The dynamics of diagnosis of salivary gland tumours: histopathology matters

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1 Interntionl Journl of Reserch in Medicl Sciences Venugopl M et l. Int J Res Med Sci Jun;4(6): pissn eissn Reserch Article DOI: The dynmics of dignosis of slivry glnd tumours: histopthology mtters Mdhushi Venugopl*, Chgnti Pdmvthi Devi, Kuppili Deepthi, Koteswri Mutte Deprtment of Pthology, Guntur Medicl College, Guntur, Andhr Prdesh, Indi Received: 02 My 2016 Accepted: 09 My 2016 *Correspondence: Dr. Mdhushi Venugopl, E-mil: Copyright: the uthor(s), pulisher nd licensee Medip Acdemy. This is n open-ccess rticle distriuted under the terms of the Cretive Commons Attriution Non-Commercil License, which permits unrestricted non-commercil use, distriution, nd reproduction in ny medium, provided the originl work is properly cited. ABSTRACT Bckground: Tumours of slivry glnds re rre neoplsms of hed nd neck region ccounting for less thn one percent of ll tumours. Protid glnd ccounts for mjority of tumors followed y sumndiulr glnd. As such mny chllenges re encountered in estlishing histologicl dignosis, clssifiction, grding nd mngement of slivry glnd neoplsms. This study is tken up to study the incidence of slivry glnd tumours in our institution nd nlyse histologicl criteri for dignosis nd grding systems in vogue for common mlignnt lesions. Methods: Clinicl dt t presenttion, resected specimens received from Government Generl Hospitl, Guntur nd tissue sections stined with Hemtoxylin & Eosin re retrieved from the rchives in the Deprtment of Pthology for the study. Relevnt Immunohistochemicl mrkers re done in difficult cses. Slivry glnd tumours reported etween 2011 nd 2015 in the Deprtment of Pthology, Guntur Medicl College, Guntur, re tken for the study. Results: Mjority of the slivry glnd tumours in our study were oserved in the fourth nd fifth decdes with mle prepondernce (62.68%). Protid glnd ws the most common site (83.63%) for ll tumours nd pleomorphic denom ws the most common tumour with 76 out of 110 cses (69.09%). Other enign tumours in the study included three cses ech of Wrthin tumour nd sl cell denom. Mlignnt tumours ccounted for 28 out of 110 tumours (25.45%). Mucoepidermoid crcinom (MEC) ws the most common mlignnt lesion in the study with 13 cses (46.42%). Conclusions: Slivry glnd tumours re rre. But the wide spectrum of tumour entities nd histologicl complexities led to dignostic prolems in mny cses. Pleomorphic denom ws the most common tumour overll nd protid glnd ws the most common site for oth enign nd mlignnt tumours. Key words: Slivry glnd tumours, Histologicl diversity, Grding of slivry crcinoms, Muocoepidermoid crcinom, Adenoid cystic crcinom INTRODUCTION Tumours of slivry glnds re rre constituting less thn one percent of ll tumours nd 3% to 10% of the neoplsms of hed nd neck region. 1,2 They re heterogeneous group of tumours nd present distinct clinicopthologicl fetures. Protid glnd ccounts for 80% of slivry glnd tumors followed y sumndiulr glnd (10-15%). 3 Mjority of the primry tumours of slivry glnds re enign ut dignosis of mlignnt tumours pose mny difficulties in routine prctice due to wide spectrum of entities with overlpping in morphology. The histopthologicl fetures re intricte nd differences etween different types re very sutle nd s such mny chllenges re encountered in estlishing histologicl dignosis, clssifiction nd grding of slivry glnd neoplsms. The present work is tken up to study the incidence of slivry glnd tumours in our Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1855

