Gynaecological neoplasms in common familial syndromes (Lynch and HBOC)

Lynch syndrome and BRCA-1 and BRCA-2-associated hereditary breast and ovarian cancer are hereditary cancer syndromes frequently involving the gynaecological tract but tumours associated with similar molecular alterations may also occur sporadically. Thus, the molecular phenotype of mismatch repair deficiency, microsatellite instability or hypermutator phenotype may be attributable to germline or somatic events. Similarly, homologous recombination deficiency or 'BRCAness' in ovarian cancers may be syndromic or sporadic. While hereditary syndromes are well recognised, the prognostic and predictive implications of these molecular phenotypes have only recently been elucidated and these aspects will finally ensure that molecular screening may become standard of care. Thus, nowadays pathologists are asked to designate the molecular phenotype of these cancers and then determine whether it is due to hereditary or sporadic causes.