Metastatic potential of small and minimally invasive breast carcinomas

Invasive ductal mammary carcinomas (IDC) of 1 cm in tumour size or less account for less than 20% of all IDC. We have observed 167 such cases at our Institution between 1985 and 1989. These were divided into carcinomas with an extensive or predominant intraductal component (EIC or PIC, being least 2× or 4× larger than the invasive component; 90) and compared statistically with the control group (no EIC or PIC; 77) for known prognostic factors and for their metastatic behaviour. Lymph nodes were step sectioned in order to detect occult micrometastases. The median follow up time was 62.6 months. Lymph node metastases were seen in 10% of pT1a and 19% of pT1b cases. Significant differences were found when comparing the EIC/PIC group with the control group (pT1a: 11% vs. 0%, pT1b: 37% vs. 11% lymph node metastases). Also, axillary and infraclavicular recurrence rates were higher for EIC/PIC carcinomas compared with other IDC of 1 cm (9.3% vs. 4.2%). This significantly adverse metastatic behaviour of the EIC/PIC tumours may be in part due to the more frequent occurrence of multifocal tumours in this group (in 43% vs. 6%), resulting in a greater tumour burden. We conclude that the overall risk of lymph node metastasis is not negligible in carcinomas of 1 cm or less in diameter with the risk being more than doubled for carcinomas with an intraductal component exceeding the invasive tumour by a factor of two. These differences were relevant only to regional metastases; the risk for distant metastasis and survival was identical after 5 years.This work has been dedicated to the 80th birthday of Prof. Drs. h.c. W. Doerr.     

Pathology and breast screening

Following the publication of the Forrest Report in 1986, the Department of Health has established a national breast screening programme in the United Kingdom, to be fully implemented in 1990. Women aged between 50 and 64 years will be invited to undergo mammographic screening on a 3-year cycle. Funding has been allocated on the basis that a basic screening unit will serve a population of half a million and that specialist assessment centres will cover the work from up to three basic units. The organization of screening services requires careful planning and close cooperation between specialties; histopathologists and cytopathologists must ensure that they are fully consulted. There will be a considerable impact on laboratories and appropriate funding and manpower are required for the additional workload. Pathologists will be asked to provide a specialist service in the interpretation of diagnostic samples from such techniques as fine needle aspiration cytology and needle localization biopsies. Diagnostic difficulties will be encountered in the assessment of impalpable screen-detected abnormalities and special training in breast screening is being provided. To ensure the success of the programme a national quality assurance scheme is being implemented. This will include validation of pathology data through regional coordinators.     

Neuroendocrine differentiation in male breast carcinomas.

The presence of neuroendocrine differentiation, as expressed by cellular chromogranin immunoreactivity, was investigated in paraffin-embedded tissue material from 51 consecutive cases of male breast carcinoma. From six of these cases electron microscopic studies were included. Chromogranin-immunoreactive cells were present in solid cords and delineated tubular structures. Ultrastructurally, dense core secretory granules could be detected. The expression of neuroendocrine differentiation was 45%, which is between two and eight times higher than reported for female breast carcinomas by other investigators. The present findings suggest that male breast carcinoma is an exclusive tumour disease showing both similarities and discrepancies when compared to its female counterpart.     

Loss of E-cadherin expression associated with lymph node metastases in small breast carcinomas

The National Breast Screening Programme affords the opportunity to study breast carcinomas at an early stage in their development. E-cadherin is a calcium-dependent, intercellular adhesion molecule whose loss of expression may facilitate the processes of invasion and metastasis of some human tumours. From a group of screen-detected ductal carcinomas less than or equal to 10 mm in diameter, 16 with lymph node metstastasis were identified and matched for grade, size and patient age with node negative tumours. The level of expression of E-cadherin (detected by immunocytochemistry) was compared in the matched pairs using a simple semi-quantitative intensity distribution scoring system. The results showed a significant (P = 0.05 Wilcoxon paired rank test) reduction of E-cadherin expression in tumours with lymph node metastases compared to those without. In the context of the small size of these tumours it is proposed that these results support the hypothesis that reduction in E-cadherin expression is an early event in the development of metastases.     

Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma

The clinical and pathologic features of 26 examples of a histopathologically distinct form of metaplastic carcinoma of the breast are reported. All neoplasms had overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic giant cells. Therefore, we designate this distinctive form of metaplastic carcinoma as "matrix-producing carcinoma" (MPC). All patients were women, the average age was 58 years, and all patients were eligible for a minimum of 5 years follow-up (mean follow-up period, 8.6 years). Twenty-three patients were treated by a form of mastectomy and three were treated by local excision. The 5-year survival rate for patients following mastectomy or partial mastectomy was 70%, contrasted with 50% for patients treated by local excision. The cumulative 5-year survival rate for MPC was 68%. All of the nine lesions that recurred did so within 2.5 years of initial therapy. Eight of these patients (89%) died from tumor within 4 years of initial therapy. The ninth was alive at last contract. Radiation and chemotherapy were of limited effectiveness. Significant features of the neoplasm associated with progression were large size, diffuse cellularity of the stromal matrix, and atypical cartilaginous metaplasia. Ultrastructural examination of one case and immunohistochemical evaluation of 12 cases revealed MPC to have myoepithelial characteristics.     

