An unusual case of Cowden syndrome associated with ganglioneuromatous polyposis

Abstract

BackgroundGanglioneuromatous polyposis (GP) is a very rare disorder which may be associated with other clinical manifestations and syndromes, such as Cowden syndrome, multiple endocrine neoplasia (MEN) type II and neurofibromatosis (NF) 1. The risk for malignant transformation of ganglioneuromas is unknown, and the combination of GP with colon cancer has been only very seldom reported.Methods and resultsWe report the case of a 60-year old male patient with adenocarcinoma, adenomas and lipomas of the colon and multiple gastroduodenal lesions combined with generalised lipomatosis and macrocephaly. Based on the initial endoscopic and histological findings, a (restorative) proctocolectomy was recommended but declined by the patient. Instead, a colectomy was performed. The histological examination revealed an unforeseen GP in addition to the colon cancer. Extensive molecular diagnostics allowed for the differential diagnosis of the causes of the clinical manifestations, and the clinical suspicion of Cowden syndrome could not be confirmed using Sanger Sequencing and MLPA for the analysis of PTEN. Finally, a pathogenic germline mutation in PTEN (heterozygous stop mutation in exon 2: NM_000314 (PTEN):c.138C > A; p.Tyr46*) could be detected by next-generation sequencing (NGS), confirming an unusual presentation of Cowden syndrome with GP.ConclusionsCowden syndrome should be considered in cases of GP with extracolonic manifestation and verified by combined clinical and molecular diagnostics. Because GP may represent a premalignant condition, a surgical-oncological prophylactic procedure should be considered. Based on our experience, we recommend early implementation of Panel NGS rather than classical Sanger sequencing for genetic diagnostics, especially if various diagnoses are considered.

Colonic ganglioneuromatous polyposis in a 6-year-old girl – A case report and review of literature

“…It is often associated with Cowden syndrome where multiple polypoid ganglioneuromas are seen in addition to several other types of polyps, including hyperplastic polyps, adenomas, inflammatory polyps, and hamartomatous polyps. 1 Diffuse ganglioneuromatosis may manifest as bowel wall thickening or a more discrete mass. 6 It has an association with MEN type 2B and less commonly with NF1 with germline mutations identified in RET, and NF1 respectively.…”

Mesenchymal Tumors of the Gastrointestinal Tract—Beyond GIST—A Review

“…Multiple and diffuse lesions have a strong association with multiple endocrine neoplasia (MEN) type 2B or neurofibromatosis type 1; the latter is less common [127]. Multiple ganglioneuromatosis polyposis is frequently with Cowden syndrome, PTEN mutations [128]. Microscopically, the polypoid lesions show an expansion of the lamina propria by ganglion and Schwan cells, accompanied by eosinophils, sometimes with cystic colonic glands.…”

Next-generation panel sequencing identifies NF1 germline mutations in three patients with pheochromocytoma but no clinical diagnosis of neurofibromatosis type 1

“…The patient did not, however, consent to further medical examinations regarding subtle NF1 symptoms. (27,28,29). The second patient was suspected to have MEN2A syndrome, based on the rare co-occurrence of bilateral pheochromocytomas and MTC and therefore the initial molecular diagnostics was done by Sanger sequencing of the RET gene using DNA derived from the pheochromocytoma.…”