Oncocytic carcinoma (malignant oncocytoma) of the breast.

Three cases of oncocytic carcinoma of the breast observed in two women and one man are reported. One tumor was in situ and two were invasive. All three tumors were composed mostly of cells with "low-grade" nuclei and abundant granular eosinophilic cytoplasm. More than 70% of the neoplastic population in each case was immunoreactive with an antimitochondrion antibody. The presence of numerous mitochondria also was demonstrated at the ultrastructural level. Apocrine cells and oncocytes share similar morphologic features at the hematoxylin-eosin level; however, there are some differences that allow a confident distinction between these two cell types. Mitochondria in apocrine cells usually are in a perinuclear location and are not so numerous and diffusely dispersed as in oncocytes. In addition, apocrine cells display features of active secretory elements: prominent microvilli, well-developed Golgi complex, and electron dense secretory granules polarized toward the luminal pole; all these features were lacking in the three cases described. The cells constituting the present cases were not positive at the immunohistochemical and molecular levels for GCDFP-15/PIP mRNA, which are typical markers of apocrine differentiation. We suspect that mammary oncocytoma is a more common tumor than the meager number of reported cases suggests.

Recurrent phyllodes tumor in a man.

The case of a 35-year-old man with a borderline-type cystosarcoma phyllodes is presented. Four years after the primary excision of the tumor, wide excision of a local recurrence and postoperative radiotherapy were performed. No repeated relapse was observed during a 5-year follow-up. Neither significant endocrine changes nor genetic alteration could be proven. However, a slightly increased SHBG concentration was detected, resulting in a decreased biologically available androgen level reduced testosterone/SHBG index. This phenomenon might be a consequence of the chronic liver disease of the patient due to his type II diabetes mellitus and alcohol abuse. In addition to the conventional histopathological examinations, immunohistochemical and electron-microscopic investigations were carried out on tissue sections, and the steroid receptors, EGF receptors and EGF-like activity of the tumor were also studied.

Fine needle aspiration of breast myofibroblastoma. A case report.

BACKGROUND: The use of fine needle aspiration cytology (FNAC) for the diagnosis of breast diseases in men has received little attention. We report the cytologic and histologic findings of myofibroblastoma of the breast in a 52-year-old man. CASE: Smears disclosed irregular and cohesive sheets of cells, with ill-defined cytoplasm and oval nuclei containing single nucleoli. The nuclear membrane was frequently grooved, and occasional intranuclear cytoplasmic inclusions (pseudoinclusions) were also found. The background was clean and contained scarce collagenous stroma and fragments of myxoid material. To the best of our knowledge, there have been only seven previous reports of breast myofibroblastoma in which the cytologic features are well documented, and none of them mention the presence of pseudoinclusions. CONCLUSION: FNAC could suggest the diagnosis of this distinctly uncommon tumor if evaluated together with the clinical and radiologic findings.

Fine needle aspiration cytology of a male breast carcinoma exhibiting neuroendocrine differentiation. Report of a case with immunohistochemical, flow cytometric and ultrastructural analysis.

We present the cytologic, immunohistochemical, flow cytometric and ultrastructural findings of a case of invasive ductal carcinoma of the breast with features of neuroendocrine differentiation occurring in an 83-year-old male. Fine needle aspiration (FNA) cytology of the patient's tumor demonstrated a markedly cellular specimen to discohesive tumor cells, present primarily singly, with occasional loose groups. The cells were relatively large, with pleomorphic, eccentrically placed, round to oval nuclei. The cytoplasm was abundant and contained prominent red granules (Papanicolaou stain) that were also argyrophilic. Immunohistochemical studies performed on the aspirate and the subsequently excised malignant breast tissue revealed positive staining for neuron-specific enolase, chromogranin A, synaptophysin and gastrin. Also, the majority of the tumor stained positive with antibodies to both estrogen and progesterone hormone receptors. DNA flow cytometry demonstrated an aneuploid stemline population with a DNA index of 1.73 and an S-phase fraction of 4.5%. Electron microscopy was performed on the FNA material, and numerous variable-sized, membrane-bound, dense-core granules diffusely scattered within the cytoplasm of the neoplastic cells were identified. The specific cytologic features of this tumor, along with the immunocytochemical and ultrastructural features, can aid the pathologist in rendering an accurate FNA diagnosis of this specific subtype of breast carcinoma.

