Ultrastructural and immunohistochemical observations of a true malignant mixed tumor (carcinosarcoma) of the tongue.

True malignant mixed tumor (TMMT) of salivary glands, with both carcinomatous and sarcomatous components, is exceedingly rare. We offer a case of TMMT in a 79-yr-old man, which may represent the first report example of this unusual neoplasm arising in the tongue. The carcinomatous component was mainly of solid basaloid carcinoma with focal glandular differentiation, while the sarcomatous component was composed of pleomorphic elements such as chondrosarcoma, myxosarcoma and fibrosarcoma. Carcinoma cells at the periphery of solid nests occasionally merged into these sarcomatous elements. Immunohistochemically, basaloid carcinoma cells showed positive reaction for both low molecular weight cytokeratin and S-100 protein, whereas carcinoma cells lining ductal spaces were positive for a wide spectrum of keratin and EMA. The sarcomatous elements revealed the presence of vimentin and S-100 protein. Ultrastructurally, basal lamina-like material and/or mucoid precipitates often accumulated separating the tumor cells from each other singly or into a few cell group. Some sarcomatous cells assumed the myoepithelial features, such as the presence of microfilament bundles with dense bodies and pinocytotic vesicles along the cell periphery. These findings may indicate that TMMT shares a common histogenesis with pleomorphic adenoma.

Granular cell tumor of the tongue: an electron microscopical and immunohistochemical study.

Granular cell tumor of the tongue in a 29-year-old woman is reported including details of studies using electron microscopy and immunohistochemistry. Immunohistochemically, the tumor cells showed moderate positivity for S-100 protein. Electron microscopically, basal lamina, angulate bodies, myelin-like figures and axon-like structures were observed in the tumor. These findings may indicate that this tumor is a lesion of Schwann cell origin. The Japanese literature on oral granular cell tumor is also reviewed and discussed.

Oral hairy leukoplakia.

Oral hairy leukoplakia was first described in homosexual men infected with the human immunodeficiency virus. It is thought to be caused by infection with both the Epstein-Barr virus and human papillomavirus. We report 59 cases of oral hairy leukoplakia. The disease was diagnosed in patients in all risk groups and was categorized in all classes of the Walter Reed classification without significant differences in prevalence. Epstein-Barr virus could be demonstrated in all tissue samples examined; human papillomavirus was found in only a few specimens. In our series oral hairy leukoplakia had a chronic course, although temporary spontaneous healing occurred in some cases. Its appearance was a poor prognostic sign because acquired immunodeficiency syndrome developed in a significant proportion of patients within a few months of onset.

Prognostic implications of DNA ploidy in squamous cell carcinomas of the tongue assessed by flow cytometry.

A total of 47 primary squamous cell carcinomas of the tongue were analysed by DNA flow cytometry. With respect to their clonal DNA content two distinct tumor groups could be distinguished. In 14 cases the tumors (29.8%) were dipoid, whereas in 33 cases (70.2%) additional cell lines characterized by abnormal DNA content could be detected. A significant increase of aneuploid cases with tumor size as well as with decreasing histological differentiation could be detected. Aneuploid cell lines are lacking in T1 as well as in most G1 carcinomas but predominate in T3 and G3. Furthermore, cervical lymph node involvement was recognized in the majority of aneuploid primary carcinomas (81.8%) but was largely lacking in diploid tumors (21.4%). Hence, the presence of aneuploid cell lines is clearly connected with clinical and histopathological parameters, each of which have turned out to worsen the prognosis in tongue carcinomas.

Adenoid cystic carcinoma. A clinicopathologic study with flow cytometric analysis.

Forty-five patients with adenoid cystic carcinoma (ACC) of salivary glands were retrospectively studied to determine the prognostic use of DNA ploidy analysis compared with clinicopathologic features. Nuclear suspensions were prepared from 37 of these tumors by the Hedley technique on paraffin-embedded material. The DNA content was analyzed by flow cytometry after propidium iodide staining. Thirty-five tumors were diploid and 2 were tetraploid. Mean survival was 117 and 52 months for the diploid and tetraploid patients, respectively. The median S-phase fraction (Spf) of the 35 diploid tumors was 4.45%. Of the 17 diploid patients who died of disease, there were 11 tumors with high Spf (greater than 4.45%) and 6 tumors with a low Spf (P less than 0.05 chi-square test). The presence of more than 30% of a solid pattern in the tumor was strongly associated with poor median survival in Kaplan-Meier survival curve analysis (P less than 0.05 log rank test). Grade, stage, recurrence, and metastases were also found to be important prognostic factors. Because few tumors were nondiploid, these results suggest that S-phase fraction analysis may be a more useful prognostic indicator than ploidy classification.

