RESUMO
Understanding the pathology of familial pancreatic carcinoma may provide important insights into pancreatic tumorigenesis. We now describe in detail the pancreatic pathology of an autosomal dominant pancreatic carcinoma kindred with distinct clinical, genetic, and pathologic manifestations differing from all other reported forms of sporadic or familial pancreatic neoplasia. Affected individuals develop a prodrome of diabetes mellitus, pancreatic exocrine insufficiency, and characteristic pancreatic imaging abnormalities. Eleven family members have undergone total pancreatectomy, revealing a unique and characteristic fibrocystic, lobulocentric pancreatic atrophy. This was patchy to diffuse in distribution and was invariably associated with a nesidioblastosis-like endocrine cell hyperplasia. All but one resected pancreas demonstrated glandular epithelial dysplasia: 10 had low-grade dysplasia (pancreatic intraductal neoplasia grade II of III or PanIN II) and seven also had high-grade dysplasia (pancreatic intraductal neoplasia grade III of III or PanIN III). Dysplasia was multifocal in small-to medium-sized duct-like structures within areas of acinar atrophy, microcystic change, and mucinous hyperplasia. Two pancreata had carcinomas of multiple and unusual histologic subtypes, including small cell undifferentiated carcinoma and giant cell anaplastic carcinoma. The findings in this kindred yield important information on a distinctive and previously unrecognized pancreatic cancer precursor. Recognition of this entity may help identify additional kindreds and perhaps the underlying genetic defect. As is the case for other familial cancers, the as yet unknown specific genetic defect may have wider implications for pancreatic cancer in general.
Assuntos
Carcinoma/patologia , Fibrose Cística/patologia , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/patologia , Predisposição Genética para Doença , Ilhotas Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Adulto , Atrofia/patologia , Biomarcadores/análise , Carcinoma/complicações , Carcinoma/genética , Fibrose Cística/complicações , Fibrose Cística/genética , Feminino , Genes Dominantes , Humanos , Hiperplasia/patologia , Imuno-Histoquímica , Ilhotas Pancreáticas/química , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/genética , Linhagem , Lesões Pré-Cancerosas/patologiaAssuntos
Bloqueio Cardíaco/congênito , Lúpus Eritematoso Sistêmico/congênito , Miocárdio/patologia , Adulto , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/sangue , Arritmias Cardíacas/congênito , Arritmias Cardíacas/patologia , Evolução Fatal , Feminino , Bloqueio Cardíaco/patologia , Humanos , Recém-Nascido , Fígado/patologia , Cirrose Hepática/patologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Masculino , Gravidez , SíndromeRESUMO
Two brothers demonstrated a severe variant of trichothiodystrophy. Both had brittle hair, developmental delay with severe failure to thrive, recurrent infections, cataracts, and angioendotheliomas of the liver at autopsy. The elder died at 12 weeks, the younger at 6 months. The younger had the typical appearance of banded hair on polarizing microscopy and a low cystine content measured by ion exchange chromatography. The history, clinical findings, and basic defects of trichothiodystrophy are discussed.
