RESUMEN
Reed Syndrome, or hereditary leiomyomatosis and renal cell carcinoma syndrome, is a rare, autosomal dominant genetic condition that predisposes individuals to a triad of cutaneous leiomyomas, uterine leiomyomas and renal cell carcinoma. Cutaneous leiomyomas are often the first manifestation of the syndrome, occurring in 76% of patients and average 26 in number. We present a case of a 47 year old female with Reed Syndrome with an unusually extensive cutaneous burden, with a total of 361 cutaneous lesions, far above the average reported number of 26. Due to the extent of her cutaneous burden, painful nature of the lesions and failure to respond to standard therapies, she was referred for fully ablative Erbium:Yag laser resurfacing therapy. The use of fully ablative Erbium:YAG laser resurfacing therapy for treatment of cutaneous leiomyomas has not been reported in the literature to date. One year following laser therapy, the treatment area not only began to repigment, but there was also no evidence of cutaneous leiomyomas recurrence or associated pain. Given the effectiveness of this unique therapy, fully ablative Erbium:YAG laser resurfacing should be kept in mind as a treatment option for both cosmetic and symptomatic cutaneous leiomyomas.
RESUMEN
Dermal melanocytosis refers to a spectrum of benign melanocytic proliferations that includes Mongolian spot, nevus of Ota and nevus of Ito. These lesions most commonly occur in persons of Asian or African descent and are often present at birth or develop during childhood. Very rarely, dermal melanocytoses undergo malignant transformation. There have been only 13 reports in the literature of primary cutaneous melanoma arising in dermal melanocytoses. We report a case of a Chinese woman with melanoma arising in a congenital nevus of Ito. We performed targeted next-generation sequencing of the tumor which revealed mutations of GNAQ and BAP1, suggesting that alterations in these two genes led to malignant transformation of the nevus of Ito. We also provide a summary of reports in the literature regarding primary cutaneous melanoma arising in the context of dermal melanocytosis.
Asunto(s)
Transformación Celular Neoplásica/genética , Melanoma/genética , Mutación , Nevo Pigmentado/genética , Neoplasias Cutáneas/genética , Adolescente , Adulto , Anciano , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Melanocitos/patología , Melanoma/patología , Persona de Mediana Edad , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Adulto Joven , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: The purposes of this study were 1) to determine the impact of primary tumor-related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC). METHODS: An institutional review board-approved, retrospective review of patients with MCC treated between 1988 and 2011 at a single center was performed. Patients were categorized into 5 groups: 1) negative SLN, 2) positive SLN, 3) clinically node-negative but SLN biopsy not performed, 4) regional nodal disease without a known primary tumor, and 5) primary MCC with synchronous clinically evident regional nodal disease. Factors predictive of the SLN status were analyzed with logistic regressions, and overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox models and competing risk models assuming proportional hazards, respectively. RESULTS: Three hundred seventy-five patients were analyzed, and 70% were male; the median age was 75 years. The median tumor diameter was 1.5 cm (range, 0.2-12.5 cm), and the median tumor depth was 4.8 mm (range, 0.3-45.0 mm). One hundred ninety-one patients underwent SLN biopsy, and 59 (31%) were SLN-positive. Increasing primary tumor diameter and increasing tumor depth were associated with SLN positivity (P = .007 and P = .017, respectively). Age and sex were not associated with the SLN status. Immunosuppression, increasing tumor diameter, and increasing tumor depth were associated with worse OS (P = .007, P = .003, and P = .025, respectively). DSS differed significantly by group and was best for patients with a negative SLN and worst for those with primary MCC and synchronous clinically evident nodal disease (P = .018). CONCLUSION: For patients with MCC, increasing primary tumor diameter and increasing tumor depth are independently predictive of a positive SLN, worse OS, and worse DSS. Tumor depth should be routinely reported when primary MCC specimens are being evaluated histopathologically.
Asunto(s)
Carcinoma de Células de Merkel/patología , Neoplasias Cutáneas/patología , Anciano , Carcinoma de Células de Merkel/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/patología , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/mortalidadRESUMEN
The field of cutaneous oncology is exploding with innovative treatment options, specifically in the field of targeted therapy. These advances offer new hope to select patients with high risk skin cancers. Here we provide a two part series reviewing targeted therapy for non-melanoma skin cancer. We begin our discussion with basal cell carcinoma, moving beyond the first-in-class hedgehog inhibitors and highlighting promising clinical trials.
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Antineoplásicos/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Ensayos Clínicos como Asunto , Dermatología/tendencias , Proteínas Hedgehog/antagonistas & inhibidores , Humanos , Terapia Molecular Dirigida , Neoplasias Cutáneas/genéticaRESUMEN
The field of cutaneous oncology is exploding with innovative treatment options, specifically in the field of targeted therapy. These advances offer new hope to select patients with high risk skin cancers. In part two of our series on targeted therapy for skin cancer, we focus our attention on squamous cell carcinoma. We begin with the epidermal growth factor receptor inhibitors and branch out into newer areas of active research.
