Uterus-Like Ovarian Mass with Elevated Serum Levels of CA 19-9 and CA 125: A Case Report and Review of the Literature

TurkiyeKlinikleriJMedSci2010;30(5)1732 terus-likeovarianmass(UOM)wasfirstdescribedbyCozzuttoin 1981.1‘Endomyometrioma’,‘adenomyoma’and‘tumorofmulleri- antype’arerepresentativeofsomeoftheterms,reportedforUOM since1981.Thislesionshowsacentralcavitylinedbyendometrialmuco- sasurroundedbythickmusclewall.Toourknowledge,11casesofUOM, aged11-54yearsold,werereported .1-7 Itwasdocumentedthatfiveoutof 11caseswerefollowedbecauseofinfertility,three hadrenalanomalies, twohadbreastcancersandthreehadelevatedserumCA 125 levels(Table 1).UOMwasalsofoundinsomeotherlocationssuchascervixuteri,broad Uterus-LikeOvarianMasswith ElevatedSerumLevelsof CA 19-9andCA 125:A CaseReportand ReviewoftheLiterature AABBSS TTRRAACCTT Ute rus-li ke ova ri an mass is a ra re be nign en tity with con tro ver si al eti o pat ho ge ne sis. A 37 -ye ar-old wo man, gra vi da 2, pa ra 2, pre sen ted with the comp la int of pa in in right lo wer ab do - mi nal qu ad rant. Physi cal eva lu a ti on re ve a led ten der ness in this are a and the ul tra so nog rap hic ex - a mi na ti on sho wed a right ad ne xi al mass. Bi oc he mi cal blo od tests sho wed mi ni mal le u cocy to sis and ele va ted se rum le vels of both CA 19-9: 117.79 mI U/mL (N: 0-37) and CA 125: 41.4 u/mL (N: 0-35). To exc lu de a ma lig nancy, the spe ci men was exa mi ned with fro zen sec ti ons and was sub se qu ently di ag no sed as en do met ri o sis. The re fo re, the sur gi cal pro ce du re was li mi ted to right sal pin go-oop - ho rec tomy. The right ovary was 6 x 4 x 2.5 cm in si ze and the dis sec ted sur fa ce of ovary re semb led a mi ni a tu re ute rus. His to lo gic sec ti ons as well as im mu no his toc he mistry (smo oth musc le ac tin, cal - des mon and CD10) we re con sis tent with the en do met ri al mu co sal tis su e that sur ro un ded the bun - d les of smo oth musc le. KKeeyy WWoorrddss:: En do met ri o sis; CA 19-9 an ti gen; ade nom yo ma ÖÖZZEETT Ute rus-ben ze ri ovar yan kit le et yo pa to ge ne zi tar tış ma lı, na dir gö rü len, be nign bir lez yon - dur. 37 ya şın da ka dın has ta, gra vi da 2, pa ra 2, sağ alt ab do mi nal kad ran ağ rı sı ile baş vur du. Fi zik mu - a ye ne ile has sa si yet göz le nen ay nı böl ge de, ul tra son ile in ce le me de sağ ad nek si yel kit le sap tan dı. Bi yo kim ya sal in ce le me ler de, mi ni mal lö ko si to zis ya nı sı ra se rum Ca19.9: 117.79 mI U/mL (N: 0-37) ve Ca 125: 41.4 u/mL (N: 0-35) de ğer le ri yük sek li ği iz len di. Ma lig ni te dış lan ma sı için ol gu fro zen ile in ce len di ve kit le en do met ri o zis ola rak de ğer len di ril di. Bu nun üze ri ne cer ra hi uy gu la ma sağ sal - pin go o fe rek to mi ile sı nır lan dı rıl dı. Sağ over 6 x 4 x 2.5 cm bo yut la rın da olup ke si yü zü min ya tür bir ute rus gö rü nü mün dey di. His to lo jik ke sit le ri ya nı sı ra düz kas ak tin, kal des mon ve CD10’u içe - ren im mün his to kim ya sal in ce le me le ri, düz kas de met le ri ile çev re len miş en do met ri yal mu ko za ile uyum lu idi. AAnnaahh ttaarr KKee llii