Fibroadenomas in patients receiving oral contraceptives: a clinical and pathologic study.
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The levels of thymus-derived lymphocytes (T-cells) in samples of peripheral blood from 47 patients with carcinoma of the breast, 36 patients with benign mammary lesions, and 33 matched normal controls were determined. Results were analyzed with three statistical tests. It was found that the mean percentages of T-lymphocytes differed significantly among the three groups of patients (p less than 0.001). The mean percentages of rosette-forming lymphocytes were 72.8 for the normal group, 60.6 for patients with benign mammary lesions, and 45.1 for the patients with carcinoma. The finding of lower levels of T-lymphocytes in the peripheral blood of individuals with mammary cancer is of particular significance since all the patients in this study were otherwise in apparently good general health and undergoing no treatment.
The extant literature pertaining to the ultrastructural features of disorders of the human breast is reviewed and annotated with findings derived from a personal study of 82 patients whose specimens encompassed a wide variety of such lesions. In addition, observations of lesions heretofore undescribed are presented.
Hyperplastic lesions of the prostatic stroma with atypical changes are presented and discussed. One lesion was a leiomyoma with atypical organization and a limited area of nuclear pleomorphism without mitotic figures. One was a lesion which in many portions was histologically indistinguishable from leiomyosarcoma. It, however, had certain features probably connoting less sinister behavior, and at autopsy 16 months after resection there was no evidence of recurrence or metastasis. One lesion histologically resembled fibroadenoma of the female breast. These three lesions occurred in patients more than 50 years who had symptoms and signs of prostatism. Reference is made to two previously reported lesions reminiscent of cystosarcoma phyllodes of the female breast. All the lesions were located in the craniad prostate, which is estrogen-influenced. A parallel is drawn between these atypical changes in prostatic fibromuscular stroma and atypical changes in the connective tissue stroma of the female breast.
A murine monoclonal antibody, OC125, reacts with a surface component of ovarian tumor cells from humans, but fails to react with normal adult ovarian cells. The spectrum of reactivity of OC125 in ovarian tumors from humans was defined by testing cryostat tissue sections from 60 selected ovarian tumors by indirect immunofluorescence. OC125 stained 7/7 benign, and borderline serous ovarian tumors, 19/23 (83%) serous adenocarcinomas, 2/2 mixed serous and endometrioid carcinomas, 2/3 endometrioid carcinomas, 1/4 clear cell carcinomas, and 2/2 undifferentiated carcinomas. No reactivity was found in eight mucinous ovarian tumors or any of the other 11 epithelial sex cord, germ cell, on hematopoietic tumors tested. In neoplastic cysts, papillae, and glands, the staining was most intense on the luminal surface or in subjacent cytoplasm. Cells in solid sheets also showed peripheral staining. Within a reactive tumor, both negative and positive cells could be found, intimately intermixed. There were no differences in these staining patterns between tissues from primary and metastatic sites. The expression of the OC125 antigen was not related to the degree of malignancy as judged by pathologic criteria. Although mucinous tumors lacked reactivity with OC125, seven of eight mucinous adenomas and adenocarcinomas bound a monoclonal antibody against carcinoembryonic antigen (CEA). Thus, OC125 recognizes a common antigen in some but not all ovarian tumors of serous, clear cell, endometrioid, or undifferentiated type. OC125 may prove useful in the pathologic and cytologic identification of certain types of ovarian tumor cells. Its lack of reactivity with mucinous tumors suggests these belong in a distinct subgroup of ovarian epithelial tumors.
This study reports the distribution of 3H-estradiol incorporation as assessed by thaw-mount autoradiography after in vitro incubation of fresh tissue obtained from a series of 17 benign human mammary lesions. In four out of nine cases of fibroadenoma examined, putative estrogen target cells were identified in ducts where the specific labeling was confined to some but not all epithelial cells. Elsewhere in these lesions, negative ducts could be found. Similarly, in three out of eight cases of fibrocystic disease specific labeling was seen over epithelial cells in some areas but not others. Histologically identifiable myoepithelial cells were negative as well as the vast majority of stromal cells.