Pathology of the male breast

The male breast encompasses a number of benign and malignant breast conditions. The commonest cause of male breast enlargement is gynaecomastia. This can be physiological, idiopathic or pathological. Male breast cancer (MBC) is a rare disease comprising less than 1% of all breast cancers. The commonest histology is grade 2 ductal no special type carcinoma. Unlike the female breast, papillary in situ and invasive carcinomas are not uncommon in the male breast. MBC is often of the luminal A phenotype, similar to the post menopausal female breast cancer. Here we review a range of benign and malignant lesions of the male breast with a special emphasis on the two most common lesions: gynaecomastia and MBC. We describe the risk factors, pathogenesis, diagnostic criteria and management of those lesions.     

Molecular classification of breast carcinomas using tissue microarrays.

The histopathologic classification of breast cancer stratifies tumors based on tumor grade, stage, and type. Despite an overall correlation with survival, this classification is poorly predictive and tumors with identical grade and stage can have markedly contrasting outcomes. Recently, breast carcinomas have been classified by their gene expression profiles on frozen material. The validation of such a classification on formalin-fixed paraffin-embedded tumor archives linked to clinical information in a high-throughput fashion would have a major impact on clinical practice. The authors tested the ability of tumor tissue microarrays (TMAs) to sub-classify breast cancers using a TMA containing 107 breast cancers. The pattern of expression of 13 different protein biomarkers was assessed by immunohistochemistry and the multidimensional data was analyzed using an unsupervised two-dimensional clustering algorithm. This revealed distinct tumor clusters which divided into two main groups correlating with tumor grade (P<0.001) and nodal status (P = 0.04). None of the protein biomarkers tested could individually identify these groups. The biological significance of this classification is supported by its similarity with one derived from gene expression microarray analysis. Thus, molecular profiling of breast cancer using a limited number of protein biomarkers in TMAs can sub-classify tumors into clinically and biologically relevant subgroups.     

Fibronectin: a discrimination marker between small invasive carcinomas and benign proliferative lesions of the breast

The connective tissue glycoprotein, fibronectin (FN) is known to be increased in the stromal desmoplastic response associated with invasive breast carcinoma (IBC). In a previous study of 77 IBCs we found that all tumours, irrespective of desmoplasia, displayed an intense stromal immunoreactivity for FN, although those with a high metastatic potential tended to lack this in foci along their infiltrating border (Christensen et al. 1988). In order to test the diagnostic value of this observation, FN immunoreactivity was estimated semiquantitatively in 131 small primary IBCs, 23 in situ carcinomas, 20 borderline lesions, 142 benign proliferative breast lesions and 35 samples of normal breast tissue. All IBCs, including those without apparent desmoplasia, were accompanied by an intense stromal staining for FN forming a diffuse or pericellular pattern around the tumour cells (FN positive reaction). This was not seen in the benign lesions (FN negative reaction) with the exception of an FN positive, linear staining around some cysts and ectatic ducts and a diffuse staining of the connective tissue core of some intraductal papillomas. Intraductal carcinomas, multiple papillomas and radial scars could display a substantial staining for FN, sometimes enclosing small islands or tubules of epithelial cells. However, the fact that all IBCs of this study produced an overall reliable and consistent FN positive stromal reaction, which was only interrupted in minute foci along the infiltrating border in a few of the largest tumours (11/131), makes immunohistochemical staining for FN an excellent adjunct to morphology in tracing small, primary IBCs.     

Microcalcifications in breast carcinomas. A histological and histochemical study

Microcalcification in breast carcinomas were studied histologically and histochemically in 332 prospectively collected mastectomy consecutive specimens, without previous roentgenographic examination. Microcalcifications were found in 41% of breast carcinomas. The incidence was higher in comedo-carcinomas, duct carcinomas nonotherwise specified (N. O. S.) and papillary carcinomas. In situ and infiltrative lobular carcinomas did not show any microcalcification. Histochemically, calcium was shown to be deposited in compound lipids. The morphology and localization of microcalcifications was similar to those described in fibrocystic disease. This should be ascribed to similar structural and cellular conditions in both diseases.     

Demystifying basal-like breast carcinomas

"Basal" breast cancers are dominating the breast research literature at present and pathologists are under increasing pressure to evaluate for such a phenotype by their surgical and oncological colleagues. There is also much confusion about how to assess cancers, which immunohistochemical markers to use, what meaning and benefit this provides, and what the surgeons and oncologists will do with the information. Much remains to be done to answer all these questions but here we try to shed light on some of the issues and suggest what is still to come.     

Pathology of large-caliber stereotactic biopsies in nonpalpable breast lesions.

We report the surgical pathology experience with large caliber stereotactic biopsies for non-palpable breast lesions in 217 patients. The aim is to compare the demographics to another somewhat similar center (#2), and to published results with the much smaller stereotactic needle biopsies, including our own historical controls. The large caliber tissue specimens yielded proportionally fewer nonspecific diagnoses, with remaining areas of difficulty. An evolving diagnostic strategy is outlined.     

Simplified method of grading primary carcinomas of the breast.

AIMS: To produce a simplified prognostic index for breast cancer. METHODS: A retrospective study of 105 cases of primary infiltrating breast adenocarcinoma (not otherwise specified) was performed. Mitotic counts and semiquantitative assessment of tumour necrosis, fibrosis tubule formation, nuclear pleomorphism were made in histological sections of the primary tumour. Statistical analysis was performed to determine which of these parameters best predicts the observed survival. RESULTS: Mitotic count and necrosis correlated best with survival. This allowed the formation of a simple prognostic index based on these two parameters. CONCLUSIONS: This new prognostic index, with four tumour grades, seemed to be superior to Bloom's grading method, with greater separation of the prognostic groups. In particular, there is clear segregation of a group of patients with a distinctly poor prognosis.