mmee lleerr::En do met ri yo zis; CA 19-9; ade nom yo ma TTuurrkkiiyyee KKlliinniikklleerrii JJ MMeedd SSccii 22001100;;3300((55))::11773322--66 Cana n KELTEN, MD, a Nagihan YALÇIN, MD, a Şermin ÇO BAN, MD, a Erkan ALATAŞ, MD, b Metin AKBULUT, MD a Departments of aPathology bObstetrics and Gynecology, Pamukkale University Faculty of Medicine, Denizli Ge liş Ta ri hi/ Re ce i ved: 10.10.2008 Ka bul Ta ri hi/ Ac cep ted: 16.03.2009 This case report was presented as a poster at 18 th National Pathology Congress (25-29 October, 2008, Antalya, TURKEY). Ya zış ma Ad re si/ Cor res pon den ce: Canan KELTEN, MD Pamukkale University School of Medicine, Department of Pathology, Denizli, TÜRKİYE/TURKEY [email protected] Cop yright © 2010 by Tür ki ye Kli nik le ri OLGU SUNUMU Turkiye Klinikleri J Med Sci 2010;30(5) 1733 Medical Pathology Kelten et al li ga ment, pe ri to ne um, pel vic lymph no des, scro - tum, small bo wel, blad der and co nus me dul la ris.8-11 Two hypot he ses ha ve be en pro po sed for the ori gin of UOM:1-In the pre sen ce of en do met ri o sis, thro - ugh the me tap la si a of en do met ri al stro mal cells to the smo oth musc le cells, 2- In the pre sen ce of the uro ge ni tal ano maly, the pro ba bi lity of be ing a part of con ge ni tal mal for ma ti on.1-5,12,13 CA SE RE PORT A 37-ye ar-old wo man pre sen ted with ab do mi nal pa in. The pa ti ent had al ler gic ast hma. Physi cal eva - lu a ti on re ve a led ten der ness in the right lo wer ab - do mi nal qu ad rant. The ul tra so nog rap hic exa mi na ti on sho wed a right ad ne xi al mass (6 cm) and no ot her gyne co lo gic or uri nary ab nor ma li ti es. On ab do mi nal com pu ted to mog raphy (CT), li ver, sple en, gall blad der and bi la te ral kid neys we re nor- mal in si ze and lo ca ti on. The re were no sus pi ci o us lympha de no pathies in the ab do men or ret ro pe ri - to ne al are a. Du ring bi oc he mi cal la bo ra tory eva lu - a ti on, mi ni mal le u cocy to sis (12.1 K/uL), ele va ted se rum CA 19-9: 117.79 mI U/mL (N: 0-37) and slightly ele va ted se rum CA 125: 41.4 u/mL (N: 0- 35) le vels we re de tec ted. Blood count, TSH, f T3, f T4, CE A and AFP va lu es we re wit hin the nor mal ran ges. To exc lu de a ma lig nancy, the spe ci men was exa mi ned with fro zen sec ti ons and di ag no sed as en do met ri o sis. The re fo re ,the sur gi cal pro ce du re was li mi ted to right sal pin go-oop ho rec tomy. In tra - o pe ra ti vely, the right ovary was ob ser ved in Do ug - las sac ad he red to the left ovary and rec tal se ro sa. The ute rus was of nor mal si ze and ap pe a ran ce. No fo ci sus pi ci o us for en do met ri o sis we re fo und in the pel vic or ab do mi nal re gi on or in anot her or gan of ge ni tal tract. The right ovary was 6 x 4 x 2.5 cm in si ze and com po sed of two ad he rent no du les. One of the no du les re semb led a mi ni a tu re ute rus sin ce the cut sec ti on had a ca vity with he morr ha gic ap - pe a ran ce, which was sur ro un ded with the bund les of smo oth musc le (Fi gu re 1). Mic ros co pic eva lu a ti - on re ve a led a ca vity li ned with co lum nar epit he