Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

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1 Interntionl Journl of Orl Science (2013) 5, ß 2013 WCSS. All s reserved /13 CASE REPORT Cler-cell vrint of clcifying epithelil odontogenic tumor (Pindorg tumor) in the mndile Ching-Yi Chen 1, Chung-Wei Wu 2, Wen-Chen Wng 1,3, Li-Min Lin 1,3 nd Yuk-Kwn Chen 1,3 We present n uncommon cse (femle ptient ged 59 yers) of the cler-cell vrint of clcifying epithelil odontogenic tumor (CEOT) (lso known s Pindorg tumor) in the mndile. The clinicl chrcteristics nd prole origins of the cler tumor cells of previously reported cses of cler-cell vrint of introsseous CEOT re lso summrized nd discussed. Interntionl Journl of Orl Science (2013) 5, ; doi: /ijos ; pulished online 24 My 2013 Keywords: clcifying epithelil odontogenic tumor; cler cell; Pindorg tumor INTRODUCTION Clcifying epithelil odontogenic tumor (CEOT) (lso known s Pindorg tumor), which ws first designted s distinct disese entity y Pindorg, is n uncommon enign odontogenic lesion tht ccounts for less thn 1% of ll odontogenic tumors. It most often occurs in the posterior mndile nd is most frequently found in ptients etween 30 nd 50 yers of ge, with no sex predilection. 1 In ddition to the introsseous lesion, numer of extrosseous counterprts of CCEOT hve lso een documented. 1 Cliniclly, CEOT is usully slow-growing pinless swelling. Rdiogrphiclly, uniloculr rdiolucency destructive lesion is oserved. The clssicl histopthologicl chrcteristics of CEOT comprise sheets nd islnds of polyhedrl eosinophilic epithelil cells with clcifictions s well s deposition of n myloid-like sustnce; however, occsionlly, focl res of cler cells cn e oserved in the cler-cell vrint of CEOT (CCCEOT). 2 Through MEDLINE serch for CCCEOT in the English-lnguge literture ( ), 14 cses were found; 3 16 however, this unusul lesion still needs continul documenttion in order to hve more informtion regrding clinicl, microscopic fetures or ehvior, prticulrly, the potentil origins of the cler tumor cells. Therefore, the im of the current report ws to descrie the clinicl, rdiogrphic, nd histologicl findings in cse of mndiulr CCCEOT. The clinicl fetures s well s the potentil origins of the cler tumor cells of previously reported cses of introsseous CCCEOT re reviewed. CASE REPORT A 59-yer-old femle ws referred for evlution of pinless swelling over the left retromolr re. The ptient s medicl history ws significnt for the dignosis of hypertension. Introrl exmintion showed hrd, non-tender 3 cm32 cm mss on the lingul spect of the left retromolr re up to hlf of the mndiulr rmus. The overlying mucos ws intct (Figure 1). A pnormic rdiogrph showed well-defined uniloculr rdiolucence with corticted mrgin extending from the distl root of tooth 38 up to hlf of the left rmus re, nd from the left retromolr re down to the mndiulr ody, which mesured out 3 cm32 cm in dimeter (Figure 1). The differentil dignosis included kertocystic odontogenic tumor, melolstom, melolstic firom nd CEOT. An incisionl iopsy ws performed under locl nesthesi. The specimen ws sent to the Orl Pthology Deprtment of our institution for histologicl exmintion. Microscopic exmintion of the incisionl iopsy showed tht lrge portion of the tumor ws rrnged in pseudoglndulr pttern consisting of nests of ple, uniform, cler cells with drk-stined nuclei without norml mitotic figures nd necrosis (Figure 2), wheres some res were dmixed with clusters of polyhedrl epithelil cells (Figure 2). The cells were seprted y thin nds of connective tissue in res showing deposits