The involvement of Nonspecific Crossreacting Antigen (NCA) in the immunohistological demonstration of Carcino Embryonic Antigen (CEA) in 56 benign and 92 malignant lesions of the breast was analyzed. For this purpose, the authors utilized both polyclonal antisera and monoclonal antibodies. Polyclonal anti-CEA sera were used after absorption with normal tissue antigens, in order to remove crossreactivity, and without such an absorption. Ninety-three percent of breast carcinomas, 85% of mastopathic lesions not associated with a carcinoma, and 66% of fibroadenomas showed positive reactions with commercial unabsorbed polyclonal anti-CEA serum, which contained antibodies to NCA, whereas incubation with monospecific anti-CEA antiserum resulted in 42% positivity in carcinomas and negativity in mastopathic lesions and fibroadenomas. Forty-eight percent of breast cancer, 84% of mastopathic lesions, and 50% of the fibroadenomas contained NCA in different quantities. The staining pattern of carcinomas and fibroadenomas obtained with unabsorbed anti-CEA antibody and anti-NCA did not run parallel in all cases. Monoclonal antibodies against CEA and NCA confirmed the results obtained with polyclonal antiserum. This study suggests a cancer specificity of CEA in breast lesions.
Electron microscopic studies were conducted on 11 cases of cystosarcoma phyllodes (6 benign, 3 malignant, 2 recurrent), 1 stromal sarcoma, and 15 cases of fibroadenomas. Particular emphasis was placed on examination of the epithelial-stromal junction. The epithelial cells were basically similar in all cases. The basal lamina of fibroadenomas tended to be reduplicated, whereas in cystosarcoma phyllodes the basal lamina was less reduplicated and even focally absent. A continuous layer of delimiting fibroblasts was not present in either type of tumor. Stromal cells were generally fibroblasts, with 2 of 15 being fibroadenomas and 2 of 11 cystosarcoma phyllodes showing myofibroblastic differentiation. The stromal sarcoma also showed smooth muscle differentiation. The authors conclude that the epithelial-stromal junction is abnormal in both fibroadenomas and cystosarcomas, but the abnormality is different in these two tumors. Increasing prominence of stromal cell junctions and of lysosomes also correlated with the diagnosis of cystosarcoma, particularly the malignant variant.
A retrospective double-blind examination of the cytologic smears and frozen section tissue slides from 140 lesions of the breast was performed in order to assess the diagnostic accuracy of each method. The cases with diagnostic errors were reevaluated to define the pitfalls encountered in the intraoperative diagnosis of breast lesions by both methods. Results with the cytologic technics are more variable than with frozen sections, but when read by experienced observers the smears are as accurate as frozen sections and have the additional advantages of rapidity, sparing of tissue for other studies, better correlation with fine-needle aspiration cytologic results, and more complete sampling of large or multiple specimens. The authors recommend that intraoperative cytologic examination be employed routinely in breast diagnosis, initially always in conjunction with frozen section examination but eventually in many cases as an alternative technic.
The authors reviewed the fine-needle aspiration biopsy smears from 62 subjects with proven fibroadenoma, 60 subjects with proven ductal carcinoma, and 42 subjects with proven fibrocystic disease. All smears were coded as to the presence or absence of the following variables: epithelial cells, stroma, honeycomb sheets, antler horn clusters, naked nuclei, nucleoli, marked cellularity, foam cells, apocrine cells, anisokaryosis, atypical nuclear hyperchromasia, single cells with cytoplasm, mitotic figures, and nuclei greater than two red blood cell diameters. Step-wise logistic regression analyses were performed to determine the variables predictive of fibroadenoma. The statistical analyses selected stroma, antler horn clusters, and marked cellularity as the key cytologic criteria to differentiate fibroadenomas from fibrocystic disease. The statistical analyses selected stroma, antler horn clusters, and honeycomb sheets as the key cytologic criteria to differentiate fibroadenoma from ductal carcinoma.
