PATHOLOGY OF SALIVARY GLANDS

-salivary glands can be classified according to prevailing type of secretory cells -serous glands, mucous glands and mixed seromucous -salivary gland tissue consists of- acinar cells of serous and mucous typemyoepithelial cells- epithelial cells of salivary ducts, mesenchymal cells of the connective tissue (adipose and fibrous, nerves, blood vessels), and inflammatory cells

according to the anatomic location - salivary glands include paired major glands (parotid, submandibular, sublingual) and minor glands of upper aerodigestive tract
-1.- major glands include parotid- the largest gland, enclosed by capsule, located anterior to the ear, composed of serous acini, secretory ducts -about 20 lymph nodes located in each parotid gland -submandibular-located in the submandibular triangle, seromucous gland -subligual gland, the smallest of major glands, in the floor of mouth, prevailing mucous acini, -2.- minor glands o !"# oral m$%osa -minor glands have mixed serous and mucous acini in varying proportions cellular components: -of particular interest- myoepithelial cells (M !) - believed to have contractile properties that assist in secretion of saliva -microscopical examination sho"s that M !s are thin and spindle-shaped cells around acini and intercalated ducts situated bet"een basement membrane and epithelial ductal cells -they display features of both smooth muscle cells and epithelium

#$%&'# '% &( % !' )$&* &#ros!omi#- dry mouth-decrease in the secretion of the saliva, it is a symptom and not a disease
-xerostomia is important-accompanied by infection, ulceration and rapid dental caries, in addition- there is difficulty in eating, spea+ing and s"allo"ing -conditions that may lead to xerostomia-

-flo" rate of saliva may be normal-there is only a feeling of dry mouthbecause of local factors, smo+ing, mouth breathing, etc -in other cases-real decrease of flo" associated "ith stress, fear as a effect of increased sympathetic activity -common side effect of many drugs, such as sedatives, antihypertensives, and anti-emetics, antihistamines, etc-normal capacity of glands -functional capacity of salivary glands may be reduced due to a loss of secreting cells- irradiation sialadenitis- salivary glands "ere damaged by therapeutic radiotherapy of head and nec+ region because of cancer -autoimmune sialadenitis in %jogren syndrome- permanent and severe xerostomia -other disorders, such as dehydratation, uremia, diabetes mellitus, hypovolemic shoc+

Sialorr"o# 'P!(alism)- true increase in salivary flo" is rare

-may be present in mercury poisoning, rabies, in some neurological disturbances, epilepsy

&,%)'-!)$. /*# $*(0/MM/)&'1 #$%&'# '% )hese include mucus escape reactions, "hich are not lined by epithelium, (extravasation mucocoele, ranula), mucus retention cyst (true cyst lined by epithelium), sialolithiasis and a variety of other conditions (e2g2 tumours) that can cause obstruction
!ommon to all causes are the effects of obstruction, "hich are acinar atrophy, stasis, secondary infections, epithelial damage and scarring, and these can aggravate the obstruction2 -they occur as a result of stasis of saliva, acute and chronic inflammation and sialolithiasis

-sialoli!"iasis -sialoliths are calcified masses (calculi, stones)- that develop in ductal system of salivary glands
- they occur mainly in the large ducts of submandibular gland - (due to thic+er mucous secretion than in parotid) -obstruction of salivary duct by stones

-%"roni% s%l#rosing sialad#ni!is '*$!!n#r !$mor) - is chronic inflammatory disorder, in most cases secondary to calculi, it can occur at any age, though the mean is about 34 yr, considerably more common than acute sialadenitis
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- it is most often seen in submandibular gland, patients present "ith pain and5or s"eeling of the gland associated "ith eating -grossly it is characteri6ed by enlargment and firm consistency of the gland- in the end-stages of the disease there is little remaining glandular tissue- gland is totaly replaced by fibrous tissue - mimic tumor (7uttner tumor) microscopically: chronic sialadenitis is characteri6ed by fibrosis, progressive atrophy of salivary gland acini and abundant mixed inflammatory infiltrationgerminal centres, some neutrophils, ductal epithelium may sho" hyperplasia and metaplasma +$%$s ,s%a-# R#a%!ion. )his is defined as pooling of mucus in a cavity in the connective tissue not lined by epithelium- called 8extravasation mucocele92 )he sites are (minor) lo"er lip :4;, palate 3;, buccal mucosa <0;, and (major) parotid 02:;, submandibular <22; and sublingual (ranula) <2<;2 -most patients are young - pathogenesis is traumatic damage of a duct, leading to mucus pooling2 $n the lip, it presents as a raised s"elling, "hich is sometimes blue2 )he sublingual ranula presents as a s"elling of the floor of the mouth2 Microscopy sho"s a "ell-defined mucin-filled cavity "ithout epithelial lining2 )here is a mixed inflammatory infiltrate, including foamy histiocytes, and later proliferation of granulation tissue - salivary gland tissue sho"s chronic sialadenitis, acinar atrophy and fibrosis2 )he outcome is that recurrences are fre=uent, especially in sublingual ranula.

