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Fibroadenoma in oral contraceptive users: a histopathologic evaluation of epithelial atypia.

We have reviewed histologically a series of 120 fibroadenomas which formed part of the case material from a previous case-control epidemiological investigation of the relationship between oral contraceptive use and breast disease. We evaluated the epithelial component of the fibroadenoma for degree of cytologic atypia. This study indicates that the reduced risk for fibroadenoma among long-term users of oral contraceptives does not vary according to the degree of epithelial atypia present. This is in contrast to our previously reported findings for fibrocystic disease, in which the decreased frequency of occurrence of the disease in long-term users of oral contraceptives was found only for cases with no minimal epithelial atypia.

Adenofibroma↗

DNA synthesis of benign human breast tumors in the untreated athymic "nude" mouse. An in vivo model to study hormonal influences on growth of human breast tissues.

DNA synthesis in 33 human benign breast tissue biopsy specimens (HBT) was determined by 3H-thymidine radioautography 0, 15, 30, and 60 days after s.c. transplantation to female nude mice. A third of the grafts was removed from each mouse at each time period. Grafts and 0-day slices were exposed to 3H-thymidine in vitro. Labeling indices (LI) [number of radiolabeled epithelial cells per unit area epithelium (0.1 mm2)] were calculated for 0-day slices and grafts from each mouse at each time period. The LI of high 0-day HBT grafts (LI greater than 15) decreased significantly between 0 and 15 and 0 and 30 days. The LI of low 0-day HBT grafts (LI less than 15) increased significantly at 15 days then decreased to 0-day levels at 30 days. No significant differences in LI of HBT grafts were observed between 30 and 60 days. Thus, a model has been proposed for studies of factors effecting the growth of human breast tissues transplanted to nude mice in which (1) each mouse is used as its own control by measuring DNA synthesis of grafts before and after treatment, and (2) the treatment is initiated 30 days or more after transplantation of breast tissues when graft DNA synthesis is stabilized. Using this model, we have observed marked increases in HBT graft DNA snythesis induced by human placental lactogen treatment of host nude mice from day 42 to day 60 after HBT transplantation.

Adenofibroma↗

Detection of alpha-lactalbumin in breast lesions and relationship to estrogen receptors and serum prolactin.

Alpha-lactalbumin, the B protein of lactose synthetase secreted by the mammary epithelial cells, was isolated and purified from fresh human milk and injected into rabbits for antibody production. Indirect immunofluorescence (IIF) was done on various types of breast lesions to assess the relationship, if any, between histologic type and production of alpha-lactalbumin. Fifty percent of fibroadenomas and fibrocystic disease and 63% of infiltrating ductal carcinoma showed positive reaction. No false positives were found on IIF of alpha-lactalbumin of several tumors of nonmammary tissue. These findings suggest that IIF for alpha-lactalbumin may be helpful in ascertaining the site of origin of metastatic breast tumors. However, serum alpha-lactalbumin was detected by radioimmunoassay in only 10% of women with infiltrating ductal carcinoma, indicating that this may not be a useful marker for the presence of breast cancer at least by the method employed. This discrepancy between serum and tissue alpha-lactalbumin may be due to the short half-life of serum alpha-lactalbumin or to the lack of secretion of the protein into the blood. There was no apparent relationship between the presence of estrogen receptors or serum prolactin and alpha-lactalbumin in the 27 mammary carcinomas investigated.

Adenofibroma↗

Tubular carcinoma developing within a recurring cystosarcoma phyllodes of the breast.

Malignant alteration in cystosarcoma phyllodes is uncommon and almost always confined to the stromal component. A rare case of recurring cystosarcoma is reported. In the first recurrence, lobular carcinoma in situ was present within the tumor and the second recurrence revealed tubular carcinoma within the cystosarcoma. Epithelial proliferation of various sorts is not uncommon in cystosarcomas but only two previous instances of infiltrating carcinoma have been observed within these tumors. The problem of mammary carcinoma coexisting with cystosarcoma is reviewed and comparisons are made with a closely related neoplasm, the fibroadenoma.

Adenocarcinoma↗

Most cystosarcoma phyllodes and fibroadenomas have progesterone receptor but lack estrogen receptor: stromal localization of progesterone receptor.