2 Venugopl M et l. Int J Res Med Sci Jun;4(6): institution with the primry ojective of nlysis of criteri for dignosis nd grding of primry mlignnt epithelil tumours of slivry glnd. sloid intermedite cells nd polygonl epidermoid cells (Figure 3). METHODS Slivry glnd tumours reported during the lst five yers in our institution were tken for this retrospective study. Clinicl dt nd gross fetures of tumours were recorded nd tulted. Hemtoxylin nd eosin (H&E) stined sections nd corresponding prffin tissue locks were retrieved from the rchives nd reviewed. Specil stins were done wherever necessry. Immunohistochemistry ws done in specific cses for confirmtion. Sections of 4 micron thickness were used for H nd E stining s well s immunohistochemicl study. The tumours were ctegorized ccording to the WHO clssifiction. 3 Histologicl hllmrks for dignosis of vrious mlignnt tumours nd criteri for grding of mucoepidermoid crcinom nd denoid cystic crcinom were nlyzed. Figure 2: Wrthin tumour; () ppillry nd glndulr pttern 4x nd () oncocytic chnge nd suepithelil lymphocytes 10x. RESULTS Mjority of the slivry glnd tumours in our study were oserved in the fourth nd fifth decdes with mle prepondernce (62.68%). Protid glnd ws the most common site (83.63%) for ll tumours nd pleomorphic denom ws the most common tumour with 76 out of 110 cses (69.09%) (Figure 1). Other enign tumours in the study included three cses ech of Wrthin tumour (Figure 2) nd sl cell denom. Mlignnt tumours ccounted for 28 out of 110 tumours (25.45%). Figure 3: Mucoepidermoid crcinom (MEC); () cystic spces with mucin 10x nd () squmoous cells nd mucin 40x. Figure 1: Pleomorphic denom; () epithelil differentition 10x; nd () chondroid differentition 10x. Mucoepidermoid crcinom (MEC) ws the most common mlignnt lesion in the study with 13 cses (46.42%). (Tles 1-3) Grossly, these tumours were multicystic with solid component. Infiltrtion of glnd prenchym ws evident in most of the cses. The dignosis of MEC ws sed on the presence of mucus cells, intermedite cells nd epidermoid cells. The proportion of the cell types nd their rchitecture vried within the sme tumour nd in etween tumours. Cystic spces were lined y lrge mucous cells interspersed y Figure 4: Adenoid cystic crcinom; () cririform pttern 10x, () smll sloid cells 40x nd (c) mucin filled spces 40x. C Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1856

3 Venugopl M et l. Int J Res Med Sci Jun;4(6): Adenoid cystic crcinom ws the second most common cncer in our study with seven cses in minor slivry glnds nd two cses in protid glnd (Tle 3). Bsloid nture of the tumour with epithelil nd myoepithelil cells rrnged in tuulr, cririform nd solid ptterns were evident in these cses. The cririform pttern ws the most frequent one with nests of cells nd microcystic spces filled with sophilic mucoid mteril (Figure 4). Tle1. Age distriution of mlignnt slivry glnd tumours. Age group Ppillry cystdenocrcinom crcinom Epithelil myoepithelil MEC Ad CC ACC BCAC in yers All ges Tle 2: Sex distriution of mlignnt slivry glnd tumours Histologicl type Mle Femle Totl Mucoepidermoid crcinom Adenoid cystic crcinom Acinic cell crcinom Bsl cell denocrcinom 1-1 Ppillry cystdenocrcinom Epithelil myoepithelil crcinom Two cses of cinic cell crcinom (ACC) were reported in the protid glnd, one in 50 yer old mn nd the other in 41 yer old womn (Tles 1 nd 2). Gross exmintion showed cpsulted nodulr msses. Microscopy reveled lrge polygonl cells with sophilic grnulr cytoplsm nd round eccentric nuclei. PAS positivity for mucin ws chrcteristic ut ws ptchy. Smller interclted duct type cells, nd vcuolted cells were lso seen (Figure 5). Other mlignnt entities in the study included two cses ech of ppillry cystdenocrcinom nd cinic cell crcinom nd one cse ech of sl cell denocrcinom nd epithelil myoepithelil crcinom, ll rising in the protid glnd (Tle 3). c Figure 5: Acinic cell crcinom (ACC); () solid ptern 10x; () solid pttern 10x; (c) cells with cler cytoplsm 40x nd (d) grnulr cytoplsm 40x. d Figure 6: Ppillry cystdenocrcinom; () stroml infiltrtion 10x; () cystic spces filled with mucin 40x nd (c) ppillry pttern 10x. c Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1857

