RESUMO
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9â years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27â months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Colorretais/diagnóstico , Síndromes Neoplásicas Hereditárias/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina Trifosfatases/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Lactente , Masculino , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Mutação , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Proteínas Nucleares/genética , Resultado do Tratamento , Adulto JovemAssuntos
Estenose Esofágica/diagnóstico , Enteropatias/epidemiologia , Síndrome de Stevens-Johnson/complicações , Adulto , Endoscopia Gastrointestinal , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/imunologia , Estenose Esofágica/epidemiologia , Estenose Esofágica/imunologia , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Enteropatias/diagnóstico , Enteropatias/imunologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/imunologiaRESUMO
In most cases, fibrolamellar hepatocellular carcinoma has specific and distinctive histopathological features that distinguish it from hepatocellular carcinoma. Magnetic resonance imaging can provide characteristic features to obtain a diagnosis of this entity. We report a case of fibrolamellar hepatocellular carcinoma with a radiological-pathological correlation in a 37 year-old man with chronic viral hepatitis B without cirrhosis who underwent right hepatectomy.
Assuntos
Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Adulto , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , MasculinoRESUMO
Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.
Assuntos
Artéria Pulmonar , Sarcoma/diagnóstico , Neoplasias Vasculares/diagnóstico , Adulto , Terapia Combinada , Humanos , Angiografia por Ressonância Magnética , Masculino , Artéria Pulmonar/patologia , Sarcoma/patologia , Sarcoma/terapia , Tomografia Computadorizada por Raios X , Túnica Íntima/patologia , Neoplasias Vasculares/patologia , Neoplasias Vasculares/terapiaRESUMO
The molecular basis for the resistance of tumor cells to cell-mediated cytotoxicity remains poorly understood and thus poses a major challenge for cancer immunotherapy. The present study was designed to determine whether the WNT1-inducible signaling pathway protein 2 (WISP2, also referred to as CCN5), a key regulator of tumor cell plasticity, interferes with tumor susceptibility to cytotoxic T-lymphocyte (CTL)-mediated lysis. We found that silencing WISP2 signaling in human breast adenocarcinoma MCF7 cells impairs CTL-mediated cell killing by a mechanism involving stem cell marker Kruppel-like factor-4 (KLF-4) induction and microRNA-7 (miR-7) downregulation. Inhibition of transforming growth factor beta (TGF-ß) signaling using the A83-01 inhibitor in MCF7-shWISP2 cells resulted in a significant reversal of the epithelial-to-mesenchymal-transitioned (EMT) phenotype, the expression of KLF-4 and a partial recovery of target susceptibility to CTLs. More importantly, we showed that silencing KLF-4 was accompanied by a reduction in MCF7-shWISP2 resistance to CTLs. Using human breast cancer tissues, we demonstrated the coexpression of KLF-4 with EMT markers and TGF-ß pathway signaling components. More importantly, we found that KLF-4 expression was accompanied by miR-7 inhibition, which is partly responsible for impairing CTL-mediated lysis. Thus, our data indicate that WISP2 has a role in regulating tumor cell susceptibility through EMT by inducing the TGF-ß signaling pathway, KLF-4 expression and miR-7 inhibition. These studies indicate for the first time that WISP2 acts as an activator of CTL-induced killing and suggests that the loss of its function promotes evasion of immunosurveillance and the ensuing progression of the tumor.
Assuntos
Neoplasias da Mama/imunologia , Proteínas de Sinalização Intercelular CCN/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Imunidade Celular , Fatores de Transcrição Kruppel-Like/imunologia , MicroRNAs/imunologia , RNA Neoplásico/imunologia , Proteínas Repressoras/imunologia , Linfócitos T/imunologia , Neoplasias da Mama/patologia , Proteínas de Sinalização Intercelular CCN/genética , Linhagem Celular Tumoral , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , RNA Neoplásico/genética , Proteínas Repressoras/genética , Linfócitos T/patologia , Via de Sinalização WntRESUMO
Uterine lipomas are uncommon. Several histology hypotheses are described. Ultrasound is firstly performed but diagnosis is sometimes difficult. Magnetic resonance imaging is more specific and helpful to make a differential diagnosis with a dermoid ovarian cyst. Despite those imaging exams we detail a case of a patient where a laparoscopic hysterectomy with bilateral salpingo-oophorectomy and preliminary adhesiolysis has been necessary to establish diagnosis. Among her medical history some previous abdominal surgeries could be the cause of this lesion.