of morphous eosinophilic mteril. Smll foci of clcifictions were lso noted, ut no Liesegng rings were oserved (Figure 2c). Stining ws negtive for periodic cid fst stin (PAS) stins with nd without distse digestion (dt not shown), s well s mucicrmine stin (dt not shown), ut positive for Congo red stin throughout the intercellulr eosinophilic mteril (Figure 3). With regrd to immunohistochemicl stinings, the tumor cells were positive for cytokertin only (Figure 3), nd negtive for S-100 protein (Figure 3c) nd smooth muscle ctin (Figure 3d). The findings for Ki- 67 were positive in only smll numer of scttered cells (Figure 3e). Therefore, the histologicl dignosis ws CCCEOT. The swelling ws then removed under generl nesthesi. Similr microscopic findings to the incisionl iopsy were oserved for the surgicl specimen (Figure 2d). The histologicl dignosis of the surgicl specimen ws confirmed gin to e CCCEOT. The postopertive course of the ptient ws uneventful, nd there ws no evidence of disese t the 2-yer follow-up. 1 Division of Orl Pthology & Dignosis, Deprtment of Dentistry, Kohsiung Medicl University Chung-Ho Memoril Hospitl, Kohsiung, Tiwn; 2 Division of Orl & Mxillofcil Surgery, Deprtment of Dentistry, Kohsiung Medicl University Chung-Ho Memoril Hospitl, Kohsiung, Tiwn nd 3 School of Dentistry, College of Dentl Medicine, Kohsiung Medicl University, Kohsiung, Tiwn Correspondence: Dr YK Chen, School of Dentistry, College of Dentl Medicine, Kohsiung Medicl University, 100 Shih-Chun 1st Rod, Kohsiung, Tiwn E-mil: Received 2 Novemer 2012; ccepted 22 April 2013

2 116 Figure 1 Introrl view nd pnormic rdiogrphy. () Introrl exmintion showed mss on the left retromolr re up to hlf of the mndiulr rmus. () Pnormic rdiogrph showed well-defined uniloculr rdiolucence with corticted mrgin extending from the distl root of tooth 38 up to hlf of the left rmus re, nd from the left retromolr re down to the mndiulr ody. c d Figure 2 Histologicl spects of the incisionl nd excisionl iopsies. Incisionl iopsy showed tht lrge portion of the tumor ws rrnged in pseudoglndulr pttern consisting of nests of ple, uniform, cler cells with drk-stined nuclei (, 340), wheres some res were dmixed with polyhedrl epithelil cells (, 3100) nd contined smll foci of clcifiction (rrow, c, 3200). (d) Similr histopthologicl findings to the incisionl iopsy were oserved for the surgicl specimen (340). Interntionl Journl of Orl Science

3 117 d e c Figure 3 Histochemicl nd immunohistochemicl spects. Stining ws positive for Congo red stin for the intercellulr eosinophilic mteril (, 3200). The tumor cells were positive for immunochemicl stining of cytokertin (, 3100), negtive for S-100 (c, 3100) nd smooth muscle ctin (d, 3200) s well s low Ki-67 leling index (e, 3100). DISCUSSION The histopthology of CEOT, in its clssic pttern, comprises sheets of polyhedrl epithelil cells with well-defined cell orders nd distinct intercellulr ridges; these neoplstic cells my demonstrte pleomorphism, ut only rrely typicl mitoses. Additionlly, the other most chrcteristic findings re the presence of myloid-like sustnces nd clcified concentric Liesegng rings. To dte, five histopthologic ptterns of CEOT hve een documented:17 18 (i) strnds/ sheets/islnds of polyhedrl cells with intrcellulr ridges; (ii) cririform rrngement with mny spces contining n eosinophilic (myloid-like) sustnce; (iii) densely-populted neoplstic cells with interspersed multinucleted gint cells; (iv) nests of epithelil cells similr to neoplsm of the slivry glnd; nd (v) prominent cler-cell rrnged in pseudoglndulr mnner. The lst