Salivary gland pathology. Markéta Hermanová Parotid gland: serous Sublingual gland: mucous Submandibular gland: seromucous + Minor salivary glands (oral mucosa - tongue, lips, the floor of the mouth,…), usually mixed seromucinous nDevelopmental anomalies nSialoadenitis nObstructive and traumatic lesions nSjögren syndrome (SS) nSialoadenosis nHIV-associated salivary gland disease nSalivary gland tumor nAge changes in salivary glands Developmental anomalies nAplasia (congenital, parotid gland, ass. with other facial abnormalities – mandibulofacial dysostosis, aplasia of the lacrimal glands, hemifacial microsomia) nAtresia of one or more salivary gland ducts nHeterotopic salivary tissue (in the mandible – Stafne´s idiopathic bone cavity) Sialoadenitis (1) nBacterial sialoadenitis -acute (mainly parotid; ascendent infection; Staphylococcus aureus, Streptococcus pyogenes, Haemophilus,…; in patients with SS, xerostomia, immunocompromised patients,..; swelling, pain, fever, malaise, redness of the skin) -chronic (in duct obstruction, calculi, ascending infection) + chronic sclerosing sialoadenitis -recurrent (attacks ascending infection in children and adults; calculi, duct strictures, congenital anomalies of the duct system) n nViral sialoadenitis -Mumps (epidemic parotitis) – paramyxovirus, parotid, bilateral; occasionally involvement of testes, ovaries, CNS, pancreas -Cytomegalic inclusion disease – CMV , severe disease in immunocompromised and HIV+; disseminated disease (kidney, liver, lungs, brain,….) - Chronic sclerosing sialoadenitis -submandibular>parotid -acinar atrophy, periductal fibrosis, chronic inflammation, replacement fibrosis -lesion associated with IgG4 n Sclerosing lesions associated with IgG4 nAutoimunne pancreatitis nSclerosing cholangoitis nLymphoplasmocytic cholecystitis nSclerosing sialoadenitis nIdiopathic retroperitoneal fibrosis (M. Ormond) nInflammatory pseudotumor of the liver, lung and hypophysis nTubulointerstitial nefritis ass. with IgG4 nInterstitial pneumonia ass. with IgG4 nSclerosing prostatitis nSclerosing thyreoiditis n -M>F; steroid responsive, lymfadenopathy; pseudoneoplastic lesions -Sclerosing lesions with diffuse lymphoplasmocytis infiltration, irregular fibrotisation, sometimes infiltration by eosinophils, obliterative phlebitis, and the presence of IgG4 positive plasmocytes. -increased risk of the malignant lymphoma Chronic sclerosing sialoadenitis 07-02-28-1-18 Chronic sclerosing sialoadenitis 5592-11-01 5592-11-02 5592-11-03 IgG4 CD20 Acinar atrophy, periductal fibrosis, chronic inflammation + IgG4+ plazmocytes Sialoadenitis (2) nPostirradiation sialoadenitis (fibrous replacement of acini, squamous metaplasia of ducts) n nSarcoidosis (minor glands, parotid; Heerfordt sy: sarcoidosis of salivary and lacrimal glands) n nSialoadenitis of minor gland -in sarcoidosis, in Sjögren syndrome -associated with mucous extravasation cysts, with stomatitis nicotina of the palate -stomatitis glandularis (multiple involvement, multiple swelling, cystic dilatation of the ducts, chronic suppuration); lips affected - n Obstructive and traumatic lesions nSalivary calculi (sialoliths) -the most common cause of obstruction -70-90 % in submandibular gland -usually unilateral; calcium phosphate+carbonates -pain, recurrent swelling -predisposes to ascending infection and chronic sialoadenitis n nNecrotizing sialometaplasia -hard palate in middle aged patients; M>F -deep crater like ulcer -lobular necrosis of salivary glands, squamous metaplasia of ducts and acini, mucous extravasation, inflammatory cell infiltration, pseudoepiteliomatous hyperplasia of the ovelying palatal mucosa -etiology unknown; ischaemia and infarction???, previous trauma, surgery Sjögren syndrome (SS) nChronic autoimmune disease; F>M; ass. with other AI diseases – non-organ specific AI disease – multisystem involvement -Primary (dry mouth (xerostomia)+dry eyes (xerophtalmia or keratoconjuctivitis sicca) -Secondary (xerostomia+xerophthalmia+AI connective tissue disease (e.g. rheumatoid arthritis) nLymphocytic infiltration and acinar destruction of lacrimal and salivary glands→dry eyes and dry mouth; hyperplasia of ductal epithelium – benign lymphoepithelial lesion nass. with particular combination of HLA class II major histocompatibility genes + viruses (EBV) nIncreased risk of B cell malignant lymphoma (MALT) n n n European diagnostic criteria of SS nOcular symptoms (xerophtalmia) nOral symptoms (xerostomia predisposing to candidosis, caries, sialoadenitis, oral dysfunction) nSalivary gland function (sialography, scintiscanning, salivary flow rates, sialochemical studies) nLabial salivary gland histology (lymphocytic sialoadenitis) nAnti-Ro and anti-La autoantibodies (nuclear factors)+ RF, ANA, antithyroid and antigastric parietal autoantibodies Lymphocytic infiltration, destruction of acinar structures + epithelial and myoepithelial proliferation → epimyoepithelial islands (benign lymphoepithelial lesion) Sialoadenosis (or sialosis) nnon-inflammatory, non-neoplastic, recurrent bilateral swelling of salivary glands nHypertrophy of serous acinar glands nParotid commonly affected nAbnormality of neurosecretory control (hormonal disturbances, malnutrition, liver cirrhosis, chronic alcoholism, and following administration of various drugs). HIV-associated salivary gland disease nSjögren syndrome-like disease associated with a benign lymphoepithelial lesion nparotid swelling as a part of persistent glandular enlargement nmultiple lymphoepithelial cysts Salivary gland tumors n n85 % in glandula parotis n65-80 % of tumors in gl. parotis benign nin other glands 35-50 % tumors malignant nsurgical treatment (n. facialis!!!), radiotherapy nlate metastases nnon-painful, palpable nodules Structure of salivary glands Luminal cells: -acinar serous (SA) and mucinous (MA) -ductal (DC) Abluminal cells: -myoepithelial (MC) -basal (BC) BC SA MC DC BC Immunophenotype: CEA, EMA, LMW CK, amylase Immunophenotype: HMW, SMA, S100, GFAP Benign epithelial salivary gland tumors – WHO classification nPleomorphic adenoma – mixed tumor, myxochondroepithelioma (28-74 %) nWarthin tumor (cystadenolymphoma), (3,5 – 12 %) nMonomorphic adenoma n - basal cell adenoma (1,5-2 %) n - myoepithelial adenoma – myoepithelioma (1-2,9 %) n - oncocytoma (1-2 %) n - canalicular adenoma (1 %) n - cystadenoma (2 %) n - sebaceous adenoma/lymphadenoma nDuctal papilloma n n Pleomorphic adenoma and Warthin tumor _parotis-mixed-tumor-307c _parotid-warthin-307c Pleomorphic adenoma (myxochondroepithelioma, mixed tumor) 07-02-28-1-15 07-02-28-1-16 Oncocytoma – oncocytic adenoma 07-02-28-1-12 07-02-28-1-11 Cystic adenolymphoma – Warthin tumor 07-02-28-1-14 Malignant epithelial salivary gland tumors – WHO classification nMucoepidermoid carcinoma (15,5 %) nAdenocarcinoma, NOS (9 %) nAcinic cell carcinoma (6 %) nAdenoid cystic carcinoma (4 %) nPolymorphous low-grade adenocarcinoma (7,4 %) nMalignant mixed tumor (3,6 %) nBasal cell carcinoma nEpithelial-myoepithelial carcinoma nOncocytic carcinoma nSquamous cell carcinoma nUndifferentiated carcinoma (lymphoepithelioma-like, small cell and large cell carcinoma) nMalignant myoepithelioma nSalivary ductal carcinoma nothers (e.g. malignant variants of some benign tumors – carcinoma ex pleomorphic adenoma, cystadenoma, sebaceous adenoma and lymphadenoma, …..) n Low grade malignant salivary gland tumors nAcinic cell carcinoma nMucoepidermoid carcinoma (low grade a intermediate grade) nPolymorphous low-grade adenocarcinoma nBasal cell carcinoma nEpithelial-myoepithelial carcinoma nAdenocarcinoma NOS, low grade nCystadenocarcinoma nMalignant mixed tumors, low grade n Intermediate grade malignant salivary gland tumors nAdenoid cystic carcinoma nSebaceous adenocarcinoma nMalignant myoepithelioma nLymfoepithelioma – like carcinoma High grade malignant salivary gland tumors. nMucoepidermoid carcinoma, high grade nAdenocarcinoma NOS, high grade nSquamous cell carcinoma nSaliváry duct carcinoma nMalignanat mixed tumor, high grade nOncocytic carcinoma nUndifferenciated carcinomas nDedifferenciated adenoid cystic carcinomas andacinic cell carcinomas Mucoepidermoid carcinoma 07-02-28-1 07-02-28-1-3 Low grade Intermediate grade Production of mucus – mucoepidermoid carcinoma 07-02-28-1-2 07-02-28-1-4 PAS+AB mucikarmín Polymorhous low-grade adenocarcinoma and acinic cell carcinoma 07-02-28-1-5 07-02-28-1-13 Epithelial-myoepithelial carcinoma 07-02-28-1-8 Luminal and abluminal differentiation 07-02-28-1-6 07-02-28-1-7 SMA CEA Adenoid cystic carcinoma 07-02-28-1-10 -Perineural invasion! -Relapsing Thank you for your attention …