Biochemical study of fibroepithelial tumors of the female breast showed presence of progesterone receptor (PgR) in all five cystosarcoma phyllodes (two malignant, three benign), and in 11 of 13 fibroadenomas tested. Estrogen receptor (ER) was detected in only one of five cystosarcomas and 2 of 13 fibroadenomas. The relative volumes occupied by epithelium and stroma in each tumor were measured from histologic sections. The results were consistent with presence of PgR in the stroma and ER in the epithelium. Different types of cystosarcoma (benign and malignant) and different types of fibroadenomas (intracanalicular, pericanalicular, and mixed) did not differ significantly in content of PgR, and mean levels of PgR in cystosarcoma were comparable with those in fibroadenomas. The presence of PgR in cystosarcomas suggests that progestational therapy, and possibly other forms of hormonal therapy, should be tested in the treatment of advanced, malignant cystosarcoma phyllodes.

Adenofibroma↗

Ovarian endometrioid adenofibromatous and cystadenofibromatous tumors: benign, proliferating, and malignant.

Ovarian endometrioid tumors with an adenofibromatous pattern have been described but the entire spectrum of these tumors has not been analyzed. A series of ten cases was studied and divided into two benign, four proliferating, and four malignant tumors on the basis of their morphologic characteristics. The most useful criterion for distinguishing proliferating from benign adenofibromatous tumors is increased epithelial proliferation, associated with glandular complexity and crowding in the former. Proliferating tumors may represent one form of the endometrioid tumor of borderline malignancy. The presence of a confluent growth pattern with invasion of the stroma distinguishes malignant from proliferating tumors. The various tumors in this group frequently show squamous metaplasia and are often associated with endometriosis. Because of the relatively small series, the biologic behavior of these histologic variants cannot be evaluated at this time.

Adenocarcinoma↗

Atypical endometrioid cystadenofibroma with Meigs' syndrome: ultrastructure and S-phase fraction.

A case of an ovarian endometrioid cystadenofibroma with epithelial atypia and Meigs' syndrome is described. The patient had a large pleural effusion that resolved rapidly after extirpation of the tumor. The S-phase fraction, measured by in vitro incorporation of tritiated thymidine, was extremely low, suggesting that this unusual tumor has a limited growth potential despite its atypical features. Ultrastructurally, the epithelial component has few features described in other ovarian endometrioid tumors. The cells have deeply clefted nuclei and numerous secondary cytolysosomes, features more commonly seen in Brenner tumors; the morphologic similarities may reflect a low epithelial turnover rate. Despite a review of the literature and an analysis of the case, the authors were unable to determine the pathogenetic mechanism of Meigs' syndrome.

Adenofibroma↗

A pathologic study of benign breast diseases in Tokyo and New York.

Two hundred thirty-two biopsies of benign breast conditions from the National Cancer Center Hospital in Tokyo and 263 comparable biopsies from Memorial Hospital in New York City were reviewed. The component lesions of benign breast disease were identified and evaluated according to their relative frequency for different ages. Apocrine cysts, apocrine hyperplasia, intraductal hyperplasia, sclerosing adenosis, blunt duct hyperplasia, and atypical lobular hyperplasia were at least twice as common in biopsies from American women. Solitary papillomas were twice as common among biopsies from Japanese patients and tended to show more epithelial proliferation and sclerosing papillomatosis than did Americans. No major differences were found in the frequency of cysts, duct stasis, periductal mastitis, sclerosing intraductal papillomatosis, fibroadenomatoid mastopathy or fibroadenomas. Assuming intraductal hyperplasia and atypical lobular hyperplasia may represent premalignant epithelial changes, the high frequency of these lesions in New York biopsies when compared to Tokyo biopsies correlates well with the higher rate of breast cancer in the United States as compared to Japan. The greater frequency of lobular proliferative lesions and apocrine disease in New York suggests that these lesions may be produced by factors which also predispose American women toward breast cancer.

Adenofibroma↗

CEA-like material in cytosols from human breast carcinomas. Correlation with biochemical and pathologic parameters.

CEA-like material was found in 51 of 62 primary human breast carcinomas and in only 2 of 12 fibroadenomas. Levels of carcinoma CEA-like material correlated weakly with cytoplasmic estradiol receptor levels, total cytosol estrogens, and cytosol progesterone. Levels of CEA-like material showed no significant correlation with carcinoma stage, grade, cellularity, size or histologic type. Levels, however, correlated inversely with lymphocyte infiltration.

