Carcinosarcoma ex Pleomorphic Adenoma of the Submandibular Gland in a 64-Year-Old Man: A Case Report.

Carcinosarcoma (CS) is a rare tumor, consisting of both carcinomatous and sarcomatous components. In this paper, we present a case of CS arising from a pleomorphic adenoma (PA) of the submandibular gland. A 64-year-old Japanese man presented with a left submandibular mass that had developed for 20 years with complaints of pain for the last 3 months. Magnetic resonance imaging showed a lesion involving the left submandibular gland. The patient underwent total dissection of the left submandibular gland and left cervical lymph nodes. Upon gross examination, the mass appeared completely covered by fibroadipose tissue measuring 46×42×45 mm; sectioning revealed a solid-white nodule with central bleeding and necrosis, invading into the surrounding adipose tissue. Microscopically, the presence of carcinomatous and sarcomatous components in the fibro-myxomatous stroma was detected, suggestive of pre-existing PA. The carcinoma component was diagnostic of salivary adenocarcinoma, not otherwise specified, whereas the sarcomatous component exhibited features of osteosarcoma characterized by formation of osteoid. As the border between the carcinomatous and sarcomatous components was not evident, CS may have occurred via transformation of the carcinoma into sarcoma. Tumor metastasis was detected in the cervical lymph nodes. Immunohistochemically, AE1/AE3 expression was noted in the carcinomatous component, but not in the osteosarcoma component. Both components were diffusely positive for vimentin. Four months after the operation, the patient developed a metastatic CS lesion in the lung, suggesting tumor aggression.

Head and Neck Extranodal Interdigitating Dendritic Cell Sarcoma: Case Report and Review of the Literature.

Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm originating from professional antigen presenting cells normally located in the T zone of the lymph node. The purpose of this report was to describe the first case of the IDCS of the submandibular gland and perform a review of the literature of head and neck IDCS. We present a case of an 81-year-old man with a 5 months history of slowly enlarging painless mass in right submandibular region. Fine needle aspiration cytology was suggestive of squamous cell carcinoma. The patient underwent surgical resection of the right submandibular gland and neck dissection. A malignant spindle cell proliferation involving the submandibular gland and colonizing one laterocervical lymph node was found. Morphology and immunophenotype prompted a differential diagnosis of a metastatic spindle cell melanoma versus an IDCS. Transmission electron microscopy was performed and supported a diagnosis of IDCS. The diagnosis of IDCS is a challenging task and may require a large array of techniques.

Salivary duct carcinoma with rhabdoid features: report of 2 cases with immunohistochemical and ultrastructural analyses.

BACKGROUND: Salivary duct carcinoma with rhabdoid features is extremely rare. METHODS: We report 2 cases of salivary duct carcinoma with rhabdoid features treated at our institution. RESULTS: Case 1 was a 44-year-old Japanese man who had swelling in the left parotid region. This tumor consisted of residual pleomorphic adenoma and widely invasive carcinoma, which showed a diffuse growth pattern by atypical rhabdoid cells. Case 2 was a 66-year-old Japanese man who had swelling of the right cervical region. This submandibular tumor was also composed of both residual pleomorphic adenoma region and invasive adenocarcinoma components, whereas some metastatic lesions were purely composed of rhabdoid cells. Such cells were strongly and diffusely positive for cytokeratins (CKs), gross cystic disease fluid protein-15 (GCDFP), and androgen receptor (AR). Case 1 was also positive for Her-2 and p53. CONCLUSION: Both patients were diagnosed with carcinoma ex pleomorphic adenoma and their carcinomatous components were composed of salivary duct carcinoma with rhabdoid features, which is a highly aggressive tumor, similar to salivary duct carcinoma.

Inmunohistochemical expression of PCNA, p53 and bcl-2 in pleomorphic adenomas / Expresión inmunohistoquímica de PCNA, p53 y bcl-2 en adenomas pleomórficos

The aim of the study was to determine the immunohistochemical expression of the PCNA, p53 and bcl-2 proteins in pleomorphic adenomas. Nineteen specimens of pleomorphic adenomas were selected for analysis by the streptavidin-biotin-peroxidase method with antibodies againstp53, PCNA and bcl-2 proteins. It was observed weak labeling for p53 in 12 cases (63.1 percent) andforPCNA in 8 (42.1 percent). With respect to the bcl-2 labeling index, o no expression of this protein was detected in 12 cases, corresponding to 63.1 percent of the sample. Based on these findings, it was concluded that p53 and PCNA can favour the proliferative activity of pleomorphic adenomas, whereas bcl-2 probably does not effectively participate in the pathogenesis of this tumor.

