Experts and performance in histopathology--a study in breast pathology.

This study was undertaken to determine if it was possible to identify expertise within Histopathologists (trainees, district general pathologists and pathologists with a special interest in breast disease) using an objective measure of performance. The method of assessment of performance is based on the CWS (Cochran-Weiss-Shanteau) ratio formed by the individual's ability to discriminate between a spectrum of disease categories and their level of inconsistency when assessed at intervals. The slides circulated represented the spectrum of breast disease seen in routine practice. The results demonstrated the average CWS ratio to be lowest in trainees and highest in pathologists with a special interest in breast pathology although there was no statistical difference in the CWS scores obtained between the district general pathologists and pathologists with a special interest. Differences in inconsistency rather than discriminatory ability mainly accounted for the difference in the CWS ratio observed between the groups studied. The study shows that the CWS ratio is potentially a very useful tool in the assessment of pathologists with regard to assessing their progress through training.

Adenomyoepithelioma of the breast with malignant features.

The clinico-pathological features of 7 cases of adenomyoepithelioma of the breast with features suggestive of malignancy are presented. There was a high incidence of local tumour recurrence, in 2 cases as high-grade infiltrating carcinoma of the breast of no special type ("ductal", grade III). One patient died as the result of a clinically diagnosed cerebral metastasis. Histological examination of the primary breast tumours reveals two main patterns: (1) tumours consisting in part of typical adenomyoepitheliomas but which merge with areas of obviously invasive malignant cells and (2) neoplasms that have the overall architecture of an adenomyoepithelioma but which, on close examination, are found to contain foci of cellular atypia and increased mitotic activity. The two patterns of tumour exhibit the same clinical behaviour and should be distinguished from adenomyoepitheliomas, which are cytologically bland throughout.

Carcinoma in situ involving sclerosing adenosis: a mimic of invasive breast carcinoma.

The distinction between invasive and in situ carcinoma of the breast is important with regard to the treatment and prognosis of the patient. When carcinoma in situ involves breast tissue in which the normal architecture is altered by pre-existing sclerosing adenosis, the resulting histological picture may closely mimic an invasive carcinoma. We record the histopathological features in 13 cases where there was difficulty in identifying the presence or extent of invasive carcinoma. The most useful clue was attention to the low power appearances of distorted lobular units in the areas of malignancy and comparison with surrounding breast tissue which usually showed recognizable sclerosing adenosis. The use of immunohistochemical stains for myoepithelium (alpha-actin and S-100 protein) and for basement membrane (collagen type IV and laminin) proved to be of considerable value in identifying the preservation of these features around glandular structures in areas of sclerosing adenosis containing in situ carcinoma.

Discordance between cytologic and histologic reports in cervical intraepithelial neoplasia. Results of a one-year audit.

In order to investigate the factors contributing to cases in which the cytology and histology reports of cervical intraepithelial neoplasia (CIN) differ, we assessed the impact of careful review of the biopsy and its corresponding cervical smear. In a one-year audit of all cervical biopsies we found that 18.8% of biopsy-smear pairs disagreed by at least two grades of CIN. Following review the mismatch rate fell by 47%, mainly due to a drop in the number of cases in which the smear showed less severe CIN than did the biopsy. The proportion of cases in which the cytologic impression of CIN was greater than the histologic was changed little. The fall in the mismatch rate was seen after review of the smears, while a similar review of the histology did not alter the rate of mismatch. Neither the presence of koilocytotic changes on either cytology, histology or both, nor the size of the biopsy (punch vs. cone/hysterectomy) influenced the occurrence of such discrepancies. A similar review of the smears and biopsies of matching cases of CIN revealed no significant changes. This suggests particular difficulties of interpretation in the mismatching cases. In those cases with persistent mismatch an additional element of sampling error must be assumed to be the main cause even though all smears were considered of adequate quality.

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma.

The use of chemotherapy as a form of primary treatment for breast cancer is increasing and, as a result, more resection specimens contain tumours which have been exposed to cytotoxic drugs. We have studied the effects of chemotherapy on the tumour morphology and various biological features of breast carcinoma in a group of 35 patients. These were a group who responded to treatment in a clinical study of the use of primary chemotherapy designed to reduce tumour bulk prior to surgery. Characteristic morphological changes, temporally related to the administration of cytotoxic agents, are seen. The malignant cells become enlarged with vacuolated cytoplasm and vesicular nuclei containing prominent nuclei; occasionally the nuclei were angular and hyperchromatic. These features are interpreted as degenerative in nature. In 15 cases sufficient material was present in the pretreatment biopsies to compare the grade of the tumours before and after chemotherapy: changes were found in six tumours. Cytotoxic drugs do not induce a consistent pattern of change in the proliferation and apoptotic indices of individual tumours, but there is a tendency to reduce proliferative activity over all the tumours as a group. It was also found that chemotherapy is capable of modifying the expression of the oncoproteins c-erbB-2 and p53 in a minority of cases of breast cancer, usually resulting in an acquisition of immunoreactive oncoprotein. It is important to be aware of these effects when studying breast carcinomas removed after chemotherapy.

