Diseases of the salivary glands:

Transcription

1 Diseases of the salivary glands: Sialoadenitis Sialolithiasis Mikulicz syndrome/disease

2 Sialolithiasis Most frequently occures in the submandibular duct, rarely in the parotid duct and in the ducts of the minor salivary glands Bright yellow stone, with dilatation of the ducts (ductectasia), the saliva is collected in the lumen, the stone frequently solitary Not linked to hyperparathyreoidism, dietary Genesis: detached epithelial cells+ Ca++ (calcium phosphate +glycoproteins) sialolith (stone) chronic obstruction chronic sialoadenitis, on the long run sialoadenitis chronica fibrosa (in the submandibular gland: Sialoadenitis chronica sclerotisans submandibularis Küttner tumor (it is also a tumor-like lesion). Symptomes: pain during eating when saliva excretes, palpable submandibular gland, enlarged, firm gland Mikroscopy: focal/diffuse lymphoid cell infiltrate, variable scarring, acinar degeneration

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5 Sialoadenitis Causes: ductal occlusion (eg. stone) viral, or bacterial infection autoimmune disease: Sjögren syndrome Viral sialoadenitis: causes the mumps virus, which belongs to the paramyxoviridae, usually in children, infective disease, 2-3 months incubation, bilateral, rarely unilateral parotid swelling, fever, fatigue, headache, increased Se amylase-level, pain during salivation. Histology: interstitial oedema+mononuclear infiltration Bacterial/suppurative sialoadenitis: in elderly, after extensive chest or abdominal surgery, if the saliva production reduced, it predisposes a retrograde infection, bacterial invasion pathogen: Staphylococci, Streptococci Clinically unilateral swelling, pain, purulent ductal excretion

6 Autoimmune sialoadenitis (Sjögren synrome) Minor and major salivary glands and lacrimal glands are involved, keratoconjuctivitis sicca, corneal ulcers, xerostomia, parotid swelling, anti SSA/SSB+ Histology: LESA, lymphoepithelial sialoadenitis: periductal small lymphocytic (B+T) + plasmacytic sialoadenitis, ductctasia, acinar atrophy/destruction, (benign lymphoepithelial laesion-lel: condenzed-cohesive epithelial aggregates surrounded by hyalinized BM + lymphoid cell infiltrate), Dg.: from minor salivary gland biopsy (eg.: from the lower lip) High risk of malignant lymphoma (40:1) Sjögren syndrome may combine with other systemic autoimmun diseases (RA, SLE, Hashimoto thyreoiditis, CAH)

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11 Mikulicz disease (MD) vs. Mikulicz syndrome 1888, first description of Mikulicz disease Symmetric, bilateral swelling of lacrimal and salivary gland (parotid, submandibular) Lymphocytic infiltration xerostomia and xerophthalmia J. von Mikulicz-Radecki: Über eine eigenartige symmetrische Erkrankung der Thränen- und Mundspeicheldrüsen. Beiträge zur Chirurgie. Festschrift gewidmet Theodor Billroth. Stuttgart, 1892:

12 J. von Mikulicz-Radecki: Über eine eigenartige symmetrische Erkrankung der Thränen- und Mundspeicheldrüsen. Beiträge zur Chirurgie. 1892: Oral Surg Oral Med Oral Path Oral Rad Endod Sep;100(3):334-9.

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14 Mikulicz disease (MD) today (vs. Mikulicz syndrome) Mikulicz disease: idiopathic, painless, bilateral lacrimal and salivary gland swelling (at the beginings Sjögren syndrome belonged to this category) today this is the part of the IgG4-related systemic disease (IgG4 RSD) Mikulicz syndrome: similar/the same symptomes, but known background disease, like TB, sarcoidosis, HIV infection, lymphoma) A Sjögren syndrome and the Mikulicz disease are different diseases (see table below)

15 Tumour-like lesions of the salivary glands Sialoadenosis Oncocytosis Necrotizing sialometaplasia (salivary gland infarct) LESA (benign lymphoepithelial laesion, in relation to Sjögren s syndrome) Salivary gland cysts Chronic sclerozing sialoadenitis in the submandibular gland (Küttner s tumor) Cystic lymphoid hyperplasia (AIDS-related)

16 Sialoadenosis Recurrent, painless, bilateral salivary gland swelling, not an inflammatory process, related to endocrine diseases (Diabetes mellitus, chronic aethylismus, cirrhosis, malnutrition). It is a dysfunction of the autonom nerve system: prolonged storage phase (large zymogenic-secretory granules are stored in the cytoplasm of the acinic cells, the size of the acini are increased) EM: myoepithelial atrophy and axonal degeneration (axolysis, decrease in the number of the neurosecretory granules) Morphology: swollen, enlarged, serous acinar cells, (60μ instead of the normal 40-45μ) basally-placed nuclei, mild duct compression in minor salivary glands: adenomatoid hyperplasia

