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Gonadotrophin-Releasing Hormone (GnRH) Analogues in the Treatment of Mixed Mullerian Tumours of the Uterus: Two Case Reports and Review

Gonadotrophin-Releasing Hormone (GnRH) Analogues in the Treatment of Mixed Mullerian Tumours of... Subjects/Discussion. Two c ases o f clinical a nd r adiol ogical r esponse of recur rent m i xed M u llerian t um o ur s fo llowing treatme nt w ith e ither n a sal ( Bu s erilin) o r i ntramu scular (Go s erilin) G n RH a nalog ue s a re reported a nd a s hort r eview of the e vide nc e to s up port t his t reatme nt o p tion p resent ed. Key words: mi xe d M u llerian uterine tumours, Gn RH a n alogues. ing o -oophorec tomy and o me n tec tomy . Th ere w as Int roduc tion no e v idenc e o f ex tra-ut er ine s prea d at l aparotom y Mi xed M u l ler ian tumo u r s, de r ived f rom the m e s- and h istology co n® rmed a poor ly di fferentiated c a r- en c hymal remn a nts of the u r ogen i tal r idg e a nd ci no sarcoma with n o m y ome t rial inv asion ( Stage ep ithel ium origi na ting f rom the c o el omi c c avity, are 1a). rare but u s ually rapidly fatal ut erine t um o u r s of De spite t he e a rly stage a t p res en tation , within a post-reprodu ct ive w ome n . Recur ren ce a fter surge ry yea r (Ma rch 19 9 4 ) s he dev elop ed p el vic p ain associ- is co mm o n e ven i n a pparently e arly di sease and ated w ith a palpable v agina l ma ss. A CT s ca n survival de s pite s ubsequen t r adiothe rapy or che mo - co n® rmed a soft tissue m a ss 4 3 5 c m above the the rapy ext rem e ly p oor. vagina l vault ca using p artial righ t u r et eric o b struc- The in vitro ® nd ing o f GnR H rec ep tors on s ome tum o ur lines led u s to t ry treatme nt w ith n a sal GnR H analogu e s in t wo p atient s with s ome sign i ® c ant , a lbeit t emp orary, succ es s. Case 1 A 70 y ear-old m o t her o f ei gh t c hi ldr en, present ed i n April 19 9 3 w ith a short h istory of post me n op ausal- bleed i ng . S he h ad passed thr ough the m e no p ause age d 3 8 a nd h ad nev er taken h ormon e r eplacem e nt the rapy. Her past me di cal h istory inc l ud ed r ec en t ly di agn o sed n o n- insulin d e pe nd e nt d i abetes me l litus with n o thi ng e lse o f relev ance . Th ere w as no e v idenc e o f ut erine e nl argem e nt o n ex a mination , but V a bra cur ettage s ugge s ted a het - er olog ou s ma lign ant m i xed M u l ler ian tumo u r (Ca r- Fig. 1. CT s can (pelvis) o f p at ient (Ca se 1) b e fore treatme nt ci no sarcoma ) and s he s ubsequen t ly u n d e rwe nt a with a G n RH a nalogue de mo nstrating a r ight -side d m a ss o f tot al a bdom i na l hysterec tomy with b ilateral s alp- recurrent tumour (arrowe d) c ausing ureteric obs truction. Co rrespon dence t o: M. Ka tesma rk, D e partme nt o f O b stetrics & G ynaecol ogy, K i ng’ s Co llege H ospital, De nmark H ill, Lo ndon S E5 9RS, UK. The authors w ould w elcome e nquires from r esearch ers able t o o ffer r eliable m eans o f d emo nstratin g G nRH receptor s o n p atholog ical specimens o btained i n t he above c ases. 1357-714X/ 9 8/030197± 04 $9.00 Ó 1998 Ca rfax P ublishing L t d 198 M. Kat esmark & F . Lawt on 19 9 6 . Fr om Fe br ua ry 199 6 t he re w as rapid loc al gr owth i n t he p el vis and s he d i ed f rom ob structive rena l failure in A pril 19 9 6 . Case 2 A 49 y ear-old m o ther of two w as ref erred f rom a me n op ause cl ini c w ith a short h istory of irregu l ar vagina l bleed ing o n c o mb ined h ormon e r eplace me n t ther apy, which she had taken f or ® ve y ears. She h ad a com p lex p ast me di ca l histor y featur ing s ever al op eratio ns for aden o carcin om a of the b owel ( co m- plicati ng p olyposis col i), c ul mi nating i n a panproc- toc olect om y with i leo stomy formation i n 1 98 6 . A Fig. 2. MR I s can (pelvis) o f p a tient (Ca s e 1) t hree mo nths after further o peration f or bowel o bstruc t ion h ad taken comme ncing treatment with a G n RH a n alogue de mo nstrating place i n 1 9 8 9 , w ith n o e vide n ce o f tum o u r recu r - central necrosis of t umour with no signi® cant enlargeme nt rence. (arrowed). Va bra cur et tings ob taine d o n 5 J uly 1 9 9 3 d e mo n- strated a pparent ly