li - um as so ci a ted with en do met ri al stro ma and sur ro un ded by a thick mus cu lar wall (Fi gu re 2). Cells with aty pi a such as ple o morp hic nuc le i, hy - perc hro ma si a, nuc le ar ve si cu la ti on, pro mi nent nu - c le o lus and eo si nop hi lic cytop lasm we re ob ser ved in the wi de are as of sur fa ce co lum nar epit he li um (Fi gu re 3). He mo si de rin-la den mac rop ha ges we re pre sent in en do met ri al stro ma, which we re sur ro - un ded by thick walls of smo oth musc le bund les. From the block of this tis su e, im mu no his toc he mi - cal sta i nings we re app li ed for CD 10 (56C6 clo ne, 1:60 di lu ti on, Ne o mar ker Lab vi si on), smo oth mus- c le ac tin (1A4 clo ne, 1:100 di lu ti on, Bi o ge nex) and cal des mon (h-CD clo ne, 1/100 di lu ti on, Bi o ge nex) Case Year, Author Age Urogenital System Anomaly Breast Cancer CA 125 Other 1 1981 , Cozutto C 32 Unilateral renal agenesis -- - 2 1985 , Peublitz-Peredo et al. 1 8 Double excretory system, double ureter, bifid pelvis -- - 3 1991 , Rahilly et al. 38 -- - Endometrioid cancer in both ovary and endometrium 4 1994 , Noel et al. 49 -- - Cytogenetic anomaly (+), congenital anomaly (-) 5 1997 , Mitra et al. 34 Not known -- - 6 1998 , Pai-Sanjay et al. 39 -+ + - 7 1998 , Pai-Sanjay et al. 43 -- + - 8 1998 , Pai-Sanjay et al. 38 -+ - - 9 2005 , Shutter 1 1 Resected right pelvic kidney -- - 10 2007 , Gurel et al. 54 -- - Uterus unicornis 11 2007 , Zannoni et al. 33 -- + Histologic atypia 1 2 2008 , Present 37 -- + Elevated CA 19-9 and histologic atypia TABLE 1: Clinicopathologic features in patients with uterus-like ovarian masses . Turkiye Klinikleri J Med Sci 2010;30(5)1734 Kelten ve ark. Tıbbi Patoloji with use of a stan dard la be led strep ta vi din bi o tin pe ro xi da se met hod. Po si ti ve sta i ning with CD10 (con sis tent with en do met ri al stro ma), smo oth mus- c le ac tin and cal des mon (con sis ting with smo oth musc le tis su e) con fir med the his to lo gi cal di ag no - sis. In one po le of this no du le, the bund les of smo - oth musc les we re in ter ming ling with the spind le cells of the ova ri an stro ma of the ot her no du le, com po sed of ova ri an stro ma with fol li cu lar cysts and he morr ha gic cor pus lu te um. No ab nor ma lity was fo und in the sec ti ons of right tu bal tis su es.The pa ti ent had be en fol lo wed for two ye ars du e to in - fer ti lity. Me anw hi le, the only preg nancy ac hi e ved thro ugh in vit ro fer ti li za ti on was di ag no sed as ‘bligh ted ovum’, thus fi nally cu ret ta ge was app li ed to the pa ti ent. The re has be en no preg nancy sin ce then. DI S CUS SI ON The eti o pat ho ge ne sis of UOM is con tro ver si al. The re are two ma in hypot he ses. Coz zut to sug gests that me tap la si a of ova ri an stro ma in the back gro - und of en do met ri o sis may exp la in the ca u se of the le si on.1This hypot he sis has be en sup por ted by se - ve ral ot her ca ses.3,4,13 On elec tron mic ros co pic eva l- u a ti on, Coz zut to ob ser ved myo fib rob lasts as well as smo oth musc le cells,and con se qu ently ,he sug - ges ted that myo fib rob lasts co uld be a tran si ti o nal cell du ring the me tap las tic chan ges. Sup por ting this vi ew, Scully sug gested that pres su re of an ex pan - ding en do met ri o tic cyst co uld trig ger a me tap la si a thro ugh smo oth musc le cells in the cells sur ro un - ding the cyst.14 H e al so in di ca ted that smo oth mus- c le fi bers could be se en in so me of ot her ova ri an le si ons such as le i om yo ma, mu ci no us cysta de no ma and ova ri an stro mal hyperp la si a . In ca ses with ab - sen ce of de mons trab le en do met ri al mu co sa du e to bleeding or pres su re, dif fe ren ti a ti on from ova ri an stro mal hyperp la si a and le i om yo ma sho uld be con - si dered. Alt ho ugh the pe ri od which trig gers the me tap la si a cannot be cle arly de ter mi ned, the re is so me evi den ce to sup port the ro le of ova ri an hor- mo nes. Bre ast can cers we re de ter mi ned in two out FI GU RE 1: Gross pho to of the sal pin go-oop ho rec tomy: right-top is the ute rus-li ke ova ri an m ass, con ta i ning a ca vity sur ro un ded with the thick wall of musc les and right-bot tom is the ova ri an stro ma with a he morr ha gic cyst and fol li cu lar cysts. FI GU RE 2: Thick myom etrium -like smooth mu scle comp onent surrounds en - dom etrial mucosa (H&E, original magnification x40). FI GU RE 3: En do met ri al co lum nar cells with aty pi a, (a) Stra ti fi ca ti on, tuf ting, ple o - morp hic nuc le i, nuc le ar ve si cu la ti on, pro mi nent nuc le o lus and eo si nop hi lic cytop - lasm we re ob ser ved (H&E, ori gi nal mag ni fi ca ti on x40), (b) in set shows si mi lar aty pi a (H&E, ori gi nal mag ni fi ca ti on x40). Turkiye Klinikleri J Med Sci 2010;30(5) 1735 Medical Pathology Kelten et al of three ca ses re por ted by Pa i et al.4En do met ri o id car ci no ma was iden ti fi ed in both ovary and ute rus as well as en do met ri o sis in the ca se of Ra hilly et al.13 Pe ter son et al. re por ted a ca se with precocious puberty and this po ints to the ro le of es tro gen in for ma ti on of UOM.9 The ot her hypot he sis pro po sed by Ro sen is that this le si on may be a part of uro ge ni tal con ge - ni tal mal for ma ti on as a fu si on de fect of Mul le ri an duct or a re al par ti al dup li ca ti on of Mul le ri an sys- tem.12 The de tec ti on of re nal age ne sis in the ca se of Coz zut to ret ros pec ti vely and the pre sen ce of uri- nary ano maly in two ot her ca ses al so sup port this hypothesis.2,5 The hypot he sis of me tap la si a se ems mo re li kely in the ca ses wit ho ut any ute rus and/or re nal con ge ni tal ano maly.3,4,13 It is known that the ca ses with en do met ri o sis sho uld be eva lu a ted ca re fully by the pat ho lo gists in terms of the pre sen ce of cyto lo gic aty pi a. Epit - he li al ab nor ma li ti es (hyperp la si a or aty pi a) ha ve be en con si de red as a step in the prog res si on to ma lig nancy.15,16 En do met ri o id car ci no mas and cle - ar cell car ci no masare the two most com mon tu - mors de ve lo ped in ova ri an en do met ri o sis.15,16 Ra rely, va ri o us tu mors in the back gro und of ova ri - an en do met