165 Journl Orl Science, Vol. 43, No. 3, 165-169, 2001 Ppillry orl mucos: immunohistochemicl comprison with or s orl mucosl origin Astrct: Ppillry (PSCC) is poorly descried vrint, nd my e confused with verrucous hed nd neck. To dd to existing knowledge this rre tumor, we descrie two cses PSCC rising in orl mucos. The lesions were composed exophytic prolifertion typicl to overtly mlignnt s similr to those conventionl, nd invsion into superficil region underlying firous tissue ws seen in form islnds nd cords mlignnt s. Immunohistochemicl ssessment ulr prolifertive ctivity showed significntly high men percentge Ki-67 expression in comprison with verrucous, ut re ws no significnt difference Ki-67 expression mong PSCC, conventionl nd microinvsive. These results suggest tht iologicl ehvior PSCC is nlogous to tht SCC. (J. Orl Sci. 43, 165-169, 2001) Key words: ppillry ; orl ; prolifertive ctivity; Ki-67. Introduction Ppillry (PSCC), recently (Received 12 April nd ccepted 19 June 2001) descried ut poorly documented vrint, ppers mcroscopiclly s n exophytic ppillry prolifertion, ut microscopiclly is composed ppille covered y overtly mlignnt s (1-3). PSCC my e completely exophytic (PSCC in situ or noninvsive PSCC), ut ten re is n underlying component nonppillry, invsive (PSCC or invsive PSCC). The smll numers reported cses PSCC hve shown mle predilection, nd site involvement is upper erodigestive trct (4-6). PSCC should not e confused with verrucous or conventionl, not only in terms pthology ut lso clinicl fetures nd tretment modlities. To our knowledge, only four ppers documenting clinicl nd pthologicl fetures PSCC hve ppered in English literture (4-7), nd few investigtions hve descried iologicl differences etween PSCC nd or types t moleculr level or in terms ulr prolifertive ctivity. The present communiction reports histopthologicl fetures two cses PSCC rising in orl mucos, nd ttempts to clrify different ptterns immunohistochemicl expression Ki-67 mong PSCC, conventionl, microinvsive nd verrucous in order to dd to existing knowledge this tumor. Correspondence to Dr. Ysunori Tked, Deprtment Orl Pthology, School Dentistry, Iwte Medicl University, 19-1 Uchimru, Moriok, Iwte 020-8505, Jpn Tel: +81-19-651-5111 ext. 3521 Fx: +81-19-621-3321 E-mil ddress: ytked@iwte-med.c.jp Clinicl Summry Cse 1 ws tumor in orl floor 68-yer-old, edentulous Jpnese mn who hd een wre mss for four months. Clinicl exmintion reveled well circumscried, erymtous, ppillry tumor mss
166 mesuring 12 ~8 ~5 mm on left side orl floor. The tumor ws moile nd elstic st in consistency. No regionl lymph nodes were plple. The lesion ws cliniclly dignosed s prole enign tumor orl floor, nd surgicl resection ws performed under locl nessi. The heling process ws norml without ny signs recurrence. Cse 2 ws tumor in st plte 72-yer-old Jpnese mn who hd een wre mss for three months. The clinicl fetures tumor, which mesured 8 ~6 ~4 mm, were similr to those cse 1. There ws no cervicl lymphdenopthy. The clinicl dignosis ws prole enign tumor st plte, nd surgicl resection ws performed. The heling process ws norml without ny signs recurrence. Mterils nd Methods The surgiclly resected specimens were fixed in 10% neutrl-uffered formlin nd emedded in prffin y routine procedure. In ddition to hemtoxylin-eosin stining for histopthologicl exmintion, sections were used for monoclonl ntiody MIB-1 (Immunotech SA, Mrseilles, Frnce). Negtive controls for immunostining were creted y replcing primry ntiody with phosphteuffered sline. Four cses conventionl well differentited (SCC), two cses microinvsive (MSCC), nd three cses verrucous (VC) were selected to mtch ge (seventh to eighth decde), sex (mle) nd tumor size (under 15 