Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Cancer Control ; 31: 10732748241251572, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751033

RESUMO

OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.


Assuntos
Melanoma , Mutação , Proteínas Proto-Oncogênicas B-raf , Humanos , Melanoma/genética , Melanoma/terapia , Melanoma/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , América Latina/epidemiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico , Guias de Prática Clínica como Assunto
2.
Ther Adv Med Oncol ; 14: 17588359221138386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506107

RESUMO

Background: A significant proportion of patients with non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICIs). Since metabolic reprogramming with increased glycolysis is a hallmark of cancer and is involved in immune evasion, we used 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) to evaluate the baseline glycolytic parameters of patients with advanced NSCLC submitted to ICIs, and assessed their predictive value. Methods: 18F-FDG PET/CT results in the 3 months before ICIs treatment were included. Maximum standardized uptake values, whole metabolic tumor volume (wMTV), and whole-body total lesion glycolysis (wTLG) were evaluated. Cutoff values for high or low glycolytic categories were determined using receiver-operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were evaluated. Patients with a complete response and a matching group with resistance to ICIs underwent immunohistochemistry analysis. An unsupervised k-means clustering model integrating programmed cell death ligand 1 (PD-L1) expression, glycolytic parameters, and ICIs therapy was performed. Results: In all, 98 patients were included. Lower baseline 18F-FDG PET/CT parameters were associated with responses to ICIs. Patients with low wMTV or wTLG had improved PFS and OS. High wTLG, strong tumor expression of glucose transporter-1, and lack of responses were significantly associated. Patients with low glycolytic parameters benefited from ICIs, regardless of chemotherapy. Conversely, those with high parameters benefited from the addition of chemotherapy. Patients with higher wTLG and lower PD-L1 were associated with progression and worse survival to ICIs monotherapy. Conclusions: Glycolytic metabolic profiles established through baseline 18F-FDG PET/CT are useful biomarkers for evaluating ICI therapy in advanced NSCLC.

3.
An. bras. dermatol ; 97(5): 583-591, Sept.-Oct. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403156

RESUMO

Abstract Background: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative ‟en face" freezing technique evaluates all peripheral and deep margins. Objective: To report the results of the ‟en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. Methods: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. Results: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative ‟en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. Study limitations: Not having a minimum follow-up time of 5 years for all patients. Conclusion: The ‟en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

4.
An Bras Dermatol ; 97(5): 583-591, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35803765

RESUMO

BACKGROUND: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative "en face" freezing technique evaluates all peripheral and deep margins. OBJECTIVE: To report the results of the "en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. METHODS: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. RESULTS: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative "en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. STUDY LIMITATIONS: Not having a minimum follow-up time of 5 years for all patients. CONCLUSION: The "en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Feminino , Secções Congeladas , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos
5.
SAGE Open Med Case Rep ; 10: 2050313X221100407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619747

RESUMO

Chromosomal rearrangements involving the c-ros oncogene 1 (ROS1) gene define a subset of non-small cell lung cancers highly sensitive to small-molecule tyrosine kinase inhibitors. However, little is known about the impact of different fusion partners on tyrosine kinase inhibitor efficacy. We herein describe a case of a 26-year-old never-smoker patient from southern Africa with metastatic lung adenocarcinoma driven by SLC12A2-ROS1 fusion, who had a pronounced and durable response to crizotinib. The present case underscores the importance of pursuing actionable alterations in patients with similar clinical and epidemiological characteristics. In addition, provides the second report of crizotinib activity against lung malignancies harboring the unique SLC12A2-ROS1 fusion and highlights the importance of a deeper understanding of molecular alterations in underrepresented subgroups of patients to tailor the decision-making in daily practice.

6.
Arch Dermatol Res ; 314(6): 563-571, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34152481

RESUMO

Facial melanoma presents itself as a brownish macula, being difficult to differentiate it from benign pigmented lesions of the face on clinical examination. Reflectance confocal microscopy (RCM) assists in diagnosing facial lesions in which dermoscopy has limitations, allowing to increase the diagnostic accuracy. The study aimed to analyze the RCM features of pigmented isolated lesions of the face for diagnosing melanoma. Also, we sought to establish the chance of a pigmented lesion on the face being a melanoma using RCM criteria. In this retrospective and prospective study, 105 clinical pigmented lesions on the face underwent RCM, and cytoarchitectural features in the epidermis, the dermo-epidermal junction (DEJ), and dermis were described. For statistical analysis, the exact chi-square test was applied to the RCM criteria. The odds ratio was estimated using univariate logistic regression. Finally, we used the multiple logistic regression method for creating a nomogram to predict the chance of a lesion being a melanoma. After univariate and multivariate logistic regression, atypical round nucleated cells within the epidermis, pagetoid spread, and follicular dendritic cells presented as statistically significant features. Then, a complex nomogram was created to give the chance of a pigmented lesion on the face being a melanoma. The presence of these three features resulted in a 98% probability for melanoma. This study allowed to estimate the diagnosis of melanoma on the face, using RCM, practicable and feasible in the daily routine, through the presence of some RCM nomogram criteria.