4 Venugopl M et l. Int J Res Med Sci Jun;4(6): Two cses of ppillry cystdenocrcinom were dignosed in protid glnd one cse in mle ptient nd the other in femle ptient, oth in the fourth decde of life. Gross exmintion showed irregulr gry white msses with centrl cystic res nd ppillry projections. Microscopy showed cystic tumours with cuoidl nd columnr cells proliferting in ppillry pttern (Figure 6). Nuclei were lnd though occsionl nucleoli were seen. Tle3. Site wise distriution of mlignnt slivry glnd tumours. Histologicl type Protid glnd Su mndiulr glnd Minor slivry Sulingul glnd glnds Totl Mucoepidermoid crcinom Adenoid cystic crcinom Acinic cell crcinom Bsl cell denocrcinom Ppillry cystdenocrcinom Epithelil myo epithelil crcinom 1 1 In our study cse of sl cell denocrcinom (BCAC) ws dignosed in protid lesion in 74 yer old mle. Gross specimen showed loulted gry white tumour with infiltrtive mrgins. On microscopy, nests nd islnds of cells with peripherl plisding were evident. A cse of epithelil myoepithelil crcinom ws reported in protid lesion in womn in seventh decde who presented with slowly growing mss in the protid glnd. Grossly n irregulr nodulr mss ws seen. The histologicl dignosis ws sed on the typicl iphsic nture with inner lyer of duct lining epithelil type cells nd outer lyer of cler myoepithelil type cells. The iphsic pttern ws conspicuous in ppillry-cystic res where s in solid res exclusively vcuolted cells were noted. IHC mrkers cytokertin nd S 100 were positive in our cse (Figure 7). c d DISCUSSION Age nd sex incidence nd locliztion In our study, protid glnd ccounted for most of the tumours with 92 out of 110 cses (83.63%) followed y sumndiulr glnds with eleven cses(10.00%) nd minor slivry glnds with seven cses (6.36%). Literture shows tht mjority of slivry glnd tumours rise in the protid glnd. 4 Aout 64 nd 80% of ll primry epithelil slivry glnd neoplsms re seen in the protid glnd, followed y sumndiulr glnds nd minor slivry glnds. However the incidence in minor slivry glnds ccount for 9-23% of totl tumours s per world literture. 5,6 e Figure 7: Epithelil myoepithelil crcinom (EMC); () solid pttern 10x; () tuulr pttern 10x; (c) imodl morphology 40x; (d) imodl morphology 40x; (e) cytokertin positive nd; (f) S 100 positive. f Most of the tumours in the study were seen in the sixth nd seventh decdes. This is in ccordnce with the literture. 3 In cse of mlignnt tumours, mjority of our cses were dignosed in seventh decde followed y fourth nd sixth decdes (Tle 1). In our study, definite mle prepondernce ws oserved for enign tumours (66.66%). In mlignnt tumours, however mle femle rtio ws even with 14:14. (Tle 2) Though mny studies show tht femles re more frequently ffected, there is some gender vrition in different types of tumour. 3 Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1858

