Giant condyloma acuminatum (GCA) or Buschke-

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1 J Soc Co lon Rec tal Sur geon (Taiwan) De cem ber 2002 Case Re port Gi ant Condyloma Acuminatum (Buschke-Loewenstein Tumor) of the Anorectum Chau-Jiunn Hwang 1 Hong-Arh Fan 1 Cheng-Ching Lin 2 1 Di vi sion of Colorectal Sur gery, De part ment of Sur gery, Jiann Ren Hos pi tal, Kaohsiung, Tai wan, R.O.C. 2 Di vi sion of Pa thol ogy, Chang Gung Me mo - rial Hos pi tal, Kaohsiung, Tai wan, R.O.C. Key Words Gi ant condyloma; Papillomavirus; Buschke-loewenstein tu mor Gi ant condyloma (Buschke-Loewenstein tu mor) is a rare dis ease that most com monly af fects the uro gen i tal area. We pre sented a 41-yearold man who got a cau li flower-like, warty mass around the perianal re - gion. There was a mass of mm in size, cir cumfer ential, pap il lary and soft tu mor at the anal or i fice. He re ceived to tal ex ci sion of the tu mor with fulgurations and anoplasty re con struc tion on De cem - ber 25, Post op er a tively, the wound heal ing was un event ful. Hu - man papillomavirus type 6 was iden ti fied in the spec i men. Af ter the fol low up of six months, the pa tient was free of tu mor, and had nei ther the signs of anal ste no sis nor in con ti nence. He re turned to nor mal ac - tive life. [J Soc Co lon Rec tal Sur geon (Taiwan) 2002;13: ] Giant condyloma acuminatum (GCA) or Buschke- Loewenstein tu mor is a rare dis ease that most com monly af fects the uro gen i tal area. In 1896, Buschke 1 first de scribed a gi ant condyloma acumina - tum of the pe nis. In 1925,Buschke and Loewenstein fur ther elab o rated upon this med i cal phe nom e non. It was termed Buschke-Loewenstein tu mor or gi ant condyloma acuminatum due to its histologic sim i lar ity to the be nign condyloma acuminatum. 2 In 1966, Knoblich and Fail ing 3 de scribed the first case with perirectal in volve ment. They char ac ter ized these tu - mor by their unique lo ca tion, large size, slow growth, cau li flower-like ap pear ance and of ten pre sent ing with ne cro sis, sec ond ary in fec tion, hem or rhage, fistu - lization and pen e tra tion into deeper tis sue with out in - va sion of lymphatics, blood ves sels, and dis tal me tas - ta sis or other histopathologic cri te ria of ma lig nancy. It is ap par ent that these tu mors oc cupy a twi light zone in the clas si fi ca tion be tween condyloma acumi - natum and frank squamous car ci noma, in that they be - have in a lo cally ma lig nant fashion de spite their histologically be nign ap pear ance. Case Re port A 41-year-old man pre sented a soft tu mor- like mass about cm in size around the perianal re - gion for one year pe riod (Fig. 1). It was just an ir reg u lar perianal exophytic, warty mass a year ago with out any bleed ing but slowly in creas ing in size. It ap peared cau li - flower-like, cir cumfer ential around the perianal and had no any pain ex cept dull pain on pres sure with some dis - charge of foul smell. He had been treated in main land China with dif fer ent herbal med i cines for lo cal ap pli ca - tion but all in vain. Then he re turned to Tai wan and vis - ited local colorectal clinic, where Giant condyloma acuminatum was di ag nosed and was re ferred to this hos - Re ceived: July 16, Cor re spon dence to: Hong-Arh Fan, MD, Di vi sion of Pa thol ogy, Chang Gung Me mo rial Hos pi tal, Kaohsiung 833, Tai wan. Tel: ext. 3009; Fax: ; fanhong2@ms53.hinet.net 125

126 Chau-Jiunn Hwang, et al. J Soc Co lon Rec tal Sur geon (Taiwan) De cem ber 2002 pi tal for fur ther man age ment. He was not in volved in ho mo sex ual or any other sex ual ac tiv i ties.