Assuntos
Melanoma , Neoplasias Cutâneas , Dermoscopia/métodos , Diagnóstico Diferencial , Humanos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Microscopia Confocal/métodos , Probabilidade , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
7.
Ecancermedicalscience ; 15: 1306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824629

RESUMO

Immunotherapy has recently been incorporated into the treatment guidelines for metastatic urothelial carcinoma. Nevertheless, the role of prognostic and predictive biomarkers in this setting is not completely defined. To date, PD-L1 expression and a high tumour mutational burden (TMB) seem to predict better responses to immune checkpoint inhibitors, but patients without these biomarkers may still respond to immunotherapy. There are some caveats regarding these biomarkers, such as lack of standardisation of techniques, tumour heterogeneity and other factors influencing the tumour microenvironment. Genomic signatures are other promising emerging strategies. We hereby discuss the management of a 70-year-old man with a metastatic recurrence of urothelial carcinoma within 1 year after neoadjuvant chemotherapy and radical cystectomy. Tumour next-generation sequencing showed a high TMB and a CD274 (PD-L1) amplification. The patient was treated with pembrolizumab and achieved a complete response.

8.
JCO Glob Oncol ; 7: 1141-1150, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34270331

RESUMO

PURPOSE: Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer. MATERIALS AND METHODS: We determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil. RESULTS: The TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria. CONCLUSION: The identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation.


Assuntos
Síndrome de Li-Fraumeni , Brasil , Genômica , Células Germinativas , Mutação em Linhagem Germinativa , Humanos , Síndrome de Li-Fraumeni/genética , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética
9.
An. bras. dermatol ; 95(6): 691-695, Nov.-Dec. 2020. graf
Artigo em Inglês | LILACS, Coleciona SUS | ID: biblio-1142133

RESUMO

Abstract Background: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. Objectives: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. Material and methods: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. Results: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). Study limitation: Unicentric study. Conclusion: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.


Assuntos
Humanos , Neoplasias Cutâneas/patologia , Melanoma/patologia , Prognóstico , Estados Unidos , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Metástase Linfática , Índice Mitótico , Estadiamento de Neoplasias
10.
Ecancermedicalscience ; 14: 1130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33209121

RESUMO

BACKGROUND: Tumour budding (TB) refers to loss of tumour cohesiveness and is defined as isolated cells or a cell cluster of up to four tumour cells at the microscopic analysis. The International Tumour Budding Consensus Conference (ITBCC) in 2016 proposed a scoring system to standardise the pathology evaluation of TB in colorectal cancer (CRC) as high (H), intermediate (I) and low (L) TB. OBJECTIVE: To evaluate the recurrence-free survival (RFS) of stage II CRC patients as per the ITBCC 2016 classification and associations between TB and clinical pathological features. METHODS: Cases of stage II CRC undergoing surgery with available tumour tissue underwent central pathology review for TB. Prognostic factors, retrospectively retrieved from electronic medical charts, were evaluated in univariate and multivariate Cox regression analyses for RFS (primary end point). RESULTS: Among 137 patients included, L-TB was observed in 107 (78.1%), I-TB in 21 (15.3%) and H-TB in 9 (6.6%). In a median follow-up of 69 months, the median RFS was 134 months, with 14 patients (10.2%) presenting with tumour recurrence: 10 (9.3%) with L-TB, 2 (9.5%) with I-TB and 2 (22.2%) with H-TB. Perineural invasion was more commonly seen in the H-TB group. In multivariate analysis, TB (H and I versus L; HR = 2.6; p = 0.059) and not receiving adjuvant chemotherapy (HR 3.7; p = 0.020) were independently associated with RFS. Adjuvant chemotherapy was associated longer RFS (HR = 3.7; p = 0.022). CONCLUSION: In this series of Western patients, TB grade was associated with perineural invasion and increased risk of disease relapse.

