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The success of needle core biopsy procedures and the validity of pathologic diagnoses made on material from the procedures are key determinants in planning the optimal management of a wide variety of breast diseases. The most common diagnostic problems encountered in these biopsy specimens include lobular and ductal proliferations, sclerosing and papillary lesions, cellular fibroepithelial tumors, and minimally invasive or microinvasive carcinoma. This review provides practical guidance to help narrow the differential diagnosis of lesions on needle core biopsies and offers guidelines for the pathologic reporting of these specimens.

Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in 14 of 60 (23%) patients with MGA listed in the authors' files. This article describes the clinicopathologic and immunohistochemical features and prognosis of these carcinomas. The median patient age was 47 years (range, 26-68 years). All patients had a mass. Six (43%) had a family history of breast carcinoma. Lymph node metastases were found in 3 of 11 axillary dissections. Ten patients treated by mastectomy were recurrence-free, with a median follow-up of 57 months (range, 3-108 months). Two of three patients treated by excisional surgery were recurrence-free 12 and 105 months later. The third woman had bone metastases at 51 months and was alive 98 months after treatment. Carcinoma arose in the MGA in 13 patients. In these patients, in situ carcinoma was found in expanded MGA glands composed of cells with vesicular poorly differentiated nuclei. One patient with benign MGA had carcinoma develop in the opposite breast that was not associated with MGA. When it arose in MGA, basement membranes were present in benign MGA and in situ carcinoma but tended to be disrupted in invasive foci that appeared to be formed by coalescent MGA glands. Strong immunoreactivity for cytokeratin, S-100, and cathepsin D was detected in carcinomas. Two carcinomas had nuclear progesterone receptors, and one of these had estrogen receptors. One carcinoma had positive findings for HER-2neu, and four had immunoreactivity for p53 protein. The following conclusions were drawn from these observations: (1) carcinomas arising in MGA have a distinctive histopathologic pattern; (2) the carcinomas are composed of epithelial cells (cytokeratin positive, actin negative) that are strongly immunoreactive for S-100 protein and cathepsin D; and (3) with a median follow-up of nearly 5 years, patients with these carcinomas had a relatively favorable prognosis, despite histopathologic and immunohistochemical features usually associated with a poor prognosis.

Juvenile papillomatosis (JP) is a benign proliferative breast tumor rarely found in women older than 30 years of age that may exhibit considerable histologic atypia. Often these findings would be regarded as precancerous in older patients. Rarely, carcinoma and JP have been coexistent at diagnosis, but little is known about the risk for development of carcinoma after excisional biopsy of JP. To examine this issue, the authors reviewed a series of 41 patients with JP who had biopsies between 1960 and 1978 with a median follow-up of 14 years. Age at diagnosis ranged from 15 to 35 years (median, 19 years), whereas at last follow-up the patients were 22-48 years old (median, 36 years). Overall, 21 (58%) reported a positive family history for breast carcinoma, with mothers and maternal aunts being at highest risk. Six had bilateral JP. Subsequent breast carcinoma was diagnosed in four (10%) of the patients with JP. All of these patients were unusual because they had recurrent and bilateral JP. In two instances the changes were multifocal. Each had a positive family history for breast carcinoma. In this series, none of the patients with nonrecurrent unilateral, unicentric JP has thus far had subsequent mammary carcinoma develop. When counseling the JP patient one should take care not to exaggerate her near term risk for development of carcinoma. The present data suggest that concern should be greatest for women with a positive family history and recurrent bilateral JP.

Eight cases of a rare, distinctive variant of infiltrating mammary carcinoma featuring benign multinucleated osteoclast-like giant cells are reported. The multinucleated osteoclast-like giant cells are reported. The multinucleated giant cells were associated with ductal carcinoma in five cases and with infiltrating lobular carcinoma in three cases. Although three patients had lymph nodal metastases in level one, none of the nodal metastases contained giant cells. From the limited follow-up data of this report, it seems likely that the prognosis for patients who have this type of adenocarcinoma is not especially favorable. The observation that the giant cells generally occurred in areas of prominent angiogenesis suggests that the angiogenesis may be induced by some chemical substance produced by the tumor cells. Biochemical and immunologic investigations may eventually provide an explanation for this unusual morphologic manifestation of host reaction to mammary carcinoma.

