RESUMO
We describe a female toddler with rectal bleeding from extensive colonic polyposis, and diagnosed with familial adenomatous polyposis. She has epilepsy from infancy attributed to focal cortical dysplasia. Hepatoblastoma was diagnosed at 13 months of age. Germline testing detected a pathogenic APC (adenomatous polyposis coli gene) variant. We discuss the anecdotal management of this case, including the clinical utility of genetic confirmation. We review the genotype-phenotype correlation of the APC mutational spectrum, and the existing evidence supporting the hypothesis that cortical dysplasia is part of the APC-related spectrum.
Assuntos
Polipose Adenomatosa do Colo , Neoplasias Hepáticas , Malformações do Desenvolvimento Cortical , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/genética , Feminino , Genes APC , Estudos de Associação Genética , Mutação em Linhagem Germinativa , Humanos , Neoplasias Hepáticas/genética , Malformações do Desenvolvimento Cortical/genéticaRESUMO
BACKGROUND: Lung cancer is a major cause of death in New Zealand. In recent years, targeted therapies have improved outcomes. AIM: To determine the uptake of anaplastic lymphoma kinase (ALK) testing, and the prevalence, demographic profile and outcomes of ALK-positive non-small-cell lung cancer (NSCLC), in New Zealand, where no national ALK-testing guidelines or subsidised ALK tyrosine kinase inhibitor (TKI) therapies are available. METHODS: A population-based observational study reviewed databases to identify patients presenting with non-squamous NSCLC over 6.5 years in northern New Zealand. We report the proportion tested for ALK gene rearrangements and the results. NSCLC samples tested by fluorescence in situ hybridisation were retested by next generation sequencing and ALK immunohistochemistry. A survival analysis compared ALK-positive patients treated or not treated with ALK TKI therapy. RESULTS: From a total of 3130 patients diagnosed with non-squamous NSCLC, 407 (13%) were tested for ALK gene rearrangements, and patient selection was variable and inequitable. Among those tested, 34 (8.4%) had ALK-positive NSCLC. ALK-positive disease was more prevalent in younger versus older patients, non-smokers versus smokers and in Maori, Pacific or Asian ethnic groups than in New Zealand Europeans. Fluorescence in situ hybridisation, ALK immunohistochemistry and next generation sequencing showed broad concordance for detecting ALK-positive disease under local testing conditions. Among patients with ALK-positive metastatic NSCLC, those treated with ALK TKI survived markedly longer than those not treated with ALK TKI (median overall survival 5.12 vs 0.55 years). CONCLUSION: Lung cancer outcomes in New Zealand may be improved by providing national guidelines and funding policy for ALK testing and access to subsidised ALK TKI therapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Detecção Precoce de Câncer , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Nova Zelândia/epidemiologia , Inibidores de Proteínas Quinases , Receptores Proteína Tirosina Quinases/genéticaRESUMO
Desmoid fibromatosis is a myofibroblastic neoplasm of intermediate biologic potential, which has a strong predilection for local recurrence but does not metastasize. Arranged in long, sweeping fascicles with infiltrative borders, desmoid fibromatosis typically consists of uniform, bland myofibroblastic spindle cells that harbor mutation of CTNNB1 (or less often APC). In this report, we present a remarkable case of desmoid fibromatosis associated with striking nuclear pleomorphism. We hypothesize that this striking pleomorphism is due to a germline TP53 mutation, a finding first suspected due to strong and diffuse p53 staining by immunohistochemistry and subsequently confirmed by molecular testing. The combination of the pleomorphism and TP53 mutation in desmoid fibromatosis represents a novel finding unreported in the literature.
Assuntos
Fibromatose Agressiva , Humanos , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/genética , Proteína Supressora de Tumor p53/genética , Mutação , Mutação em Linhagem Germinativa , Imuno-Histoquímica , beta Catenina/genéticaRESUMO
Haemophagocytic lymphohistiocytosis (HLH) is an uncommon disorder of histiocyte function which presents with fever, cytopaenias and end-organ dysfunction. We report the case of a 62-year-old man with acute liver dysfunction as an initial presentation of HLH.
Assuntos
Hepatopatias/diagnóstico , Fígado/patologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Medula Óssea/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report a case of Epstein-Barr-virus-(EBV-) positive primary cutaneous plasmablastic lymphoma in a human-immunodeficiency-virus-(HIV-) negative, immunocompetent 62-year-old female patient. We postulate that her lymphoma development is due to the longstanding use of pyrimethamine for essential thrombocythemia. This has never been described in the literature.