Its color was brown and par tially pink ish, al though the sur face of the nod ules in side the folds was whit ish gray with mac er a tion. In gui nal lymph node was im pal pa ble.

2 126 Chau-Jiunn Hwang, et al. J Soc Co lon Rec tal Sur geon (Taiwan) De cem ber 2002 pi tal for fur ther man age ment. He was not in volved in ho mo sex ual or any other sex ual ac tiv i ties. On ex am i na tion, it ap peared as a huge grape-like mass com posed of mul ti ple small papillomatous nod ules, cau li flower-like, form ing a big cir cumfer - ential condyloma of perianal re gion. Its color was brown and par tially pink ish, al though the sur face of the nod ules in side the folds was whit ish gray with mac er a tion. In gui nal lymph node was im pal pa ble. Sig moidoscopy re vealed the pres ence of mi nor condyloma in the anal ca nal but there was no ev i - dence of tu mor above 25 cm from the anal verge. Lab o ra tory tests in clud ing a com plete blood count, liver func tion test, and uri nal y sis were within the nor mal range. Serological test for syph i lis was neg a - tive. Smears and cul tures re vealed no ev i dence of gono cocci. The pa tient failed to re act to HIV an ti - bod ies. Hu man papillomavirus type 6 was iden ti fied in the spec i men. The pa tient was treated with to tal ex ci sion of tu - mor, fulgurations and anoplasty re con struc tion on De - cem ber 25, Af ter the to tal ex ci sion of the le sion, the cir cumfer ential skin de fect around the anal verge about 2.5 cm width was re con structed with four guardant full thick ness ad vanced flap anoplasty. Post - op er a tively the wound heal ing was un event ful. At fol - low-up six months later the pa tient was free of tu mor, had no signs of anal ste no sis or in con ti nence. He retured to nor mal ac tive life Pa thol ogy Fig. 1. Mas sive (8 6 6 cm) cir cumfer ential tu mor of the anal or i fice. Mi cro scopically, the le sion bears a strong re sem - blance to condyloma acuminatum. It ex hib its marked pap il lary pro lif er a tion of well-differentiated, ma tur - ing squamous ep i the lium that pro jects above the skin or mucosal sur face and dis plays an ex ten sive sur face keratinization (Fig. 2). There is ex ten sive acanthosis, parakeratosis, and vacuolation of the su per fi cial lay - ers. In di vid ual cells or group of cells can have koilo - cytotic change as found in condyloma acuminatum. 4 Scat tered dyskeratotic and/or slightly atyp i cal squa - mous cells are pres ent but no ma jor de gree of cy to - logic atypia or ma lig nancy is not pres ent. (Fig. 3). There is no evidene of in va sion of lymphatics, or other histopathologic cri te ria of ma lig nancy. Discussion Fig. 2. Orig i nal mag ni fi ca tion show the cau li flower-like ep i the lial hy per pla sia,pap il lary and exophytic.no base ment mem brane de struc tion is noted, nor in di - vid ual cell anaplasia, H.E 1. Gi ant condyloma acuminatum or Buschke- Loewenstein tu mor is a well-described, but in com - pletely un der stood dis ease. It was first de scribed by Buschke in at pe nis, and later by Buschke and Loewenstein in It was Knoblish and Fail ing who first de scribed this tu mor in the anorectal lo ca tion in Condyloma acuminatum is com posed of clin i cally and hisotologically be nign papillomatous

Vol. 13, No. 4 Gi ant Condyloma Acuminatum 127 Fig. 3. Koilocytosis of ep i the lium and in tact stroma, H.E 10. le sions. They are trans mis si ble and autoinoculable.