5 Venugopl M et l. Int J Res Med Sci Jun;4(6): Pleomorphic denom ws the most common tumour in the study with 76 out of 110 (69.09%). This compres well with other studies. 3 Wrthin tumour nd sl cell denom ccounted for three cses ech. Literture shows tht Wrthin tumour is second in frequency mong enign tumours nd nerly ll Wrthin tumours occur in the protid glnd or periprotid lymph nodes while most cnliculr denoms nd polymorphous low-grde denocrcinoms rise from minor glnds. 7 In our study lso ll the three cses of Wrthin s tumour were oserved in the protid glnd. The rte of mlignncy vries lot etween vrious studies; this is ttriuted to geogrphicl or distinct settings of the studies. Generl ENT clinics mnge oth enign nd mlignnt lesions ut hed nd neck nd orl surgery clinics del minly with mlignnt tumours. Incidence of mlignncy in these tumours rnges etween 21 nd 46% s per different studies. 4 The distriution of mlignnt tumours lso vries gretly y site. The protid glnds predominte, representing 45%, with 7% for sumndiulr glnds nd 1% in sulingul glnds. 3,8 The most frequent intr-orl sites re the plte nd uccl mucos. In our study the rte of mlignncy ws 28.12% (19 out of 64) in protid glnd, 25% (2 out of 8 tumours) in sumndiulr glnd nd 100% in minor slivry glnds s ll the seven tumours reported turned out to e mlignnt (Tle 3). It hs een well documented in literture tht, mucoepidermoid crcinom is the most common mlignnt tumour. 5,6 In our study lso mucoepidermoid crcinom ccounted for 48% of the mlignnt lesions (13/28). Most of our cses were seen in the protid glnd. This is in ccordnce with other studies. 3 It ws oserved tht two low grde tumours in our study were recurrent lesions while one cse occurred in the ckground of pleomorphic denom. Differentil dignosis of MEC includes necrotizing silometplsi, inverted ductl ppillom, cystdenom, crcinoms composed of cler cells including denosqumous crcinom, squmous cell crcinom nd metstses. Adenoid cystic crcinom ws the second most common cncer in our series with seven cses in minor slivry glnds nd two cses in the protid glnd. Adenoid cystic crcinoms (AdCC) constitute pproximtely 10% of ll epithelil slivry neoplsms nd most frequently involve the protid, sumndiulr nd minor slivry glnds. 3 In the study of Shrest S et l sumndiulr glnd ws the most common site for denoid cystic crcinom. 9 In contrst they comprise 30% of epithelil minor slivry glnd tumours with the highest frequency in the plte. 3 The tumour occurs in ll ge groups frequently in middleged nd older ptients. In our study lso, denoid cystic crcinom ffected different ge groups with pek incidence in the fifth decde nd slight mle prepondernce. These cses usully presented s pinful slow growing tumour due to the tendency of perineurl invsion. The cse of epithelil myoepithelil crcinom in our study occurred in womn in the seventh decde of life which is in ccordnce with literture. 10 Histologicl complexity nd difficulty in grding of mlignnt tumours Histologicl grde is n independent predictor of prognosis of mlignnt slivry glnd tumours. But the diversity nd the rrity of different tumours pose mny hurdles in grding. In review of grding systems of slivry glnd cncers, Seethl RR opined tht the current pproch is prone to mny chllenges nd n idel system is still to emerge. 11 Slivry glnd mlignncies cn e ctegorized into high risk nd low risk groups sing on histologicl nd iologicl profile ut with cvet tht morphologicl grde of slivry glnd mlignnt lesion my not lwys predict its ctul iologicl ehviour. High grde versions of intrinsiclly low grde tumours do exist s well s low grde versions of typiclly high grde versions nd cse in point is crcinom ex pleomorphic denom which is conventionlly considered high grde lesion, ut intrcpsulr nd minimlly invsive vrints ehve in n indolent mnner. In this context, Seethl RR recommends tht in reporting of these tumours, dditionl comments regrding percentge of crcinom nd extent of invsion of crcinomtous component i.e. intrcpsulr, minimlly invsive, nd invsive should e included prt from histologicl type nd grde for specified prognostic implictions. Mucoepidermoid crcinom Mucous cells constitute less thn 10% of the tumour wheres intermedite cells re the dominnt popultion. Cler, columnr nd/or oncocytic cell popultions my lso e present. 