Myofibroblastoma of breast--an appraisal of cytoskeletal phenotypes.

Myofibroblastoma of the breast is a recently described entity. Since its first description in 1987, less than 50 cases have been reported. We present the first (reported) myofibroblastoma to be detected as a non-palpable mass on a routine screening mammogram and emphasize the importance of not mis-diagnosing this rare cellular lesion as malignant on frozen section. Review of the literature demonstrates changes in the clinical presentation of myofibroblastomas. Once considered more common in men than in women, myofibroblastomas are now being reported with increasing frequency in women. The age at presentation is a decade earlier, and not surprizingly, the size of the earlier detected lesion is smaller. Recently four different cytoskeletal phenotypes (V, VA, VAD and VD) of myofibroblastomas have been described, depending upon the vimentin (V), actin (A), and desmin (D) immunoreactivity. Whereas vimentin reactivity is universal, actin and desmin immunoreactivity is variable, desmin being more frequently positive than actin. As more is known about the clinical behavior of myofibroblastomas, their rate of recurrence and malignant potential, if any, the relationship of the cytoskeletal content to prognosis may become clearer. Currently, complete immunohistochemical analysis and electron microscopic examination of this interesting breast lesion is recommended. List of abbreviations-Vimentin (V), actin (A), and desmin (D), vimentin and actin (VA), vimentin and desmin (VD), vimentin, actin and desmin (VAD).

DNA content and S-phase fraction in male breast carcinomas.

Eighty-five male breast carcinomas limited to the breast, diagnosed between 1958 and 1967 in Sweden, were investigated by flow cytometry using paraffin-embedded tissue. DNA ploidy and S-phase fraction (SPF) were studied in relation to lymph node status, tumour size and malignancy grade, and with respect to clinical outcome. Median age at diagnosis was 65.5 years. Median survival time related to breast cancer was 78.7 months, and 37 patients died from the disease. Forty-nine (57.6%) carcinomas were aneuploid or had multiple stemlines. Median SPF was 8.9% for all tumours, for diploid and tetraploid (euploid) together 6.6%, and for aneuploid tumours 14.3% (p < 0.001). Ploidy was significantly related to the tumour size (p = 0.03), but no significant correlations with node status or malignancy grade were observed. In univariate survival analysis, node status, tumour size and malignancy grade predicted breast cancer mortality significantly. In a multivariate Cox's model, only node status and tumour size were independent prognostic factors. In contrast to females with breast cancer, ploidy and SPF had no significant relation to prognosis in males. This lack of predictive value of DNA analysis needs further evaluation. Studies based on extended materials are necessary to further investigated the role of DNA analysis as a predictor of outcome in male breast cancer patients.

Intraductal papilloma of the male breast: an ultrastructural and immunohistochemical study.

A case of intraductal papilloma of the male breast was studied by electron microscopy and immunohistochemistry. The major components of this lesion were the epithelial and myoepithelial cells. Intermediate cells showing ultrastructural features of both cell types were also observed. Squamous metaplasia was noted in many areas. Numerous intranuclear helioid inclusions were seen in the tumor cells. The features of this lesion are similar to those of papillomas of the female breast.

Pigmented epidermotropic ductal carcinoma of the breast in a male. Ultrastructural evidence of melanocytic colonization and melanin transfer to the tumor.

The first case of pigmented epidermotropic breast carcinoma in a male, presenting as a pigmented lesion of the areola and nipple, is described. Immunohistochemical and ultrastructural studies demonstrated that the pigmentation was found to be primarily due to colonization of tumor nests by melanocytes, with numerous melanophages interspersed in the desmoplastic stroma and only occasional compound melanosomes within the epithelial tumor cells.

Argyrophilic nucleolar organizer regions (AgNORs) in breast lesions--a study on fine needle aspirates.

Nucleolar organizer region-associated proteins are argyrophilic and may be visualized by silver stains. This study is a prospective analysis of the AgNOR counts in a range of breast lesions seen in fine needle aspiration (FNA) smears. A total of 72 cases including ductal carcinomas (n = 24), fibrocystic change (n = 24), fibroadenoma (n = 16), proliferative lesions (n = 4) and miscellaneous lesions (n = 4) were studied. The ductal carcinomas showed higher AgNOR counts (mean 16.63 +/- 7.09) compared with the non-malignant lesions (mean 6.39 +/- 1.96), the difference being statistically significant. A cut off AgNOR score of 11 could reliably discriminate malignant from non-malignant lesions. In ductal carcinomas, the AgNOR scores showed a tendency to increase with higher grades of malignancy. There was no correlation with the presence or absence of lymph node metastases at the time of presentation. It is concluded that AgNOR counting, although tedious, is inexpensive, and provides useful information regarding cellular proliferation, and can supplement information obtained by more sophisticated techniques.

