Signet ring cells in breast carcinoma. An immunohistochemical and ultrastructural study.

Two cases of breast carcinoma composed predominantly of neoplastic cells with a signet ring appearance, one a case of invasive lobular carcinoma (ILC) and the other a case of invasive ductal carcinoma (IDC), were examined electron microscopically and immunohistochemically. In signet ring cells in the ILC, mucin was demonstrated ultrastructurally in the intracytoplasmic lumina and also to a small degree in the cytoplasmic mucous granules, whereas in signet ring cells in the IDC, mucin was found only in the cytoplasmic mucous granules. Immunohistochemically, signet ring cells in the ILC were intensely positive for gross cystic disease fluid protein (GCDFP-15), but those in the IDC showed no immunoreaction for GCDFP-15. Thus ultrastructural features and GCDFP-15 immunoreactivity appear to be useful for distinguishing between the two different types of signet ring cells.     

Ampullary somatostatinoma. An immunohistochemical and ultrastructural study

Two new cases of ampullary somatostatinoma are reported. In one case the tumor is associated with an increase in somatostatin-positive cells in the adjacent duodenal mucosa. Both tumors show a predominant glandular pattern with many psammomatous calcified bodies. Such bodies seem to arise by calcium phosphate encrustation of intraluminal cellular debris. The neoplastic cells contain two distinct types of intermediate filaments: the first is located along the plasma membrane and reacts to keratin antiserum; the other, appearing as paranuclear aggregates, reacts to neurofilament antiserum. The neoplastic cells show signs of intestinal differentiation (microvilli, glycocalyceal bodies, filamentous core rootlets) as well as of neuroendocrine differentiation (secretory granules, whorls of neurofilaments).     

Prostatic malacoplakia. An ultrastructural and immunohistochemical study

A case of malacoplakia of the prostatic gland associated with prostatic nodular hyperplasia from a 69 years old man was presented, and its light and electron microscopic and immunohistochemical features were discussed along with its pathogenesis. This lesion was incidentally found in a transurethral prostatectomy specimen, and consisted of large number of epithelioid cells in which were typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. Ultrastructurally, these inclusions showed a dense, central calcified bodies of various developmental stages. Immunohistochemical study using antilysosomal antibody revealed no lysosomal activity. Based on these findings, we could suspect that main problem for this development of malacoplakia is altered intracellular digestion process of foreign biologic materials.     

Primary ovarian leiomyosarcoma. An immunohistochemical and ultrastructural study

Primary sarcoma of the ovary is rare, and only 16 reported examples of leiomyosarcoma are known to us. We encountered a primary ovarian leiomyosarcoma in a 58-year-old woman. The tumor was characterized by interlacing bundles of plump spindle cells that showed immunoreactivity for desmin, vimentin, and muscle-specific actin. Ultrastructural features included abundant smooth-muscle-type filaments, notched nuclei, pinocytotic vesicles, and extracellular collagen. This case illustrates the utility of ancillary techniques in the classification of pure ovarian sarcomas and leads us to propose ultrastructural and immunohistochemical criteria for primary ovarian leiomyosarcoma.     

Cystosarcoma phyllodes of the prostate. A pathologic and immunohistochemical study

We treated two patients who had lesions in the prostate with histologic features similar to those of cystosarcoma phyllodes of the breast. In one case, the stroma progressed to a clearly sarcomatous appearance, whereas the other tumor had a cellular stroma that was mitotically inactive. This element was immunoreactive for vimentin and desmin in both cases but was negative for epithelial markers. In contrast, the epithelial component was immunoreactive for prostate-specific antigen and epithelial membrane antigen. Following surgical resection, both patients were well two and three years later, without local recurrence or distant metastasis. The histogenesis of these tumors is unknown.     

Clear cell sarcoma. An immunohistochemical and ultrastructural study

The histogenesis of clear cell sarcoma was investigated by immunohistochemical examination of five tumors (two melanotic and three amelanotic) and electron microscopic examination of two of these tumors (one melanotic and one amelanotic). Melanin production was observed histologically in two of the tumors. The cytoplasm of cells in both types of tumor contained various numbers of melanosomes. Melanoma-specific antibody (HMB-45), anti-S-100 protein, and anti-vimentin antibodies gave positive reactions in four tumors, while all tumors showed Leu-7 immunoreactivity. No cytokeratin or epithelial membrane antigen (EMA) was detected immunohistochemically in any tumor. The immunoreactivity of this type of tumor with HMB-45 antibody strongly suggests melanocytic differentiation rather than schwannian or synovial differentiation. The reaction of the cells of one tumor with only Leu-7 indicates the existence of undifferentiated clear cell sarcoma of neuroectodermal origin that does not show definite melanocytic differentiation.     

