RESUMO
Histopathologic assessment of melanocytic neoplasms is the current gold standard of diagnosis. However, there are well recognized limitations including inter-observer diagnostic discordance. This study aimed to determine if integrating dermoscopy with histopathology of melanocytic neoplasms impacts diagnosis and improves inter-observer agreement. We conducted a prospective cohort study in a pigmented lesion clinic. Consecutive melanocytic lesions were identified for biopsy based on atypical gross or dermoscopic features. Standardized immunohistochemistry and levels were ordered on each specimen. The cases were randomized. Three dermatopathologists blinded to the clinical impression assessed each lesion. The cases were then re-randomized and re-assessed with addition of gross clinical and dermoscopic images. Inter-rater reliability (IRR) using Fleiss' kappa statistic revealed an increase from 0.447 without to 0.496 with dermoscopy amongst all dermatopathologists. The kappa increased from 0.495 before to 0.511 with dermoscopy in separating high-grade atypia or melanoma from moderate atypia or less. In 16 of 136 cases, at least 2 of 3 dermatopathologists favored a diagnosis of melanoma only after dermoscopy. In total, the consensus grade of atypia changed in 24.3% (33/ 136) of cases thereby representing changes to excisional margins and patient follow up. This study is limited by the cohort size. Dermoscopy significantly impacts diagnosis and improves identification of early melanomas in high risk populations and improves inter-observer agreement.
Assuntos
Dermoscopia/estatística & dados numéricos , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Patologistas/estatística & dados numéricos , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Biópsia/estatística & dados numéricos , Consenso , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Margens de Excisão , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Nevo Pigmentado/patologia , Nevo Pigmentado/cirurgia , Variações Dependentes do Observador , Patologistas/normas , Estudos Prospectivos , Reprodutibilidade dos Testes , Pele/diagnóstico por imagem , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adulto JovemRESUMO
BACKGROUND: Repigmentation at previous biopsy sites pose a significant diagnostic dilemma given clinical and histologic similarities between recurrent nevi and locally recurrent melanoma. Though common in melanoma, the role of TERT promoter mutations (TPMs) in recurrent nevi is unknown. OBJECTIVE: We investigated the role of TPMs in recurrent nevi and whether the presence of hotspot TPM distinguishes recurrent nevi from locally recurrent melanoma. We also characterized clinical and histologic features differentiating these lesions. METHODS: We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and melanoma and nevus controls to determine TPM status. We also assessed clinical and histologic features of the recurrent groups. RESULTS: Hotspot TPMs were more common in recurrent melanomas than recurrent nevi (P = .008). Recurrent melanomas were more likely to have solar elastosis (P = .0047), multilayering of melanocytes in the epidermis (P = .0221), adnexal involvement (P = .0069), and epidermal consumption (P = .0204). Recurrent nevi had intra-epidermal atypia limited to the area above the scar (P < .0001) and occurred earlier after the original biopsy (P < .0008). Solar elastosis, months to recurrence, and hotspot TPMs were independently associated with recurrent melanoma in multivariate analysis. LIMITATIONS: This was a retrospective study. CONCLUSION: Hotspot TPMs are significantly more frequent in recurrent melanomas and could serve as a diagnostic clue in histologically ambiguous cases.
Assuntos
Melanoma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Nevo Pigmentado/diagnóstico , Regiões Promotoras Genéticas , Neoplasias Cutâneas/diagnóstico , Telomerase/genética , Adulto , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fatores de TempoRESUMO
BACKGROUND: BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) are often the earliest sign of the BAP1 tumor predisposition syndrome. Identification of BIMTs and selection of patients for germline testing affect the lives of patients with germline BAP1 mutations. OBJECTIVE: To describe the spectrum of histomorphologic findings in BAP1-inactivated melanocytic lesions to improve their recognition. We determined the frequency of sporadic versus germline cases in our cohort, assessing whether any features were statistically linked to germline status. METHODS: Histomorphologic features of BAP1-inactivated melanocytic lesions were analyzed by comparing cases with germline mutations with those with unknown or negative status. Available clinical follow-up data were reported. RESULTS: The histomorphologic spectrum of BAP1-inactivated melanocytic lesions is broad; it includes cases with spitzoid cytomorphology (69%), smaller epithelioid cells without spitzoid features (31%), and rhabdoid cytologic features (58%). BIMTs from patients with germline mutations were statistically more likely to have an extensive junctional component of BAP1-inactivated melanocytes (P = .0177). All 11 patients with suspected or confirmed germline mutations had a history of cutaneous melanoma or multiple BIMTs. LIMITATIONS: The unknown germline status of 77 patients. CONCLUSION: Approximately 12% of patients with BIMTs have germline mutations. Extensive junctional involvement in a BIMT and a personal history of melanoma or previous BIMT may be additional indications for germline testing.