&)> ' $*(0/MM/)&'1 #$%&'# '% 1.- .#nign l(m-"o#-i!"#lial l#sion and Sjogr#n s(ndrom# -%jogren syndrome -is an autoimmune inflammatory exocrinopathy "ith multisytem manifestations-characteri6ed by lymphocytic infiltration of exocrine glands, particularly the lacrimal and salivary glands resulting in reduced secretion
-immunologically, the disease is characteri6ed by ,-cell hyperactivity and the production of many circulating auto-antibodies -in over half of cases %jogren syndrome is accompanied by another autoimmune disorder, such as rheumatoid arthritis, systemic lupus erythematodes, systemic sclerosis, polymyositis, primary biliary cirhosis clinically: glands %jogren syndrome is characteri6ed by s"elling of major salivary

-dry eyes- +eratoconjunctivitis sicca

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-dry mouth- xerostomia -rheumatoid arthritis or5and another autoimmune disorder histologically: -the affected lacrimal and salivary glands are diffuselly infiltrated by lymphocytes and plasmacytic cells, there is an atrophy of acinar salivary gland epithelium, accompanied by proliferation of epithelial and myoepithelial cellepi-myoepithelial islands and "ith fibrosis - called benign lymphoepithelial lesion or lymphoepithelial sialadenitis (0 %/) -higher ris+ of development of malignant lymphoma of M/0) type - in salivary gland affected by %2 syndrome -mis%#llan#o$s in lamma!or( disord#rs- there is a variety of noninfectious inflammatory conditions in salivary glands, such as -sarcoidosis -chronic granulomatous inflammatory lesion characteri6ed by epithelioid granulomas "ith giant cells of 0anghans type -7imura disease (epithelioid hemangioma, angiomatoid lymphoid hyperplasia "ith eosinophilia)- distinctive lesion particularly affecting soft tissues of head and nec+ area, characteri6ed by ?2

%/0$./'1 @0/*# $*( !)$&*% -m$m-s /ir$s in #%!ion- mumps is an acute infectious disease caused by a paramyxovirus "hich has predilection for parotid gland
-the gland is enlarged, s"ollen, painful, in most cases bilateral, accompanied "ith fever and headache -mumps is a self-limited disease, occurs most often in children in school age, there is typically incubation period of 2-A "ee+s, -less fre=uently, other organ may be involved, such as pancreas, testes -%(!om#galo/ir$s in #%!ion- !M. is a ubi=uitous herpes virus detectable in more than B0; of adults -infections may follo" debilitating diseases, such as malignant neoplasms, immunosupression, ac=uired immunodeficiencies, bone marro" transplantations, etc

-a%$!# 0a%!#rial -aro!i!is- rare, occurs usually in debilitated patients "ith poor oral hygiene -acute suppurative infiltration, usually "ith abscess formation

-grossly dilated ducts filled "ith pus cells (neutrophils) and diffuse interstitial acute leu+ocytic infiltration bet"een acinar cells -focal aggregations of neutrophils may form abscesses- this can only heal by fibrosis- distortion of gland architecture "hich predispose to further infections

*&*-* &C0/%)$! *&*-$*(0/MM/)&'1 0 %$&*% 1.-N#%ro!i1ing sialom#!a-lasia- is a benign self-healing lesion affecting especially the minor salivary glands of the palate
-it presents as mucosal ulcer "hich usually heals spontaneously if left alone, the major problem is that *% clinically and histologically can simulate s=uamous cell carcinoma -some cases follo" surgery or even minor trauma such as from an illfitting denture, the underlying process is considered to be ischemic, the cause is ho"ever un+no"n histology: sho"s lobular coagulative necrosis of acini, s=uamous metaplasia of ducts, a chronic inflammatory infiltration and pseudoepitheliomatous hyperplasia of the surface

2.- Sialad#nosis- is a non-inflammatory process of the salivary glands due to metabolic and secretory disorders accompanied by painless s"elling of the parotid glands
-it is related to endocrine dysfunction (thyroid and ovarian insufficiencies) and nerve dysfunction -it is also seen in malnutrition, chronic alcoholism, liver cirrhosis, may be lin+ed to drugs, etc2

2.- Ad#noma!oid "(-#r-lasia o m$%o$s sali/ar( glands - the lesion is asymptomatic, found accidentally on routine dental examination
-grossly- nodular lesion on the palate mimic+ing benign tumor -most patients Dadult, A-4th decades, etiology is un+no"n

3.- irradia!ion %"ang#s- salivary glands are very senstitive to irradiation, a xerostomia is a common complication
-acute radiation injury-s"elling of the gland- necrosis of acinar cells, acute inflammatory response -chronic injury- characteri6ed by fibrosis, loss of acini, and s=uamous metaplasia -"hen all glands are involved, loss of saliva is irreversible

