Small cell neuroendocrine carcinoma of the breast is a rare tumour with less than 30 cases reported in the literature. The clinicopathological findings of three cases of primary neuroendocrine carcinoma of the breast and a review of the pertinent literature are presented. The morphological and immunohistochemical patterns of this tumour are similar to its pulmonary counterpart. Expression of neuroendocrine markers is inconsistent, so morphology is the mainstay of diagnosis. Size is a very important prognostic factor in this tumour, as in breast carcinomas of the usual type.

Ki67 and Proliferating Cell Nuclear Antigen (PCNA) are antigens expressed in the nucleus during various phases of cell division, which can be detected immunohistochemically using monoclonal antibodies. Thirteen fibroadenomas and 39 carcinomas were examined for expression of Ki67 and PCNA. A staining index was calculated for each tumour as the percentage of positive cells in the areas of highest density. The mean index for both antibodies was significantly lower in fibroadenomas than in malignant tumours. A wide range of proliferation rates was seen in the malignant group; the mean Ki67 index of Grade I carcinomas was 9% +/- 4.4 (mean +/- SD), of Grade II 14.3 +/- 8.7 and of Grade III 26.2 +/- 15.7. These differences are statistically significant. In malignant tumours there was a good correlation between the mitotic count and the Ki67 index (r = 0.61, p < 0.005) but none between the mitotic count and PCNA index. There was a weak correlation between the Ki67 and the PCNA indices (r = 0.38 p < 0.005), but no correlation was found between either index and oestrogen receptor status, patient age or tumour size. Ki67 immunohistochemistry is a convenient method for assessing cell proliferation, applicable in most laboratories. The validity of measuring proliferation in this way has yet to be established but the wide variation of expression even within the conventional grading categories may help to discriminate prognostically distinct subgroups. Expression of PCNA appears to correlate poorly with Ki67 expression in breast tumours and not with mitotic count; therefore its usefulness as a marker of proliferative activity, on current evidence, appears to be limited.

SUMMARY Four children each exhibiting a profound deficiency of phytanic acid oxidase activity in cultured skin fibroblasts but with very different phenotypes, are described. A consistently raised plasma phytanic acid value, generally considered to be pathognomonic for Refsum's disease (phytanic acid oxidase deficiency), was observed in three of these children but not in the fourth, who also showed no evidence of accumulation of phytanic acid in liver or fat biopsies. Our data suggest that the clinical diagnosis of Refsum's disease in children is more difficult because the full spectrum of clinical features usually observed in adults with the disorder is not always present. Moreover, a failure to detect a raised plasma phytanic acid value may not necessarily indicate normal fibroblast phytanic acid oxidase activity.

SUMMARY Fraser syndrome without cryptophthalmos is described in monozygotic twins concordant for bilateral renal agenesis.

In an open non-comparative prospective trial of 12 months' duration, we investigated the role of a novel hormone replacement therapy regimen in 40 post-menopausal women who sought hormone replacement therapy. The regimen consisted of continuous administration of 0.625 mg of conjugated equine estrogen coupled with a fixed low-dose of micronized oral progesterone administered for 23 days every calendar month. The regimen was well-tolerated, producing no major side-effects and was effective in relieving menopausal symptoms. The study showed that 40% of the women experienced side-effects and 20% withdrew from the study. Half of the 20% of the women who dropped out did so for reasons not related to treatment. All symptomatic women experienced improvement after the 1st month, and virtually all were asymptomatic by the 3rd month of treatment, persisting until the end of the trial with the average number of hot flushes per day declining from the pretreatment levels by 96%. Amenorrhea was observed in 47% of patients, amenorrhea and minimal vaginal bleeding in 78% but acyclic bleeding was present in 28% of those in whom bleeding was re-established. Endometrial atrophy was induced in the majority of patients and no atypical endometrial hyperplasia was encountered. No significant changes were observed in blood glucose or liver enzymes. The mean percentage changes from baseline for serum cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoproteins (LDL) and LDL/HDL ratio were -6%, +32% (p < 0.001), -16% (p < 0.05), +15% (p < 0.05) and -23% (p < 0.05), respectively. The regimen was clinically effective and its apparent lack of major side-effects, the protective effect on the endometrium, the added advantage of minimal vaginal bleeding and the beneficial effect on lipid/lipoprotein levels, offer an attractive therapy and improved compliance with postmenopausal hormone replacement therapy.