Nuclear morphometry in male breast carcinoma: association with cell proliferative activity, oncogene expression, DNA content and prognosis.

To investigate the prognostic value of nuclear morphometry in male breast carcinoma (MBC), histological samples from 50 patients (mean age 62.2 years) were retrospectively analyzed by computerized nuclear morphometry. All patients received surgery; 35 had multiple combinations of adjuvant therapies. Mean follow-up was 67 months (range 1-230). In each case, 100 tumor cells were measured, and the mean nuclear area (MNA), standard deviation of the nuclear area (SDNA), mean nuclear perimeter (MNP), standard deviation of the nuclear perimeter (SDNP) and shape factor (SHF) were calculated. Morphometric features were compared with tumor histological grade, size, nodal status, DNA ploidy evaluated by flow-cytometry and cell proliferative activity assessed by the quantity of argyrophilic nucleolar organizer region-associated proteins (AgNORs), monoclonal antibody (MAb) PC10 against proliferating cell nuclear antigen and MAb MIB-1. Comparison was also made with the immunohistochemical detection of p53, bcl-2, c-erbB-2 and c-myc proteins. Significant association was found between nuclear morphometric parameters and tumor grade, DNA content and cell proliferation indices. SDNA was greater in p53-positive and bcl-2-negative cases; SDNP was greater in p53-positive cases; SHF was lower in p53- and c-myc-positive cases. Overall survival was shorter in carcinomas with high MNA, SDNA, MNP and SDNP and low SHF. In multivariate analysis, performed by testing nuclear morphometric parameters, histological grade, tumor size, nodal status and p53 immunostaining in the Cox model, p53 over-expression and histological grade retained independent prognostic significance. When p53 was excluded, only SDNP appeared as an independent prognostic variable. Our results indicate that nuclear morphometric parameters can identify an aggressive tumor phenotype and provide additional prognostic information for patients with MBC.

Myofibroblastoma of breast: evidence favoring smooth-muscle rather than myofibroblastic differentiation.

A histopathological study of two cases of the tumor known in the literature as myofibroblastoma of the breast is presented. The tumors occurred in Caucasian males aged 57 and 62 years. Histologically, these were moderately cellular, lobulated spindle-cell lesions, each with a reasonably well-delineated edge with surrounding fatty connective tissue. No breast ducts or lobules were present. Tumor cell nuclei were bland, with small nucleoli and some nuclear grooving. Nuclear atypia and mitoses were absent. Immunostaining revealed positivity for a-smooth-muscle actin, desmin, and CD34. Tumor cells contained rough endoplasmic reticulum, bundles of myofilaments with focal densities, intermediate filaments, attachment plaques alternating with plasmalemmal caveolae, and focal lamina. Ultrastructural findings pointed to true smooth-muscle differentiation, and the cell-surface in particular lacked surface features of myofibroblasts (fibronectin fibrils [microtendons] and fibronexus junctions). These and published data suggest that at least some of the lesions referred to in the literature as myofibroblastoma may not be myofibroblastic and may be better designated as myogenic stromal tumors or as variants of leiomyoma.

Immunohistochemical staining patterns of type VI collagen in the normal, hyperplastic, and neoplastic adult male breast.

Ten cases of primary invasive male breast ductal carcinomas (N.O.S.), one case of male breast fibroadenoma, seven cases of pure florid gynecomastia and four cases of normal mammary glands were examined immunohistochemically for type VI collagen expression and distribution. In normal male breast type VI collagen was absent in the whole fibrous stroma. On the contrary this collagen was markedly expressed in the stroma of invasive carcinoma as well as fibroadenoma and gynecomastia. In all these proliferative diseases, type VI collagen gave a distinct basement membrane-like deposition at the epithelial-stromal junctions while organized a fibrillar network in the interstitium. Our immunohistochemical findings showed that type VI collagens is involved in the stromal response of benign and malignant male breast proliferative diseases.