Assuntos
Testes Genéticos , Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Nevo Pigmentado/genética , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adulto , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Anamnese , Melanoma/metabolismo , Melanoma/patologia , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Primárias Múltiplas/patologia , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patologia , Seleção de Pacientes , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismoRESUMO
Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.
Assuntos
Melanoma/patologia , Nevo/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Luz Solar/efeitos adversos , Adulto , Idoso , Variações do Número de Cópias de DNA/genética , Análise Mutacional de DNA , Feminino , Pé/patologia , Genes Supressores de Tumor , Mãos/patologia , Humanos , Masculino , Melanoma/etiologia , Melanoma/genética , Pessoa de Meia-Idade , Mutação , Nevo/etiologia , Nevo/genética , Oncogenes/genética , Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genéticaRESUMO
BACKGROUND: Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. OBJECTIVE: We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. METHODS: Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. RESULTS: Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007). LIMITATIONS: This study was retrospective. CONCLUSION: Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma.
Assuntos
Dermoscopia/métodos , Melanoma/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Biópsia por Agulha , Estudos de Casos e Controles , Diagnóstico Diferencial , Síndrome do Nevo Displásico/diagnóstico , Síndrome do Nevo Displásico/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanócitos/patologia , Melanoma/diagnóstico , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo Pigmentado/diagnóstico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnósticoRESUMO
Paragangliomas are rare neoplasms that arise from chromaffin cells of the sympathetic and parasympathetic nervous system. These tumors are often cured by surgical resection but the risk for metastatic disease exists, particularly for extra-adrenal paragangliomas. The behavior of these tumors is unpredictable, and clinical and histopathological features associated with malignancy have not been determined. The most common sites of metastases include local and distant lymph nodes, bone, liver, and lung. Cutaneous metastases are exceedingly rare with only 2 reported cases, both of which presented on the scalp. Here we describe a 78-year-old woman with cutaneous metastatic paraganglioma presenting as a forehead nodule, which developed 15 years after her initial diagnosis of paraganglioma.
Assuntos
Paraganglioma Extrassuprarrenal/secundário , Neoplasias Retroperitoneais/patologia , Neoplasias Cutâneas/patologia , Idoso , Neoplasias Ósseas/patologia , Feminino , HumanosRESUMO
Importance: Patients with germline mutations in BAP1 may develop several flesh-colored melanocytic BAP1-mutated atypical intradermal tumors (MBAITs). These tumors generally develop earlier than other BAP1-associated tumors, highlighting an important role for dermatologists in identifying and screening patients with a history suggestive of a germline mutation. Objective: To describe 8 new families with germline mutations in BAP1 and provide a comprehensive review of reported cases. Design, Settings and Participants: Patients were identified in an outpatient dermatology clinical setting over a 6-month period (10 mutation carriers from 8 families) and through a literature review using PubMed (205 patients). Exposures: Mutations were identified through next-generation sequencing of saliva or blood samples, and RNA was extracted from fibroblasts cultured from a patient with an intronic variant to determine the impact of the mutation on the coding sequence. Main Outcomes and Measures: All 215 patients were assessed for personal and/or family history and genotype. These findings were compiled and assessed for any association between genotype and phenotype. Results: Overall, this study included 215 patients (108 women, 91 men, and 16 gender unspecified; median [range] age, 46.5 [10.0-79.0] years). Nine of the 10 patients who were identified in the outpatient dermatology setting were found to have MBAITs on clinical examination. Forty of 53 patients (75%) identified in the literature review who underwent total-body skin examinations (TBSE) were found to have MBAITs, suggesting a high penetrance in patients who have undergone TBSE. The most prevalent malignancies among BAP1 mutation carriers were uveal melanoma (n = 60 [28%]), mesothelioma (n = 48 [22%]), cutaneous melanoma (n = 38 [18%]), and renal cell carcinoma (n = 20 [9%]). A total of 71 unique mutations in BAP1 have been reported. Conclusions and Relevance: Our results indicate that germline mutations in both coding and noncoding regions throughout the BAP1 gene can impair protein function, leading to an increased risk for several associated malignancies. Four of the 8 probands we present had no history of BAP1-associated malignancies and were assessed for germline mutations when found to have MBAITs on dermatologic examination. Dermatologists can identify patients with a high likelihood of the BAP1 cancer syndrome through personal and family history and TBSE for the presence of possible MBAITs.