17 Oncocytosis The other name is focal adenomatous oncocytic hyperplasia, probably the precursor of the oncocytoma or multiple oncocytoma (oncocytomatosis), it is characterized by lesions below 1 cm in diameter, diffuse oncocytosis: rare, more frequent in women

18 Shellenberger T et al. AJNR Am J Neuroradiol 2008;29: Oncocytosis

19 Necrotizing sialometaplasia (salivary gland infarct) Localization: palate 20%, parotid 35%, submandibular gland 15%, other macroscopy: exulcerated mucosa microscopy: Intraductal metaplastic squamous cell proliferation (squamous metapl.), which contains entrapped mucinous cells, the lobular structure is preserved no true infiltrative pattern superficial pseudoepitheliomatous hyperplasia prominent inflammatory infiltrate vascular changes: thrombosis, obliteration, ischaemic lesion partial necrosis in the salivary gland zonality: squamous metaplasia in the centre, necrosis and inflammation at the periphery differential diagnosis: SCC, mucoepidermoid cc., postirradiation changes

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23 Salivary gland cysts Epidermoid cyst: a cyst lined by keratinizing squamous epithelium, filled with laminated keratin Salivary duct cyst: mainly in the parotid gland, dilated duct filled with mucus, epithelial lining, (generally flattened cuboideal epithel), obstruction or narrowing of the duct plays important role in the pathogenesis, similar to that of the retention type of mucokele Lymphoepithelial cyst: branchial cyst, in the parotid and the soft tissues of the neck, lined by non-keratinizing or keratinizing squamous epithel with massive lymphoid stroma + follicles Mucokele (minor glands): 2 types, retention and extravasation types Retention type: in older ages (in the 6th, 7th, or 8th decade), mainly on the lower lip, may occure anywhere in the minor glands, epithelial lining in the cyst Extravasation type: more than 70% on the lower lip, 7% on the floor, 6% in the bucca, the rest in the palate. Mainly in youngs in their 2nd-3rd decadei, morphology: foamy histiocytes, macrophages and extravasated mucus to the extracellular space, no epithelial lining, there is a mechanical trauma in the background (damage in he minor gland duct) Ranula: mucus cyst on the floor beneath the tongue, due to the dysgenetic developement of the sublingual duct, characterized by mucus extravasation+ inflammatory reaction

24 Epidermoid cyst

25 Epidermoid cyst

26 Lymphoepithelial cyst

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28 Mucokele/ranula mucokele ranula mucokele

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31 Mucokele, retention type

32 Mucokele, retention type

33 Sialoadenitis chronica fibrosa submandibularis (Küttner tumor) , 4 cases, H. Küttner, slightly painful, firm submandibular gland swelling in mid-aged adults 2. Swollen, firm, tumour-like lesion in the submandibular gland 3. Focal, or diffuse inflammation with variable intensity, interstitial fibrosis (stages 1-4) acinar cell atrophy, duct cell metaplasia Pathogenesis: not fully understood ductal obstruction with sialolithiasis disorders of the ductal system secretion dysfunction irradiation (after head and neck irradiation) immune mechanism: part of the IgG4 RSD

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37 Cystic lymphoid hyperplasia (AIDS-related) HIV-associated lymphoepithelial cyst Generally in the parotid, swelling of the gland beside the AIDS-related generalized lymphadenopathy mainly in young adults Histology Similar to the conventional lymphoepithelial cyst Diffuse or follicular lymphoid hyperplasia, polyclonal B-cell and mainly CD8+T-cell component, hypervascularisation Cyst in the middle of the lesion, lined by stratified squamous epithel (which is of duct epithel origin) HIV-associated antigenes in the lymphoid cells Not progress to lymphoma

38 Benign salivary gland tumours Monomorphic adenoma (trabecular, tubular, canalicular) Basal cell adenoma Pleomorphic adenoma Warthin tumour (cystadenoma lymphomatosum papillare) Oncocytoma Myoepithelioma

39 Monomorphic (canalicular) adenoma: Trabecular, tubular, canalicular types, benign, no mesenchymal component, 70%- in the parotid, the rest in the minor glands, mainly on the upper lip, bucca, palate Basal cell adenoma: Mainly in the parotid and in the minor glands, vast majority occures in elderly, solid-trabecular appearance, rarely tubular, the tumour cells show basal phenotype, they form cellular palisade, produce basal membrane-like material (PAS+) Oncocytoma: Rare, mainly in the parotid, 3-4 cm in size, encapsulated, brown, lobulated tumour, takes 1% of all salivary gland tumours Microscopy: solid microcystic growth pattern, fine fibrovascular stroma, consist of cells with large, granular, eosinophilic cytoplasm and pycnotic, hyperchromatic nuclei

