TYPES and FREQUENCY of SALIVARY GLAND TUMORS in MAJOR and MINOR. Karl Donath Department of Oral Pathology (Director:Prof. Dṛ Dr.

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1 TYPES and FREQUENCY of SALIVARY GLAND TUMORS in MAJOR and MINOR SALIVARY GLANDS Karl Donath Department of Oral Pathology (Director:Prof. Dṛ Dr. Karl Donath) University of Hamburg, Salivary gland tumors were classified by different criteria, e. g. localization, tissue struc ture, cytodifferentiation, histogenesis. In the daily routine diagnostics of salivary gland tumors the international histological classification (WHO, Thackray et Sobin 1972) has proved worthwhile. This classification is also used in the Hamburg Speicheldrusen-Register, which contains 12,672 biopsies accumu lated over 22 years ( ). These biopsies of salivary glands include 3,698 cases of epithelial salivary gland tumors (30%), 205 cases of mesenchyrnal tumors (1.6%) without malignant lymphomas, 71 cases of tumor metastasis (0.6%) and 83 cases of periglandular tumors (0.65%). For further details see Table 1. Table 1 FREQUENCY OF EPITHELIAL TUMORS IN MAJOR AND MINOR SALIVARY GLANDS N=4068 (Hamburger Speicheldrusen Register ) (10 double diagnosis)

2 Karl Donath The percentage of benign tumors in all salivary glands is 67.75%. Most of the tumors (87%) occurred in major salivary glands. Another statistic reports about 86% (Eveson and Cawson 1985). The reports about the occurrence of adenomas in major glands are around 78%. A great variation exists in the percentage of adenomas in minor glands which varies between 52 and 57.5% (Chaudhry et al 1984, Eveson and Cawson 1985, Waldron et al 1988). Uni-or bilateral multiple tumors in one patient are described several times (Turnbull and Franzell 1969, Bab et Ulmansky 1979). Bilateral tumors are more frequent in adenolym phomas, less often pleomorphic adenomas, acinic cell carcinomas, adenocarcinomas or epithe lial-myoepithelial salivary duct carcinomas. Multiple unilateral tumors may occur in different combinations. There are reports about pleomorphic adenomas and adenolymphomas (Gaynor and Hershberg 1976, Mason and Chis holm 1975), pleomorphic adenoma and oncocytoma (Trejo 1972), pleomorphic adenoma and mucoepidermoid carcinoma. Multiple uni-or bilateral tumors may occur in pleomorphic adenomas or adenolymphomas. The pleomorphic cases in major salivary glands. adenoma is the most frequent salivary gland tumor and is located in 90% of The parotid gland is the place in which 84% of them develop. The percentage of pleomorphic adenomas in minor salivary glands is 41%. Most pleomorphic adenomas of minor salivary glands are located in the palate, lip and cheek. The tongue, floor of the mouth and trigonum retromolare are less affected. Females are more affected than males (1.5:1). The mean age is in the 4th to 7th decade in major salivary glands, in minor salivary glands around 50 years. The pleomorphic adenomas are well encapsulated in major salivary capsule is developed in minor glands. glands, an incomplete Histologically, most of the tumors in minor salivary glands are cell-rich, whereas most of the tumors in major glands are stroma rich. The myoepithelioma is a special type of pleomorphic adenoma and occurs predominantly in the palate. The most frequent epithelial cell forms are salivary duct and myoepithelial cells, as well as epidermoid cell clusters. Less often there are hornified squamous epithelium and other cell forms (oncocytes, goblet cells, sebaceous glands). The stromal differentiation is mainly mucoid, occasionally chondroid, hyaline, fibrous, osseous. Seifert et al 1976 distinguish four subtypes of pleomorphic adenomas by the epithelial and stroma content. The stroma-rich pleomorphic adenomas show the tendency of recurrence. Carcinomas are mostly seen in cell rich types. Most of the monomorphic adenomas occur in, the parotid gland (97.4%) and less in the submandibular (2.6%). The distribution in minor glands is palate (27.3%), upper lip (27.3%), cheek (23.6%), trigonum retromolare and other locations (21.8%). The main incidence of monomorphic adenomas is the 7th decade in major as well as in minor salivary glands.

