Adenomyoepithelial adenosis of the breast is a form of adenosis not previously described. It is similar in several ways to microglandular adenosis, but one significant difference is the presence of myoepithelial cells. The present case originated as adenomyoepithelial adenosis in a 46-year-old woman. In the course of 18 years it proliferated and changed into a low-grade malignant adenomyoepithelioma. Electron microscopy confirmed the presence of myoepithelial cells in the adenosis, and immuno-histochemical study demonstrated cells containing actin (representing myoepithelial cells) in the adenosis as well as in the adenomyoepithelioma.

Mecillinam (FL 1060) is a new β-lactam antibiotic particularly active against gram-negative organisms. When given intravenously, very high serum levels were maintained for a short period of time. Lower peak levels but comparable bioavailability were obtained after intramuscular administration. Gastrointestinal absorption of mecillinam is poor, and for effective oral therapy the drug must be given in the form of its pivaloyl-oxymethyl ester pivmecillinam (FL 1039) which is well absorbed and rapidly transformed to mecillinam by enzymatic hydrolysis in the body. Urinary recovery of mecillinam after orally administered pivmecillinam was 45% in the first 6 h compared with 55 and 59% after mecillinam given by the intravenous and intramuscular routes, respectively. By increasing the dose the orally active ester produced proportionally higher levels of mecillinam, and the area under the serum curve was doubled with the dose. Higher peak levels and prolonged maintenance of high serum concentrations were seen after administration of pivmecillinam with probenecid. The presence of food in the stomach did not influence the absorption of pivmecillinam to any great extent.

Design An open, prospective study in postmenopausal women.Setting Fifty-four menopause clinics in the UK.Participants 2028 postmenopausal women: 13 12 (Group A) taking sequential oestrogen-progestogen hormone replacement therapy (HRT), and 716 (Group B) not taking HRT, were recruited. In Group A, 388 women took preparations containing 10 days of progestogen, 921 had 12 days, and 3 had 13 days per cycle.Endometrial aspiration biopsies were taken towards the end of a three-month run-in period (Group A) or at study entry (Group B), before administration of the continuous combined HRT regimen. Biopsies were repeated at the end of the nine month treatment period. MethodsMain outcome measure Endometrial histology.Results Initial endometrial biopsy data were available for 1106 women in Group A, who by the time of endometrial investigation had been taking HRT for a median duration of 2-56 years (5th to 95th centiles: 0.77 to 8.49 years). Data were available for 661 untreated women, who had no bleeding and had not taken HRT within the last year (Group B). Complex hyperplasia was found in 59 women (5.3%), and atypical hyperplasia in a further eight (0.7%) in Group A. In Group B there were no cases with complex hyperplasia, but one woman showed atypical hyperplasia (0.2%). At the end of the nine months of continuous combined therapy there was no case of hyperplasia among 1196 biopsies (upper 95% confidence limit of risk 0.31%) in women completing the study. Within this Group all of the women with complex hyperplasia arising during previous sequential HRT and who completed the study (n = 38) reverted to normal endometrial patterns. There was no case of endometrial carcinoma during the study.Despite taking standard regimens of sequential HRT containing at least 10 days of progestogen, there was a 5.3% prevalence of complex endometrial hyperplasia, and a 0.7% prevalence of atypical hyperplasia. However, continuous combined HRT (Kliofem) containing daily progestogen is not associated with an increased risk of hyperplasia and will convert the endometrium to normal in those with complex hyperplasia arising during previous sequential HRT. Conclusions

Twenty-seven cases of palpable and/or tumour-forming adenosis in the female breast, called adenosis tumour, have been investigated. It is a rare lesion, which most often presents as a breast mass that clinically and histologically is sometimes misinterpreted as carcinoma. The majority of patients were under the age of 45 years. Grossly, most tumours were firm or elastic and showed a grey or greyish-white cut surface. Furthermore, seven (26%) were granular and nine (34%) were microcystic, whereas none showed chalky streaks. Microscopically, 20 cases were poorly circumscribed and seven cases were well circumscribed. In contradistinction to the often uniform growth pattern of tubular carcinoma, the adenosis tumours characteristically showed adenosis arranged in a mixture of eight different growth patterns. The most frequent and also most extensive growth pattern was classical sclerosing adenosis and the least frequent was tubular adenosis. Another conspicuous feature in adenosis tumours was patchy growth in contrast to the stellate configuration of tubular carcinoma which is the most likely differential diagnosis. Other findings separating adenosis tumours from carcinomas were microcysts (93%), apocrine metaplasia (63%), luminal histiocytes (52%) and pseudopapillomas, called glomeruloid structures (48%). Epithelial changes that could cause anxiety about malignancy were frequently found and comprised epithelial hyperplasia (44%), epithelial atypia (26%) and fat or nerve infiltration (30%). Three patients were subjected to unnecessary mastectomy because of incorrectly diagnosed adenosis tumours. Adenosis tumours and non-infiltrating carcinoma were found together in five cases, but their association is probably over represented due to selection. None of 18 pure adenosis tumours solely treated by excision had recurred at follow-up 1-9 years later (mean 3.75 years).

Three cases of invasive mammary carcinoma with stromal osteoclast-like giant cells are reported. All the specimens were grossly of reddish-brown colour. On microscopical examination two were invasive ductal carcinomas and the third was of mixed ductal and mucoid type. In the stroma all specimens showed numerous osteoclast-like giant cells, vascular proliferation, and accumulation of haemosiderin pigment. Supplementary immunohistochemical and electron microscopical investigations indicated that the giant cells originated from mononuclear stromal cells with only slight histiocytic properties. The giant cell formation was probably induced by the infiltrating carcinomatous tissue which is also believed to induce new blood vessel formation. However, there is no evidence of a direct relationship between these features.