Radiation-induced epithelial-myoepithelial carcinoma in a patient previously treated with mantle-field radiation therapy for Hodgkin lymphoma.

BACKGROUND: Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands. METHODS AND RESULTS: We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period. CONCLUSION: Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population.

Schwannomatosis presenting as pancreatic and submandibular gland schwannoma.

Schwannomatosis is a well-established third form of neurofibromatosis, characterized by the presence of multiple non-vestibular, non-intradermal schwannomas, often associated with chronic pain. Herein, we report a 41-year-old man with a history of paternal neurofibromatosis 1, who presented with partially cystic tumors in the pancreas and in the right submandibular gland. Besides, he complained of neuropathic pain in the right inguinal and suprapubic area. Magnetic resonance imaging revealed multiple intradural-extramedullary tumors at the cervical, thoracic and lumbar spinal canal, suggestive of schwannomas. The vestibular nerves were not involved. Pathological examination of the glandular tumors disclosed benign schwannomas. These tumors had substantial myxoid stroma and prominent cystic change, and showed a mosaic pattern of loss of INI1/SMARCB1 expression by immunohistochemistry. Later, the patient developed three nodules in the right lung which were interpreted as schwannomas. To our knowledge, this is the first report of schwannomatosis presenting as pancreatic and salivary gland schwannomas.

HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status.

AIMS: In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC). METHODS AND RESULTS: In 31 cases, we examined the MAML2 fusion status using reverse transcriptase-polymerase chain reaction, and HER2 and EGFR status using immunohistochemistry and chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of 26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%) intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high-polysomy) were each detected in four of 28 (14.3%) MECs analysed. Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas such abnormalities were extremely rare in low- and intermediate-grade MEC. CONCLUSIONS: These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC. Furthermore, we suggest that high-grade MEC comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML2 fusion status.

Fibromatosis of the submandibular region.

Fibromatoses are benign tumors that can occur anywhere in the body. They are locally aggressive and tend to recur; they also cause considerable morbidity, particularly when they arise in the head and neck. Fibromatosis in the submandibular region is rare. Here, we present a case of fibromatosis of the submandibular region in a 42-year-old female who presented with a right submandibular mass. The patient underwent complete excision of the fibromatosis, showed negative margins and had no adjuvant therapy. Her recovery was uneventful, and there was no recurrence or neurological deficit 1 year after the operation.

Undifferentiated carcinoma of the submandibular salivary gland with fulminant clinical course: a case report.

Undifferentiated carcinoma of salivary glands is too poorly differentiated to be classified as any of the specific group of carcinomas. This is a rare disease, the incidence of which is rather low-to-very low in the Indian subcontinent. The tumor can assume an aggressive clinical behavior characterized by disseminated metastases. The prognosis is rated as dismal; as evidenced by this clinical report of a tumor in the submandibular salivary gland with synchronous metastases to the skull bones and in to the intracranial fossa. The putative relationship of the tumor to Epstein-Barr virus (EBV) infection is discussed.

No association between the use of cellular or cordless telephones and salivary gland tumours.

AIM: To investigate the association between the use of cellular or cordless telephones and the risk for salivary gland tumours. METHODS: Cases were assessed from the six regional cancer registries in Sweden. Four controls matched for sex and age in five year age groups were selected for each case. A total of 293 living cases and 1172 controls were included. RESULTS: There were 267 (91%) participating cases and 1053 (90%) controls. Overall no significantly increased risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI 0.68 to 1.43) for use of cordless phones. Similar results were found for different salivary gland localisations. No effect of tumour induction period or latency was seen, although few subjects reported use for more than 10 years. CONCLUSIONS: No association between the use of cellular or cordless phones and salivary gland tumours was found, although this study does not permit conclusions for long term heavy use.

[MALT lymphomas of the salivary glands. Review of the literature apropos of a case in a patient with hepatitis C virus infection]. / Linfomi MALT delle ghiandole salivari. Revisione della letteratura a proposito di un caso insorto in paziente con infezione da HCV.

We describe a 68-year old woman affected by chronic hepatitis C virus infection; hypertransaminasemia was first observed at the age of 46 years, when the patient was diagnosed uterus carcinoma. Since 1994 she had complained of xerostomia, xerophtalmia, pain at the left parotid and laterocervical adenomegaly. Neck ultrasound examination revealed enlarged intraglandular, submandibular and laterocervical lymph nodes. Fine-needle aspiration of both left parotid and laterocervical lymph nodes was not diagnostic. The histologic examination of the surgical biopsy of the left parotid and the right submandibular salivary gland allowed to diagnose mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). The patient was given alpha-interferon obtaining a clinical remission of the lymphoma and transitory normalization of transaminase level. The authors review the literature about some aspects of MALT lymphomas: a) the etiopathogenesis of MALT lymphomas and the mechanisms suspected to be involved in the evolution from a "benign" lymphoepithelial infiltrate to a neoplastic disorder; b) the relationship between chronic inflammatory diseases as Sjögren's syndrome and chronic C virus infection and MALT lymphomas, particularly MALT lymphomas of the salivary glands; c) the significance of the evidence of a B-cell clonality in the context of a lymphoepithelial lesion; d) diagnostic and therapeutic aspects of MALT lymphomas of the salivary glands.