pttern is referred to s the cler-cell vrint of CEOT, nd the histopthologicl findings of the current cse were consistent with this pttern, showing undnt cler cells rrnged in pseudoglndulr pttern contining n myloid-like mteril. In the current cse, reltively high proportion of the cler tumor cell components were oserved. The dignosis of CCCEOT in the present cse ws reched ccording to the positivity of cytokertin stining, the sence of PAS-positive stining, the presence of Congo red-positive mteril etween tumor islnds (myloid-like mteril) nd the sence of mitotic figures. Mlignnce of slivry glnd origin ws ruled out y the sence of ctin nd S-100 expression, nd cler-cell odontogenic crcinom ws ruled out y the lck of overt cellulr typi, well-circumscried lesion, nd the presence of myloid-like mteril s well s the very low Ki-67 leling index. Additionlly, lck of mitotic figures nd the generlly good circumscription of the lesion re not chrcteristics of metsttic diseses of ny origin. It should e noted tht cler cells my lso occur in other epithelil odontogenic leisons such s melolstom,19 nd clcifying odontogenic cyst.20 It hs een demonstrted tht the cler cells of the melolstom ws clerly of odontogenic epithelil origin.19 Moreover, it hs lso een of opinion tht the cler cells of the clcifying odontogenic cyst re possily odontogenic epithelil cells, which hve undergone errnt degenertion.20 For CCCEOT, it hs een climed tht the cler cells represent degenertive process,4,10 wheres nother suggestion indicted tht the cler tumor cells represent feture of cytodifferentition rther thn the degenertive phenomenon.8 In order to otin some vlule informtion, we herey summrize the reported histochemicl, immnohistochemicl, nd electron microscopic findings (including the current cse) for the potentil origins of cler tumor cells in CCCEOT in Tle 1. As oserved from Tle 1, in two cses, the cler tumor cells hve een proved to e Lngerhns cells, s evidenced y the presence of Bireck s grnules using electron microscopy.9,14 Indeed, some uthors hve regrded CEOT contining Lngerhns cells s nonclcifying CEOT (Pindorg tumor) with Lngerhns cells. On the other hnd, it hs een shown tht the cler cells of CCCEOT contin glycogen in four cses y PAS stin8,12 13,15 nd in two cses y electron microscopy.8,13 An odontogenic epithelil origin hs lso een demonstrted for the cler tumor cells in three cses y positive immunohistochemicl stinings (chiefly cytokertin) together with negtive stinings for PAS nd mucicrmine stins13 14 nd the present cse, nd in one cse y electron microscopy.10 Both PAS nd cytokertin positivity hve een simultneously reported in one cse, in which trnsition etween cler cells nd CEOT tumor cells ws evident throughout the tumor tissues.13 Tken together, it my e speculted tht the cler-cell chnge might e derived from the Interntionl Journl of Orl Science

4 118 Tle 1 Clinicl chrcteristics of reported cses of the cler-cell vrint of centrl clcifying epithelil odontogenic tumor Cse Reference Sex (Age/ yer) Mximum dimension/ cm Loction Clinicl presenttion Rdiogrphic finding Tretment/follow-up Summry of HC/IHC/EM studies for origins of cler cells 1 3 Mle (50) 1.2 Posterior mndile Tender mss Uniloculr mixed rdiolucency & rdiopcity 2 4 Femle (68) 3.0 Posterior mndile, left Uniloculr mixed rdiolucency & rdiopcity 3 5 Femle (37) 0.5 Anterior mndile None Uniloculr mixed rdiolucency & rdiopcity 4 6 Mle (65) Posterior mndile, 5 7 Femle (36) 10 Anterior & posterior mndile (ilterl) 6 8 Mle (36) 2.5 Anterior & premolr mndile () 7 9 Femle (44) Anterior & posterior mxill, presthesi