Granular cell lesions of the jaws and oral cavity: a clinicopathologic, immunohistochemical, and ultrastructural study.

A clinicopathological, immunohistochemical, and ultrastructural study of 44 oral granular cell lesions was performed. A total of 35 mucosal granular cell tumors, 4 granular cell ameloblastomas, 1 lichen planus with granular cell change, and 3 congenital epulides of the newborn were studied. Pseudoepitheliomatous hyperplasia was found to occur in only a minority of these cases. Immunohistochemically, the majority of granular cell lesions were uniformly positive for S-100 protein and focally positive for vimentin in one half of the cases, suggestive of origin from a Schwann cell or a precursor mesenchymal cell. Congenital epulis of the newborn and central odontogenic granular cell tumor were negative for S-100 protein, epithelial membrane antigen (EMA), and prekeratin, suggesting a mesenchymal origin for these lesions.

Two squamous cell carcinomas not associated with humoral hypercalcemia produce a potent bone resorption-stimulating factor which is interleukin-1 alpha.

Conditioned medium (CM) from two squamous cell carcinoma cell lines, SCC-9 and SCC-13, stimulated bone resorption in neonatal mouse calvariae in organ culture. Enhanced bone resorption induced by CM was associated with an increased production of prostaglandin-E2 (PGE2) by the calvariae. Complete inhibition of stimulated PGE2 synthesis by indomethacin only partially inhibited bone resorption-stimulating activity (BRSA) in the CM. Neither SCC-9 nor SCC-13 CM stimulated cAMP production in rat osteosarcoma cells (ROS 17/2.8). The BRSA in CM was completely inhibited by an antibody to interleukin-1 alpha (IL-1 alpha). Fractionation of SCC-9 CM by gel filtration and HPLC ion exchange chromatography revealed a single peak of BRSA and PGE2 synthesis-stimulating activity at 17-20K (termed SCMII). In mouse calvariae, SCMII increased medium Ca2+ and PGE2 in a dose-dependent manner at concentrations from 20 ng protein/ml to a maximum of 500 ng protein/ml. Preincubation of SCMII with antibody to IL-1 alpha completely inhibited SCMII-induced bone resorption. SCMII also enhanced thymocyte proliferation with activity that was equivalent to 353 U/ml IL-1. Antibodies to IL-1 beta and tumor necrosis factor had no effect on SCMII-induced bone resorption. Using specific enzyme-linked immunosorbent assays for IL-1 alpha and IL-1 beta, IL-1 alpha was measured in high concentrations in both crude and partially purified fractions of SCC-9 and SCC-13 CM. In contrast, IL-1 beta was either undetectable or present in amounts below those that stimulate bone resorption. In addition, SCMII did not enhance cAMP production in bone cells. We conclude that the BRSA produced by the two squamous cell carcinoma cell lines SCC-9 and SCC-13 is IL-1 alpha.

Spindle cell squamous carcinoma of the tongue in the first decade of life.

A case of spindle cell squamous cell carcinoma of the tongue in a 4-year-old boy is presented. The diagnosis is supported by immunohistochemical demonstration of cytokeratins within the tumor cells. The authors believe this report represents the first case of "nonkeratinizing" spindle cell squamous carcinoma of the tongue in the first decade of life.

Oral nerve sheath myxoma. Report of a case with findings of ultrastructural and immunohistochemical studies.

The first Asian case of oral nerve sheath myxoma is presented, along with the findings of light and electron microscopy, and immunohistochemistry. Ultrastructurally, intracytoplasmic microfilaments and convoluted basement membrane were identified in the tumor cells. Immunohistochemically, S-100 protein and neuron-specific enolase were positive in the tumor cells. These findings may indicate that the tumor is a lesion of Schwann-cell origin. The literature on oral nerve sheath myxoma is also reviewed and discussed.

Myoglobin content of granular cell tumor of the tongue. An immunoperoxidase study.