Assuntos
Mutação em Linhagem Germinativa , Melanoma/patologia , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Feminino , Genótipo , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Melanoma/epidemiologia , Melanoma/genética , Mesotelioma/epidemiologia , Mesotelioma/genética , Mesotelioma/patologia , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/genética , Adulto JovemRESUMO
The management of pediatric and adolescent patients with pure aortic valve regurgitation remains challenging and controversial (Christos et al., Eur J Cardiothorac Surg 17:125-133, 2000; Gersony and Sommerville, ACC Curr J Rev 31:97-98, 2000; Hasaniya et al., J Thorac Cardiovasc Surg 127:970-974, 2004; Sabet et al., Mayo Clin 74:14-26, 1999; Tweddell et al., J Thorac Cardiovasc Surg 129:551-558, 2005). We evaluated pediatric and young adult patients who underwent aortic valve replacement (AVR) primarily for aortic regurgitation in an effort to identify preoperative echocardiographic variables that are predictive of left ventricular (LV) recovery following AVR. Twenty-one patients with severe aortic valve regurgitation who underwent AVR were identified. Retrospective chart review for each patient was performed and transthoracic echocardiograms prior to and 6-months after AVR were analyzed. Improvement in LV size based on preoperative LV end-systolic dimension index when compared to 6-months post-AVR was observed in 68% of the patients. Patients with persistent dilation of their left ventricles had a greater preoperative LV end-systolic dimension index (p ≤ 0.05), a greater preoperative LV end-systolic dimension z-score (p ≤ 0.002), and a lower preoperative ejection fraction (EF) (p ≤ 0.001). A similar trend was present between the two cohorts in regards to LV end-diastolic parameters (LV end-diastolic dimension index and z-score), with patients with abnormal LV size at 6-month follow-up having larger preoperative dimensions. Increasing LV systolic dimensions and declining EF appear to be predictors of poor LV recovery following AVR in pediatric and young adult patients. LV end-systolic indices appear to be more predictive than LV end-diastolic indices. AVR should be performed prior to severe LV enlargement defined as an LV end-systolic dimension z-score >4.5.
Assuntos
Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Remodelação Ventricular/fisiologia , Adolescente , Fatores Etários , Análise de Variância , Criança , Pré-Escolar , Estudos de Coortes , Ecocardiografia Doppler/métodos , Feminino , Seguimentos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Hospitais Pediátricos , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Cuidados Pós-Operatórios/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Volume Sistólico , Resultado do Tratamento , Adulto JovemRESUMO
Lichen planus is an inflammatory dermatosis of unknown origin that is relatively uncommon in children. Demographic data for lichen planus of children in the United States are lacking, with most large case reports originating from India, Kuwait, Mexico, and the United Kingdom. We hypothesized that a greater proportion of our pediatric lichen planus patients were African American, an observation not previously documented. A retrospective chart review was performed to investigate characteristics of our pediatric lichen planus patients. The ethnicity of the lichen planus patients was compared with the data for our general patient population. The proportion of African American patients in each group was compared using the chi-squared test. We report 36 children (female to male ratio 2:1) who presented with lichen planus to the pediatric dermatology clinic at Children's Hospital of Wisconsin. Twenty-six (72%) of these patients were African American (OR 9.63, p < 0.0001). A personal or family history of autoimmune disease was present in six (17%) patients. Although there has been no reported racial predominance of lichen planus, we observed lichen planus to occur more commonly in African American children. Interestingly, the incidence of autoimmune disease was higher than has previously been reported. Future studies will confirm or refute these observations and advance our understanding of potential genetic or environmental risk factors for the development of lichen planus.