Collagenous spherulosis. A comment on its histogenesis.

Collagenous spherulosis is a benign breast lesion involving lobular acini and ductules consisting of eosinophilic spherules measuring up to 100 mu in diameter. It is a myoepithelial product. We described similar lesions in salivary gland tumors and a benign lymphoepithelial lesion of the parotid gland.

The expression of intermediate filaments in canine mammary glands and their tumors.

Monoclonal antibodies specific for different types of intermediate filaments (cytokeratin, vimentin, desmin and neurofilaments) were used to study the histogenesis of canine mammary glands and 57 canine mammary tumors by immunocytochemistry. The intra- and interlobular duct epithelium, acinar, and intralobular myoepithelial cells stained positively for cytokeratin. Peripheral ductal and acinar cells, as well as interstitial cells, stained positively for vimentin. A similar staining pattern was seen in adenomas, complex adenomas, benign mixed tumors, ductular carcinomas, and one myoepithelioma-like tumor. Additionally, cytokeratin positive cells were scattered interstitially in one single adenoma, most complex adenomas, some benign mixed tumors, complex carcinomas, and in the malignant mixed tumors. All stromal cells stained positively for vimentin. The fibrosarcomas were positive only for vimentin, while the following expressed both desmin and cytokeratin: epithelial-like cells in one adenoma, three complex adenomas, the myoepithelioma-like tumor, the single comedo carcinoma, two complex carcinomas, the single lobular carcinoma, one malignant mixed tumor, and three osteosarcomas. Epithelial-like cells in one adenoma, six complex adenomas, two benign mixed tumors, two complex carcinomas, the lobular carcinoma, and the malignant schwannoma stained for neurofilaments. Three tumors, one adenoma, one complex adenoma, and the lobular carcinoma expressed both desmin and neurofilaments in addition to cytokeratin and vimentin. The results show the expression of different types of intermediate filaments and indicate that there might be a stem cell origin in most of the canine mammary tumors.

Different contents of glycosaminoglycans in a human neoplastic salivary duct cell line and its subclone with a myoepithelial phenotype.

The glycosaminoglycans (GAG) biosynthesized by a neoplastic human salivary duct cell line, HSGc, and by its nontumorigenic subclone, HSGc-E1, having a myoepithelial-like phenotype, were examined by incorporation of [3H]-acetate into GAG. The rate of GAG radiolabeling in HSGc-E1 was significantly greater than that in HSGc. The radiolabeled GAG recovered from HSGc-E1 showed a distribution of 22-32% in the cells and 68-78% secreted into the medium, while the amounts of GAG in the cells and medium of HSGc were equal. Two-dimensional electrophoresis of GAG extracted from the cells demonstrated that HSGc-E1 contained a much greater amount of heparan sulfate (HS, 53.5% of total), while HSGc synthesized hyaluronic acid (HA, 17.5%), HS 38.8%, chondroitin sulfate (Ch-S, 27.6%) and dermatan sulfate (DS, 16.1%). Moreover, treatment of HSGc with sodium butyrate or dibutyryl cyclic AMP (each is a potent inducer of differentiation to myoepithelial-like cells) strongly enhanced GAG synthesis, while dexamethasone (an inducer of differentiation to a more functional duct epithelium) did not stimulate GAG synthesis. These findings suggest that biosynthetic changes in the GAG content of neoplastic salivary cells are associated with their myoepithelial differentiation.

Salivary gland myoepithelioma variants. Histological, ultrastructural, and immunocytological features.

The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was widespread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonal-shaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.

Spindle-cell adenomyoepithelioma of the breast. A microscopic, ultrastructural, and immunocytochemical study.

Two patients developed nodular, well-circumscribed tumors of the breast, discovered by mammography. They were fibroadenoma-like by gross examination and biphasic by light microscopy, containing both tubular glands and spindled myoid cells. Immunocytochemical studies revealed cytokeratin and S-100 immunoreactivity in both the spindled myoid cells and in the tubuloglandular cells (S-100 was focal in the latter). In addition, the spindled myoid cells were immunoreactive for vimentin but negative for desmin. Ultrastructural studies showed the tubular glands to be composed of luminal epithelial cells focally surrounded by myoepithelial cells, but the stroma contained spindled myoepithelial cells admixed with occasional fibroblasts. The diagnostic term, "adenomyoepithelioma," is appropriate for biphasic tumors having both glandular and myoepitheliomatous differentiation. Although additional experience is necessary to be conclusive regarding the biologic behavior of these unusual lesions, the authors believe the adenomyoepitheliomas described here are benign. They were well circumscribed without invasion of adjacent breast, contained neither mitotic figures nor cytologic atypia, and have not recurred or metastasized (6 and 10 months after removal).