3 In our cses, mucus extrvstion with lymphocytic infiltrte t the tumour edge were noted. Lymphocytic infiltrte with germinl centre formtion cn mimic nodl invsion in some cses. 12 Three different grding systems hve een proposed, ll sed on cytomorphology nd rchitecture to ctegorize MEC s low, intermedite or high grde lesions. 13 Armed Forces Institute of Pthology (AFIP) scoring system nd Brndwein system re point sed, giving points to ech histologicl feture. 7,14 The AFIP system is sed on five histologic fetures: intrcystic component, neurl invsion, necrosis, mitotic ctivity, nd cellulr nplsi. Brndwein MS et l proposed n lterntive grding scheme with dditionl criteri of lymphovsculr nd ony invsion nd the pttern of tumor invsion in the form of smll nests/islnds to enhnce predictility nd reproduciility. The modified Heley system is sed on certin qulittive histologicl prmeters. 14,15 In our study, we pplied AFIP grding system nd nine out of 13 MEC were reported s low grde, three cses s high grde nd one cse s intermedite grde. In the three cses of MEC of high grde, the consistent fetures Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1859

6 Venugopl M et l. Int J Res Med Sci Jun;4(6): were miniml intrcystic component, presence of cellulr typi, necrosis nd invsion y nests of tumour cell nd they would e designted s high grde lesions in oth AFIP nd Brndwein systems. Nine cses of MEC were reported s low grde s there ws no nplsi or perineurl invsion or necrosis in multiple sections nd importntly there ws no discordnce etween the two systems. But, the remining one cse of MEC in our study, which ws reported s intermedite grde s per AFIP system, would come under high grde ctegory if Brndwein system is to e pplied. Seethl S et l lso oserved tht AFIP system tends to down grde tumours while the Brndwein system ppers to upgrde tumours especilly in cse of intermedite grde tumours wheres the Heley system does not hve this limittions. 11 Jysooriy PR et l felt tht pitflls in grding could e ecuse of indequte smpling of tumours nd risk of flse negtivity in counting of mitotic figures. 16 Appliction of grding schemes to sclerosing nd oncocytic vrints nd sumndiulr glnd tumours is suject to disgreement. Oncocytic mucoepidermoid crcinoms tht re considered high grde my ehve indolently ut still these vrints lso should e grded. 11 In cse of sumndiulr glnd tumours even low grde MEC tend to ehve more ggressively ecuse of metsttic potentil nd AFIP grding my not predict ccurtely their outcome. 13 Adenoid cystic crcinom Ech of tuulr, cririform nd solid ptterns cn e seen s the dominnt feture or s component of composite tumour The strom within the tumour is usully hylinized nd my e mucinous or myxoid. Extensive stroml hyliniztion with ttenution of the epithelil component my e seen in some tumours. Perineurl invsion is consistent feture of AdCC. Extension long nerves eyond the tumour mrgins nd one invsion re seen in some cses. AdCC should e distuinguished from pleomorphic denom, sl cell denom, sl cell denocrcinom sloid squmous crcinom, polymorphous low-grde denocrcinom nd epithelil myoepithelil crcinom. Dignostic chllenges re encountered when Adenoid cystic crcinom occurs with other different neoplsms. 20,21 In our study, one cse of denoid cystic crcinom ws seen to e ssocited with sl cell denocrcinom. AdCC is grded sing on predominnt growth pttern. Grde1 is ssigned to tuulr pttern, Grde 2 to predominntly cririform pttern with <30% nd solid component nd grde 3 is given in cse of >30% solid component. 