Loose teeth, swelling Uniloculr mixed rdiolucency & rdiopcity Multiloculr mixed rdiolucency & rdiopcity Enucletion, free of disese 3 yers Curettge, recurrence t 4 months Enucletion, free of disese 13 months Excision, free of disese 22 months Enucletion, free of disese 2 yers Uniloculr rdiolucency Prtil resection, free of disese 2 yers Uniloculr rdiolucency Prtil mxillectomy, follow-up: not reported 8 10 Mle (38) 2.5 Anterior mndile Uniloculr mixed rdiolucency & rdiopcity Resection, free of disese 2 yers 9 11 Mle (58) 2.0 Posterior mxill Loose teeth Uniloculr rdiolucency Enucletion, free of disese 10 yers Femle (59) 3.8 Posterior mndile, Femle (14) Posterior mxill, Mle (27) 1.0 Posterior nd premolr mndile Femle (44) Mndiulr ngle, Mle (18) 3.5 Anterior mxill,, extension to mxillry sinus 15 Present cse Femle (59) 3.0 Retromolr nd mndiulr rmus, left Uniloculr mixed rdiolucency & rdiopcity Uniloculr rdiolucency; Rdiopcity (t recurrence) Resection, free of disese 3 yers Prtil resection, recurrence t 13 yers Uniloculr rdiolucency Excision, free of disese 1 yer Multililoculr mixed rdiolucency & rdiopcity Uniloculr mixed rdiolucency & rdiopcity Enucletion, free of disese 1 yer Excision, follow-up: not reported Uniloculr rdiolucency Excision, free of disese 2 yers EM: Swollen & emptyrtumor cell degenertion HC: PAS (2) HC: PAS (1) EM: glycogen grnules IHC: CK (2) EM: Bireck s grnules (1), S100 (1)R Lngerhns cell EM: tonofilment remnnt, desmosomes HC: PAS (1, initil; -, lter stge) Rtumor cell degenertion EMRLngerhns cell HC: PAS (miniml focl 1); mucicrmine (2) IHC: CK 8, 13, 19, filggrin, ntimelolstom (1)Rodontogenic epithelil origin HC: PAS (1) EM: glycogen grnules IHC: CK (1); S-100, ctin (2) HC: PAS, mucicrmine (2) HC: PAS (1)Rglycogen grnules IHC: CK (1); S-100, ctin (2) HC: PAS (1); mucicrmine (2) CD, cytokertin; EM, electron microscopy; HC, histochemistry; IHC, immunohistochemistry; PAS, periodic cid fst stin. cytokertin-positive CEOT tumor cells; these tumor cells initilly showed congregtion of initilly PAS-positive sustnce, ut when the cler-cell phenomenon enhnces, the PAS positivity is consistently sent. 10 Consequently, the potentil origin nd function of the cler tumor cells in CCCEOT would e more complex s compred to other epithelil odontogenic lesions, nd the cler-cells in CCCEOT my in fct, represent more diversity of cell origins encompssing Lngerhns cells, degenerted cells contining glycogen grnules, nd cells of overt odontogenic epithelil origin. Additionlly, one my lso question whether the presence of cler cells is of clinicl relevnce. In 1994, Hicks et l. 12 suggested tht the existence of cler tumor cells in CCCEOT my imply more ggressive performnce. However, other uthors considered tht too few cses of CCCEOT hve een descried to dte to ttin confirmtive conclusion concerning the impct of the cler-cell popultion on the iologic ctivity of CCCEOT (ref. 2). Tody, the choice of surgicl mngement of the CEOT depends on the site, size, nd mount of one destruction of the lesion. For mndilulr lesions, the suggested surgicl pproch is enucletion with vigorous curettge; however, for lesions with more dvnced one infiltrtion, resection of the tumor should e considered. 1 2 The tretment of choice in the current mndiulr cse is totl excision of the tumor. On the other hnd, Interntionl Journl of Orl Science

