Rare tumors as leading symptom of hereditary tumor syndromes

Abstract

Monogenic hereditary tumor syndromes or tumor disposition syndromes (TDS) are based on germline/constitutional mutations in key genes of carcinogenesis. Early onset and aclustering of tumors belonging to atypical spectrum in the personal or family history are indicators for ahereditary form. In particular, rare specific tumors occur relatively frequently in the context of TDS. Based on aliterature search the current article presents information on which TDS should be considered for differential diagnosis (DD) in the presence of arare tumor. The identification of acausal 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. 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 amore effective genetic diagnosis, but also poses achallenge for the interpretation of findings and counseling. Referral to multidisciplinary expert centers is useful for care of the families.