El objetivo del estudio fue determinar la expresión inmmunohistoquímica de las proteínas PCNA, p53 y bcl-2 en adenomas pleomórficos. Fueron seleccionados 19 especímenes de adenomas pleomórficos para análisis a través del método de la estreptavidina-biotina-peroxidasa con anticuerpos contra las proteínas p53, PCNA y bcl-2. Fue observada leve marcación para p53 en 12 casos (63,1 por ciento) y para PCNA en 8 (42,1 por ciento). Con relación al índice de marcación para bcl-2, ono fue detectada en 12 casos (63,1 por ciento) expresión de esta proteína. En base a los resultados, se concluyó que las proteínas p53 y PCNA pueden favorecer la actividad proliferativa de adenomas pleomórficos, y por otro lado, la bcl-2 probablemente ono participaría efectivamente de la patogenia de este tumor.

Clear-cell myoepithelial carcinoma of the salivary glands: a clinicopathologic, immunohistochemical, and ultrastructural study of two cases involving the submandibular gland with review of the literature.

Myoepithelial carcinoma (MC) is an uncommon neoplasm of the salivary glands, and cases of the clear-cell (CC) variant are extremely rare. Two cases of MC of the CC variant arising in the left submandibular gland are described herein. Both cases, which involved elderly women, almost exclusively consisted of large glycogen-rich CCs. Both cases were immunopositive for several epithelial and myoepithelial markers, and electron microscopy (EM) demonstrated hybrid epithelial and myoid differentiation in both. Case 1 arose in a pre-existing pleomorphic adenoma ("ex mixed tumor MC"), while Case 2 was a "de novo MC". CC-MC is an aggressive tumor with frequent recurrence, lymph node, and systemic metastases. A total of 14 cases of this type of neoplasm have been reported so far in the salivary glands, two arising from the submandibular gland. To date, only four cases have been studied using EM. The cases of CC-MC presented here are the third and fourth ones, respectively, originating from the submandibular glands, and the first two cases arising from this location, in which EM investigation succeeded in demonstrating myoepithelial differentiation. CC-MC needs to be distinguished from diverse primary and secondary CC neoplasms.

Small cell undifferentiated carcinoma of the submandibular gland: immunohistochemical evidence of myoepithelial, basal and luminal cell features.

A primary small cell undifferentiated carcinoma of the submandibular gland is reported. Histological studies revealed that the major part of this tumor was composed of cells slightly larger (10-14 microm) than lymphocytes. These tumor cells showed myoepithelial-cell differentiation, which was confirmed by the immunohistochemical and ultrastructural findings. Furthermore, some of them showed luminal-cell and basal-cell differentiation immunohistochemically. However, there was no evidence of neuroendocrine differentiation. These findings demonstrated that the tumor had the features of all the salivary ductal components (myoepithelial, basal, and luminal cells) and supported that the tumor might arise from the salivary duct. Furthermore, it supports the hypothesis of multipotential stem cells as the origin for small cell undifferentiated carcinomas in salivary glands.

[Neuroendocrine tumor of the submandibular gland. Report of one case and review of literature]. / Tumor neuroendocrino de glándula submaxilar. Presentación de un caso y revisión de literatura.

Report on one case of primary neuroendocrine tumor of the submandibularis gland, early detected without initial spread. Immunohistochemistry and electron microscopy were realized in order to determine the presence of intracytoplasmatic hypersecretory thick granules, these being the laboratory trials to differentiate between neuroendocrine tumors and undifferentiate carcinomata. Bibliographic review and proposal of classification of this sort of tumors.

Sebaceous carcinoma of the submandibular gland with high-grade malignancy: report of a case.

A case of sebaceous carcinoma arising in the left submandibular gland of a 66-year-old man is reported. The clinical and pathological examinations revealed a carcinoma, which was to salivary gland in origin, with regional lymph nodal metastases. Pathological findings showed features of high-grade sebaceous carcinoma with spindle myoepitheliomatous differentiation. Neither squamous cell nor duct epithelial-like cell differentiation was noted. Immunohistochemically, tumor cells were positive for cytokeratin, S-100 protein and vimentin. Lipid was demonstrated in the cytoplasm of the tumor cells. Ultrastructurally, tumor cells contained numerous intracytoplasmic lipid droplets. Myoepitheliomatous differentiation is rare in sebaceous carcinoma of the salivary gland. Presented is the second reported case of sebaceous carcinoma arising in the submandibular gland.

