Contrast-enhanced sonography in the examination of benign and malignant adnexal masses.

Our objective was to characterize the properties of an intravascular ultrasonographic contrast agent in examination of adnexal masses and to compare contrast agent properties between benign and malignant adnexal tumors. Fifty-eight consecutively examined women with suspected ovarian tumors were examined preoperatively by power Doppler ultrasonography, first without and then with contrast agent enhancement (Levovist). Fourteen women had ovarian cancer, 3 had borderline ovarian tumors, 18 had benign ovarian neoplasms, and 23 had functional adnexal cystic masses or endometriomas. The effect of the contrast agent was evaluated visually and by using computerized power Doppler signal intensity measurements. In visual evaluation, the brightness of the power Doppler signal and the amount of recognizable vascular areas increased in each tumor after contrast agent administration. The number of vessels in power Doppler ultrasonograms, both before and after contrast agent enhancement, was significantly higher in malignant than in benign adnexal masses, as also was the increase in the number of recognizable vessels after contrast agent administration. Contrast agent uptake time was significantly shorter in malignant than in benign tumors. No significant differences were found in the power Doppler signal intensities or their changes between benign and malignant tumors. In conclusion, use of sonographic contrast agent facilitates imaging of tumor vessels. For differentiation of benign and malignant tumors, the kinetic properties of the contrast agent, such as uptake and washout times, may have more potential than the use of the contrast agent in anatomic imaging of the tumor vessels.

Eccrine syringofibroadenoma (Mascaro): an ultrastructural study.

To confirm the eccrine acrosyringeal differentiation of eccrine syringofibroadenoma (ESFA) and to elucidate the histogenesis of its angiofibrotic stroma, a case of ESFA from a 45-year-old man was examined by light and electron microscopy. Histologically, the parenchyma featured anastomosing, slender epithelial cords containing small cuboidal cells and occasional duct-like structures. The stroma had increased numbers of mast cells, increased capillaries with swollen endothelial cells, and prominent fibrosis. Ultrastructurally, the following findings were characteristic of ESFA: a) abundant glycogen particles in epithelial cells, b) numerous intracytoplasmic and extracellular spaces lined with microvilli, c) intraepithelial duct formation, consisting of microvilli, vesicles, rod-shaped dense bodies, multivesicular dense bodies, and peripheral network of tonofilaments, and d) large numbers of mast cells, closely associated with fibroblasts, surrounding increased numbers of capillaries containing swollen endothelial cells. These ultrastructural features support the acrosyringeal differentiation of ESFA. We hypothesize that mast cell hyperplasia and degranulation may play an important role in the formation of the angiofibrotic stroma.

Eccrine syringofibroadenomatosis: a clinical and histologic study and review of the literature.

A 56-year-old man had an 11-year history of a psoriasiform eruption of the palms, soles, and shins. An examination revealed well-demarcated patches and plaques of erythematous, fissured, and hyperkeratotic skin with focal erosions. There was no clinical evidence of ectodermal dysplasia. On histologic examination these lesions proved to be eccrine hamartomas that consisted of anastomosing cords and strands of cuboidal epithelial cells with well-formed ducts and a fibrovascular mucinous stroma. Eccrine ductal origin was indicated by histopathologic, histochemical, immunopathologic, and electron microscopic evaluation. These multiple palmoplantar eccrine hamartomas, unassociated with ectodermal dysplasia, represent a sporadic hamartomatous condition that is best designated as "eccrine syringofibroadenomatosis."

Changes in the extracellular matrix of the normal human breast during the menstrual cycle.

The normal human mammary gland undergoes a well defined sequence of histological changes in both epithelial and stromal compartments during the menstrual cycle. Studies in vitro have suggested that the extracellular matrix surrounding the individual cells plays a central role in modulating a wide variety of cellular events, including proliferation, differentiation and gene expression. We therefore investigated the distribution of a number of extracellular matrix molecules in the normal breast during the menstrual cycle. By use of indirect immunofluorescence, with specific antibodies, we demonstrated that laminin, heparan sulphate proteoglycan, type IV collagen, type V collagen, chondroitin sulphate and fibronectin undergo changes in distribution during the menstrual cycle, whereas collagen types I, III, VI and VII remain unchanged. These changes were most marked in the basement membrane, sub-basement membrane zone and delimiting layer of fibroblasts surrounding the ductules where basement membrane markers such as laminin, heparan sulphate proteoglycan, and type IV and V collagens appear greatly reduced during the mid-cycle period (days 8 to 22). These results suggest that some extracellular matrix molecules may act as mediators in the hormonal control of the mammary gland, whereas others may have a predominantly structural role.