5 119 hemimxillectomy is suggested s the tretment of choice for lesions of the mxill, ecuse mxill tumors could esily intrude on vitl structures. 1 2 Finlly, Anvi et l. 14 presented clinicl review of CCCEOT in After lmost ten yers, s shown in Tle 1, we hve updted the dt of Anvi et l. 14 y dding three more cses, including the present cse. With only three dditionl cses, it is unsurprising to oserve tht the min clinicl dt shown in Tle 1 re lrgely comptile with the report of Anvi et l. 14 CONCLUSIONS We report n uncommon cse of CCCEOT rising in the mndile, nd dditionlly, review of pertinent literture s well s discussion of the potentil origins of the cler tumor cells hve een presented. 1 Neville B, Dmm DD, Allen CM et l. Orl nd Mxillofcil Pthology. 3rd ed. Phildelphi: WB Sunders, 2009: Philipsen HP, Reichrt PA. Clcifying epithelil odontogenic tumor: iologicl profile sed on 181 cses from the literture. Orl Oncol 2000; 36(1): Arms AM, Howell FV. Clcifying epithelil odontogenic tumors: report of four cses. J Am Dent Assoc 1967; 74(6): Anderson HC, Kim B, Minkowitz S. Clcifying epithelil odontogenic tumor of Pindorg: n electron microscopic study. Cncer 1969; 24(3): Greer RO, Richrdson JF. Cler-cell clcifying odontogenic tumor viewed reltive to the Pindorg tumor. Orl Surg Orl Med Orl Pthol 1971; 42(6): Wllce J, McDonld GD. Clcifying epithelil odontogenic tumour ( Pindorg tumour ): cse report. Br J Plst Surg 1974; 27(1): Oikrinen VJ, Clonius PEB, Meretoj J. Clcifying epithelil odontogenic tumor (Pindorg tumor): cse report. Int J Orl Surg 1976; 5(4): Ymguchi A, Kokuu JM, Tkgi M et l. Clcifying odontogenic tumor: histochemicl nd electron microscopic oservtion of cse. Bull Tokyo Med Dent Univ 1980; 27(3): Asno M, Tkhshi T, Kusm K et l. A vrint of clcifying epithelil odontogenic tumor with Lngerhns cells. J Orl Pthol Med 1990; 19(9): Schmidt-Westhusen A, Philipsen HP, Reichrt PA. Cler cell clcifying epithelil odontogenic tumor: cse report. Int J Orl Mxillofc Surg 1992; 21(1): Tkt T, Ogw I, Miyuchi M et l. Non-clcifying Pindorg tumor with Lngerhns cells. J Orl Pthol Med 1993; 22(8): Hicks MJ, Flitz CM, Wong ME et l. Cler cell vrint of clcifying epithelil odontogenic tumor: cse report nd review of the literture. Hed Neck 1994; 16(3): Kummoto H, Sto I, Tteno H et l. Cler cell vrint of clcifying epithelil odontogenic tumor (CEOT) in the mxill: report of cse with immunohistochemicl nd ultrstructurl investigtions. JOrlPtholMed1999; 28(4): Anvi Y, Kpln I, Citir M et l. Cler-cell vrint of clcifying epithelil odontogenic tumor: clinicl nd rdiogrphic chrcteristics. Orl Surg Orl Med Orl Pthol Orl Rdiol Endod 2003; 95(3): Germnier Y, Bornstein MM, Stuffer E et l. Clcifying epithelil odontogenic (Pindorg) tumor of the mndile with cler cell component treted y conservtive surgery: report of cse. J Orl Mxillofc Surg 2005; 63(9): Mohtshm N, Hii A, Jfrzdeh H et l. Extension of Pindorg tumor to the mxillry sinus: cse report. J Orl Pthol Med 2008; 37(1): Krolls SO, Pindorg JJ. Clcifying epithelil odontogenic tumor. A survey of 23 cses nd discussion of histomorphologic vritions. Arch Pthol 1974; 98(3): Pindorg JJ, Vedtofte P, Reiel J et l. The clcifying epithelil odontogenic tumor. A review of recent literture nd report of cse. APMIS 1991; 23(Suppl): de Aguir MC, Gomez RS, Silv EC et l. Cler-cell melolstom (cler-cell odontogenic crcinom): report of cse. Orl Surg Orl Med Orl Pthol Orl Rdiol Endod 1996; 81(1): Ng KH, Sir CH. Cler cell chnge in clcifying odontogenic cyst. Orl Surg Orl Med Orl Pthol 1985; 60(4): This work is licensed under Cretive Commons Attriution-NonCommercil-NoDerivtive Works 3.0 Unported License. To view copy of this license, visit cretivecommons.org/licenses/y-nc-nd/3.0 Interntionl Journl of Orl Science

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