3 Vol. 13, No. 4 Gi ant Condyloma Acuminatum 127 Fig. 3. Koilocytosis of ep i the lium and in tact stroma, H.E 10. le sions. They are trans mis si ble and autoinoculable. The re spon si ble vi rus is sim i lar to the vi rus that causes ver ruca vulgaris. The growth re mains re stricted to the sur face of the skin or mu cous mem brane. Gi ant condyloma acuminatum, on the other hand, be haves in a lo cally ma lig nant fash ion, bur row ing deeply into ad ja cent struc tures, de stroy ing tis sue with the for ma - tion of mul ti ple si nuses and fis tu las. Histologically, on the other hand, gi ant condyloma acuminatum and verrucous car ci noma have dif fer ent char ac ter is tic fea tures. A gi ant condyloma acumina - tum had epi der mal hy per pla sia with out ex ten sive hyperkeratosis. 4 Many koilocytes are ob served, but the ob vi ous hall marks of true ma lig nancy are not com monly found. It is a gi ant form of vi ral wart, 5,6 al - though it has rather high prob a bil ity of be com ing a premalignant or a truly ma lig nant squamous tu mor. 7-9 A verrucous car ci noma has char ac ter is tic crustic hyperkeratosis and acanthosis with only a few or no koilocytes. It has cy to log i cal ab nor mal i ties with ve - sic u lar nu clei and intercellular edema, al though well-formed cel lu lar bridges are usu ally ob served. 10 There still ap pears to be doubt con cern ing the true neo plas tic po ten tial of the gi ant condyloma acumina - tum. Buschke and Loewenstein used the lack of histologic in va sion and of me tas ta sis to de fine this en - tity. How ever, there have been sev eral re ports of in va - sive squamous cell car ci noma de vel op ing in a gi ant condyloma acuminatum. 11 In 1948, Ackerman pub - lished the nonmetastasizing vari ant of a well dif fer en - ti ated squamous cell car ci noma in the oral cav ity and des ig nated it as a verrucous car ci noma, later in a wide va ri ety of site in clud ing the perianal and the rec - tum. 26,17 Sev eral au thors have re ported that a Buschke-Loewenstein tumor is iden ti cal with verrucous car ci noma. 12 Much ev i dence sup ports the the ory, how ever, that the le sion rep re sents an in ter me - di ate state be tween condyloma acuminatum and squamous cell car ci noma. 13 The ex act interelations are still con tro ver sial in be tween these four en ti ties; i.e. condyloma acuminatum, gi ant condyloma acu - minatum, squamous cell car ci noma, and verrucous car ci noma, Many au thors be lieve that giant con - dyloma prob a bly rep re sent verrucous car ci noma, and what condyloma acuminatum with ma lig nant trans - for ma tion be ing verrucous car ci noma from the on - set Creasman et al. be lieve that gi ant con dyloma acuminatum rep re sents an in ter me di ate le sion in a patho logic con tin uum from condyloma acu minatum to squamous cell car ci noma. An in creased ten dency of ma lig nant trans for ma tion had been noted in HIV-positive pa tients. 27 When mul ti ple si nuses or fis tu lous tracts are found, tu mor invsion should be con sid ered. There may be an ex ten sive in va sion to un der neath soft tis - sues, perirectal tis sues. The ex tent of in volve ment can be pre cisely de ter mined by CT scan. 23 Prasad and Abcarian have termed the clin i cal sit u a tion by ul cer - ation, in fil tra tion and pro lif er a tion into deeper tis sues with out histologic ma lig nant change as ma lig nant be - hav ior of condylomata. The rec om mended treat ment of gi ant condyloma acuminatum is wide lo cal ex ci sion. If the rec tal sphincter has been in fil trated, abdominoperineal ex -

