RESUMO
A 28-year-old female with PIK3CA-related segmental overgrowth presented with headaches. She also had a unilateral vestibular schwannoma (VS), as well as 3 small (<2 cm) meningiomas, which according to the Manchester consensus diagnostic criteria for neurofibromatosis 2 (NF2) is sufficient for a clinical diagnosis. Analysis of blood revealed a mosaic PIK3CA c.2740G>A (p.Gly914Arg) mutation, confirming the diagnosis of PIK3CA-related overgrowth, but no mutations in NF2 were detected. Although VS has not previously been reported in PIK3CA-related segmental overgrowth, meningiomas have, raising the question of whether this patient's VS and meningiomas represent coincidental NF2 or phenotypic extension of her overgrowth syndrome. Genetic analysis of the VS revealed a heterozygous NF2 mutation c.784C>T (p.Arg262Ter) and loss of a portion of 22q, including NF2, SMARCB1, and LZTR1 genes. These results suggest that the patient has 2 different mosaic disorders, NF2 and PIK3CA-related overgrowth. The PIK3CA mutation was also present in the VS. Confirmation of the clinical diagnosis of mosaic NF2 in this patient has implications for monitoring and highlights the possibility of co-occurrence of mosaicism for multiple rare disorders in a single patient.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Mutação , Neuroma Acústico/genética , Adulto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Mosaicismo , Neurofibromatose 2/genética , Neurofibromatose 2/patologia , Neuroma Acústico/patologia , Doenças Raras/genética , Doenças Raras/patologiaRESUMO
Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.
Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Inibidor de Quinase Dependente de Ciclina p18/genética , Neoplasias Esofágicas/genética , Hibridização in Situ Fluorescente/métodos , Proteínas Proto-Oncogênicas c-myc/genética , Receptor ErbB-2/genética , Transativadores/genética , Adenocarcinoma/patologia , Idoso , Esôfago de Barrett/patologia , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina , Sondas de DNA , Progressão da Doença , Neoplasias Esofágicas/patologia , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de RiscoAssuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Mutação , Panitumumabe/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , PrognósticoRESUMO
Pancreatobiliary tract carcinoma is a lethal disease with low survival rates and limited treatment options. Diagnosis is complicated by benign conditions that can mimic malignancy on radiological studies (e.g. primary sclerosing cholangitis or PSC) and the suboptimal sensitivity of endoscopic biopsy/brushings obtained by endoscopic retrograde cholangiopancreatography (ERCP). The detection of multiple chromosomal gains by fluorescence in situ hybridization (FISH), referred to as polysomy, has demonstrated improved sensitivity over routine cytological evaluation. The evaluation of brushings by both routine cytology and FISH in our cytopathology laboratory has been in clinical practice since 2003. Strong morphological and screening skills enable cytotechnologists to become proficient in the assessment of FISH slides, which translates into cost and time savings. Multiple reports from various institutions have demonstrated the utility of FISH for patients with and without PSC. The incorporation of routine cytology and FISH results into the management algorithm for patients under suspicion for pancreatobiliary malignancy is a testament to the clinical success of these cytological assays.