Naturally occurring mucoepidermoid carcinoma in the submandibular salivary gland of two mice.

Mucoepidermoid carcinomas in two mice were investigated histologically, immunohistochemically and ultrastructurally. The neoplastic cells showed divergent differentiation into periodic acid-Schiff-positive mucous cells, keratin-positive squamous cells, and cells with both mucous granules and sheaves of tonofilaments. Gland formation and keratinization were not observed. At the periphery of tumour cell nests, some cells were immunolabelled for smooth muscle actin or contained concentrated thin filaments, and these observations were interpreted to indicate that murine mucoepidermoid carcinomas are associated with both myoepithelium and duct epithelium.

The congenital basal cell adenoma of salivary glands. Contribution to the differential diagnosis of congenital salivary gland tumours.

Congenital epithelial tumours of the salivary glands are very rare. The Salivary Gland Registry maintained in the Department of Pathology. University of Hamburg, contains only three cases among a total of 6,646 salivary gland tumours from the years 1965-1994. The three cases were classified as congenital basal cell adenoma, two of the parotid gland and one of the submandibular gland. Histologically, the three adenomas were similar in structure to the adult counterpart of basal cell adenoma with solid, trabecular or tubular (duct-like) patterns. In some cystic spaces of the duct-like structures PAS- and Astra blue-positive substances were secreted. On immunocytochemistry, the luminal duct-like cells showed membranous expression of cytokeratins 3, 5, 6, 7, 13 and 19. In the isomorphic basaloid cells of the solid and trabecular cell nests few cells expressed cytokeratin. On the outside of the solid cell nests there were smaller elongated myoepithelial-like cells, which expressed cytokeratin 14 and vimentin. Cytokeratins 1, 2, 4 and 18 were not expressed. The pattern of expression reflects the different stages of maturity of the tumour cells and is related to the development of the salivary glands until the end of the 3rd embryonal month with an arrest of further cell differentiation. No acinic cells, invasive growth, recurrence or metastases were observed. The differential diagnosis includes other congenital salivary gland tumours, such as hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma or embryoma, carcinoma, hamartoma and teratoma.

Characteristics of a rat fibrosarcoma-derived transplantable tumour line (SS) and cultured cell lines (SS-P and SS-A3-1) showing myofibroblastic and histiocytic phenotypes.

A transplantable tumour line (SS) was established in syngeneic rats from a spontaneous fibrosarcoma that had arisen in the submandibular salivary gland of a 24-month-old male F344 rat. A cell line (SS-P) was induced from SS, and a cloned cell line (SS-A3-1) was isolated from SS-P. The primary tumour consisted of oval to spindle-shaped cells arranged in bundles with abundant collagen fibres; ultrastructurally, neoplastic cells exhibited fusiform morphology with prominent rough endoplasmic reticulum. SS tumours showed marked interlacing fascicle and herring-bone growth patterns. SS-P and SS-A3-1 were similar morphologically to each other, consisting of oval, spindle or polygonal cells and occasional multinucleated giant cells. Tumours induced by SS-P and SS-A3-1 were histologically similar to SS tumours. Immunohistochemically, all cells in the primary tumour, SS tumours and tumours induced both by SS-P and SS-A3-1 and by SS-P and SS-A3-1 cultures gave a positive reaction to vimentin. Interestingly, neoplastic cells reacting to ED1 (rat macrophage/histiocyte-specific antibody) and alpha-smooth muscle actin (alpha-SMA) appeared in SS tumours and tumours induced by SS-P and SS-A3-1 and by SS-P and SS-A3-1 cultures. Cells with histiocytic fine structures and myofibroblastic cells with cytoplasmic actin-like microfilaments were also observed by electron microscopy. The present rat fibrosarcoma-derived transplantable tumour line (SS) and cell lines (SS-P and SS-A3-1) might express myofibroblastic and histiocytic phenotypes, probably depending on the surrounding conditions. These cell lines may prove useful for studying the mechanisms of phenotypic plasticity in neoplastic fibroblasts.

