Search

Background: Gastrointestinal polyposis syndromes are the second most common cause of hereditary colorectal carcinomas after Lynch syndrome (hereditary non-polyposis colon cancer, HNPCC). The detection of a causal germline mutation in an affected family member serves for differential diagnosis, assessment of the recurrence risk and predictive testing of healthy individuals at risk., Objectives: The present article aims to provide an overview of the differential diagnosis of different gastrointestinal polyposis syndromes based on the endoscopic findings, polyp histology, extraintestinal phenotype and molecular genetic diagnostics., Materials and Methods: The present article is based on a literature search on gastrointestinal polyposis syndromes., Results: In addition to familial adenomatous polyposis (FAP), there are further subtypes of adenomatous polyposis that can often only be distinguished by the detection of a causative germline mutation and are sometimes associated with different extracolonic manifestations. In hamartomatous polyposis syndromes, the clinical overlaps often cause differential diagnostic problems. Serratated polyposis syndrome is possibly the most frequent polyposis syndrome, although its cause is currently largely unexplained., Conclusions: Early detection and correct classification of polyposis is crucial for adequate prevention and therapy. Access to multidisciplinary expert centres is useful for the care of families.

Background: Monogenic hereditary tumor syndromes or tumor disposition syndromes (TDS) are based on germline/constitutional mutations in key genes of carcinogenesis. Early onset and a clustering of tumors belonging to a typical spectrum in the personal or family history are indicators for a hereditary form. In particular, rare specific tumors occur relatively frequently in the context of TDS., Methods: Based on a literature search the current article presents information on which TDS should be considered for differential diagnosis (DD) in the presence of a rare tumor., Results: The identification of a causal germline mutation in the index patient is important for the DD, the evaluation of recurrence risks, and predictive testing of asymptomatic at-risk family members. In TDS with autosomal dominant inheritance, it is often possible to identify several high-risk individuals in the affected families., Conclusion: Early detection and correct classification are of high clinical relevance as the patients and persons at risk can often be offered effective preventive procedures (surveillance, prophylactic operations), and in some cases, special therapeutic options exist. TDS are paradigmatic for an extremely successful concept of preventive oncology and personalized medicine. The introduction of new methods of high-throughput sequencing (next generation sequencing) enables a more effective genetic diagnosis, but also poses a challenge for the interpretation of findings and counseling. Referral to multidisciplinary expert centers is useful for care of the families.

Hereditary gastrointestinal polyposis syndromes account for around 1% of all colorectal cancers; most of them are associated with a broad spectrum of extracolonic tumors. The initial diagnosis is based on endoscopic findings and polyp histology. Molecular genetic screening is important for the delineation of conditions with a similar phenotype such as autosomal dominant familial adenomatous polyposis (FAP) and autosomal recessive MUTYH-associated polyposis (MAP). Identification of the germline mutation in an affected person is a prerequisite for the exact evaluation of the recurrence risk in relatives and the predictive testing of asymptomatic persons at risk. Beside cases with attenuated adenomatosis or few colorectal adenomas, diagnostic difficulties are common among the hamartomatous polyposes such as the juvenile polyposis syndrome due to their broad clinical overlap and uncertainties in histological assessment. Several poorly defined nonhereditary polyposis syndromes and those with an as yet unknown etiology exist including hyperplastic polyposis syndrome. Early detection and accurate classification are essential since effective methods for surveillance and treatment are available.