Stromal changes in early invasive breast carcinoma. An immunohistochemical, histoenzymological and ultrastructural study

The purpose of this work was to detect in periductal connective tissue of breast carcinoma in situ changes induced by intraductal tumor cells before any dehiscence in basement membrane. Histological, electron microscopic, immunohistochemical and histoenzymological methods were used in 3 carcinomas in situ, 4 microinvasive carcinomas and 13 control invasive carcinomas. We could demonstrate a high functional activity of fibroblasts with secretion of mucopolysaccharides and type III collagen around intraductal carcinomas. These changes occurred simultaneously to those of the basement membrane which was either thinning or thickening. Any dehiscence in basement membrane secondarily induced in this periductal stroma the usual changes seen in invasive stroma, peculiarly numerous vascular pedicles, myofibroblasts, elastic material. These periductal stromal changes are interpreted according to recent concepts about the possible influence of tumor cells upon their environment: stimulation of mitotic and metabolic activity of fibroblasts: stimulation of angiogenesis by means of an angiogenic factor.     

Primary leiomyosarcoma of bone. An immunohistochemical and ultrastructural study

Primary leiomyosarcoma of bone is extremely rare. A 60-year-old woman had a mass in the right femur that was studied immunohistochemically and by electron microscopy. Human smooth-muscle actomyosin was detected in tumor cells, but human skeletal-muscle myoglobin and lysozyme (muramidase) were not. Electron microscopy of the tumor showed findings suggestive of a smooth-muscle origin, such as myofilaments, dense bodies, pinocytotic vesicles, and basement membrane. The results were diagnostic of leiomyosarcoma rather than rhabdomyosarcoma, fibrosarcoma, or malignant fibrous histiocytoma, which are similar neoplasms. We believe that ours is the first case of primary leiomyosarcoma of the bone proved by immunohistochemistry.     

Parachordoma: An ultrastructural and immunohistochemical study

A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6- sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells.     

Cystosarcoma phylloides with lobular and ductal carcinoma in situ

Malignant change of the epithelium in cystosarcoma phylloides is a rare occurrence, the most frequent occurrence being infiltrating carcinoma of various types and lobular carcinoma in situ, while ductal carcinoma in situ is much more rare. We describe a case of lobular and ductal carcinoma in situ in the same case of cystosarcoma phylloides.     

Hepatic giant cell carcinoma. An ultrastructural and immunohistochemical study

Hepatocellular carcinoma with osteoclast-like giant cells (hepatic giant cell carcinoma [HGCC]) is a rare entity, with only three cases reported. The tumor is histologically similar to giant cell tumor (GCT) of bone, and the origin of the multinucleated giant cells and mononuclear stromal cells has not been determined. The purpose of this report is to present a case of this rare tumor and compare its ultrastructural and immunohistochemical features with those of a conventional GCT of bone. Histologically, the HGCC consists of sheets of osteoclast-like giant cells with a background of mononuclear cells. The giant cells lack the pleomorphism seen in hepatocellular carcinomas with anaplastic giant cells. At the light microscopic level, most of this tumor was nearly identical to a GCT of bone, but several microscopic fields (less than 5% of the tumor) had the histologic appearance of a "usual" hepatocellular carcinoma. The hepatic tumor was negative for HAM 56, epithelial cytokeratins, muramidase, and alpha-1-antitrypsin, with only focal positivity for chymotrypsin in mononuclear and giant cells. The GCT was strongly positive for alpha-1-antitrypsin and chymotrypsin in both the mononuclear and giant cells and showed focal, weak staining for AE1 and AE3 in the mononuclear stromal cells. Ultrastructurally, both mononuclear and giant cells of the HGCC showed features typical of hepatocellular carcinoma. Although the patient presented in this report died, the pattern of growth was different from most hepatocellular carcinomas. The overall histologic features of this tumor are distinctive and appear to justify separating this variant from other types of hepatocellular carcinoma.     

An ultrastructural and immunohistochemical study of central neurocytoma

A case of central neurocytoma was studied by electron microscopic and immunohistochemical methods. Immunohistochemical examinations showed the tumor cells to be positive for neuron-specific enolase, sporadically positive for synaptophysin, and negative for glial fibrillary acidic protein. The Ki-67 (MIB-1) positive index value for the tumor cells was a low 1.5%. Ultrastructurally, thin cytoplasmic processes of tumor cells showed differentiation to neuronal cells containing parallel bundles of microtubules and abortive synapses with dense core vesicles and/or clear vesicles. Microvessels composed of endothelial cells without fenestrations and tight junctions in the endothelial clefts appeared in fibrillary stromas as revealed by light microscopy. Neurosecretory granules in thin cell processes may have been secreted around microvessels.     