N-3, n-6 and n-9 dietary fatty acids modulate the growth parameters of murine salivary gland tumors induced by dimethylbenzanthracene.

Variations in dietary fatty acid composition influence the biological behaviour of certain tumours. Diets enriched with oleic acid (18:1 n-9) seem to promote tumour progression on several lines due perhaps to the development of essential fatty acid deficiency (EFAD), whereas n-3 fatty acids have a protective effect. Since the role played by lipids on salivary gland tumorigenesis has not yet been studied, an experimental model is presented. BALB/c mice were fed on four different diets: control, corn oil, fish oil and olein groups. Salivary gland adenocarcinomas were chemically induced by using 9,10-dimethyl-1,2-benzanthracene. Animals were sacrificed at the 20th post-injection week and several tumour parameters were analysed. Linoleic acid showed no promoting activity. Tumour size was larger in the olein group than in fish oil fed mice, indicating that the oleic acid, linked to the induced EFAD condition, has a protumorigenic activity whereas n-3 polyunsaturated fatty acids appear to exert a protective effect.

Immunohistochemical detection of extracellular matrix proteins in the irradiated rat mandibular gland.

UNLABELLED: BACKGROUND/MATERIAL AND METHODS: In 59 rat mandibular glands we investigated the distribution of extracellular matrix proteins (EMP) in rat salivary gland tumors. The animals differed in age and pretreatment status (irradiation versus no irradiation). For immunohistochemical analysis we used polyclonal EMP antibodies [anti-laminin (AL), anti-fibronectin (AF), anti-collagen-III (AC-III), anti-collagen-IV (AC-IV)]. RESULTS: The antibodies identified the different structures of the extracellular matrix: components of basement membranes [(BM); laminin, collagen IV] and components of BM-associated structures (fibronectin, collagen III). Immunoreactivity was found in glandular tissue, in vascular walls, in nerve tissue and the interstitial connective tissue. Various EMP showed different patterns. Significant differences were seen between irradiated and non-irradiated glands, often with generally stronger and more extended staining in the irradiated group. Thus, both nerve tissue and excretory ducts (ECD) were in part strongly stained for AL, while ECD were intensely positive for AF. CONCLUSIONS: Preceding radiation has to be considered when interpreting salivary gland tissue, especially in tumor differentiation studies following irradiation.

Malignant oncocytoma of major salivary glands. Report of a post-irradiation case.

The fourth case of malignant oncocytoma arising in the submandibular gland is here reported. This tumor arose in a 48-year-old man after radiation exposure, a finding never described before for malignant oncocytoma. In addition, several regional metastatic lymph nodes were found. The diagnosis was confirmed by histochemical and ultrastructural findings. The tumor cells showed easily recognizable mucus production and, ultrastructurally, abundant mitochondria, intracytoplasmic lumina lined by microvilli and lipid droplets. These last features have only seldom been described in malignant oncocytoma. Furthermore, the neoplastic cells were alpha-1-antitrypsin positive and S100, thyroglobulin, carcinoembryonic antigen, and smooth muscle actin negative. A thorough review of the literature is also presented.

[Mucoepidermoid carcinoma of the submandibular gland after high-dose radioiodine therapy: case report and review of the literature]. / Mukoepidermoid-Karzinom der Glandula Submandibularis nach hochdosierter Radioiodtherapie: Fallpräsentation und Literaturübersicht.

Case report of a 42 year old female, who received 14th-20th year of life six radioiodine therapies with altogether 19.2 GBq131I because of a papillary thyroid carcinoma. 17 years after the last therapy, she developed a histologically proven chronic radiogenic sialadenitis of the left submandibular gland. Further four years later, the right submandibular gland has been extirpated because of a mucoepidermoid carcinoma with infiltration of a regionary lymphatic node. Review of the previous published secondary-malignancies of the salivary glands after high-dose radioiodine therapies.

Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans.

To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the submandibular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple so that a total of 31 cancers were found. Eleven of these carcinomas were in the vicinity of transplanted islets, eight of which showed intra-insular ductular or cyst formation as seen in the pancreas of hamsters during pancreatic carcinogenesis. The formation of ductular structures within islets was also demonstrated in vitro. Some tumor cells in the vicinity of these islets were reactive with anti-insulin. Y chromosome message was found by polymerase chain reaction analysis in one of the three tumors examined. Also, like the induced pancreatic tumors, all three submandibular gland tumors that were examined had the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood group A antigen. These and other findings strongly suggest that some components of islets, most probably stem cells, are the origin of ductal-type adenocarcinomas in this model.