19 But Spiro RH et l suggested different grding scheme where in the cut off for solid component is 50% for Grde 2 nd mostly solid for grde In our study seven out of nine cses Ad CC were ctegorized s low grde, one cse s high grde nd one cse s intermedite grde. However, regrdless of the grde, ll denoid cystic crcinoms re mnged with surgery nd rdiotherpy s they re considered loclly ggressive nd high risk tumours. Rrely, dedifferentition cn occur in conventionl denoid cystic crcinom of ny grde. This trnsformtion is represented y incresed mitotic ctivity, necrosis nd micro-clcifictions nd is ssocited with lymph node metstsis. Other tumours Other infrequent mlignnt tumours in the study included ACC, BCAC, Ppillry cystdeno crcinom nd epithelil myoepithelil crcinom ll of which occurred in protid glnd. Acinic cell crcinom is mlignnt tumour chrcterized y serous cinr cell differentition. Frequent mitoses, necrosis, neurl invsion nd pleomorphism indicte more ggressive course. In ACC, stging rther thn grding is considered etter indictor of prognosis. 22 Bsl cell denocrcinom is chrcterized y sloid epithelil cells. Infiltrtion into djcent slivry glnd premchym nd perineurl invsion re the importnt fetures to distuinguish it from sl cell denom s BCAC is ssocited with locl invsion leding to destruction, recurrence nd occsionlly metstsis. Presence of tumour infiltrtion into slivry prenchym is n importnt clue to ppillry cystdenocrcinom nd hence multiple sections should e studied to clinch the dignosis. Cystic MEC cn e distuinguished from ppillry cystdenocrcinom y the presence of vriety of cells in the former. In our study, one cse of EMC ws reported (1/28) with n incidence of 3.57% in mlignnt lesions nd 0.90% of ll slivry glnd tumours. According to literture EMC represents <1% of ll slivry glnd tumours nd rises usully in the protid glnd. 23 Our findings re in concordnce with these oservtions. Differentil dignosis includes cler cell tumours like pleomorphic denom, myoepitheliom, oncocytom nd MEC nd metsttic tumours of renl nd thyroid origin. Solid growth pttern, nucler typi, DNA neuploidy, necrosis, positive surgicl mrgins nd high prolifertive ctivity indicte more ggressive nture. 24,25 The sttus of tumour mrgin is very importnt ecuse indequte surgicl excision is ssocited with recurrence nd metstsis. CONCLUSION Slivry glnd tumours re rre. But the wide spectrum of tumour entities nd histologicl complexities led to dignostic prolems in mny cses. Pleomorphic denom ws the most common tumour overll nd protid glnd ws the most common site for oth enign nd mlignnt tumours. Histologicl grding of mlignnt tumours hs independent prognostic vlue nd should e pplied meticulously. Vrious grding systems hve een dvocted for mucoepidermoid crcinom though n idel system is still to e evolved. The Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1860

7 Venugopl M et l. Int J Res Med Sci Jun;4(6): prognostic outcome in the intermedite grde lesions of MEC depends on the specific grding system used. Adenoid cystic crcinom is grded sing on the growth pttern with solid pttern indicting worse outcome. In other mlignnt tumours, ssessment of tumour mrgin sttus nd stging re considered etter indictors of outcome thn grding lone Funding: No funding sources Conflict of interest: None declred Ethicl pprovl: The study ws pproved y the Institutionl Ethics Committee REFERENCES 1. Pons-Vicente O, Almendros-Mrqués N, Berini- Aytés L, Gy Escod C. Minor slivry glnd tumors:a clonicopthologicl study of 18 cses. Med Orl Pthol Orl Cir Bucl. 2008;13: Ethunndn M, Dvies B, Prtt CA, Puxeddu R, Brennn PA. Primry epithelil sumndiulr slivry glnd tumors-review of mngement in district generl hospitl setting. Orl Oncol. 