Male breast carcinoma. An ultrastructural study.

A case of infiltrating ductal carcinoma of the male breast was studied by electron microscopy. The ultrastructure of the tumor is similar to that described in the female breast. Myofibroblasts are the preponderant cells in the stroma. Their significance and possible relation to hormonal stimuli are discussed.     

Nasal glioma: An immunohistochemical and ultrastructural study

A case of a 14 month old Japanese female infant presenting with nasal glioma Is reported. The tumor had been noticed at the nasal radix since birth and had slowly and progressively enlarged. There was no communication between the tumor and the cranial cavity on radiological examination. The tumor was macroscopically anchored to the nasal septum by a fibrous stalk, and histologically consisted of nests or trabeculae of either polygonal or spindle cells with plump eosinophilic cytoplasm and oval nuclei, separated by vascular-rich connective tissue intermingled with multinu-cleated giant cells. These tumor cells were immunohisto-chemically positive for glial fibrillary acidic protein as well as for S-100 protein and vimentin. An electron microscopic examination revealed collagen fibers and basal lamina between the tumor cells and the fibroblasts. Tumor cells possessed abundant intermediate filaments, which showed occasional Rosenthal fiber-like structures, in their cytoplasm and processes. A few oligodendrocytes and cilia of 9 micro-tubule doublets either with or without 2 central microtubules were also noted. These clinicopathological findings suggested that this tumor was once an encephalo(meningo)cele, which probably degenerated as a result of the loss of intracranial communication and then appeared to be isolated from the intracranial tissue.     

Fibrolamellár hepatocellular carcinoma. An immunohistochemical and ultrastructural study

Two cases of fibrolamellar carcinoma of the liver are reported in young female patients of 12 and 21 years of age. Small amounts of perinuclear alpha-fetoprotein were found, unrelated to hyaline globules, as well as alpha 1-antitrypsin in a periglobular fashion in isolated cells. Ferritin was present in a large number of cells. Ultrastructurally, the well differentiated nature of the neoplasm was substantiated by previously unreported findings such as intercellular lumina analogous to bile canaliculi and peroxisome-like bodies containing a central crystalloid. Filamentous material resembling Mallory's type of hyaline was also found. We conclude that both immunohistochemical and ultrastructural features reflect a high degree of differentiation.     

Gingival granular cell tumors of the newborn. An ultrastructural and immunohistochemical study

Gingival granular cell tumor of the newborn, or congenital epulis, is a rare congenital lesion of uncertain histogenesis located exclusively on the alveolar ridge with marked predilection for female infants. Although histologically similar to the more ubiquitous granular cell tumor or myoblastoma, ultrastructural and immunohistochemical studies support separate histogenetic pathways for the two lesions. A newborn female infant with three gingival granular cell tumors is described herein along with immunohistochemical and ultrastructural observations. There was positive immunostaining for vimentin but staining for S100 protein was uniformly negative. Immunocytochemical assay for estrogen and progesterone receptors was also negative. The findings indicate a mesenchymal origin and the demonstration of intermediate filaments with fusiform electron densities suggests that some of the granular cells have morphologic attributes of myofibroblasts.     

Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural study

The clinicopathological features of six cases of breast carcinomas showing features of acinic cell differentiation, which are similar to those seen in homologous tumors of salivary glands, are presented. The patients, all women, were 35–80 years of age. One case recurred after 4 years, and in two cases axillary lymph-node metastases were found at the time of surgery. Histologically the tumors showed a microglandular pattern merging with solid areas. Cytologically, immunohistochemically, and ultrastructurally the tumors were very similar to cases of acinic cell carcinoma of the parotid gland.The differential diagnostic criteria with microglandular adenosis and carcinomas showing granular cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have to be added to the long list of tumors that affect the salivary glands and can also arise in the breast. Received: 19 November 1999 / Accepted: 7 February 2000     

An immunohistochemical and ultrastructural study of 20 chordomas]

Altogether 20 chordomas were reported. The site distribution included 9 cases at the sacrococcygeal region, another 9 cases at the spheno-occipital region, 1 at the cervical vertebra, and another 1 at the lumbar vertebra. Histologic examination revealed that characteristic "physaliphorous cells" were easily identified in all the 19 cases. Tissue for immunohistochemistry study was available in 18 cases. Among them, tumor cells were found strongly positive to EMA, but negative for CEA. 16/18 cases also showed positive for keratin and S-100 protein. Totally, 2 cases were studied ultrastructurally and there were abundant RER and microfilaments seen in the cytoplasm of the tumor cells but only few surface microvilli detected. The epithelial nature of chordoma is strongly supported by the ultrastructural and immunohistochemical findings of these 20 cases.