4.- on%o%(!i% l#sions- oncocytic change of salivary glands is relatively common particularly in elderly, it is characteri6ed by cells "ith abundant granular eosinophilic cytoplasm due to increased number of mitochondria
-it is a non-neoplastic metaplastic change, spectrum of lesions -focal and diffuse oncocytic metaplasia -ductal oncocytosis -multifocal oncocytic hyperplasia exact cause is speculative %/0$./'1 @0/*# !1%)% -non-neoplastic cysts and pseudocysts account for about <0; of salivary gland lesions -they can be classified as congenital (dysgenetic) D salivary polycystic dysgenetic disease ac=uired- true cystic lesions "ith epithelial lining- salivary duct cyst, lymphoepithelial cyst pseudocysts- "ithout epithelial lining- mucus escape reaction, ranula cystic neoplasms should be distinguished- 0@ mucoepidermoid carcinoma, Earthin tumor, cystadenoma, etc2

m$%$s #s%a-# r#a%!ion- is defined as a pooling of mucus in a cavity

"ithin the connective tissue that is not lined by epithelium -results from traumatic rupture of a salivary duct of major or minor gland clinically appears as:

mucocele- most commonly lesions of lips -more often lo"er lips ranula- is a type of mucus escape reaction that occurs in the floor of mouth- bluish in color
histologic features: -early lesion consists of "ell-defined cavity in the soft tissue of the oral mucosa - filled "ith mucinous material "ith admixture of inflammatory cells and foamy macrophages

later, granulation tissue gro"s organi6ation of the mucocele

progressively

into

the

cavity-

m$%$s r#!#n!ion %(s! -is a true cyst, less common than mucus escape reaction
-clinical presentation is that of slo"ly gro"ing painless, circumscribed lesion of variable si6e and location- more often in parotid and submandibular glands sali/ar( d$%! %(s! 'sialo%(s!)- represents true cysts "ith epithelial lining, it develops as a conse=uence of duct obstruction2 )he lesions are unilocular, but rarely they may be multicystic2 )he absence of lymphoid infiltrate allo"s to distinguish salivary duct cyst from Earthin tumor, lymphoepithelial cyst and branchial cleft cyst2

5(s!i% l(m-"oid "(-#r-lasia in AIDS 'arely patients "ith /$#% present "ith unilateral or bilateral enlarging cystic masses in parotid glands2 )hese lesions have been reffered to as /$#%-related parotid gland cysts or cystic lymphoid hyperplasia in /$#% (cystic benign lymphoepithelial lesions) -)he cysts measure up to 3 cm in diameter and are lined by s=uamous epithelium2 )he surrounding parotid gland tissue is replaced by hyperplastic lymphoid tissue "ith irregular enlarged follicles2 -)he distinction bet"een /$#%-related parotid gland cysts and benign lymphoepithelial lesion (,0 0) may be difficult, bue "ell developed cases related to /$#% are characteri6ed by a presence of large irregularly branching cysts "ith prominent follicular hyperplasia2 .#nign l(m-"o#-i!"#lial %(s!- "ell circumscribed and predominantly unilocular
->istologically the cyst is lined by stratified s=uamous epithelium, although mucin producing cells may be also present2 -)he cyst "all reveals a dense lymphoid tissue "ith prominent germinal centres of follicles2 Sali/ar( Pol(%(s!i% D(sg#n#!i% Dis#as#. )his very rare condition resembles cystic anomalies of other organs, such as the +idney, liver and pancreas, although no association has been described2 -%ome cases are familial, and almost all cases occurred in females2 Most - $t only affects the parotid glands, usually bilaterally2 Microscopically, the glands maintain their lobular architecture, the cysts vary in si6e up to a fe" mm, and they are irregular in shape and often interconnect2 )he lining epithelium is flat, cuboidal to lo" columnar, sometimes "ith an apocrine li+e appearance2 )he lumen contains secretion "ith spherical microliths2 'emnants of salivary acini are seen bet"een the cysts, and thic+ fibrous interlobular septa are often prominent2 $nflammation is at most mild

S%l#rosing -ol(%(s!i% ad#nosis

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-rare benign pseudoneoplastic condition of major salivary glands similar to fibrocystic disease of the breast -$t affects mainly females, adult -grossly- slo"-gro"ing masses in the parotid gland, gland is largely replaced by multiple discrete firm, rubbery nodules2 -microscopic examination- "ell-circumscribed, unencapsulated lesion composed of a lobular arrangement of proliferating ducts and acini "ith cystic ducts containing viscous secretion )here is often intraluminal epithelial proliferation, the lining comprises a spectrum of apocrine, mucous, s=uamous cells and balooned sebaceous-li+e cells, although true goblet cells are not seen2 )here is sometimes nuclear pleomorphism, even occasionally suggesting dysplasia -bening neoplasm, the lesion is monoclonal !linical features- in <5A cases recurrences, benign lesion