Myoglobin is a protein with a molecular weight of 16,900 daltons that is normally found in adult and fetal striated and cardiac muscle cells. Its synthesis relates to the total ATP requirements of the muscle cell. The histogenesis of the granular cell tumor is controversial, but an origin from striated muscle has been postulated. Seven cases of tongue GCT were evaluated for the presence of myoglobin using the unlabeled antibody (PAP) technique. Normal human striated muscle was used for both positive and negative controls. None of the tumors showed positive staining of the granular cells. Positive controls showed specificity of staining for skeletal muscle. The negative controls did not stain. Granular cell tumors of the tongue do not appear to contain myoglobin. This suggests that either the GCT is not of muscle origin or that, if it is, there may be a metabolic change in the granular cells so that myoglobin is not synthesized. It may be possible that a change in the antigenic determinant has occurred.

Oral granular cell lesions. An immunohistochemical study with emphasis on intermediate-sized filaments proteins.

Six cases of oral granular cell lesions were studied with respect to intermediate-sized filaments (IF), peanut lectin binding (PNL) and muramidase activity by means of the peroxidase antiperoxidase technique. The tumours included three granular cell myoblastomas of the tongue (GCM) two cases of congenital gingival granular cell tumour (CGGT) and one granular cell ameloblastoma (GCA). Every tumour studied showed intracytoplasmic PNL binding whereas muramidase was negative in all cases. Vimentin expression was demonstrated in the CGGT and to a lesser extent in the GCM, but was absent in the GCA which was positive for keratin. Desmin and glial fibrillary acidic protein (GFAP) were not present in any of the lesions. These data demonstrate that PNL binding might be considered to be a common feature of granular cells regardless of their histogenesis. Lysosomes are supposed to represent the intracellular binding sites for this marker. Moreover it is shown that histomorphological identity between the granular cells of CGGT and GCA does not signify identity in histogenesis since the former are of mesenchymal derivation while the latter, from their intermediate filament protein types appear to originate from epithelium.

Five human tumour cell lines derived from a primary squamous carcinoma of the tongue, two subsequent local recurrences and two nodal metastases.

Five tumour cell lines have been derived from a primary squamous carcinoma of the tongue, from 2 subsequent local recurrences, and from 2 lymph-node metastases--all from the same patient. While the cell lines shared many morphological and biochemical characteristics, those derived from recurrences and metastases appeared to be less differentiated, were less well organized in culture, and displayed fewer desmosomes and tonofilaments than cells in the primary tumour line. A recurrent line showing greatest morphological divergence from the primary tumour line also demonstrated the greatest differences at the ultrastructural level, in increased production of plasminogen activator and in the composition of cell-surface glycoproteins.

Comparative ultrastructure of thyroid, tongue and eyelid lesions in the neuroma phenotype of medullary carcinoma of the thyroid: association of amyloid with fibroblasts in thyroid tumor and in mucosal neuromas.

Electron-microscopic and histochemical studies of thyroid tumor, tongue neuromas and eyelid neuromas from the lesions of a patient with medullary thyroid carcinoma were compared. In the thyroid tumor, a significant number of the C cells showed heterogeneity of granule types; no C cells, however, were identified in the tongue and eyelid neuromas. Amyloid was clearly shown by Congo red staining in the thyroid neoplasm and in the tongue neuromas. In all tissues, amyloid fibrils were found to be ultrastructurally closely associated with fibroblasts. These fingings suggest that the fibroblast rather than the C cell may have played the important role in the deposition of amyloid in this patient's thyroid carcinoma.

DNA contents of individual cells from squamous cell carcinomas of the larynx and tongue.

In previous work a new method of histologic grading of malignancy in squamous cell carcinomas of the larynx was described. It was based on morphologic criteria representing the tumor cell population itself and the tumor host relationship. Nuclear polymorphism was revealed to be a very important factor for determining prognosis. This method of histologic grading of malignancy was in this work further analyzed by cytophotometric DNA determinations on individual cells obtained by scraping the surface of squamous cell carcinomas of the larynx and the tongue. Increased heterogenous cellular DNA distributions were found in cases with high histological malignancy grading. Cells in the carcinoma cases with a normal epithelial morphology had the same DNA content as that of control cells of normal buccal mucosa. Cells with higher DNA values all had malignant or suspicious morphology.