3 Types and Frequency of Salivary Gland Tumors in Major and Minor Salivary Glands Males are less affected than females (1:2). Histologically, monomorphic adenomas are distinguished from pleomorphic adenomas by two characteristics. The epithelial cells form certain structures and these structures are sharply delineated from the stroma. A further subdivision can be made on the basis of cell type:basal cell adenoma, oncocytoma, clear cell adenoma, sebaceous gland adenoma. Or differentiation by histostructure:trabecular,. tubular, canalicular. A special form of monomorphic adenoma is the dermal analogous tumor which might occur at several places in one gland at one time without any fibrous demarcation. Every tumor cell cluster is clearly demarcated by a basal membrane-like hyaline band. The adenolymphoma develops in the parotid gland mainly of males in the 6th and 7th decade of life. After pleomorphic adenomas, adenolymphomas are the most common benign salivary gland tumors (15%). The adenolymphoma is histologically characterized by cystic cavities lined by oncocytic cells and a lymphoreticular stroma. Malignant salivary gland tumors The frequency of benign and malignant tumors in major and minor glands is different. The proportion of benign to malignant tumors in major glands is 3.5:1 and in minor glands it is 1.08:1. Acinic cell carcinomas are characterized by acinar and partially duct-like structures. The content of acinar and duct-like structures is different in the single tumor cases, so that low-grade (well-differentiated) and high-grade (less differentiated) tumors are distinguished. Most of the acinic cell carcinomas arise in the parotid gland (96%), less frequently in the submandibular gland or minor glands. The main incidence is in the 7th decade of life, predominantly in females. Histologically, the acinar differentiated tumor parts contain PAS-positive granules. Im munohistochemically the amylase-positive reaction in these tumor cells is the main diagnostic criteria. Mucoepidermoid carcinomas occur in 64.5% of the cases in major salivary glands, especially in the parotid gland (89.6%). The main localization of mucoepidermoid carcinomas in minor salivary glands is the palate (44.8%), cheek (12.1%), tongue (12.1%) lip (8.6%), trigonum retromolare and other (22.4%). Histologically, mucoepidermoid carcinomas consist of two cellular components:solid epidermoid cell clusters and complexes of mucous-producing goblet cells. The relation of epidermoid and mucous-producing cells varies in the tumor cases. Well-differentiated (low grade) carcinomas have a high content of mucous-producing cells, low-differentiated (high grade) are rich in epidermoid-differentiated tumor parts. This epidermoid part could be less differentiated or consist of clear cells.

4 Adenoid-cystic carcinomas localized in the parotid gland (59%). develop in 57.5% of cases in major salivary glands and are mainly In minor glands the palate is involved in 27.9% of cases. The main age peak is the 6th decade of life. Females are more affected than males (1.8:1). Histologically, adenoid cystic carcinomas consist of epithelial and myoepithelial cells. The histological pattern varies also in one tumor and may be cribriform, tubular or solid. The tumor prognosis of cribriform and tubular differentiation is better than solid. The adenoidcystic carcinoma is characterized by multiple recurrences (60%), perineural spread (50%), vessel invasion (15%) and the tendency towards metastasis. The metastases occur more frequently in the solid forms than tubular or cribriform. Adenocarcinomas occur in 66.5% of cases in major salivary glands. The parotid gland is the main localization (81%), less frequently the submandibular gland (16%) and sublingual gland (3%). In minor glands there is equal distribution of adenocarcinomas in the palate (20%), lip (20%) and cheek (17.1%). The main incidence is in the 7th decade. Females are more affected than males. Histologically, the adenocarcinomas are a heterogenous group. There is one group which is not mentioned in the WHO (1972) called salivary duct carcinomas, which have a different clinical behaviour and prognosis. Polymorphous low-grade adenocarcinomas (terminal duct carcinoma), epithelial-myoepithelial duct carcinoma and sailvary duct comedo carcinoma be long in the group of salivary duct carcinomas. The polymorphous lowgrade adenocarcinoma occurs mainly in the palate, very rarely as carcinoma in a pleomorphic adenoma. The low-grade adenocarcinoma is variously designated as low-grade papillary adenocarci noma, terminal duct carcinoma and lobular carcinoma. Some authors divided this tumor group into terminal duct carcinomas and low-grade papillary adenocarcinomas. Between both there should be a difference in clinical behaviour and prognosis. The terminal duct carcinoma occurs anywhere in the mouth, the mean age was 59.1 years. The low-grade papillary adeno carcinoma occurred mainly in the palate, the mean age was 64.2 years (Slootweg and Mueller 1987). Recurrences were observed in patients with terminal duct carcinomas, metastases in patients with a low-grade papillary adenocarcinoma. The myoepithelial duct carcinoma occurs predominantly in the parotid gland of females in the 7th decade. It has a good prognosis. The salivary duct comedocarcinoma with epithelial nests and central necrosis is analo gous to the ductal breast carcinoma, infiltrating growth, poor prognosis. It develops mainly in the parotid gland. Other types of adenocarcinomas are papillary adenocarcinoma, oncocytic adenocarcinoma, basal cell adenocarcinoma etc. Carcinomas in pleomorphic adenomas are most common in major salivary glands (82.5%), and are localized in 83% of cases in the parotid gland. In minor salivary glands the palate is