40 Warthin tumour (cystadenoma lymphomatosum papillare) Forms 15% of all the salivary gland tumour, invovlves mainly the parotid, the submandibular and the minor salivary glands May appear as bilateral and multifocal tumour Tight relation to smoking Macroscopy: cystic-solid appearance, grayish, gelatinous consistency, fragile Microscopy: oncocytaer epithel in solid areas, lines the cysts, interstitial lymphoid stoma+ reactive lymphoid follicles, squamous metaplasia Myoepithelioma: 50% in the parotid, 40 % in the minor glands, mainly on the palate, grows slowly Microscopy: spindle cell, clear cell and plasmocytoid variants (debatable whether it is a true myoepithelial tu.), cytokeratin, SMA, GFAP, S100+

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42 Pleomorphic adenoma 75-80% in the parotid, 5-10% in the submandibular gland, and 10% in the minor glands, slowly growing neoplasm, has a capsule, develops satellite nodules/pseudopods, painless swelling, occures most frequently between years of age Histology: trabecular, tubular, cystic growth, epithelial (areas with glandular or epidermoid differentiation+myoepithelial islands+ mesenchymal elements (cartilage, bone, primitive mesenchymal elements, myxoid/mucoid matrix) Malignant transformation: in 2-7%, true histological malignant transformation: adenocarcinoma, salivary duct carcinoma, spindle cell (myoepithelial) or sarcomatoid carcinoma Characteristics of the malignnancy: vascular invasion, perineural invasion, atypical mitoses Benign metastatizing pleomorphic adenoma: Histologically benign, but produce multiple organ involvement. Extremely rare.

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45 Malignant salivary gland tumours Adenoid cystic carcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Myoepithelial carcinoma Salivary duct carcinoma

46 Adenoid cystic carcinoma: Makes 10% of all the salivary gland tumour (first described by Billroth in 1859 as cylindroma) Localization: 17% in the parotid, 15% in the submandibular gland, ~60% in the minor salivary glands!!! (palate, antrum, tongue) Characteristically infiltrative growth, spread far away from the grossly palpable borders, perineural (facial nerve) infiltration paralysis, painful, long clinical course, tendency for recurrency, haematogenous spread to the lungs Histology: consist of cells with basaloid character, cells elaborate basament membrane-like material (PAS+), tumour shows cystic or crybriform appearance, perineural invasion, histology subtypes: crybriform/classical type, tubular type, solid basaloid type

47 Adenoid cystic carcinoma

48 Mucoepidermoid carcinoma: Takes 5% of all salivary gland tumours, 67% in the parotid, 33% in the minor glands eg. palate (this is the 3rd. Most frequent tumour of the minor salivary glands, 1. pleomorphic adenoma 2. adenoid cystic carcinoma 3. mucoepidermoid carcinoma, There are low- and high grade variants, low grade: grows slowly, has capsule, painless, involvement of the facial nerve is not characteristic, high grade: infiltrative, fixed to the surrounding tissues, produces LN metastases Microscopy: epidermoid cells+mucin producing PAS+ cells +intermedier cells

49 Mucoepidermoid carcinoma:

50 Acinic cell carcinoma: 2% of all the salivary gland tumours, 90% in the parotid, can be also multiple and bilateral, types: solid acinar, microcystic, papillary-cystic Biological behaviour: encapsulated, there s no vascular invasion, may show local recurrences, but have good prognosis, if the capsule is incomplete and the tumour is invasive, then it has poorer prognosis. Recurrence rate is 20%, chance for LN metastasis is 10%, 6% distant metastases. Microscopy: consists of serous, normal acinar cells, the tumour cells contain zymogenic granules, PAS+

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52 Myoepithelial carcinoma: -on grounds of myoepithelioma or pleomorphic adenoma -spindle cell/plasmocytoid proliferation in a mucoid/myxoid background -cytologic atypia, infiltrative growth

53 Salivary duct carcinoma: -Occures mainly in the parotid gland (80%), 5% of them develop in the minor salivary glands -origin: de novo from the excretory ducts or from the ductal cells in pleiomorphic adenoma -facial nerve symptomes -in 50% local recurrence -frequent LN metastases -2/3rds of the patients develop brain, liver and adrenal metastases -histology: remarkable similarity to the ductal carcinoma of breast (papillary, comedo and crybriform pattern)

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55 Salivary gland MALT lymphoma -MALT lymphoma (extranodal marginal zone lymphoma), most frequent -DLBCL, FL, CLL -origin: from the lymphoid tissue/node in the gland -good prognosis in MALT -pathogenesis: Sjögren, Syst. Scler., AIDS (chr. antigen presentation) -involves more than one gland, frequently bilateral -histology: consists of monocytoid B cells, malignant lymphoepithelial lesion, blastic areas (DLBCL-like) in the low grade tumor indicate high-grade transformation

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