Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan-Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9-50.8). The risk to males is 26.5% (95% CI 22.6-30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.

Mammary hamartomas are macroscopically well-delineated tumours composed of a variable mixture of epithelial elements, fat and fibrous tissue. Such lesions are an under-recognized entity and, as they can be visualized by mammography, may be seen more frequently with the advent of the UK National Breast Screening Programme. The clinical and pathological features of 35 cases of mammary hamartoma seen at the Imperial Cancer Research Fund Clinical Oncology Unit at Guy's Hospital between 1979 and 1990 have been reviewed. Hormone receptor analysis on nine cases gave high progesterone with low oestrogen levels, probably reflecting their premenopausal status. Immunohistochemistry showed that the positive receptor staining was confined to the epithelial elements. In 25 cases pseudo-angiomatous hyperplasia was evident in the stroma of the lesion. The importance of distinguishing the inter-anastomosing stromal spaces seen in the latter condition from low-grade angiosarcoma is emphasized; the relationship between pseudo-angiomatous hyperplasia and mammary hamartoma is discussed; and the possibility that the former represents a permanently dilated form of the lymphatic labyrinth suggested.

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