2009;45: Everson JW, Auclir P, Gnepp DR, Ei-Nggr AK. Tumors of the slivry glnds. In: Brnes L, Eveson JW, Reichrt P, Sidrnsky D, editors. World Helth Orgniztion Clssifiction of Tumours. Pthology nd Genetics of Hed nd Neck Tumors. Lyon: IARC Press. 2005; Kızıl Y, Aydil U, Ekinci O, Dilci A, Köyşıoğlu A, Düzlü M, et l. Slivry Glnd Tumors in Turkey: Demogrphic Fetures nd Histopthologicl Distriution of 510 Ptients. Indin J Otolryngol, Hed Neck Surg. 2013; 65(Suppl 1): Eveson JW, Cwson RA. Slivry glnd tumours. A review of 2410 cses with prticulr reference to histologicl types, site, ge nd sex distriution. J Pthol. 1985;146(1): Spiro RH Slivry neoplsms: overview of 35 yer old experience with 2807 ptients. Hed Neck Surg. 1986;8(3): Ellis GL, Auclir PL. Tumors of the slivry glnds. Atls of tumor pthology, 3rd series, fscicle 17. Wshington DC: Armed Forces Institute of Pthology; Tin Z, Li L, Wng L, Hu Y, Li J. Slivry glnd neoplsms in orl nd mxillofcil regions: 23- yer retrospective study of 6982 cses in n estern Chinese popultion. Int J Orl Mxillofc Surg. 2010;39: Shresth S, Pndey GK, Pun CB, Bhtt R, Shhi R. Histopthologicl Pttern of Slivry Glnd Tumors. Journl of pthologyof Nepl. 2010; Silvers AR, Som PM, Brndwein M. Epithelil - Myoepithelil C rcinom of the Protid Glnd AJNR. 1996;17: Seethl RR. An updte on grding of slivry glnd crcinoms. Hed nd Neck Pthol. 2009;3: Auclir PL. Tumor-ssocited lymphoid prolifertion in the protid glnd. A potentil dignostic pitfll. Orl Surg Orl Med Orl Pthol. 1994;77(1): Goode RK, Auclir PL, Ellis GL: Mucoepidermoid crcinom of the mjor slivry glnds: clinicl nd histopthologic nlysis of 234 cses with evlution of grding criteri. Cncer. 1998;82: Brndwein MS, Ivnov K, Wllce DI, Hille JJ, Wng B, Fhmy A, et l. Mucoepidermoid crcinom: clinicopthologic study of 80 ptients with specil reference to histologicl grding. Am J Surg Pthol. 2001;25(7): Heley WV, Perzin KH, Smith L. Mucoepidermoid crcinom of slivry glnd origin. Clssifiction, clinicl-pthologic correltion, nd results of tretment. Cncer. 1970;26: Jysooriy PR, Krunthilke PRCL, Siriwrden BSMS, Amrtung EAPD, Attygll AM. Comprison of grding systems of mucoepidermoid crcinom nd the impct on ptient survivl Journl of Dignostic Pthology. 2012;7(1): Perzin KH, Gullne P, Clirmont AC. Adenoid cystic crcinoms rising in slivry glnds: correltion of histologic fetures nd clinicl course. Cncer. 1978;42(1): Spiro RH, Huvos AG. Stge mens more thn grde in denoid cystic crcinom. Am J Surg. 1992;164(6): Sznto PA, Lun MA, Tortoledo ME, White RA. Histologic grding of denoid cystic crcinom of the slivry glnds. Cncer. 1984;54(6): Croitoru CM, Surez PA, Lun MA. Hyrid crcinoms of slivry glnds. Report of 4 cses nd review of the literture. Arch Pthol L Med. 1999;123(8): Seifert G, Donth K. Hyrid tumors of slivry glnds. Definition nd clssifiction of five rre cses. Orl Oncol Eur J Cncer. 1996;32: Btskis JG, Lun MA, El-Nggr AK. Histopthologic grding of slivry glnd neoplsms: II. Acinic cell crcinoms Ann Otol Rhinol Lryngol. 1990;99: Btskis JG, El - Nggr AK, Lun MA. Epithelil myoepithelil crcinom of slivry glnds. Ann Otol Rhinol Lryngol. 1992;101: Seethl RR, Brnes EL, Hunt JL. Epithelilmyoepithelil crcinom: A review of the clinicopthologic spectrum nd immunophenotypic chrcteristics in 61 tumors of the slivry glnds nd upper erodigestive trct. Am J Surg Pthol. 2007;31: Trlongo V, Dniele E. Epithelil-myoepithelil crcinom of the slivry glnds: A review of literture. Anticncer Res.1998;18:603-8 Cite this rticle s: Venugopl M, Devi CP, Deepthi K, Mutte K. The dynmics of dignosis of slivry glnd tumours: histopthology mtters. Int J Res Med Sci 2016;4: Interntionl Journl of Reserch in Medicl Sciences June 2016 Vol 4 Issue 6 Pge 1861

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