mm in gretest dimeter) ptients with PSCC, nd served s comprtive specimens (Tle 1). Ki-67-positive s were defined s s with cler rown stining in nuclei. For ech cse, men percentge positively stined s ws estimted y counting 500 s per re from t lest five rndomly selected res representtive lesion's histology. Dt were expressed s men percentge positive s Wllis H-test were used to investigte sttisticl significnce differences in Ki-67 expression mong specimen groups. Ki-67 immunostining y streptvidin-iotin method (Histine SAB-PO kit; BioGenex Ls, Dulin, CA, USA). The Ki-67 ntiody (diluted 1:50) ws Ki-67 mouse Tle 1 Mterils exmined nd ir immunohistochemicl quntittive results for Ki-67 expression
167 Results Histopthologic l findings The lesion cse 1 consisted n exophytic prolifertion epilil s covering ppille with firovsculr nrrow strom ( 1). The epilium vried in thickness. The ppille lcked undnt surfce kertiniztion ( 1), nd were composed typicl to overtly mlignnt s similr to those conventionl ( 1c). Invsion into superficil region underlying firous tissue ws seen in form islnds nd cords mlignnt s ( 1d). Furrmore, infiltrting involved minor slivry glnd duct epilium. Diffuse infiltrtion smll mononucler s ws seen in underlying firous tissue. The histopthologicl fetures cse 2 were similr to those cse 1, ut lesion ws surrounded y wide zone non-ppillry nd non-invsive ( 2), nd individul kertiniztion 1 Ppillry (HE, ~8). () to overtly mlignnt superficil region The ppille lck fetures cse undnt similr underlying 1. () surfce to those firous An ws prtilly evident ( 2). Immunohistochemie l findings Ki-67-positive s were scttered hphzrdly throughout cncer nests PSCC nd SCC (Figs. 3,). In MSCC, Ki-67-positive s were demonstrted in infiltrting cncer nests nd lower hlf thickened epilium with mlignnt chrcteristics ( 3c). Only slly nd prslly locted s were positive for Ki-67 in VC ( 3d). Quntittive immunohistochemicl results re summrized in Tle 1. Ki-67-positive s ccounted for 53.2-59.0% in PSCC, 56.7-70.4% in SCC, 46.1-52.2% in MSCC nd 24.6-30.6% in VC, nd frequency Ki67-positive s ws significntly low in VC when compred to PSCC, SCC nd MSCC (P < 0.001); re were no sttisticl significnces in Ki-67 expression mong PSCC, SCC nd MSCC. c d exophytic kertiniztion tissue (HE, ~100). conventionl in prolifertion form islnds (c) Proliferting nd cords epilium (HE, ~300). mlignnt vries s (d) s in show Invsion (rrows; thickness typicl into HE, ~40).
168 Discussion PSCC is vrint nd my form PSCC is uncler, some investigtors hve suggested tht rte trnsformtion to n invsive lesion is high present s eir n in situ or invsive tumor. It occurs most frequently in mle ptients from 50 to 70 yers ge, nd most common site is lrynx, followed y orophrynx nd nsophrynx (4,6). PSCC my e completely exophytic, ut ten re is n underlying component non-ppillry, invsive. Although nturl history non-invsive (4). Cliniclly, oth PSCC nd VC pper s n exophytic, ppillry tumor, ut ltter is white, wrty nd fungting with multiple filiform projections. Creful histopthologicl investigtion is needed to estlish correct dignosis, which is essentil for pproprite tretment (3-7). VCs contining res tht re indistinguishle from SCC hve 2 Ppillry surrounds exophytic cse ppillry lesion 2. () A wide (HE, ~10). zone () non-ppillry Prtilly evidence nd non-invsive individul kertiniztion (HE, ~250). c 3 Ki-67 immunostining. (c) ( ~200). Microinvsive () Ppillry. d (d) Verrucous. () Conventionl well. differentited