4 128 Chau-Jiunn Hwang, et al. J Soc Co lon Rec tal Sur geon (Taiwan) De cem ber 2002 ci sion of the rec tum with wide per i neal dis sec tion must be per formed. 19,24 Fur ther more, rad i cal sur gery ap peared to have yielded a far su pe rior re sult over a more con ser va tive ap proach in treat ing GCA of the anorectal and perianal re gions, but even then the po - ten tial for re cur rences re mained high. Creasman and Col leagues 13 sug gested that the use of abdo mino - perineal re sec tion ap peared to have had very lit tle im - pact on sur vival and that what ap peared to af fect over - all sur vival is early con trol of the dis ease with rad i cal sur gery. Creasman et al. 13 sum ma rized the fea tures of 20 cases of GCA re ported in lit er a ture. They found that the av er age age was 43 yrs, male to fe male ra tio was 2.3:1.0, re cur rence rate af ter ex ci sion was 65%, over all mor tal ity rate was 30 %, and the in ci dence of ma lig nant trans for ma tion was 30 %. The role of ra dio ther apy and che mo ther apy in treat ing GCA is un cer tain. Sev eral au thors have sug - gested that these mo dal i ties alone yielded poor out - come. Fur ther more, the threat of trans form ing these some what be nign le sions into a ma lig nant le sion by the use of ra dio ther apy was raised by sev eral au - thors. 14 It is prob a ble that the high rate of re cur rence from rad i cal sur gery may be be cause of spill age of re sid ual tu mor dur ing the op er a tion. By re duc ing these le sions pre op er a tively with chemoradiotherapy, this sit u a tion may be pre vented. So pre op er a tive chemoradio - therapy fol lowed by rad i cal sur gery may pro vide a better re sult. Ex cept the above mo dal i ties, im - munotherapy may play a ma jor role in pa tients who de vel oped re cur rence as an al ter na tive treat ment. 15 The ques tion re mains whether anal in ter course is in vari ably im pli cated in the eti ol ogy of perianal condyloma and anal can cer. There is a high in ci dence of condylomata acuminatum with intraepithelial car - ci noma in situ in ho mo sex ual pa tients with AIDS. 16 Anal dysplasia and car ci noma in situ are con sid ered pre cur sors to the de vel op ment of in va sive squamous cell car ci noma of the anus, re ferred to as anal intracellular neo pla sia (AIN). 16 More AIN in ho mo - sex ual and HIV pos i tive pa tients raise the in ci dence of in va sive anal can cer in this group. 29 There is an in - creasing ev i dence of an as so ci a tion be tween squamous cell car ci noma of the anal canal and mar gins with HPV vi ruses, par tic u larly Types 16, 18, and Though dif fer ent types of HPV vi ruses have been re - ported in the lit er a ture, it is ob vi ous that HPV vi ruses may play some role to squamous cell car ci noma. HPV 6 and 11 have also re cently been de scribed in as so ci a - tion with the gi ant condyloma or verrucous car ci - noma 13 The ap pli ca tion of DNA hy brid iza tion tech - niques is of great po ten tial in the in ves ti ga tion of the role of HPV in such con di tions. References 1. Buschke A Neisser s Sterokopischer. At las New York: Fischer, Buschke A, Lowenstein L. Uber Carcinomahnliche Con - dylomata Acuminata des pe nis. Klin Wochenschr 1925;4: Knoblich R, Fail ing JF, Jr. Gi ant condyloma acuminatum (Buschke-Loewenstein tu mor) of the rec tum. Am J Clin Pathol 1967;48: Rock B, Shah KV, Farmer ER. A morphologic,patho logic, and virologic study of anogenital warts in men. Arch Dermatol 1992;127: Gissmann L, De Villiers EM, Zur Hausen H. Anal y sis of hu - man gen i tal warts (condylomata acuminata) and other gen i - tal tu mors for hu man papillomavirus type 6. DNA Int J Can - cer 1982;29: Boshart M, Zur Hausen H. Hu man papillomavirus in Buschke-Loewenstein tu mors:phys i cal state of the DNA and iden ti fi ca tion of a tan dem du pli ca tion in the noncoding re - gion of a hu man papillomavirus 6 sub type. J Virol 1986;58: Schmauz R, Findlay M, Lalwak A, Katsumbira N, Bux ton E. Vari a tion in the ap pear ance of gi ant condyloma in an Ugan - dan se ries of cases of car ci noma of the pe nis. Cancer 1977;40: Hull MT, Eble JN, Priest JB, Mulcahy JJ. Ul tra struc ture of Buschke-Loewenstein tu mor. J Urol 1981;126: Grossman HB. Premalignant and early car ci noma of the pe - nis and scro tum. Urol Clin North Am 1992;19: Masih AS, Stoler MH, Far row GM, Wooldridge TN, Johansson SL. Penile verrucous car ci noma :A clinico - pathologic,hu man papillomavirus typ ing and flow cytometric anal y sis. Mod ern Pathol 1992;5: Sturnn JT, Christenson CE, Uecker JH, et al. Squamous cell car ci noma of the anus aris ing in a gi ant condyloma acuminatum. Re port of a case. Dis Co lon Rec tum 1975;18: South LM, O Sullivan JP, Gazet JC. Gi ant condyloma of Buschke and Loewenstein. Clin Oncol 1977;3:

