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An unusual case of Cowden syndrome associated with ganglioneuromatous polyposis.

Pistorius S, Klink B, Pablik J, Rump A, Aust D, Garzarolli M, Schröck E, Schackert HK - Hered Cancer Clin Pract (2016)

Bottom Line: Ganglioneuromatous 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Visceral, Thoracic and Vascular Surgery, Technische Universität Dresden, Fetscherstr. 74, Dresden, 01307 Germany ; University Cancer Center (UCC) and Outpatient Clinic for Hereditary Gastrointestinal Tumors, Technische Universität Dresden, Fetscherstr. 74, Dresden, 01307 Germany.

ABSTRACT

Background: Ganglioneuromatous 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 results: We 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.

Conclusions: Cowden 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.

No MeSH data available.


Related in: MedlinePlus

Preoperative gastroscopic view: gastric polypoid lesions
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Fig5: Preoperative gastroscopic view: gastric polypoid lesions

Mentions: Furthermore, the upper-GI endoscopy revealed more than 60 gastric and about 25 duodenal polypoid lesions (Fig. 5). Histological examination of the gastric lesions had revealed distinctly regeneratory foveolar hyperplasia.Fig. 5


An unusual case of Cowden syndrome associated with ganglioneuromatous polyposis.

Pistorius S, Klink B, Pablik J, Rump A, Aust D, Garzarolli M, Schröck E, Schackert HK - Hered Cancer Clin Pract (2016)

Preoperative gastroscopic view: gastric polypoid lesions
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4862217&req=5

Fig5: Preoperative gastroscopic view: gastric polypoid lesions
Mentions: Furthermore, the upper-GI endoscopy revealed more than 60 gastric and about 25 duodenal polypoid lesions (Fig. 5). Histological examination of the gastric lesions had revealed distinctly regeneratory foveolar hyperplasia.Fig. 5

Bottom Line: Ganglioneuromatous 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Visceral, Thoracic and Vascular Surgery, Technische Universität Dresden, Fetscherstr. 74, Dresden, 01307 Germany ; University Cancer Center (UCC) and Outpatient Clinic for Hereditary Gastrointestinal Tumors, Technische Universität Dresden, Fetscherstr. 74, Dresden, 01307 Germany.

ABSTRACT

Background: Ganglioneuromatous 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 results: We 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.

Conclusions: Cowden 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.

No MeSH data available.


Related in: MedlinePlus