[Fine needle aspiration in the cytologic diagnosis of swellings in the parotid and submandibular regions. Cytologic-histologic correlations in 49 cases]. / Diagnosi citologica mediante aspirazione con ago sottile di tumefazioni della regione parotidea e sottomandibolare. Correlazione cito-istologica in 49 casi.

Fine needle aspiration biopsy (FNAB) has been widely used for a number of years and offers considerable advantages in comparison to conventional surgical biopsy. A number of organs can be subject to this diagnostic procedure with good results, including the salivary glands. This paper aimed to compare the cytological diagnosis of biopsy material obtained using FNAB and the subsequent histological diagnosis formulated after surgery in 49 patients with swellings in the parotid or submandibular region who were referred to the Department of Anatomy and Pathological Histology in L'Aquila. Cytohistological concordance was present in 87.7% of the cases in this series, a percentage that is in line with that reported by other authors. The most frequent causes of diagnostic error may be ascribed to moderate nodule size and/or the scanty material obtained not suitable for diagnosis. In this series all cases of malignant neoplasia were correctly diagnosed. In spite of the limitations of this method, the authors consider that it plays an important role in the preoperative diagnosis of salivary gland pathologies.

Manejo quirúrgico de la glándula submandibular / Surgical management of submandibular gland

Se presenta la experiencia de los autores en el tratamiento quirúrgico de la glándula submandibular. Se resalta algunos aspectos a tener presente en la cirugía. Son 15 casos, reunidos entre los años 1988-1995. El 66,7 por ciento presentaba una patología inflamatoria y un 33,3 por ciento era de tipo neoplásica. A diferencia de lo que dicen algunas publicaciones, las neoplasias benignas fueron un 80 por ciento (4 casos); todos adenomas pleomorfos. Se comunica los análisis de esta casuística en relación a la edad, sexo, complicaciones y se plantean conductas a seguir en el tratamiento quirúrgico de la glándula submandibular

Karyotypic instability and viral integration in polyoma virus-induced mouse salivary gland tumors.

Stable integration of polyoma viral DNA into the host-cell genome is a prerequisite for continuous expression of the transformed phenotype. In this study we have mapped the chromosomal location of integrated viral DNA sequences in a polyoma-induced mouse salivary gland adenocarcinoma. By in situ hybridization, a major integration site was assigned to chromosome 14, band B. The combined results from in situ hybridizations to metaphase chromosomes, primary tumors, and cultured tumor cells indicate the presence of both integrated and free polyoma viral DNA in the tumors. Cytogenetically, the tumors were characterized by a pronounced karyotypic instability. No abnormal cells with the same karyotype were observed in any of the tumors. Nevertheless, it was possible to recognize a preferential pattern of chromosomes variation with certain common recurrent and sporadic deviations. Clonal gains and/or losses of single chromosomes were seen in all tumors. It is concluded from these results that karyotypic instability may play an important role in the genesis and progression of polyoma virus-induced salivary gland tumors.

Bilateral submandibular gland lymphoma in Sjögren's syndrome.

Salivary gland lymphoma is associated with Sjögren's syndrome. A case of bilateral submandibular gland and sublingual gland lymphoma, arising in Sjögren's syndrome, is presented. A lymphoma involving more than one salivary gland may occur in Sjögren's syndrome, and there is an increased risk of developing an extrasalivary lymphoma.

Salivary gland tumors in atomic bomb survivors, hiroshima, japan. II. Pathologic study and supplementary epidemiologic observations.

A pathological investigation was undertaken in Hiroshima on cases seen between 1945 and 1971 to determine the relationship between salivary gland tumors and exposure to atomic (A) bomb radiation. Of the 208 cases of histologically confirmed salivary gland tumors, 62 were A-bomb survivors and 146 were nonexposed. The relative risk based on the rate in the nonexposed for malignant tumors of salivary glands among the exposed in Hiroshima Prefecture was 11.0, while that of the submaxillary gland was 13.8 and that of the parotid gland was 9.8. They were all highly significant by X2 test (P less than 0.001). The latent period of malignant salivary gland tumors was shorter in the exposed than in the nonexposed. Four cases of benign salivary gland tumor, all being benign mixed tumors of the parotid gland, were observed in children whose parents had been exposed. The incidence of mixed tumors of the salivary gland among the exposed in Hiroshima City was 2.0 times higher than that among the nonexposed and showed a tendency to increase with proximity to the hypocenter (P less than 0.01).