5 Types and Frequency of Salivary Gland Tumors in Major and Minor Salivary Glands mainly affected (65.8%). The mean age in minor salivary glands is the 6th and 7th decade of life, in major salivary gland the 7th and 8th decade. Females are more affected than males. Histologically, carcinomas in pleomorphic adenomas may be divided into invasive, non invasive types and carcinosarcomas. Questionable is the existence of a pleomorphic carcino ma (malignant mixed tumor). Some authors believe that this type of tumor is a malignant myoepithelioma. Squamous cell carcinomas (epidermoid carcinomas) occur in 93.75% of cases in major salivary glands, frequently in the parotid gland (83%). The main incidence is in the 7th and 8th dec ade of life. Males are more affected than females. Clinically and histologically it might be difficult to decide in progressed tumor cases whether it is a primary or infiltrative squamous cell carcinoma. Adenosquamous carcinomas, small cell carcinomas and neuroendocrine carcinomas are rare, as are carcinomas in other adenomas. Undifferentiated carcinomas are a small group of 1.5% of all salivary gland tumors and are frequently located in the major salivary glands (77.5%). Non-epithelial tumors in salivary glands consist mainly of angiomas (52.5%), lipomas (18.5%), neural tumors (17.5%), other benign mesenchymal tumors (4%) and sarcomas (7.5%). Other tumors which might occur in salivary glands are periglandular tumors and meta stases. Of clinical interest are tumor-like conditions: Sialadenosis Oncocytosis Necrotizing sialometaplasia Benign lymphoepithelial Salivary gland cysts lesions Literature: 1 ) Thackray, A. C., Sobin, L. H.:Histological typing of salivary gland tumours. WHO, ) Eveson, J. W., Cawson, R. A.:Salivary gland tumours. A review of 2410 cases with partic ular reference to histological types, site, age and sex distribution. J. Pathol, 146:51-58, ) Chaudhry, A.P., Labay, G.R., Yamane, G.M., Jacobs, M.S., Cutler, L. S., Watkins, K. V.: Clinico-pathologic and histogenetic study of 189 intraoral minor salivary gland tumors. J. Oral Med, 39:58-84, ) Waldron, C. A., El Mofty, S. K., Gnepp, D. R.:Tumors of the intraoral minor salivary

6 glands:a demographic and histologic study of 426 cases. Oral Surg, 66: , ) Turnbull, A. D., Franzell, E. L.:Multiple tumors of the parotid gland. Am. J. Surg, 118: , ) Bab, I. A., Ulmansky, M.:Simultaneously occurring salivary gland tumors of different types. J. Oral Surg, 37: , ) Gaynor, E. B., Hershberg, R.:Unilateral multiple tumours of the parotid gland. J. Laryng, 90: , ) Mason, D. K., Chisholm, D. M.:Salivary glands in health and disease. Sounders, London- Philadelphia-Toronto, ) Trejo, I.H., Harwood, T. R., Goldstein, J.C., Summers, G. W.:Oxyphil adenoma four years after a benign mixed tumor. Arch Otolaryngol, 96: , ) Seifert, G., Langrock, I., Donath, K.:Pathomorphologische Subklassifikation der pleomor phen Speicheldrilsenadenome. HNO, 24: , ) Slootweg, P. J., Mueller, H.:Low-grade adenocarcinoma of the oral cavity. J. Cranio-Max -Fac Surg, 15: , 1987.