Oncocytomas of the submandibular gland. A series of 22 cases and a review of the literature.

BACKGROUND: Oncocytomas are benign salivary gland neoplasms that represent approximately 1.5% of all salivary gland tumors. Oncocytomas of the submandibular gland, however, are decidedly uncommon. METHODS: Twenty-two cases of submandibular gland oncocytomas from the files of the Oral and Otolaryngic Tumor Registries of the Armed Forces Institute of Pathology were reviewed, and analysis of the histologic criteria, histochemical and immunohistochemical reactions, and ultrastructural and clinical follow-up data was performed. RESULTS: The patients included 11 females and 11 males, age 21-88 years, with a mean age at presentation of 58.7 years. Clinically, the tumors were generally asymptomatic masses in the submandibular gland that increased in size over a period ranging from several weeks to 20 years and were occasionally associated with pain (n = 9). The tumors ranged in greatest dimension from 0.7 to 7 cm and were circumscribed to encapsulated. Histologically, the tumors were characterized by large epithelial cells with eosinophilic, granular cytoplasm. The cytoplasm stained positively with stains used to demonstrate mitochondria (phosphotungstic acid-hematoxylin, Novelli, Cresylecht violet V, and Kluver-Barrera Luxol fast blue stains). Immunohistochemical reactions demonstrated an epithelial origin (keratin and epithelial membrane antigen), whereas markers for myoepithelial derivation (S-100 protein, actin, and glial fibrillary acidic protein) were not identified. At the time this study was conducted, all patients with submandibular oncocytomas were either alive without evidence of disease or had died without evidence of recurrent disease, with surgical resection the only treatment. CONCLUSIONS: Submandibular gland oncocytomas are rare, benign tumors. The tumor cells are filled with mitochondria, which are easily demonstrated by histochemical reactions. Complete surgical resection is adequate therapy.

Ancient schwannoma of the submandibular gland: a case report.

Schwannomas (neurilemmomas) are neurogenic tumors that arise from the Schwann cells of the neural sheath. They are most often benign and solitary. Extracranial schwannomas are rare, and can be mistaken for metastatic disease or other non-neurogenic tumors. Ancient schwannoma is a rare variant of schwannoma with a course typical of a slow-growing benign tumor. Histologically, it can be confused with a malignant mesenchymal tumor. An unusual case of an ancient schwannoma of the submandibular gland is reported. The clinical, histological and surgical aspects of this tumor are discussed, and the literature regarding this rare entity is reviewed.

Basal cell adenocarcinoma of the submandibular gland.

Basal cell adenoma is a well recognized histopathologic variant of monomorphic adenoma of salivary gland, but in recent years there have been occasional reports of malignant basal cell tumors of major salivary glands. We present a case report of one such basal cell adenocarcinoma arising in the submandibular gland and discuss the differential diagnosis and distinction from a basal cell adenoma. We also review the published literature on basal cell adenocarcinoma. This is the first case of basal cell adenocarcinoma to be studied in detail by both immunohistochemistry and electron microscopy. There has been debate in the past as to the cell of origin of salivary gland basal cell tumors and specifically as to whether myoepithelial differentiation occurs in these tumors. The immunohistochemical and ultrastructural features of this case provide evidence for a dual population of ductal and myoepithelial cells. A flow cytometric analysis of nuclear deoxyribonucleic acid content showed the presence of DNA aneuploidy within one tissue block.

Merkel cell tumor-like neuroendocrine carcinoma associated with the submandibular gland. Report of a case with cytologic, immunohistochemical, electron microscopic and flow cytometric studies.

We report a rare case of primary Merkel cell tumor (MCT)-like neuroendocrine carcinoma (i.e., small cell carcinoma) associated with the submandibular gland in a 73-year-old man. Despite the lack of a known skin primary, the tumor exhibited cytomorphologic (predominant single cells with "intermediate filament buttons" in the background), ultrastructural (dense core granules and a globular aggregate of intermediate filaments) and immunohistochemical (paranuclear globular coexpression of cytokeratin and neurofilaments) features identical to that of MCT. The tumor contained an aneuploid peak with DNA index of 1.1 and an S phase of 20.5%. The tumor measured 5.8 cm and was situated between the skin and submandibular gland, with which it was closely associated but separated by connective tissue. The literature on MCT without a known skin primary is reviewed, and the cytomorphologic features that allow the distinction between MCT, lymphoma and oat cell carcinoma are discussed.