11.
J Immunother Cancer ; 8(2)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33203661

RESUMO

BACKGROUND: To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies. METHODS: Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set. RESULTS: Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders. CONCLUSION: Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM.


Assuntos
Biomarcadores Tumorais/metabolismo , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Melanoma/imunologia , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
An Bras Dermatol ; 95(6): 691-695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33008658

RESUMO

BACKGROUND: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. OBJECTIVES: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. MATERIAL AND METHODS: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. RESULTS: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). STUDY LIMITATION: Unicentric study. CONCLUSION: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Metástase Linfática , Melanoma/patologia , Índice Mitótico , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Estados Unidos
13.
Cancers (Basel) ; 12(7)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659967

RESUMO

Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir-Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.

14.
Ecancermedicalscience ; 14: 1069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32728385

RESUMO

BACKGROUND: Mechanisms of resistance have been described during disease progression (PD) for patients under treatment with anti-EGFR plus chemotherapy (CT). The aim of our study was to evaluate efficacy of anti-EGFR rechallenge (ReCH) and reintroduction (ReIn) in metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: This is a retrospective analysis of patients with mCRC that previously received anti-EGFR + CT and interrupted therapy due to PD in the ReCH group and other reasons in the ReIn group. We aimed to describe progression-free survival (PFS), overall survival (OS) and response rate (RR) after re-exposure and to evaluate prognostic factors associated with PFS. RESULTS: Sixty-eight patients met the inclusion criteria. The median follow-up after re-exposure was 39.3 months. ReCH was adopted in 25% and ReIn in 75%. The median anti-EGFR free interval was at 10.5 months. At re-exposure, the main CT regimen was FOLFIRI in 58.8%. Cetuximab and Panitumumab were used in 59 and 9 patients, respectively. mPFS for ReCH and ReIn was 3.3 × 8.4 months, respectively (p 0.001). The objective response rate for ReCH and ReIn was 18% and 52%, respectively. In univariate analysis, adverse prognostic factors related to PFS were: stable disease or PD at first anti-EGFR exposure (HR: 2.12, CI:1.20-3.74; p = 0.009); ReCH (HR: 3.44, CI:1.88-6.29, p < 0.0001); rechallenge at fourth or later lines (HR: 2.51, CI:1.49-4.23, p = 0.001); panitumumab use (HR: 2.26 CI:1.18-5.54, p = 0.017). In the multivariate model, only ReCH remained statistically significant (HR = 2.63, CI: 1.14-6.03, p = 0.022). CONCLUSION: In our analysis, ReCH resulted in short PFS and low RR. However, reintroduction of anti-EGFR plus CT before complete resistance arose resulted in prolonged PFS. These data could be clinically useful to guide a treatment break due to side effects or patient decisions. Our data should be confirmed by larger and prospective trials.

15.
Front Oncol ; 10: 1068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714871

RESUMO

Objectives: Approximately 60% of lung adenocarcinomas (LAs) carry mutations that can guide treatment with tyrosine-kinase inhibitors (TKI) and other targeted therapies. Data on activating mutations in EGFR and other tyrosine-kinase receptor (TKR) genes in highly admixed populations, such as that of Brazil, are scarce. In this study, we comprehensively analyzed the actionable alteration profile of LA in Brazilian patients. Materials and Methods: EGFR driver mutation data were collected from a large Brazilian LA cohort covering an 8-year period of molecular testing in a single institution. Tests were performed using three distinct methods, and demographic and histopathological data were analyzed. For a subset of patients, driver mutations in KRAS, NRAS, and BRAF and gene fusions involving TKR genes (before TKI treatment) and EGFR T790M (after TKI treatment) were assessed. Results: EGFR mutations were detected in 25% of 1,316 LAs evaluated, with exon 19 deletions and exon 21 L858R TKI sensitizing mutations representing 72.5% of all mutations. Mutation rates were higher in women and non-smokers (p < 0.001). Next-generation sequencing was very sensitive, with a lower rate of inconclusive results compared with Sanger sequencing and pyrosequencing. EGFR/RAS/BRAF hotspot gene panels were applied in 495 LA cases and detected oncogenic mutations in 51.3% of samples, most frequently in EGFR (22.4%) and KRAS (26.9%). In subgroups of 36 and 35 patients, gene fusions were detected in 11.1% of tumors and EGFR T790M resistance mutations were detected in 59% of plasma samples from patients previously treated with TKI, respectively. Conclusion: This report provides the first comprehensive actionable alteration portrait of LA in Brazil. The high rate of actionable alterations in EGFR and other driver genes in LA reinforces the need to incorporate TKI guided by molecular diagnostics into clinical routines for patients in both public and private healthcare systems.