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Antineoplásicos/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Ensayos Clínicos como Asunto , Dermatología/tendencias , Factor de Crecimiento Epidérmico/antagonistas & inhibidores , Humanos , Terapia Molecular Dirigida , Neoplasias Cutáneas/genéticaRESUMEN
BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) for desmoplastic melanoma (DM) is debated. We describe a large single-institution experience with SLNB for DM to determine clinicopathologic factors predictive of SLN metastasis. METHODS: Retrospective review identified 205 patients with DM who underwent SLNB from 1992 to 2010. Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS: Median age was 66 years, and 69 % of patients were male. Median Breslow thickness was 3.7 mm. In 128 cases (62 %), histologic subtype data was available; 61 cases (47.7 %) were mixed and 67 cases (52.3 %) were pure DM. A positive SLN was found in 28 cases (13.7 %); 24.6 % of mixed and 9 % of pure DM had SLN metastases. Multivariable analysis demonstrated that after controlling for age, histologic subtype correlated with SLN status [odds ratio: 3.0 for mixed vs pure, 95 % confidence interval: 1.1-8.7; p < .05]. Completion lymph node dissection was performed in 24 of 28 positive SLN patients with 16.7 % of cases having additional nodal disease. After a median follow-up of 6.3 years, 38 patients developed recurrence and 61 patients died. Positive SLN patients had a significantly higher risk of melanoma-related death compared with negative SLN patients (p = .01). CONCLUSIONS: The overall risk for SLN metastasis for DM is 13.7 % and is significantly higher for mixed (24.6 %) compared with pure (9.0 %) DM. We believe that these rates are sufficient to justify consideration of SLNB for both histologic variants, especially since detection of SLN disease appears to predict a higher risk for melanoma-related death.
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Ganglios Linfáticos/patología , Melanoma/secundario , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Intervalos de Confianza , Supervivencia sin Enfermedad , Reacciones Falso Negativas , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Oportunidad Relativa , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. METHODS: After institutional review board approval, our institutional database spanning the years 1998-2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. RESULTS: From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. CONCLUSIONS: Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients.
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Carcinoma de Células de Merkel/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Primarias Desconocidas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/mortalidad , Carcinoma de Células de Merkel/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Neoplasias Primarias Desconocidas/mortalidad , Neoplasias Primarias Desconocidas/terapia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
This article presents a nongeneticist's guide to understanding the genetics of Parkinson disease (PD), including clinical diagnostic criteria, differential diagnoses, symptom management, when to suspect a hereditary factor, a summary of autosomal dominant and recessive PD genes, and proposed algorithm for genetic testing. There is increasing availability of genetic testing for PD but there are few recommendations on how these tests should be used in clinical practice. This article guides clinicians on the overall management of patients with PD, with emphasis on determining which patients should have genetic testing and how to interpret the results.
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Pruebas Genéticas/métodos , Enfermedad de Parkinson , Algoritmos , Manejo de la Enfermedad , Predisposición Genética a la Enfermedad , Humanos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapiaAsunto(s)
Carcinoma Basocelular/metabolismo , Proteínas Hedgehog/antagonistas & inhibidores , Proteínas Hedgehog/metabolismo , Transducción de Señal , Neoplasias Cutáneas/metabolismo , Anilidas/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Humanos , Terapia Molecular Dirigida , Piridinas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológicoAsunto(s)
Dermatología/educación , Educación de Pregrado en Medicina/métodos , Lupus Eritematoso Cutáneo/clasificación , Lupus Eritematoso Sistémico/clasificación , Estudiantes de Medicina , Terminología como Asunto , Humanos , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Estados UnidosAsunto(s)
Competencia Clínica , Dermatología/educación , Internado y Residencia/organización & administración , Tamizaje Masivo/organización & administración , Rol del Médico , Neoplasias Cutáneas/diagnóstico , Humanos , Examen Físico/métodos , Relaciones Médico-Paciente , Neoplasias Cutáneas/prevención & controlRESUMEN
BACKGROUND: Angiogenesis and lymphangiogenesis are important in the progression of melanoma. We investigated associations between genetic variants in these pathways with sentinel lymph node (SLN) metastasis and mortality in 2 independent series of patients with melanoma. METHODS: Participants at Moffitt Cancer Center were 552 patients, all Caucasian, with primary cutaneous melanoma referred for SLN biopsy. A total of 177 patients had SLN metastasis, among whom 60 died from melanoma. Associations between 238 single-nucleotide polymorphisms (SNP) in 26 genes and SLN metastasis were estimated as ORs and 95% confidence intervals (CI) using logistic regression. Competing risk regression was used to estimate HRs and 95% CI for each SNP and melanoma-specific mortality. We attempted to replicate significant findings using data from a genome-wide association study comprising 1,115 patients with melanoma who were referred for SLN biopsy from MD Anderson Cancer Center (MDACC), among whom 189 patients had SLN metastasis and 92 patients died from melanoma. RESULTS: In the Moffitt dataset, we observed significant associations in 18 SNPs with SLN metastasis and 17 SNPs with mortality. Multiple SNPs in COL18A1, EGF receptor (EGFR), FLT1, interleukin (IL)-10, platelet-derived growth factor D (PDGFD), PIK3CA, and toll-like receptor (TLR)-3 were associated with the risk of SLN metastasis and/or patient mortality. The MDACC data set replicated an association between mortality and rs2220377 in PDGFD. Furthermore, in a meta-analysis, 3 additional SNPs were significantly associated with SLN metastasis (EGFR rs723526 and TLR3 rs3775292) and melanoma-specific death (TLR3 rs7668666). CONCLUSIONS: These findings suggest that genetic variation in angiogenesis and lymphangiogenesis contributes to regional nodal metastasis and progression of melanoma. IMPACT: Additional research attempting to replicate these results is warranted.