5 Vol. 13, No. 4 Gi ant Condyloma Acuminatum Creasman C, Haas P, Fox Jr T, Balazs M. Ma lig nant trans for - ma tion of anorectal gi ant condyloma acuminatum (Buschke-Loewenstein tu mor). Dis Co lon Rec tum 1989;32: Drut R,OntiverosR,Cabral DH. Perianal verrucose car ci - noma spread ing to the rec tum: Re port of a case. Dis Co lon Rec tum 1975;18: Baird PJ, Elliott P, Stening M, Korda A. Gi ant condyloma acuminatum of the vulva and anal ca nal. Aust NZT Obstet Gynaecol 1979;19; Croxson T, Chabon A, Rorat E, Barash I. Intraepithelial car - ci noma of the anus; ho mo sex ual men. Dis Co lon Retum 1984;27: Shah JC, Hertz RE. Gi ant condyloma acuminatum of the anorectum: Re port of 2 cases. Dis Co lon Rec tum 1972;15: Headington JT. Verrucous car ci noma. Cutis 1978;21: Elliot MS, Werner JD, Immelman EJ, Har ri son AC. Gi ant condymoma (Buschke-Loewenstein tu mor) of the ano - rectum. Dis Co lon Rec tum 1979;22: Gingrass PJ, Bubrick MP, Hitch cock CR, Strom RL. Anorectal verrucous squamous car ci noma: Re port of two cases. Dis Co lon Rec tum 1978;21: Lee SH, McGregor DH, Kuziez MN. Ma lig nant trans for ma - tion of perianal condyloma acuminatum. A case re port with re view of the lit er a ture. Dis Co lon Rec tum 1981;45: Prioleau PG, Santa Cruz MJ, Meyer JS, Bauer WC. Verrucous car ci noma. A light and elec tron mi cro scopic autoradiographic, and immunofluorescence study. Cancer 1980;32: Bal tha zar EJ, Streiter M, Megibow AJ. Anorectal gi ant condyloma acuminata ( Buschke-Loewenstein tu mor): CT and ra dio graphic man i fes ta tion. Radiology 1984;150: Lock MR, Katz DR, Samoorian S, Park AG. Gi ant condyloma of the recum: Re port of a case. Dis Co lon Rec tum 1977;20: Prasad ML, Abrican H. Ma lig nant po ten tial of perianal condyloma acuminatum. Dis Co lon Rec tum 1980;23: Ackerman LV. Verrucous car ci noma of the oral cav ity. Sur - gery 1948;23: Beck DE, Jaso R, Gm Zajac RA. Sur gi cal man age ment of anal condyloma in the HIV-positive pa tient. Dis Co lon Rec - tum 1990;33: Beckman AM, Daling KR, Sherma KJ, et al. Hu man papilloma vi rus in fec tion and anal can cer. Int J Can cer 1989; 43: Palefsky JM, Gon za les J, Greenblatt RM. Anal intra - epithelial neo pla sia and anal papilloma vi rus in fec tion among ho mo sex ual male with Group IV HIV dis ease. JAMA 1990;263:

De voted to Prof. Pavel Povinec 65-th an ni ver sary. 222 Rn in wa ter are per formed mainly in the con text of po ta ble wa ter,

De voted to Prof. Pavel Povinec 65-th an ni ver sary. 222 Rn in wa ter are per formed mainly in the con text of po ta ble wa ter, The nat u ral ra dio ac tiv ity of wa ter is de ter mined by a con tent of dis solved solid and gas eous nat u ral radionuclides, mainly by 4 K, 238 U, 234 U, 232 Th, 226 Ra and 222 Rn. 222 Rn is an in