This study assessed the value of argyrophilic nucleolar organizer region (AgNOR) staining as a potential technique for the estimation of cell kinetics in conventional histology sections, in benign and malignant breast lesions. Using a silver staining technique and immunohistochemistry, the authors correlated the numbers of argyrophilic nucleolar organizer regions (AgNORs) and Ki67 scores in 70 breast carcinomas and 27 benign breast lesions. Epithelial cells in fibrocystic disease and fibroadenomas contained a mean of 2.65-6.8 small uniform AgNORs per cell, whereas malignant cells contained 4.6-26.9 frequently highly irregular AgNORs. In benign tissue, Ki67 scores ranged from 0 to 4%; in malignant tumors, Ki67 scores ranged from 3.0 to 98%. The correlation between AgNOR counts and Ki67 scores was highly significant (P less than 0.001). The authors concluded that AgNOR counts performed on routine formalin-fixed paraffin sections furnish significant kinetic information. Furthermore, the difference in AgNOR counts between benign and malignant tumors is such that they may be of diagnostic value.
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.
Pleomorphic adenoma (or benign mixed tumor) of the breast is a rare benign neoplasm that might be misinterpreted both clinically and pathologically as a malignant tumor. The authors present an additional case of this unusual lesion studied by immunohistochemistry, electron microscopy, and flow cytometry. A 77-year-old white woman presented with a 2-cm, nontender, mobile, calcified, right subareolar mass suggestive of a fibroadenoma. Microscopically, the tumor resembled a pleomorphic adenoma occurring in salivary glands. Positive immunostaining for S-100 protein, cytokeratin, and muscle-specific actin, as well as the ultrastructural presence of intermediate filaments with dense bodies and intercellular junctions, supported the predominant myoepithelial cell differentiation within the tumor, whereas the epithelial cell component stained only with cytokeratin and contained formed lumina with surface microvilli. The DNA pattern was diploid. The patient is alive and well 14 months after surgery. The authors' findings confirm that pleomorphic adenoma of the breast is a benign neoplasm in which myoepithelial cell proliferation plays a major role in tumorigenesis.
The authors report the clinicopathologic features of 105 carcinomas arising within fibroadenomas (FAs) of the breast. The mean age of the patients was 44 years. The presentation and gross characteristics of these tumors rarely differed from those of uncomplicated FAs. Carcinoma in situ (CIS) was the predominant type of malignancy (95%) found to arise in FAs, and lobular and ductal types occurred with equal frequency. Nine of ten FAs harboring an invasive carcinoma also contained CIS supporting the origin of the infiltrative component in the FAs. CIS within FAs was associated with in situ malignancy in surrounding breast tissue in 21% of cases. Age, fibroadenoma size, and type and extent of CIS were similar in patients with disease limited to the FA and in those with associated malignant disease in the remainder of the breast. Axillary nodal metastases were not detected. Sixty-three patients were observed for a mean period of 8.4 years. Only one of 26 patients with CIS within an FA who was treated conservatively developed an ipsilateral carcinoma. None of the 26 developed contralateral carcinoma; however, 3 of 23 with similar lesions, who were treated by mastectomy, did so. The contralateral carcinomas were invasive in two patients, one of whom died with distant metastases. Seven patients with FAs harboring lobular CIS underwent bilateral mastectomy. Their postoperative course was uneventful. None of seven patients with invasive carcinoma arising in an FA, two of whom were treated conservatively, succumbed to disease. However, one developed contralateral carcinoma. The authors recommend breast-conserving therapy for CIS arising in an FA.
The cytologic features of fine-needle aspiration specimens from 16 breast carcinomas that closely simulated benign lesions were analyzed and compared to smears from fibroadenomas and fibrocystic change. No combination of features was found that accurately separated all benign and malignant cases. Many nuclei with discernible small nucleoli in smears with many single bipolar nuclei indicated a benign lesion, whereas nuclear hyperchromasia indicated a malignant one.
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