeratin 19, cytokeratin 20, chromogranin A, carcinoembryonic antigen, and S-100. The lesion was completely removed with slow-Mohs micrographic surgery. Two stages and previous debulking were necessary to obtain free margins. The second stage included the muscular fascia. The patient remains free of tumor after a year of follow-up. Solid microcystic adnexal carcinoma is a rare skin tumor that seems to occur more frequently in the scalp than in the face, but no area of the body can be excluded, as reported in our case. Differential diagnosis should include sclerosing and clear-cell basal cell carcinoma, clear-cell dermal duct tumor, or desmoplastic trichoepithelioma. Mohs micrographic surgery is the treatment of choice.
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Neoplasias de Anexos y Apéndices de Piel/patología , Neoplasias Cutáneas/patología , Neoplasias de las Glándulas Sudoríparas/patología , Anciano , Humanos , Masculino , Cirugía de Mohs , Neoplasias de Anexos y Apéndices de Piel/cirugía , Neoplasias Cutáneas/cirugía , Neoplasias de las Glándulas Sudoríparas/cirugía , MusloRESUMEN
Mutations within the promoter of gene encoding telomerase reverse transcriptase subunit are frequent in many cancers including melanoma. Previously, the TERT promoter mutations were shown to associate with markers of poor outcome and reduced survival in patients with primary melanoma. In this study, we investigated the impact of the subtypes of TERT mutations on disease-free and melanoma-specific survival in 287 patients with stage I/II nonacral melanoma. Our results showed that of the three TERT promoter mutation subtypes, in multivariate models, the -138/-139 CC > TT tandem mutation associated with worst disease-free and melanoma-specific survival. In particular, in combination with BRAF/NRAS mutations, the -138/-139 CC > TT TERT promoter mutation associated with statistically significant poor disease-free and melanoma-specific survival with hazard ratios of 6.04 (95% CI 2.03-17.94, p = 0.001) and 12.59 (95% CI 2.18-72.70, p = 0.005), respectively. In contrast to the survival data, luciferase assays showed that the highest activity was observed in experiments with a promoter construct with -124 C > T mutation followed by the -138/-139 CC > TT and -146 C > T mutations, which showed similar activity. Based on previous reports, we speculate that the tandem mutation probably leads to greater genomic instability than the common TERT promoter mutations, hence the association with worst survival. However, the results from the study are only preliminary with limited patient data, therefore, require a cautious interpretation. The observations in this study, if confirmed, could have implications for melanoma patients treated with MAP-kinase inhibitors.
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Melanoma/genética , Melanoma/mortalidad , Mutación/genética , Regiones Promotoras Genéticas/genética , Telomerasa/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Melanoma/patología , Proteínas de la Membrana/genética , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
BACKGROUND: The plaque variant of trichoblastoma has been described as a solitary tumor with diffuse infiltration of the lower dermis and hypodermis, with poorly defined borders. Herein, we report a new variant of multiple centrofacial trichoblastoma. OBJECT: To describe clinical and pathological features of a new multiple kind of plaque variant of centrofacial trichoblastoma. METHODS: Case series of patients with a multiple-plaque variant of centrofacial trichoblastoma treated in our department between 2005 and 2017. We identified eight patients with the centrofacial plaque variant of trichoblastoma treated in our department from 2005 to 2017. RESULTS: The final study sample comprised 13 trichoblastomas from four patients. All patients also developed at least one basal cell carcinoma. Mohs surgery was the method of treatment in the majority of the cases of trichoblastoma and in all the cases of basal cell carcinoma. We needed between 2 and 6 stages to obtain free margins in our cases of facial plaque trichoblastomas treated by Mohs surgery. CONCLUSION: To the best of our knowledge, a multiple-plaque variant of trichoblastoma has not been described in the literature. We suggest a genetic origin of this variant of trichoblastoma and describe its remarkable infiltrative nature, with poorly defined surgical margins.
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Enfermedades del Cabello/patología , Folículo Piloso/patología , Neoplasias Cutáneas/patología , Anciano , Cara/patología , Femenino , Enfermedades del Cabello/cirugía , Humanos , Masculino , Persona de Mediana Edad , Cirugía de Mohs , Neoplasias Cutáneas/cirugíaRESUMEN
Telomere repeats at chromosomal ends, critical for genomic integrity, undergo age-dependent attrition and telomere length has been associated with different disorders including cancers. In this study, based on 1469 patients and 1158 healthy controls, we show a statistically significant (P = 6 × 10-10 ) association between increased telomere length and melanoma risk. Mendelian randomization, using 5 telomere length-associated polymorphisms, ruled out confounding factors or reverse causality and showed association between increased telomere length and melanoma risk with odds ratio of 2.66 (95% confidence interval: 2.07-3.25). Age-dependent telomere attrition was faster in melanoma cases than controls (P = .01). The carriers of a highly penetrant germline -57A>C TERT promoter mutation, in a previously reported melanoma family, had longer telomeres than the noncarriers. The mutation causes increased TERT and telomerase levels through creation of a binding motif for E-twenty six (ETS) transcription factors and the carriers develop melanoma with an early age of onset and rapid progression to metastasis. In analogy, we hypothesize that increased telomere length in melanoma patients reflects stochastic increased telomerase levels due to common genetic variation. Paradoxically, we observed shorter telomeres (P = 1 × 10-5 ) in primary tumors from unrelated melanoma patients with (121) than without (170) somatic TERT promoter mutations that similar to the germline mutation, also create binding motifs for ETS transcription factors. However, the age-dependent telomere attrition was faster in tumors with the TERT promoter mutations than in those without such mutations. Besides a robust association between increased telomere length and risk, our data show a perturbed telomere homeostasis in melanoma.