ri o sis ha ve be en re por ted such asova r- i an se ro us cysta de no ma of low ma lig nant po ten ti al, be nign and ma lig nant mu ci no us tu mors, squ a mo us cell car ci no ma , gra nu lo sa cell tu mor, en do met ri o - id stro mal sar co ma, ma lig nant me so der mal mi xed tu mor and ade no sar co ma .16,17 Aty pi cal cells disp lay eo si nop hi lic cytop lasm, lar ge hyperc hro ma tic or pa le ple o morp hic nuc le i, in cre a sed nuc le ar to cy - top las mic ra ti o, cel lu lar crow ding, stra ti fi ca ti on or tuf ting. Zan no ni et al. re por ted the first ca se of ova - ri an en dom yo met ri o ma with his to lo gic aty pi a (hy - perc hro ma si a, ple o morp hic nuc le i, eo si nop hi lic cytop lasm) and fo ci of mu ci no us me tap la si a on ca vity li ned by co lum nar epit he li um.18 In this study ,aut hors ha ve men ti o ned that the si mul ta ne - o us pre sen ce of en do met ri al epit he li um with his to - lo gic aty pi a and me tap la si a sup por ted the me tap las tic the ory of UOM. They ha ve sug ges ted the term ‘en dom yo met ri o ma with aty pi as’ for the - se ca ses. Si mi larly, our ca se showed epit he li al tuf t- ing with ple o morp hic nuc le i, hyperc hro ma si a, nuc le ar ve si cu la ti on, pro mi nent nuc le o lus and eo - si nop hi lic cytop lasm . H igh se rum le vels of both CA 19-9 and CA 125 ha ve be en re por ted in so me be nign le si ons such as le i om yo ma, en do met ri o sis, te ra to ma of the fal lo pi - an tu be and tu ba-ova ri an abs ces ses.19-22 In en do - met ri o sis, se rum le vel of CA 125 and CA 19-9 is ex pec ted to be no mo re than 100 IU/ml and 1000 IU/ml, res pec ti vely. Ho we ver, very high se rum le - vels of CA 125 and CA 19-9 (CA 125: 9537 IU/ml, CA 19-9: 15.653 IU/ml) was re cor ded in a pa ti ent with rup tu red ova ri an en do met ri o ma.20 The mec h - a nisms that may ele va te se rum le vels of CA 125 and CA 19-9 in en do met ri o sis are not yet cle arly un - ders to od; ho we ver, the dif fu si on of cyst flu id thro - ugh the pe ri to neal sur fa ce in to the cir cu la ti on is con si de red in so me ca ses.20 We be li e ve that UOM was de ve lo ped du e to the me tap la si a of ova ri an en do met ri o ma in our pa - ti ent. First, no uro ge ni tal ab nor ma lities were found on ra di o lo gic eva lu a ti ons. Se cond, high se rum le v - els of CA 19-9 and CA 125 we re as so ci a ted with the pre sen ce of ova ri an en do met ri o sis. Third, the pre s- en ce of his to lo gic aty pi a in co lum nar epit he li um of en do met ri al mu co sa sup ports the me tap las tic the - ory. AAcckk nnooww lleedd ggee mmeenntt We wo uld li ke to thank Ha ti ce Al tun for her as sis tan ce in edi ting Eng lish language . Turkiye Klinikleri J Med Sci 2010;30(5)1736 Kelten ve ark. Tıbbi Patoloji 1. Cozzutto C. Uterus-like mass replacing ovary: report of a new entity. Arch Pathol Lab Med 1981;105(10):508-11. 2. Pueblitz-Peredo S, Luévano-Flores E, Rincón- Taracena R, Ochoa-Carrillo FJ. Uteruslike mass of the ovary: endomyometriosis or con - genital malformation? A case with a discus - sion of histogenesis. Arch Pathol Lab Med 1985;109(4):361-4. 