Aspiration biopsy of the breast tumors. Analysis of diagnostically difficult cases.

In this paper the authors described those of the breast fine needle aspirates which were difficult for interpretation e.g. clear-cut differentiation between benign and malignant character of the lesion could not be made. There were 40 such cases (1.96%) out of 2332 breast tumors biopsied between 1987-1989. In the cases that proved to be malignant on histology the authors described cytological features which speak in favour of malignancy. In the group of smears which proved to be benign on histology the authors described the features that imitate atypia and should not be misdiagnosed as malignant. The described criteria may be of some help in cytological diagnosis of breast masses.

Occurrence of epidermal growth factor receptors in benign and malignant ovarian tumors and normal ovarian tissues: an immunohistochemical study.

Epidermal growth factor receptor (EGF-R) was studied with monoclonal antibody 2E9 on 50 ovarian tumors of various histological types and 10 non-tumorous ovarian tissues by immunohistochemistry. Enhanced expression was observed in 26/50 (52%) of the tumors. Only 25 out of 46 epithelial tumors (54%) showed positivity in epithelial tumor cells. Staining was cytoplasmic in all cases. No correlation was established between EGF-R expression and the histological type of the epithelial tumor. Apart from EGF-R expression in tumor cells, low immunoreactivity was also observed in stromal and endothelial cells in both normal and tumorous ovarian tissues. Furthermore in 8/9 specimens containing necrotic areas, EGF-R was noticed in these areas as well. Both of the latter observations may have impact on the evaluation of the prognostic value of EGF-R activity in tumors, when based on EGF-R measurements using biochemical binding studies. We therefore recommend that EGF-R is measured with both methods in studies regarding its clinical value.

Frequency of cytologic features in fine needle aspirates from histologically and cytologically diagnosed fibroadenomas.

Identification of key cytologic criteria for various lesions by means of stepwise logistic regression is common today and is often claimed to facilitate cytologic diagnosis. As can be expected, there usually is good agreement between the selected criteria and those given in the cytologic literature. In a study by Bottles et al based on 64 fibroadenomas, stroma, antler horn clusters and honeycomb sheets differentiated fibroadenoma from ductal carcinoma. We applied Bottles's criteria to our fibroadenoma material in order to test their value in clinical cytologic practice. In fine needle aspirates from histologically (cytologically) diagnosed fibroadenomas, stroma was found in 41 (57%), antler horn clusters in 59 (90%) and honeycomb sheets in 62 (81%), which reduced the clinical value of the criteria.

Expression of heat shock protein 70 and c-myc protein in human breast cancer: an immunohistochemical study.

The major heat shock protein, HSP70, protects cells from a variety of stressful stimuli, while c-myc protein allegedly stimulates the expression of HSP70 by transacting on the HSP70 promotor. The present study was aimed at correlating the expression of HSP70 with that of c-myc protein in benign and malignant breast lesions. Indirect immunoperoxidase and immunoblotting techniques using monoclonal antibodies were employed. Fresh frozen sections were prepared from five fibroadenomas and 59 breast carcinomas. Immunohistochemically, both substances were localized in the nuclei and/or cytoplasm of normal and neoplastic epithelial cells. The stromal cells were positive for c-myc protein but negative for HSP70. The expressions of HSP70 and c-myc protein were comparable to each other in the malignant cells from 37 (63%) carcinomas. In 17 (29%) carcinomas, c-myc protein expression predominated over that of HSP70, whereas in five (8%) carcinomas, HSP70 was predominant. Carcinomas with high-grade nuclear atypia often showed negative HSP70 staining, whereas tumors with nuclear HSP70 localization tended to accompany lower-grade nuclear atypia. A similar relation was also observed between c-myc protein expression and nuclear atypia of the tumor. All five fibroadenomas and most of the non-neoplastic epithelial cells adjacent to cancer showed strong reactivities with both substances. Immunoblot analysis for HSP70 revealed a clear, single band in the extract of tumors with strong HSP70 staining, but no, or only faint, bands were seen in the extract of immunohistochemically HSP70-negative carcinomas. The discrepancy between the expressions of each substance in a certain percentage of breast carcinomas may suggest the presence of HSP70 production mechanisms other than the c-myc protein-triggered promotor pathway.