Myofibroblastoma of the breast. Sixteen cases of a distinctive benign mesenchymal tumor.

The clinical and pathologic findings of 16 examples of a distinctive stromal tumor of the breast designated as "myofibroblastoma" are reported. Eleven of the 16 patients were men, and the average age at presentation was 63 years. Fourteen were treated by local excision and two by simple mastectomy. None of the lesions recurred or metastasized. The tumors were grossly nodular and well-demarcated from the surrounding mammary tissue. Ducts and lobules were not engulfed by the neoplasm. Microscopically, the lesions were formed by uniform, slender, bipolar spindle cells haphazardly arranged in fascicular clusters separated by broad bands of hyalinized collagen. Ultrastructural examination of four lesions identified a predominance of myofibroblasts. Immunoreactivity for S-100 protein and cytokeratin was absent in the 10 tumors examined, but desmin immunoreactivity was focally present in three lesions. The differential diagnosis of myofibroblastoma includes reactive processes and benign neoplasms such as nodular and proliferative fascititis, fibromatosis, spindle-cell lipoma, neurofibroma, neurilemmoma, and leiomyoma. Malignant neoplasms such as stromal sarcoma, malignant fibrous histiocytoma, and spindle-cell or metaplastic carcinoma should not be confused with a myofibroblastoma. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.

Myoepithelioma of the palate in a child.

Salivary gland myoepitheliomas are rare tumors accounting for less than 1% of neoplasms of the salivary glands. We report a myoepithelioma arising in the palate of an 8-year-old female, the youngest case in the literature. Electron microscopic and immunohistochemical studies support the myoepithelial origin of this tumor.

Malignant myoepithelioma of the breast. An immunohistochemical study by light and electron microscopy.

Myoepitheliomas of the breast are extremely rare; only four cases have been reported to date. It is not clear whether these tumors behave in a benign or malignant fashion, and no metastatic spread has been documented. We report a myoepithelioma of the breast with metastatic spread to an axillary lymph node. Myoepithelial cell (MEC) differentiation in the tumor was characterized using electron microscopic (EM) criteria. Immunologic investigations at the LM and EM levels showed that the tumor cells were positive for S100 protein, actin, and epidermal cytokeratin; these findings are indicative of MEC differentiation. By immuno-EM, cytokeratin filaments were present in a perinuclear location, while actin filaments were concentrated along the cell periphery. To the authors' knowledge, this is the first report of a breast myoepithelioma that has metastasized and also the first report of the immunologic characterization of a myoepithelioma at the light and electron microscopic levels.

Myoepithelioma of the parotid gland. Report of two cases with immunohistochemical technique for S-100 protein and electron microscopic observation.

Two cases of myoepithelioma occurring in the parotid gland were reported. These tumors consisted of spindle cells that exhibited an arrangement similar to leiomyoma or fibroma. The diagnosis was made on the basis of characteristic ultrastructural as well as immunohistochemical findings: The tumor cells of the two cases likewise contained myofilaments and gave a positive result for the S-100 protein immunohistochemical technique.

A comparision of normal submaxillary gland proteins with proteins obtained from a transplantable murine salivary gland carcinoma (myoepithelioma).

A new transplantable murine salivary gland carcinoma (myoepithelioma) was further characterized by comparing total protein patterns with normal submaxillary gland proteins. Analysis by isoelectric focussing or by labelling studies with radioactive leucine showed considerable differences between tumour and normal proteins. In contrast, analysis of staining patterns after electrophoresis in sodium dodecyl sulphate containing gels revealed a striking similarity between normal proteins, tumour proteins and proteins obtained from metastatic growths. It thus appears that tumour proteins closely resemble the normal proteins from the tissue of origin with respect to molecular size as determined by electrophoretic mobility, while significant differences occur in charge and labelling kinetics.