169 een descried in literture, nd such tumors re clled hyrid s (6,8). Ishiym et l. suggested tht se hyrid s re proly identicl to PSCC (7). The reltionship PSCC to HPV is uncler. Crissmn et l. reported tht ll PSCCs were uniformly negtive for HPV DNA y in situ hyridiztion (4), lthough HPV type 6 DNA ws found y PCR in single cse reported y Judd et l (5). The expression cycle-ssocited proteins, especilly Ki-67, hs een well studied immunohistochemiclly in SCC, MSCC nd VC hed nd neck (9-13), nd present results re very similr to those in previous reports. Ki-67 is ulr prolifertion mrker expressed t ll phses cycle except GO. Incresed Ki-67 expression hs een reported to e good indictor prolifertive ctivity in premlignnt nd mlignnt orl lesions (9,11,13). In present study, men percentge Ki-67 expression ws high in PSCC, SCC nd MSCC, nd re ws no significnt difference in expression mong se lesions. On or hnd, men percentge Ki-67 expression ws significntly low in VC when compred to PSCC, SCC nd MSCC. Although numer well documented cses is smll, it is thought tht postopertive prognosis PSCC is good, nd tht distnt metstses re rre (6). Some uthors elieve tht ptients with PSCC t stge T3 or greter should undergo prophylctic neck dissection, in view possile neck metstses (7), wheres ors clim iologicl ehvior PSCC with invsion ppers to e nlogous to tht SCC equivlent stge (3,4). The present two PSCCs, which were out 10 mm in gretest dimeter, showed significntly high men percentge Ki-67 expression compred with VC, nd re ws no significnt difference in Ki-67 expression mong PSCC, SCC nd MSCC. These results suggest tht iologicl ehvior PSCC with or without invsion into underlying firous tissue ppers to e nlogous to tht SCC equivlent stge. References 1. Shnmugrtnm, K. nd Soin, L.H. (1991) Histologicl typing tumours upper respirtory trct nd er. 2nd ed., Springer-Verlg, Berlin, 29-30 2. Pindorg, J.J., Reichrt, P.A., Smith, C.J. nd vn der Wl, I. (1997) Histologicl typing cncer nd precncer orl mucos. 2nd ed., Springer- Verlg, Berlin, 13 3. Mills, S.E., Gffey, M.J. nd Frierson, H.F. (2000) Tumors upper erodigestive trct nd er. In Atls tumor pthology. 3rd series, Fscicle 26, Armed Forces Institute Pthology, Wshington, D.C., 85-87 4. Crissmn, J.D., Kessis, T., Shh, K.V., Fu, Y.S., Stoler, M.H., Zro, R.J. nd Weiss, M.A. (1988) Squmous ppillry neoplsi dult upper erodigestive trct. Hum. Pthol. 19, 1387-1396 5. Judd, R., Zki, S.R., Cfield, L.M. nd Evtt, B.L. (1991) Humn ppillomvirus type 6 detected y polymerse chin rection in invsive sinonsl ppillry. Arch. Pthol. L. Med. 115, 1150-1153 6. Ferlito, A., Devney, K.O., Rinldo, A. nd Putzi, M.J. (1999) Ppillry versus verrucous hed nd neck. Ann. Otol. Rhinol. Lryngol. 108, 318-322 7. Ishiym, A., Eversole, L.R., Ross, D.A., Rz, Y., Kerner, M.M., Fu, Y.S., Blckwell, K.E., Feneerg, R., Bell, T.S. nd Clcterr, T.C. (1994) Ppillry neoplsms hed nd neck. Lryngoscope 104, 1446-1452 8. Medin, J.E., Dichtel, W. nd Lun, M.A. (1984) Verrucos- s orl cvity. A clinicopthologicl study 104 cses. Arch. Otolryngol. 110, 437-440 9. Girod, S.C., Krueger, G. nd Ppe, H.D. (1993) P53 nd Ki-67 expression in preneoplstic nd neoplstic lesions orl mucos. Int. J. Orl. Mxillc. Surg. 22, 285-288 10. Zoeller, J., Flentje, M., Sinn, P. nd Born, I.A. (1994) Evlution AgNOR nd Ki-67 ntigen s kinetic prmeters in orl dysplsis nd s. Anl. Cell. Pthol. 7, 77-88 11. Ichikw, M., Ishii, K., Nkjim, T. nd Mogi, K. (1997) The overexpression p53 nd prolifertive ctivity in precncerous nd cncerous lesions orl epilium. J. Exp. Clin. Cncer Res. 16, 141-146 12. Nylnder, K., Schildt, E.B., Eriksson, M. nd Roos, G. (1997) PCNA, Ki-67, p53, cl-2 nd prognosis in introrl hed nd neck. Anl. Cell. Pthol. 14, 101-110 13. Sito, T, Nkjim, T. nd Mogi, K. (1999) Immunohistochemicl nlysis cyclessocited proteins p16, pr, p53, p27 nd Ki-67 in orl cncer nd precncer with specil reference to verrucous s. J. Orl Pthol. Med. 28, 226-232