16.
An Bras Dermatol ; 94(6): 747-750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31789261

RESUMO

Melanoacanthoma is a rare variant of seborrheic keratosis, which is notable for dark pigmentation and fast radial growth, making it difficult to distinguish from melanoma. Histologically, it is characterized by proliferation of keratinocytes and dendritic melanocytes. The authors report a scalp lesion, fast growing, suspected by dermoscopy and confocal microscopy examination, with dendritic cells distributed throughout the lesion. Based on these findings, it was not possible to classify this lesion as clearly benign, so it was excised. Histopathologic evaluation and immunostain were consistent with melanoacanthoma.


Assuntos
Acantoma/patologia , Ceratose Seborreica/patologia , Dermatoses do Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Idoso , Células Dendríticas/patologia , Dermoscopia , Humanos , Masculino , Melanócitos/patologia , Microscopia Confocal/métodos
17.
BMC Cancer ; 19(1): 1077, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706282

RESUMO

BACKGROUND: BRCA1 associated-protein 1 (BAP1) tumor predisposition syndrome is associated with an increased risk for malignant mesotheliomas, uveal and cutaneous melanomas, renal cell carcinomas, and singular cutaneous lesions. The latter are referred to as BAP1-inactivated melanocytic tumors (BIMTs). When multiple BIMTs manifest, they are considered potential markers of germline BAP1 mutations. CASE PRESENTATION: Here, we report a novel pathogenic BAP1 germline variant in a family with a history of BIMTs, cutaneous melanomas, and mesotheliomas. We also describe singular pathological aspects of the patient's BIMT lesions and their correlation with dermoscopic and reflectance confocal microscopy findings. CONCLUSIONS: This knowledge is crucial for the recognition of BIMTs by dermatologists and pathologists, allowing the determination of appropriate management for high-risk patients, such as genetic investigations and screening for potentially aggressive tumors.


Assuntos
Melanoma/genética , Melanoma/patologia , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermoscopia/métodos , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Masculino , Microscopia Confocal/métodos , Pessoa de Meia-Idade , Linhagem , Prognóstico , Melanoma Maligno Cutâneo
18.
An. bras. dermatol ; 94(6): 747-750, Nov.-Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1054880

RESUMO

Abstract Melanoacanthoma is a rare variant of seborrheic keratosis, which is notable for dark pigmentation and fast radial growth, making it difficult to distinguish from melanoma. Histologically, it is characterized by proliferation of keratinocytes and dendritic melanocytes. The authors report a scalp lesion, fast growing, suspected by dermoscopy and confocal microscopy examination, with dendritic cells distributed throughout the lesion. Based on these findings, it was not possible to classify this lesion as clearly benign, so it was excised. Histopathologic evaluation and immunostain were consistent with melanoacanthoma.


Assuntos
Humanos , Masculino , Idoso , Dermatoses do Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Ceratose Seborreica/patologia , Acantoma/patologia , Células Dendríticas/patologia , Microscopia Confocal/métodos , Dermoscopia , Melanócitos/patologia
19.
An Bras Dermatol ; 94(4): 452-454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644620

RESUMO

Proliferating trichilemmal cyst is an uncommon neoplasm arising from the follicular isthmus, whose histopathological hallmark is the presence of trichilemmal keratinization. We describe a case of proliferating trichilemmal cyst in a 57-year-old woman with a broad clinical, radiological, macroscopic and microscopic correlation.


Assuntos
Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/patologia , Couro Cabeludo/diagnóstico por imagem , Couro Cabeludo/patologia , Biópsia por Agulha Fina , Diagnóstico Diferencial , Cisto Epidérmico/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Couro Cabeludo/cirurgia , Ultrassonografia
20.
An. bras. dermatol ; 94(4): 452-454, July-Aug. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1038305

RESUMO

Abstract: Proliferating trichilemmal cyst is an uncommon neoplasm arising from the follicular isthmus, whose histopathological hallmark is the presence of trichilemmal keratinization. We describe a case of proliferating trichilemmal cyst in a 57-year-old woman with a broad clinical, radiological, macroscopic and microscopic correlation.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Couro Cabeludo/patologia , Couro Cabeludo/diagnóstico por imagem , Cisto Epidérmico/patologia , Cisto Epidérmico/diagnóstico por imagem , Couro Cabeludo/cirurgia , Ultrassonografia , Biópsia por Agulha Fina , Diagnóstico Diferencial , Cisto Epidérmico/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA