Benign Pelvic Masses Associated with Raised CA 125 Level: Radiological Pathological Correlation

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1 Originl Article DOI: /ijss/2015/386 Benign Pelvic Msses Associted with Rised CA 125 Level: Rdiologicl Pthologicl Correltion Rhul Rnjn 1, Supriy Ktiyr 2, Alok Kumr 1, Jy Mishr 3 1 Assistnt Professor, Deprtment of Rdiodignosis, Rm Medicl College & Hospitl, Mndhn, Knpur, Uttr Prdesh, Indi, 2 Assistnt Professor, Deprtment of Pthology, Rm Medicl College & Hospitl, Mndhn, Knpur, Uttr Prdesh, Indi, 3 Assistnt Professor, Deprtment of Ostetrics & Gynecology, Rm Medicl College & Hospitl, Mndhn, Knpur, Uttr Prdesh, Indi Astrct Introduction: The detection of pelvic mss with ssocited rised CA 125 level is highly suspicious for ovrin cncer, ut there re vrious other enign pelvic pthologies tht mimic the ove fi ndings, especilly in premenopusl women in the Indin sucontinent s seen in our cse series. Purpose: Purpose of the study ws to look for different enign pelvic msses ssocited with rised level of CA 125. Mterils nd Methods: It ws prospective study in which cses of pelvic mss with rised CA 125 level tht turned out to e enign in etiology on complete work up were evluted nd followed up on tretment t 2 months of intervl with seril mesurement of CA 125. Result: Out of 15 cses of enign pelvic msses with rised CA 125 level, 10 cses were of genitl tuerculosis nd ssocited pelvic infl mmtory disese, 4 cses were of endometriotic cysts, nd 1 cse ws of ruptured dermoid cyst of ovry. All cses showed signifi cnt reduction in CA 125 level on follow-up t 2 months. Conclusion: There re vrious enign pelvic msses tht re ssocited with rised CA 125 level. Detiled clinicl history nd rdiologicl investigtions cn e helpful in rriving t correct dignosis. This is more importnt in Indi sucontinent where genitl tuerculosis nd pelvic infl mmtory disese re common. Key words: CA 125 ntigen (cncer ssocited 125 ntigen), Endometriosis, Ovrin dermoid cyst, Femle genitl tuerculosis, Ovrin neoplsm, Pelvic infl mmtory disese INTRODUCTION The detection of pelvic mss with rised CA 125 level is highly suspicious for ovrin cncer, ut there re vrious other enign pelvic pthologies tht mimic the ove findings. This is especilly importnt in women of reproductive ge group in the Indin sucontinent where pelvic inflmmtory disese nd femle genitl tuerculosis re common. Ovrin cncer is one of common femle gynecologicl cncer nd mjority of cses re dignosed in lte stges Access this rticle online Month of Sumission : Month of Peer Review : Month of Acceptnce : Month of Pulishing : contriuting to poor prognosis nd outcome. 1 For erly detection of ovrin cncer, vrious tumor mrkers hve een studied, nd CA 125 is one of them. It is elevted in 80% of mlignnt ovrin neoplsm of non-mucinous origin. 2 Bst 3 hve proposed CA 125 s reltively specific mrker for ovrin cncer. The CA 125 molecule is 200-kD glycoprotein nd ws initilly identified on the surfce of the ovrin crcinom cell line OVCA The vlue of CA125 vries etween lortories depending on the type of ssy used ut levels <35 kiu/l is considered to e norml. 5 However, serum CA 125 level cn often e elevted in vrious enign nd inflmmtory gynecologicl conditions s well s non-gynecologicl condition such s liver nd pulmonry disese. Differentiting enign from erly mlignnt ovrin disese is importnt nd provides dignostic chllenge. The comintion of pelvic mss nd elevted level of CA 125 rouses the suspicion of ovrin mlignncy, ut other conditions should lwys Corresponding Author: Dr. Rhul Rnjn, Deprtment of Rdiodignosis, Rm Medicl College & Hospitl, Mndhn, Knpur, Uttr Prdesh, Indi. Phone: E-mil: rhulrnjnrdio10@gmil.com Interntionl Journl of Scientific Study Septemer 2015 Vol 3 Issue 6 28

2 e considered in the differentil dignosis especilly in premenopusl women. Mlksion 6 in study, found out tht out of 59 ptients with histologiclly proven enign ovrin cysts, 17 hd elevted concentrtion of CA 125 in serum. Similr findings were seen in the study y Dixi 7 in which mny cses of enign pelvic msses hd significntly elevted serum level of CA 125. These studies demonstrte tht using CA 125 in isoltion hs limited vlue in differentiting enign from mlignnt pelvic msses. Clinicl detils nd rdiologicl informtion provide crucil dditionl informtion on which to se dignosis. Pelvic ultrsound in conjunction with CA 125 represent the most frequent used initil investigtion for ptient with dnexl msses s ultrsound is widely ville nd cheper. Computed tomogrphy (CT) scn hs limited vlue in the initil ssessment of dnexl msses due to poor soft tissue discrimintion nd disdvntge of rdition exposure. Mgnetic resonnce imging (MRI) is helpful in detection of the orgn of origin of pelvic msses nd confirming the dignosis of endometriosis. As it is evident from ove studies tht ll the modlities re complimentry to ech other with ultrsound remining the first dignostic modlity of choice s it is chep nd widely ville in ll units. As the CA 125 molecule is identified in norml peritonel nd fllopin tues, it is not surprising tht inflmmtion of these tissues cn result in n incresed concentrtion of CA 125 level in serum. Similr findings were seen in our cse series where mny ptients with confirmed dignosis of enign pelvic mss lesions such s pelvic inflmmtory disese, femle genitl tuerculosis, endometriosis, nd ruptured dermoid cyst of ovry were ssocited with rised serum level of CA 125 tht showed significnt decrese t 2 months intervl on tretment. MATERIALS AND METHODS The cse series include those cses (15 cses) tht presented etween Jnury 2013 to Jnury 2015 t our institution s pelvic mss detected on ultrsound with elevted serum level of CA125, however on complete workup y rdiologicl investigtions (CT scn/mri Scn), preopertive CT/ultrsonogrphy (USG) guided fine-needle spirtion cytology (FNAC), dignostic lproscopy/ therpeutic lprotomy with histopthology exmintion of opertive specimen or iopsy mteril; turned out to e enign pelvic msses. The CA 125 level more thn 35 units/ml ws considered s elevted. These cses on tretment were followed t 2 months intervl with mesurement of CA 125 level. RESULTS Out of 15 cses, 6 cses were of tuerculr slpingitis. These presented with ilterl complex cystic dnexl msses on trnsdominl ultrsound with ovry visulized seprtely on trnsvginl sonogrphy (Figure 1). CT scn of pelvis reveled ilterl complex dnexl msses with omentl thickening nd nodulrity with miniml free fluid in pelvis rising suspicion of neoplstic etiology (Figure 1). Men CA 125 level of these cses t the time of presenttion ws 650 units/ml. The ptients were sujected to dignostic lproscopy which reveled thickened, edemtous ilterl fllopin tues with omentl thickening, nd extensive dhesions. FNAC nd iopsy were tken from omentl thickening nd thickened fllopin tue which reveled cseting grnulom with cid-fst cilli (Figure 1c nd d). Fluid cytology of scitic fluid reveled lymphocytic predominnce with sence of mlignnt cells. The ptients were put on nti-tuerculr tretment (AKT) nd on 2 months follow-up ilterl dnexl msses hve significntly reduced in size, nd men CA 125 level decresed to 115 units/ml. Two ptients were of tuerculr pyoslpingx. These cses presented with low-grde fever since 2 months ssocited with lower dominl pin. Trnsdominl nd trnsvginl sonogrphy reveled dilted tortuous tuulr structures in oth dnex with ovry visulized seprtely (Figure 2). Echoes were seen within it. Lproscopy ws done for the preservtion of Tul ptency, nd fertility nd dignosis of tuerculr pyoslpingx were mde. Men CA 125 level initilly ws 250 units/ml which reduced to 65 units/ml t 2 months follow-up on tretment with AKT. Two cses were of ilterl tuerculr tuoovrin scesses. In these cses, trnsdominl nd trnsvginl sonogrphy reveled ilterl complex tuoovrin msses with ovry not seprtely visulized. Similr findings were seen on CT scn, nd CT guided FNAC reveled lymphocytic cseting grnuloms with cid-fst cilli. Men CA 125 level t the time of presenttion ws 370 units/ml which reduced to 75 units/ml t 2 months follow-up on AKT. A single cse of ruptured dermoid cyst of the ovry ws encountered with elevted CA 125 level of 300 units/ml. This 27-yer-old ptient presented with left lower dominl pin with USG suggestive of ilterl ovrin dermoids with omentl ft strnding nd edem on the left side (Figure 3). CT pelvis reveled ft ttenution lesions in oth ovries with clcific nodule nd ft strnding nd inflmmtion in surrounding mesentery nd omentum on the left side due to ruptured dermoid (Figure 3). Lprotomy ws done in view of dhesions nd consequent smll owel 29 Interntionl Journl of Scientific Study Septemer 2015 Vol 3 Issue 6

3 c d Figure 1: () Trnsvginl ultrsonogrpy (USG) nd () contrst computed tomogrphy (CT) pelvis showing dnexl mss seprte from ovry on USG with CT scn showing heterogeneous enhncing dnexl mss with omentl thickening nd nodulrity, (c) cytology smers showed grnulom comprising of epithelioid histiocytes, (d) Ziehl-Neelsen stining showed cid-fst cilli ostruction which confirmed the dignosis with iopsy of omentum reveling kertin grnuloms nd histopthology of specimen s/o dermoid cyst (Figure 3c). Figure 2: Trnsvginl sonogrphy showing dilted tuulr tortuous structure in dnex with echoes within suggestive of pyoslpingx c Figure 3: () Ultrsonogrphy nd () computed tomogrphy scn showing ruptured dermoid cyst with omentl inflmmtion, (c) microphotogrph of dermoid shows cyst lined y strtified squmous epithelium with underlying dnexl structures Four cses of elevted CA 125 level were seen in cses of endometriotic cysts. The first cse ws of 46 yers unmrried femle presenting with pelvic mss with CA 125 level of 125 units/ml. The trnsdominl sonogrphy reveled ilterl dnexl lrge cystic msses of size more thn 10.0 cm with thick sept nd without solid component with mild ilterl hydroureteronephrosis. CT pelvis reveled ilterl dnexl complex cystic msses with ovries not seprtely visulized. Bsed on these findings differentil of endometriotic cyst versus cystdenocrcinom ws mde. The ptient underwent lprotomy with histopthology of surgicl specimen confirming the dignosis of the endometriotic cyst. On 2 months follow-up CA 125 level reduced to 25 units/ml. The second cse is of 55 yers post-menopusl women detected to hve ilterl complex ovrin lesions with suspicion of the nonenhncing solid component on left side dhering to left lower ureter with consequent mild left sided hydroureteronephrosis on USG nd CT scn. CA 125 level ws 105 units/ml nd differentil of mlignnt ovrin neoplsm versus endometriotic deposits were mde. The ptient underwent lprotomy nd dignosis of the endometriotic cyst with endometriotic deposits. In cul-de-sc nd surrounding left ovry were mde. CA 125 level t 2 months follow-up reduced to 20 units/ml. Lst two cses (ge 30 nd 32 yers) presented with ilterl complex ovrin lesions with dense echoes on USG (Figure 4) with MRI reveling lood product ppering Interntionl Journl of Scientific Study Septemer 2015 Vol 3 Issue 6 30

4 hyperintense on T1W imges (Figure 4) nd hypointense on T2W imges confirming the dignosis of chocolte cyst (endometriotic cyst). Men CA 125 level t the time of presenttion ws 85 units/ml which dropped to 20 units/ml t 2 months follow-up. Description of these cses hs een summrized in Tle 1. DISCUSSION Ovrin cncer is one of the common mlignncy in femles in the Indin popultion. Most of these cses present t lte stges nd hve poor prognosis. 1 The incidence of ovrin cncer is low in young women, nd epithelil ovrin cncers re not known to occur efore menrche, nd most of them (though rre) re germ cell tumor, juvenile grnulos cell tumor, nd serous orderline tumors. Age-specific incidence is 40/100,000 y the ge of 50 nd rises to 50 per 100,000 women y the ge of 65 yers. 2 Vrious tumor mrkers hve een studied for the erly detection of ovrin cncer nd out of them, CA 125 hs een proposed y Bst 3 s reltively specific mrker for ovrin cncer. The CA 125 molecule is 200-kD glycoprotein nd ws initilly identified on the surfce of the ovrin crcinom cell line OVCA CA 125 is widely Figure 4: () Trnsvginl sonogrphy nd () Mgnetic resonnce imging pelvis showing ilterl endometriotic cysts Tle 1: Men level of c 125 t initil presenttion nd two months follow-up in different cses of enign pelvic msses Type of cses Numer of ptients Initil CA125 level (verge/ men) CA125 t 02 months intervl (on tretment) Tuerculr slpingitis with pelvic infl mmtory disese Tuerculr pyoslpingx Complex tuoovrin msses (tuoovrin scess) of Tuerculr etiology Ruptured ovrin dermoid Endometriotic cysts distriuted on the surfce of oth helthy nd mlignnt cells of mesothelil origin, including pleurl, pericrdil, peritonel, nd endometril cells, s well s in norml genitl trct nd mniotic memrne. Interestingly, the molecule is not present on the surfce of norml ovrin cells, ut is present in 80% of mlignnt ovrin tissue of non-mucinous origin. 2 The vlue of CA 125 vries etween different lortories depending on type of ssy used, ut levels <35 kiu/l re considered to e norml. 5 In view of wide distriution of CA 125 expression, serum CA 125 levels cn e rised in vrious enign nd inflmmtory conditions such s menstrution, pregnncy, endometriosis, pelvic inflmmtory disese, nd nongynecologicl conditions including vrious liver nd pulmonry diseses. This is more common in the Indin popultion where cses of femle genitl tuerculosis nd pelvic inflmmtory disese re extensively found s seen in our cse series. It is importnt to differentite enign ovrin pthologies from erly stges of crcinom ovry s it hs n importnt impct over ptient prognosis. The comintion of pelvic mss nd elevted level CA 125 rouses the suspicion of ovrin neoplsm, ut other enign conditions should lwys e considered in the differentil dignosis, especilly in pre-menopusl femle in the Indin scenrio. Mlksion 6 studied 59 ptients with histologiclly proven enign ovrin cysts. Out of these ptients 17 hd elevted concentrtions of CA 125 (12>35 units/ml, 4>65 units/ml, nd 1>2000 units/ml). In nother study y Dixi 7 using 153 ptients with enign pelvic msses, 10 ptients hd CA 125 concentrtions >188 units/ml nd one ptient hd vlue of more thn 400 units/ml. Nolen et l. screened 65 iomrkers in ptients with dnexl msses, nd more thn hlf of the iomrkers differed significntly etween enign nd mlignnt msses. CA 125 nd HE4 in comintion provided the highest discrimintion etween enign nd mlignnt cses. 8 These studies demonstrte tht using CA 125 in isoltion hs limited vlue in differentiting enign from mlignnt pelvic msses s seen in our cse series. The clinicl detils nd rdiologicl investigtion provides crucil dditionl informtion for mking the dignosis. Pelvic ultrsound in conjunction with CA 125 represents the most frequent performed initil investigtions for ptients with dnexl msses. CT scn hs limited vlue in the initil ssessment of dnexl msses due to poor soft tissue discrimintion nd with disdvntges for irrdition, 9 ut cn help to ssess the extent of disese in the upper domen prior to primry cytoreduction nd following chemotherpy to detect resistnt disese or recurrence. 10 The CT scn in our cse study ws lso not confirmtory in differentiting infective tuoovrin msses from ovrin 31 Interntionl Journl of Scientific Study Septemer 2015 Vol 3 Issue 6

5 mlignncy. MRI hs lso een suggested to e helpful in detection of the orgn of origin for pelvic msses. MRI hs een shown to correctly identify orgn of origin in 94% compred to only 66% of ultrsound. 11 Review of literture from 1990 to 2006 which included 143 studies showed tht ultrsound findings were similr to CT nd MRI in the differentition of enign from mlignnt ovrin msses. 12 However, MRI is extremely useful in confirming the dignosis of endometriotic (chocolte) cysts in most of the cses. Currently, newer imging in the form of positron emission tomogrphy (PET) nd CT cn e used to judge the extent of the disese nd lso differentite etween mlignnt nd enign msses. 13 As it is evident from ove studies, ll the modlities re complimentry to ech other with ultrsound remining the first dignostic modlity s it is chep nd widely ville in ll units. As the CA 125 molecule is identified in norml peritonel nd fllopin tues, it is not surprising tht inflmmtion of these tissues cn result in n incresed concentrtion of serum CA 125. Ruil et l. 14 found tht nine of twelve women with suspected peritonitis hd CA 125 concentrtions of >65 units/ml with two ptients hving vlue >500 units/ml. A more definitive study exmined CA 125 vlues in 30 ptients with pelvic inflmmtory disese ssocited with fever who hd good response to ntiiotic therpy. CA 125 >100 units/ml ws seen in 5 ptients (17%) nd the highest vlue ws 550 units/ml. 15 This incresed serum concentrtion of CA 125 cn e explined y the locl expression y the inflmed tissue. Another study of 33 ptients with the pelvic inflmmtory disese showed tht 32 ptients hd incresed concentrtions of CA 125 with vlues etween 100 nd 1300 units/ml. 16 These findings re similr to findings in our cse series where the highest level of CA 125 ws seen in cses of tuerculr slpingitis nd pelvic inflmmtory disese tht were ssocited with loclized peritonitis nd inflmmtion of surrounding peritoneum nd omentum. However in our cses, the highest level of CA 125 ws never >700 units/ml. Similrly, high level of CA 125 ws seen in those cses of endometriosis tht were ssocited with peritonel implnts. The high level of CA 125 seen in the cse of ruptured dermoid cyst of ovry could e ttriuted to inflmmtion of omentum induced y kertin grnuloms. Most of our cses were followed t 2 months intervl on tretment, where there ws significnt reduction in levels of CA 125 in ll cses. CONCLUSION Detection of pelvic mss with rised CA 125 level rises suspicion for ovrin mlignncy, ut there re vrious enign pelvic conditions tht re ssocited with rised CA 125 level. This is more importnt in the Indin sucontinent where genitl tuerculosis nd pelvic inflmmtory disese is common s seen in our cse series where 66% of cses of enign pelvic msses with rised CA 125 level turned out to e tuerculr etiology. Detiled clinicl history nd rdiologicl investigtions cn e helpful in rriving t correct dignosis nd differentiting enign pelvic msses from erly ovrin mlignncy. REFERENCES 1. DeVit VT, Rosenerg SA. In: Perez CA, Young RC, editors. Principles nd Prctice of Oncology ed. Phildelphi: JB Lippioncott; Westhoff C. Ovrin cncer. Annu Rev Pulic Helth 1996;17: Bst RC Jr, A rdioimmunossy using monoclonl ntiody to monitor the course of epithelil ovrin cncer. N Engl J Med 1983;309: Bst RC Jr, Feeney M, Lzrus H, Ndler LM, Colvin RB, Knpp RC. Rectivity of monoclonl ntiody with humn ovrin crcinom. 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Int J Sci Stud 2015;3(6): Source of Support: Nil, Conflict of Interest: None declred. Interntionl Journl of Scientific Study Septemer 2015 Vol 3 Issue 6 32