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Predisposición Genética a la Enfermedad , Melanoma , Regiones Promotoras Genéticas/genética , Telomerasa/genética , Telómero/genética , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Melanoma/epidemiología , Melanoma/genética , Persona de Mediana Edad , Mutación/genética , Adulto JovenRESUMEN
The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups.
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Ganglios Linfáticos/patología , Melanoma/patología , Neoplasias Cutáneas/patología , Anciano , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Análisis de SupervivenciaRESUMEN
The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM) and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.
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Síndrome del Nevo Displásico/patología , Melanoma/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Síndrome del Nevo Displásico/mortalidad , Síndrome del Nevo Displásico/terapia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Mutación , Fenotipo , Modelos de Riesgos Proporcionales , Receptor de Melanocortina Tipo 1/genética , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , España/epidemiología , Factores de TiempoRESUMEN
Melanoma results from a complex interplay between environmental factors and individual genetic susceptibility. Familial melanoma is attributable to predisposition genes with variable penetrance. The aim of this study was to identify differences between familial melanoma and sporadic cases in our population, based on the presence of CDKN2A mutations and MC1R variants. Comparing 107 patients with familial melanoma from 87 families (17% CDKN2A mutated) with 1,390 cases of sporadic melanomas, the former were younger and exhibited an increased prevalence of atypical naevi and squamous cell carcinoma (SCC). CDKN2A mutation carriers presented more atypical naevi, multiple melanomas, and basal cell carcinoma, while non-carriers were more likely to have light-coloured hair, atypical naevi, and SCC. MC1R variants decreased the age at diagnosis in all groups and were associated with an increased prevalence of SCC, especially in patients with familial melanoma without CDKN2A mutations. These characteristics may help to establish prevention measures targeting patients with familial melanoma in the Mediterranean area.
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Biomarcadores de Tumor/genética , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Variación Genética , Melanoma/genética , Mutación , Receptor de Melanocortina Tipo 1/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Estudios Transversales , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Análisis Mutacional de ADN , Bases de Datos Factuales , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Masculino , Melanoma/epidemiología , Melanoma/patología , Persona de Mediana Edad , Linaje , Fenotipo , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , España/epidemiologíaRESUMEN
Cutaneous angiosarcoma (AS) is an uncommon, aggressive sarcoma whose incidence is rising because of the increasing use of radiation therapy, especially in breast cancer. The few studies on the relevance of prognostic factors, such as MYC status in cutaneous AS, have reported inconclusive findings, with some authors reporting MYC amplification only in postirradiation and lymphedema-associated AS and others reporting evidence of MYC amplification in idiopathic AS. We analyzed 17 cases of cutaneous AS (6 idiopathic AS, 10 postirradiation AS, and 1 lymphedema-associated AS) treated at our institute between 2000 and 2015. Follow-up data were available in all cases. We compared the presence/absence of MYC amplification by fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) MYC overexpression in the different AS subtypes. We also investigated potential associations between MYC amplification and prognosis. MYC amplification was observed by FISH in 6 of 14 informative cases. The positive cases were all secondary AS (5 postirradiation AS and 1 lymphedema-associated AS). IHC detected MYC overexpression in 8 of 15 informative cases (7 secondary AS and 1 idiopathic AS). In conclusion, MYC amplification and MYC overexpression were detected almost exclusively in secondary AS. No associations were found between MYC amplification/overexpression and prognosis. We found MYC amplification or overexpression in a similar proportion of the patients who died and who were still alive at the end of the study. In the group of 9 patients who died, MYC was detected by FISH in 4 cases and by IHC in 5. The corresponding figures in the group of 6 patients still alive were 2 by FISH and 3 by IHC.