Oestrogen and progesterone receptor expression in mammary fibromatosis.

AIMS: To investigate the oestrogen and progesterone receptor concentrations expressed on mammary fibromatoses to determine their responsiveness to oestrogenic stimuli. METHODS: Six mammary fibromatoses were examined using immunohistochemistry for the presence of oestrogen and progesterone receptors using antibodies against the receptor proteins. Enzyme immunoassays (EIAs) using the same antibodies were also performed in four patients. Immunohistochemical staining for pS2 protein was also carried out as a measure of functional oestrogen receptors. RESULTS: Neither receptor nor pS2 protein was expressed using immunohistochemistry. Very low concentrations of both oestrogen and progesterone receptors were shown by EIA. CONCLUSION: These results indicate the absence of clinically important concentrations of oestrogen and progesterone receptors in breast fibromatoses and suggest that treatment directed against oestrogen is unlikely to be beneficial.

Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma.

Two members of the cadherin family of intercellular adhesion molecules are found in normal breast tissue: E-(epithelial) cadherin is present in both luminal and myoepithelial cells, whereas P- (placental) cadherin is confined to myoepithelium. There is experimental evidence that loss of E-cadherin is associated with increased invasiveness of malignant cells in vitro, which stimulated us to examine the presence and distribution of E- and P-cadherin in breast carcinomas by means of immunohistochemical staining. E-Cadherin was present in all in situ and invasive ductal carcinomas examined, although it had a patchy distribution and the staining was of variable intensity. However, in 83 per cent of invasive lobular carcinomas and all lobular carcinomas in situ there was complete loss of E-cadherin expression. In the remaining 17 per cent of invasive lobular tumours, E-cadherin appeared to have an abnormal distribution within the cytoplasm with variable expression on the cell membrane. P-Cadherin, by contrast, was absent from all benign breast luminal epithelium and 25 carcinomas of ductal and lobular type. It was found in only one carcinoma of lobular type. We suggest that loss of cell-cell adhesion mediated by E-cadherin plays a part in the characteristic morphology of lobular carcinomas.

The enigmatic eccrine epithelioma (eccrine syringomatous carcinoma)

Eccrine epithelioma is an exceedingly rare cutaneous tumor thought to represent the malignant counterpart of the eccrine dermal syringoma. To data, only 10 accepted cases appear to have been reported. Two additional cases are described here and the literature is reviewed. The first case showed the typical histologic features of eccrine epithelioma. The second case showed extensive clear cell change (due to glycogen accumulation), reminiscent of the clear cell syringoma; conspicuous pseudo-apocrine metaplasia was also noted. The latter appearance has not been previously described in eccrine epithelioma.

A histological and immunohistological study of cervical intraepithelial neoplasia in relation to recurrence after local treatment.

A retrospective histological study was performed on 23 patients who had presented with recurrent cervical intraepithelial neoplasia (CIN) 18 months or more after apparently adequate local destructive treatment and a comparable control group of 23 patients who had no recurrence at 18 months. All recurrences were in women with CIN 3. Detailed examination of pretreatment biopsies showed that there were significant differences in both the extent of crypt involvement (P less than 0.01) and maximum depth of CIN (P less than 0.01) between the recurrent groups and the comparison group of women without recurrence. There was also a significant difference in mitotic count between the two groups (P less than 0.01). Immunocytochemical staining for Langerhans' cells or human papilloma virus common antigen showed no significant difference between the two groups. A mitotic count of 35 per ten high-power fields or a depth of crypt involvement greater than 1.7 mm in the pretreatment biopsy was invariably associated with recurrence and identified 13/22 (59%) cases of recurrent disease. The histological reporting of these features may be of value in predicting a group of women at high risk of recurrence of CIN after local treatment.

Coexistent Crohn's disease and sigmoid diverticulosis.

This study reports six patients with a diagnosis of diverticular disease with associated localized Crohn's colitis who were all treated by segmental resection. Two patients died in the post-operative period from disease unrelated to their colonic pathology. The remaining four patients remain well, show no signs of recurrent disease and have required no further surgery. The behaviour and significance of the two conditions occurring in the same patient is discussed.

Malignant nerve sheath tumour arising in a benign ancient schwannoma.

A malignant nerve sheath tumour arising in a longstanding benign schwannoma in a 75-year-old woman is described. Malignant change of this kind is extremely rare; there appear to be only four convincing previously reported cases.

Crohn's disease of the appendix.

This study reports eight patients who underwent appendicectomy between 1978 and 1986 for apparently isolated, previously undiagnosed Crohn's disease of the appendix. All patients have since remained well with no sign of disease recurrence. This may represent a less aggressive form of Crohn's disease or be a different entity, namely granulomatous appendicitis.