Human neoplastic submandibular intercalated duct cells express an acinar phenotype when cultured on a basement membrane matrix.

Culture of the human neoplastic submandibular gland intercalated duct cell line, HSG, on the basement membrane extract Matrigel induces dramatic morphologic changes and cytodifferentiation. Transmission electron microscopy demonstrated an acinar cell phenotype with polarized cells containing a well-developed Golgi apparatus, multiple microvilli-like projections from the apical surfaces into a lumenal-like area, and numerous granule-like organelles. Amylase, an acinar cell marker, was detected by both immunocytochemical and Northern blot analyses. A 50% reduction in [3H]thymidine incorporation by cells cultured on Matrigel, as compared to cells cultured on tissue culture plates, confirmed the differentiated phenotype of the cells. Multiple components of Matrigel appear to contribute to the morphologic differentiation of the HSG cells since antibodies to both laminin and collagen IV, as well as the laminin-derived bioactive peptide containing SIKVAV, have potent inhibitory effects on HSG cell organization on Matrigel. Collectively, these data indicate that culture of HSG cells on Matrigel is a useful model to study salivary gland acinar development.

Mucosubstance histochemistry of pleomorphic adenoma of parotid and submandibular salivary glands of man: light and electron microscopy.

Lumina and adluminal cells in human salivary gland pleomorphic adenomas were found to contain neutral, carboxylated, and occasionally sulphated glycoproteins. A variable component of luminal contents and secretory granules did not appear to contain glycoprotein and possibly consisted of protein. Glycosaminoglycans, which appeared to be hyaluronic acid and chondroitin sulphate, were demonstrated rarely in lumina, often between epithelial cells, and forming the matrix of myxoid tissue and, together with collagen, chondroid tissue. No differences were seen between tumours from parotid glands and those from submandibular glands. Glycoproteins demonstrated in the epithelium are similar to those of intercalary ducts of parotid and submandibular glands, and may represent a primitive form of salivary secretion. Glycosaminoglycans secreted intercellularly by epithelial cells cause their increasing separation to form myxoid or chondroid tissue. This stromalization extends to lumina to produce a loss of epithelium. Pleomorphic adenoma appears to be a manifest example of variable derepression of the genotype.

Mucinous adenocarcinoma of the submandibular gland.

A rare tumor not easily classifiable among published histologic categories for salivary gland tumors is reported. The neoplasm developed within the submandibular gland of a 78-year-old woman with invasion of the mandible and metastasis to regional lymph nodes. Histopathologically, cuboidal cells possessing clear cytoplasm and displaced round nuclei proliferated and exhibited an adenomatous pattern. Many cystic spaces surrounded by tumor cell strands were seen, mucus substance filled in the cystic spaces, and the tumor cells seemed mucus-secreting, but neither epidermoid cells nor papillary appearance could be observed. Electromicroscopically, numerous mucous droplets of low electron density were prominent in the cytoplasm, and the tumor cells had sparse irregular microvilli on the luminal surface. Mucin histochemistry, including paradoxical concanavalin A staining, revealed that the tumor cells contained neutral and acid mucins, and these were identified as class II and III mucosubstances. No other neoplastic lesion, except recurrent metastatic neck nodes, has been detected 6 years after the first examination, and it seems that the tumor is a rare primary mucinous adenocarcinoma of the submandibular gland.

Beta-adrenergic responsiveness in a human submandibular tumor cell line (A253).

Salivary epithelial functions are regulated by the autonomic nervous system. In this regard, we have been studying the morphology and neuroreceptor composition of A253, an immortal cell line isolated from a human submandibular carcinoma (Giard et al., JNCI, 51:1417-1421, 1973). Phase contrast and electron microscopic observations indicate that A253 cells are of epithelial origin. Physiologically, A253 cells possess beta-adrenergic, but not alpha-adrenergic or muscarinic-cholinergic receptors. The beta-adrenergic receptors (BARs) are composed primarily of a single class of high affinity, beta 2-subtype receptors as judged by [3H]dihydroalprenolol antagonist binding studies. The BARs are functional inasmuch as isoproterenol stimulation increases both intracellular cAMP content and [3H]mannose incorporation into endogeneous glycoproteins. Differences in ultrastructure and neuroreceptor composition between A253 and other immortal salivary tumor cell lines are discussed.