Adenofibroma↗

Tissue binding of lectins in disorders of the breast.

Twenty breast lesions including seven scirrhous ductal carcinomas, one infiltrating lobular carcinoma, one colloid carcinoma, four fibroadenomas, and seven cases of fibrocystic disease were analyzed by fluorescence microscopy for the presence and distribution of lectin-binding carbohydrates. Paraffin-embedded tissue sections were tested with wheat germ agglutinin (WGA), Ricin communis agglutinin I (RCA I), peanut agglutinin (PNA), Soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), Ulex europaeus agglutinin I (UEA I), and concanavalin A (Con A). Brightest and most consistent staining regardless of the nature of the breast lesion was obtained with WGA followed in approximate order of staining intensity by RCA, PNA, SBA/DBA and Con A. UEA I stained many of the benign breast lesions but no malignant lesions. Lectin binding carbohydrate in benign lesions was localized mainly along the apices of mammary epithelial cells but there was considerable variation in staining patterns among malignant tumors. The fluorescence microscopic arrangement of lectin binding carbohydrate appears distinct for each malignant neoplasm of breast but is more consistent in benign conditions.

Adenocarcinoma, Mucinous↗

Cytochemical and competitive protein binding assays for estrogen receptor in breast disease. A comparative study of 62 cases.

Estrogen receptor content of breast lesions was estimated using a fluorescent cytochemical technique and a competitive protein binding assay. Of 48 cancers examined, an equal proportion contained significant quantities of receptor by either method (62.5%). The concordance between methods for individual patients was also 62.5%. A greater proportion (26%) of patients younger than 45 years of age had receptor-positive cancers using the cytochemical method than were found by the biochemical method (10%). Benign breast disease was also studied using the fluorescent cytochemical method. A greater proportion of lesions containing estrogen receptors was found compared with that cited in the literature for the competitive protein-binding assay. Because of the methodologic simplicity of the fluorescent cytochemical method, further study for routine use is indicated.

Adenofibroma↗

Radial scar in the female breast. A long-term follow-up study of 32 cases.

In a retrospective histologic study of 1862 benign breast tissue specimens, 32 cases were found to have radial scar. The radial scar was multicentric in 44%, and found in breasts with fibrocystic disease and/or duct ectasia. During a follow-up period of 19.5 years (range, 15-24 years), one patient developed breast cancer compared with an expected rate of 0.94. Therefore, local excision of radial scar without further follow-up is sufficient.

Adenofibroma↗

Serial analysis of fibronectin concentration in plasma of patients with benign and malignant breast diseases.

The serial levels of fibronectin (FNp) in plasma from 65 patients with benign and malignant breast disease and from 74 healthy control women were assayed by the use of the rocket immunoelectrophoresis procedure. Mean FNp levels in patients with breast cancer were age-matched with control subjects, but no clear correlation was found between FNp levels and the presence of primary tumor. Mean FNp values for fibroadenoma patients did not differ either from controls or from patients with malignant disease. Patients were also categorized according to TNM classification, to the number of positive axillary nodes, to the histologic grade of malignancy, and to the presence of estrogen receptors. Although differences were not significant, a higher number of patients with levels greater than the normal 95% percentile were found only in the group with four or more positive axillary nodes and in the group with a greater number of histologic malignancies. Marked fluctuations in FNp concentrations were found in individual patients during the follow-up period, independently of the treatment received. FNp seems unsuitable as a tumor marker because, besides its apparent lack of specificity for cancer, it reflected neither the host-tumor burden nor the response to treatment.

Adenofibroma↗

Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation.

Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation. Of the 4 grades of differentiation, the less differentiated Grade III and IV tumors showed significantly lower levels of estrogen and progesterone receptors in infiltrating ductal and lobular carcinoma (P less than 0.001). In contrast, patients with medullary carcinoma had the lowest tissue levels of estrogen and progesterone receptors with approximately 80% of the cases with less than 10 fmol/mg protein. Patients with mucinous carcinoma had the highest percentages of positive estrogen and progesterone receptor levels (75% and 87%, respectively). Sixty-three percent of the patients with Grade IV infiltrating ductal carcinoma were younger than 53 years of age (P less than 0.001). Patients younger than 53 years of age with Grade II and III infiltrating ductal carcinoma also had significantly lower levels of estrogen receptors, but not of progesterone receptors, than those patients older than 53 years of age (P less than 0.001). Nineteen of 20 "normal" breast tissue specimens were negative (less than 3 fmol/mg protein) for estrogen and progesterone receptors. About 50% of 17 tissue specimens from benign breast lesions (fibroadenoma, fibrocystic disease, sclerosing adenosis) showed positive estrogen (greater than 10 fmol/mg protein) or progesterone receptor values. In two patients with gynecomastia, no estrogen or progesterone receptors were detectable.

Adenocarcinoma↗

Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study.

A forensic autopsy series of 519 women more than 14 years old was studied for prevalence of benign, atypical, and occult malignant breast lesions. The women included Anglos (non-Hispanic whites), Hispanics, and American Indians from New Mexico and Eastern Arizona. These three ethnic/racial groups are at markedly different risk for the development of breast cancer (Anglo 89 of 100,000 women per year, Hispanic 45.5, and American Indian 24.9. There were striking ethnic/racial and age-related differences in both the prevalence and magnitude of all forms of nonproliferative and proliferative fibrocystic disease. The various subsets of fibrocystic disease were highly associated with each other. Such lesions as apocrine metaplasia, sclerosing adenosis, and lobular microcalcification showed as much difference according to ethnic/racial background and age as the more common cystic change and duct epithelial hyperplasia. Atypical lobular and ductal hyperplasia, carcinoma in situ, and occult invasive carcinoma were uncommon and also occurred in ethnic/racial groups in a pattern that parallels the cancer risk in those groups.

Adenofibroma↗

Endodermal sinus tumor and mucinous cystadenofibroma of the ovary. Occurrence in an 82-year-old woman.

We encountered an unusual ovarian tumor consisting of a mixture of typical endodermal sinus tumor (EST) and mucinous cystadenofibroma that occurred in the ovary of an 82-year-old female patient. The EST component showed the classic histologic features of this tumor. Serum alpha-fetoprotein (AFP) level was not determined. Tumor stains were negative for AFP but positive for alpha-1-antitrypsin. The malignant germ cell component was intimately associated with the benign mucinous component. Focal production of epithelial mucin and carcinoembryonic antigen (CEA) in the EST component suggested a probable association between the two tumor types. The tumor was confined to one ovary, and the patient is disease-free 2 years after surgical therapy. This neoplasm is unique not only for the malignant germ cell component occurring in an 82-year-old woman, but for the unusual combination of tumor types. The pathogenesis is unknown.

Adenofibroma↗

Pseudoangiomatous hyperplasia of mammary stroma. Some observations regarding its clinicopathologic spectrum.

Pseudoangiomatous hyperplasia of mammary stroma (PHMS) is a benign proliferation of keloid-like fibrosis, containing slit-like pseudovascular spaces. Its main importance is its distinction from angiosarcoma; however, the clinicopathologic spectrum of PHMS remains incompletely described. We report two new cases and describe our findings in 200 consecutive breast specimens evaluated for the presence of PHMS. The first patient presented with peau-de-orange change in the overlying breast skin, thus mimicking inflammatory breast carcinoma. Furthermore, this patient's PHMS lesion had been diagnosed and treated inappropriately as a low-grade angiosarcoma. The second case showed the more typical, fibroadenoma-like presentation of PHMS. In addition, PHMS changes occur commonly in routine breast biopsy specimens. In fact, our review of 200 consecutive breast specimens showed PHMS in at least one microscopic focus in 23% of cases. The PHMS changes occurred in younger patients than the control population and were associated with fibrocystic changes, in fibroadenomas, in gynecomastia, in normal breast tissue, and in sclerosing lobular hyperplasia. Ultrastructural and immunohistochemical studies of one case showed that the capillary-like spaces were either acellular or lined by fibroblasts. Pseudoangiomatous hyperplasia of mammary stroma represents a clinicopathologic spectrum, extending from focal, insignificant microscopic changes to cases where PHMS produces a breast mass. Increased awareness of PHMS and its clinicopathologic spectrum will allow its differentiation from other vascular tumors of the breast, especially low-grade angiosarcoma.

Adenocarcinoma↗