We determined estrogen receptor protein and carcinoembryonic antigen in cytosols prepared from 189 human breast carcinoma tissues, 85 benign or normal breast biopsies, and 101 tissue specimens metastatic from breast carcinoma. Carcinoembryonic antigen was observed in 70% of the primary carcinomatous tissues, 15% of the benign or normal specimens, and 51% of the metastases. Ninety-six of the 189 primary carcinomatous specimens with increased concentrations of carcinoembryonic antigen were also positive for estrogen receptor protein, whereas 67 of the 72 benign or normal biopsies with low concentrations of carcinoembryonic antigen were also negative for estrogen receptor protein. All five fenign specimens with positive estrogen receptor protein and normal carcinoembryonic antigen concentrations were from fibroadenomas. The concordance between estrogen receptor protein and carcinoembryonic antigen in the primary carcinomatous tissue was 66%, in metastatic carcinoma 51%, and in benign and normal tissue 85%.

A collaborative immunohistochemical study was carried out to examine the expression and prognostic significance of tumor markers in a retrospective series of 233 invasive breast carcinomas. The patterns of tumor marker expression in 94 patients with short remission duration (recurrence within five years) were compared with 50 patients with intermediate (at five to ten years) and 89 patients with long (no recurrence at ten years or longer) remission durations. The antigens examined were carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), placental lactogen, alpha-lactalbumin, and pregnancy-specific beta-1 glycoprotein. Carcino-embryonic antigen was the most frequently expressed antigen, whereas HCG was demonstrated least frequently. Also, the ABH isoantigen status was examined using monoclonal antibodies; isoantigen expression was observed in a subset of breast carcinomas, contrary to previous reports of total deletion in breast cancer. Two of the markers, CEA and HCG, were examined by both laboratories, each with two different antisera and also with both PAP and ABC immunohistochemical technics. Meticulous efforts were taken to provide quality control and ensure reproducibility of results. These included the use of serial sections of duplicate pathologic material by both institutions, standardization of experimental conditions and interpretation criteria, double-blind evaluation of exchanged slides, and use of standardized data sheets to record staining extent and intensity. No significant disagreements were observed between data obtained through the different approaches. The steps that were taken to minimize interobserver and interinstitutional differences in this study are presented as a model for collaborative immunohistochemical studies. The expression of tumor markers, alone or in combination, was not found to bear any significant relationship to prognostic indicators, such as the likelihood of recurrence, interval before recurrence, or presence of metastasis.

A total of 170 axillary lymph nodes were obtained from fresh mastectomy specimens from 81 women with breast cancer. Lymph node cells were tested in vitro for T and B cells by the rosette technique and immunofluorescence microscopy and for functional capacity by response to the mitogens phytohemagglutinin (PHA) and concanavalin A. T cells showed a wide range of relative values: 32-80 percent, with a mean of 63.5 percent. B cells defined by the presence of surface immunoglobulins ranged from 14 to 61 percent (mean, 35.8 percent); those defined by the presence of C3 receptors, from 8 to 54 percent (mean, 24.9 percent); and those defined by the presence of IgG-specific (Fc) receptors, from 10 to 45 percent (mean, 27.5 percent). Cells with the C3 and Fc receptors constituted approximately two-thirds of the cells not binding spontaneously to sheep red blood cells (non-SRBC-R), whereas virtually all non-SRBC-R stained for surface immunoglobulins. The proportion of T and B cells and the response to mitogens varied widely among nodes and among patients. Differences were significant between values observed in young and old patients, nodes with and those without metastatic disease, and lymph nodes with different morphology. Lymph nodes from patients over 60 years old showed a higher proportion of B cells and a lower proportion of T cells than did those from patients 45 years of age or younger. Lymph nodes with disease metastic to them also showed a higher percent of B cells and a lower percent of T cells than the nodes that did not have metastatic disease. Lymph nodes with lymphocyte predominance showed a relatively high proportion of T lymphocytes, a high PHA response, and a low content of B lymphocytes. By contrast, lymph nodes with germinal-center predominance showed a relatively low content of T cells, a low PHA response, and a relatively high proportion of B lymphocytes.