3. Noel JC, Hustin J, Simon P, Verhest A. Uterus-like mass of the ovary. J Obstet Gy - necol 1994;14(33):209-11. 4. Pai SA, Desai SB, Borges AM. Uteruslike masses of the ovary associated with breast cancer and raised serum CA 125. Am J Surg Pathol 1998;22(3):333-7. 5. Shutter J. Uterus-like ovarian mass present - ing near menarche. Int J Gynecol Pathol 2005;24(4):382-4. 6. Gurel D, Tuna B, Yorukoglu K. Uterus-like mass of the ovary. Turkish J Pathol 2007;23(2):103-6. 7. Mitra S, Nicol A, Scott GI. Uterus-like mass of the ovary. J Obstet Gynaecol 1997;17(1):94-5. 8. Ahmed AA, Swan RW, Owen A, Kraus FT, Patrick F. Uterus-like mass arising in the broad ligament: a metaplasia or mullerian duct anomaly? Int J Gynecol Pathol 1997;16(3): 279-81. 9. Peterson CJ, Strickler JG, Gonzalez R, Dehner LP. Uterus-like mass of the small in - testine. Heterotopia or monodermal teratoma? Am J Surg Pathol 1990;14(4):390-4. 10. Fukunaga M. Uterus-like mass in the uterine cervix: superficial cervical endometriosis with florid smooth muscle metaplasia? Virchows Arch 2001;438(3):302-5. 11. Redman R, Wilkinson EJ, Massoll NA. Uter - ine-like mass with features of an extrauterine adenomyoma presenting 22 years after total abdominal hysterectomy-bilateral salpingo- oophorectomy: a case report and review of the literature. Arch Pathol Lab Med 2005;129(8): 1041-3. 12. Rosai J. Uteruslike mass replacing ovary. Arch Pathol Lab Med 1982;106(7):364-5. 13. Rahilly MA, al-Nafussi A. Uterus-like mass of the ovary associated with endometrioid carci - noma. Histopathology 1991;18(6):549-51. 14. Scully RE. Smooth-muscle differentiation in genital tract disorders. Arch Pathol Lab Med 1981;105(10):505-7. 15. Busacca M, Vignali M. Ovarian endometrio - sis: from pathogenesis to surgical treatment. Curr Opin Obstet Gynecol 2003;15(4):321-6. 16. Clement PB. Diseases of the peritoneum. In: Kurman RJ ed. Blaustein’s Pathology of the Female Genital Tract. 5 th ed. New York: Springer-Verlag; 2002. p.729-89. 17. Elagoz S, Aker H, Egilmez R, Cetin A. [Histopathological diagnostic criteria of en - dometriosis and associated lesions: review of 63 cases]. Turkiye Klinikleri J Gynecol Obst 2000;10(4):253-9. 18. Zannoni GF, Vellone VG, Fadda G, Guerriero M, Carbone A. Ovarian endomyometrioma with atypias: description of a case. Fertil Steril 2007;88(5):1438.e15-7. 19. Tsao KC, Hong JH, Wu TL, Chang PY, Sun CF, Wu JT. Elevation of CA 19-9 and chro - mogranin A, in addition to CA 125, are de - tectable in benign tumors in leiomyomas and endometriosis. J Clin Lab Anal 2007;21(3): 193-6. 20. Kurata H, Sasaki M, Kase H, Yamamoto Y, Aoki Y, Tanaka K. Elevated serum CA125 and CA19-9 due to the spontaneous rupture of ovarian endometrioma. Eur J Obstet Gynecol Reprod Biol 2002;105(1):75-6. 21. Ingec M, Kadanali S, Erdogan F. Huge ter - atoma of the fallopian tube: a case report. J Reprod Med 2007;52(3):247-9. 22. Neunteufel W, Breitenecker G. Tissue ex - pression of CA 125 in benign and malignant lesions of ovary and fallopian tube: a compar - ison with CA 19-9 and CEA. Gynecol Oncol 1989;32(3):297-302. REFE RENCES