[The 3-dimensional organization of the nucleoli of benign and malignant tumor cells from different human organs]. / Trekhmernaia organizatsiia iadryshek dobrokachestvennykh i zlokachestvennykh opukholevykh kletok razlichnykh organov cheloveka.

The method of ultrathin serial sections was used to perform a comparative ultrastructural and 3-dimensional analysis of nucleoli for the following variants of human tumours: benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) tumours of one organ (mammary gland); malignant tumours of epidermal genesis in different organs (squamous cell carcinomas of skin, larynx, lung, gullet, uterus); two forms of malignant tumours (squamous cell and small cell carcinomas) of one organ (lung). The spatial models of nucleoli in these tumour cells are given. The specific signs in architecture of tumour nucleoli was found. Nucleoli of fibroadenomas have well pronounced 1-4 fibrillar centres forming a united system with a lacunar component and intranucleolar chromatin. Unlike benign tumour cells, nucleoli of infiltrating ductal carcinomas are characterized by large, prominent nucleoli containing giant, multiform fibrillar centres with a complicated surface, a well developed granular component and an unusually organized lacunar system. In squamous cell carcinomas of various localization, active, hypertrophied nucleoli with pseudonucleolonemal organization were found. The small cell carcinoma of lung differs from the squamous cell cancer of the same organ by dense, fibrillar nucleoli with a small amount of granular component located on the periphery of the nucleolar body. Nucleolar type reflecting the functional state of malignization process may serve as an additional diagnostic criterion for tumour identification.

Glial fibrillary acidic protein immunoreactivity in normal and diseased human breast.

Immunostaining for glial fibrillary acidic protein (GFAP) identifies a minor subpopulation of immunoreactive myoepithelial cells in the normal resting human breast. The GFAP-immunoreactive cells also express a panel of myoepithelial cell markers, including cytokeratin 14 (CK 14), vimentin, smooth-muscle-specific actin isoforms, nerve growth factor receptor (NGFR) and common acute lymphoblastic leukaemia antigen (CALLA). The percentage of GFAP-immunoreactive myoepithelial cells is greatly increased in various neoplastic and non-neoplastic diseases of the breast, being highest in adenomyoepitheliomas. Furthermore, in all the instances of fibroadenoma, phyllodes tumour, epitheliosis and gynaecomastia, a variable number of epithelial cells also acquires immunoreactivity for GFAP, vimentin, CK 14, NGFR and, to a lesser extent, for CALLA. Conversely, GFAP immunoreactivity has never been encountered in the malignant cells of the different types of breast carcinoma. These findings suggest that the expression of GFAP might be a (possibly transient) feature of proliferating epithelial and myoepithelial cells in breast diseases other than carcinomas.

[Intracytoplasmic lumina of benign and malignant breast diseases--a light and electron microscopic study].

Intracytoplasmic lumina (ICLs) of 70 cases with breast carcinoma and 29 cases with benign breast diseases were observed by light and electron microscopy. ICLs were morphologically divided into two types. Type A was characterized by the presence of secretory materials stained with eosin in the lumen and Type B by the cytoplasmic vacuoles under light microscope. Electron microscopic observation on Type A ICLs showed numerous filiform microvilli projecting towards the lumen and various amounts of secretory materials in the lumen. Type B of ICLs only had scanty and short microvilli and rarely secretory materials in the lumen. The results indicated that: 1. The frequency of ICLs in breast cancer was significantly higher than that in benign breast disease (P less than 0.01). 2. The frequency of ICLs in breast cancer showed strong negative correlation with its histological grades but not with its histological types. 3. ICLs had similar frequency under both light and electron microscopes. As a relatively specific structure in breast carcinoma cells, ICLs may be helpful in the diagnosis of breast carcinoma and establishment of the breast origin for metastatic carcinoma.

Pleomorphic adenoma (benign mixed tumor) of the breast. An immunohistochemical, flow cytometric, and ultrastructural study and review of the literature.

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.

Ultrastructural analysis of fine needle aspirates from benign breast lesions.

Thirty six fine needle aspirates from various types of benign breast lesions were examined by electron microscopy and correlated with their cytological appearances. In all cases the parenchyma consisted of clumps of cohesive cells with the ultrastructural features of epithelial cells. In many cases, particularly from fibroadenomas, the parenchyma consisted of single layers of polarised epithelial cells showing lumen formation. Similar arrays of apocrine epithelial cells were observed in 60% of fibrocystic lesions. The more solid clumps from hyperplastic lesions consisted of epithelial cells of variable shape and electron density with disorganised lumen formation. Irrespective of the type of lesion, the epithelial cells were not normally subtended by myoepithelial cells or basal lamina. The extraction process seems to result in a shearing between the epithelium and basal lamina with lysis of the myoepithelial cells. Most naked nuclei probably result from lysed myoepithelial cells.

The cytokeratin profiles of ovarian common "epithelial" tumors.

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.

Semiquantitative analyses of fine needle aspirates from benign and malignant breast lesions.

A scoring system for the assessment of fine needle aspirates of benign and malignant breast lesions was devised which showed a positive correlation (r = 0.67) between the scores obtained from the fine needle aspirates from ductal carcinomas and the Bloom and Richardson-type scores for their paired excision biopsy specimens. This system permitted grades II and III ductal breast carcinoma to be distinguished reliably from grade I tumours but no correlation with the lymph node state of patients with breast carcinoma was shown. Some overlap between the scores for grade I ductal carcinomas and some benign lesions was found, and this underlines a need for caution in the reporting of such equivocal aspirates. No cytological features that distinguished reliably ductal from lobular carcinoma were identified but the same spectrum of severity of cytological abnormality in the ductal and lobular carcinoma aspirates was seen. This system may be of prognostic value in the assessment of lobular carcinoma which has hitherto defied histological grading.

The distribution of lectin receptor sites in human breast lesions.

Conflicting data regarding the status of A, B, H and T antigens in epithelium of normal, mastopathies, fibroadenomas and carcinomas of the breast stimulated us to re-examine the carbohydrate residues in these condition. Currently, we extended the number of carbohydrate residues studied by using ten different biotinylated lectins as probes and avidin-biotin-peroxidase complex (ABC) as a visualant. In addition, the pattern of lectin staining of cancerous cells in primary and metastatic sites was compared. In primary and metastatic breast carcinomas, lectin receptor sites were stained more intensely with Concanavalia ensiformi agglutinin (*Con A), Ricinus communis agglutinin-I (RCA-I) and wheat germ agglutinin (WGA), than in normal breast, in mastopathies or in fibroadenomas. Cryptic receptor sites for peanut agglutinin (PNA) were stained in all cases of breast carcinomas, while free PNA sites stained only in a few cases of well-differentiated carcinomas. Receptors sites for Ulex europaeus agglutinin-I (UEA-I) stained non-malignant epithelium of patients with blood group H but did not stain malignant cells. The results show significant differences in lectin-binding patterns and staining intensities between normal and non-malignant, and malignant epithelial breast cells. Furthermore, these results indicate that in malignant cells, there is an increased content of sialic acid-rich carbohydrates but not of asialylated glycoconjugates.

Adenofibroma of the rete testis. A case report with electron microscopy findings.

The light and electron microscopic characteristics of an adenofibroma of the rete testis in a 51-year-old man are described. The tumor was 5.5 cm in greatest diameter and situated in the anterior superior portion of the right testis. It was composed mainly of mesenchymal and secondary epithelial proliferation. Long slit-like spaces and short tubules lined by a layer of epithelial cells were seen in the mesenchymal tissue. The epithelium was histochemically and ultrastructurally similar to that of the rete testis, and the tumor was considered to be of rete testis origin.