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Hemangiosarcoma/genética , Neoplasias Inducidas por Radiación/genética , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Amplificación de Genes , Hemangiosarcoma/mortalidad , Hemangiosarcoma/patología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patologíaRESUMEN
Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon in angiosarcomas (AS) and creates a challenging differential diagnosis with other superficial or soft tissue tumors. Herein, we report a new case of superficial AS presenting as a tumor lesion on the little finger of the right hand of a 52-year-old man. The tumor displayed CD56, chromogranin-A, and synaptophysin immunoreactivity. Tumor cells were positive for vascular markers (CD31, FLI1, ERG, D2-40, VE-cadherin, VEGR1,2, and 3), CD99, and EMA, but were negative for S100, CK (AE1/AE3), CK20, polyomavirus, and myogenic (desmin and myogenin) and melanocyte markers (melan-A and HMB45). Ki67 immunostains indicated high proliferative activity (>50%). The whole-body computed tomography did not reveal distant disease. The initial assessment considered several tumor subtypes as possible histological diagnoses, including Ewing sarcoma, Ewing-like sarcoma, Merkel cell carcinoma, and undifferentiated "small round cell sarcoma". Fluorescence in situ hybridization analysis was negative for EWSR1 translocation and molecular analysis failed to detect any EWSR1, CIC, SYT or BCOR rearrangement. As a follow-up investigation, we tested 17 cutaneous/superficial AS for neuroendocrine markers; however, only one of these showed focal CD56 and synaptophysin expression. In conclusion, the present findings indicate that neuroendocrine differentiation is a very infrequent feature in AS. We report an AS of the finger with an uncommon histological appearance and immunohistochemical profile: predominant round cell tumor proliferation and neuroendocrine differentiation. Pathologists should be aware of these potential histological and immunohistochemical pitfalls in AS.
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Carcinoma Neuroendocrino/patología , Diferenciación Celular , Hemangiosarcoma/patología , Sarcoma de Ewing/patología , Sarcoma de Células Pequeñas/patología , Neoplasias Cutáneas/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Carcinoma Neuroendocrino/química , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/cirugía , Proliferación Celular , Diagnóstico Diferencial , Dedos , Hemangiosarcoma/química , Hemangiosarcoma/genética , Hemangiosarcoma/cirugía , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sarcoma de Ewing/química , Sarcoma de Ewing/genética , Sarcoma de Células Pequeñas/química , Sarcoma de Células Pequeñas/genética , Sarcoma de Células Pequeñas/cirugía , Neoplasias Cutáneas/química , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) typically affects the dermis and subcutaneous tissue. The subcutaneous variant is rare. OBJECTIVE: We sought to characterize the subcutaneous DFSP (SC-DFSP) variant and compare it with cutaneous DFSP (C-DFSP). METHODS: This work was a retrospective study of DFSP treated in our institution. RESULTS: Of 124 cases of DFSP, 18 were SC-DFSP (14.5%). Except for the deep location, the pathologic and genetic features were indistinguishable from the C-DFSP variant. Histologically, of 18 SC-DFSP cases, 13 were classic DFSP, 3 fibrosarcomatous DFSP (FS-DFSP), 1 Bednar tumor, and 1 giant-cell fibroblastoma. All tumors expressed CD34 and the COL1A1-PDGFB fusion transcripts. In our series, higher proportions of SC-DFSP tumors (61%) than C-DFSP tumors (8.5%) were located on the head (P < .001). Of the 20 DFSP tumors on the head (16.1%), 11 were SC-DFSP and 9 were C-DFSP. In addition, half the SC-DFSP tumors affected muscle or periosteum, compared with a quarter of the C-DFSP tumors (P = .009). SC-DFSP needed a higher number of Mohs stages than did C-DFSP (P = .009). Median follow-up time was 63 months, and 2 FS-DFSP tumors recurred (1 SC-DFSP, 1 C-DFSP). LIMITATIONS: Limitations include the retrospective aspect of the study. CONCLUSIONS: Most DFSP tumors involving the head were subcutaneous and required more complex surgery. Dermatologists should be aware of this atypical presentation, especially in lesions involving the head.
Asunto(s)
Dermatofibrosarcoma/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias Cutáneas/patología , Tejido Subcutáneo , Adolescente , Adulto , Dermatofibrosarcoma/clasificación , Femenino , Neoplasias de Cabeza y Cuello/clasificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Cutáneas/clasificación , Adulto JovenRESUMEN
We describe 3 cases of multiple histiocytic cutaneous tumors that began in childhood and affected 3 members from 2 generations of the same family: a mother, a daughter and a nephew. The lesions were mostly skin-colored papules distributed symmetrically on the dorsum of the forearms and hands and on the face and thighs. There were no signs of spontaneous regression. The clinical and histopathological features were consistent with a diagnosis of hereditary progressive mucinous histiocytosis (HPMH), but phenotypic expression varied somewhat between the 3 patients. HPMH has only been described in 8 families to date, and just one of the reports included 3 well-documented cases. Our cases confirm that HPMH can affect males and expands the clinical spectrum of skin lesions in this disease.