p oor ly differen t iated a deno - ca rcino ma of en d o me trial o r igin, b ut imm u n o cy toc he mi stry of the s ubsequent h yster- ec tomy specime n c on ® rmed a heter ologo u s ma lig- na nt m i xed m e sode rma l tum o u r . Tu m o ur volume was small and i n® ltration c on ® ne d t o t he s uper® c ial my omet rium on l y (St age 1 b ). After some i nitial c om p lica tions arising f rom her previous ext ens ive pelvic s urger y, she r em a ined w el l un t il D e c em b er 19 9 4 , when s he dev eloped p el vic pain and h aematur ia associated w ith a pel vic m a ss. MR I sca nni ng c o n® rmed a 5 3 5 c m vault ma ss ex ten di ng t o S 3, with n o p elvic l ymphaden o pathy. Sub sequent c y stoscop y ex c lud e d i nvasive t um o u r i n Fig. 3. MR I s can (pelvis) o f p a tient (Ca s e 1) t hree mo nths after the b ladde r. compl eting treatme nt with a G n RH a n alogue. Post-treatme nt She w as com m e n c ed o n G os erelin a ce tate 3 . 6 evide nce of e nlargeme nt is now present (arrowe d) b u t areas of central necrosis pe rsist and t here is compression rathe r t han mg / 2 8 d a ys in F e b ruary 19 9 4 . Th er e w as rapid invasion of l ocal structures. cl ini ca l regr ession, and b oth a CT s ca n and M R I per formed i n J un e 1 99 4 s howed n o e v idenc e o f tum o ur progr es sion. After co mp let ing s ix c y cles o f Goserilin s he tion a nd r ight -sided p elvic l ymphadeno pathy rema ined i n r em i ssion un til N o v emb er 19 9 4 , when ex t en d ing t o t he p ara caval regi on ( Fi g. 1) . inc r ea sing p elvic a nd l ow back pain was found t o b e In v iew of her pain and t he r apid retur n o f di sea se associated w ith r adiol og ical r ec ur ren ce . S he w as she was com m e n c ed o n G osereli n a ce tate 3 . 6 m g / 2 8 co mm e nc e d o n s alvage r adiother apy (Mi d p lain da ys (Zo l adex , ICI, UK) w ith r apid resolut ion o f do se o f 40 G y in 2 0 d a ily fractions); de s pite s ome symptoms . Pe lvic e x ami nation w as no rmal in J une ini tial s ucces s in s ymptom red uc t ion, she dev elop ed 19 9 4 a nd m a gne t ic r es ona nce i ma gi ng ( MR I) p er - recu rrent s mall bowel o b struction a ssociated w ith formed t he s ame m o nt h s howed n o s ign i ® c ant progressive l eft i liac l ymphadeno pathy. Th e fo rmer incr ea se in t um o u r s ize o r progressio n o f the p el vic was thou gh t m o r e l ikely t o b e d u e t o s urgi cal a dhe- lymphadeno pathy (Fi g. 2) . sions rather than tumo u r , and w ith c a reful d i etary She r em a ined i n b oth r adiol ogi ca l and c lini cal adjustment a nd p ain con t rol s he r ema ined r ea son- remi ssion and c o mp leted t he s ix- mont h c o ur se of ably well u n t il A pril 199 6 . treatme nt . F u rther MR I assessmen t i n D e ce mb er Inc reasing b ack pain was associated w ith t um o ur 19 9 4 s howe d e vide nc e o f ce nt ral ne c rosis in t he re-gr owth a nd w as treated w ith t hree c ycles o f tum o ur ma ss and n o l ymphaden op athy (Fi g. 3 ) . Cycl op hosphamide ( Fa rmitalia, UK) a nd C isplatin In M a rch 19 9 5 a further e pi sode o f vagina l bleed - (Fa rmitalia, UK) i n e arly 19 9 6 ; cl ini cally ther e w as ing h eralded t he r etur n o f progressiv e t um o ur . An a partial res ponse, but r adiol og ical c o n® rmation w as of fensive polypoid t umo u r arising f rom the v aginal di f® cul t b eca use of her prev ious surge r y. Inc on tro- vault w as exc i sed a nd c o mb ined r adiother apy and ver tible e v iden c e o f tum o u r progression w as, how- na sal Bu s er el in a ce tate 1 5 0 m g T D S (Su prec ur , ev er, shown o n P E T s canning i n M a rch 19 9 7 , and Hoes ch st, UK) s uppressed h er d i sease un til e arly she is cu rrent ly m a naged o n M S T 3 0 0 m g b d, Gn RH a n alogues i n treat ment of mixed M u llerian tumours 199 Table 1. Cl assi® cation of m i xed M u llerian tumours Epithelial Epithelial component component Me senc hyma l component Benign Malignant Tumour type Benign Ad eno® b roma Ad enosar com a H om o log ou s Un d escribe d Ad enosar com a H eterolo g ous Malignant Carcino® broma Carcino sarcom a H om o log ou s Carcinom e senchym o ma C arcino sarcom a H eterolo g ous Ami triptyl ine 1 0 m g n o ct e a nd O r omo r ph 40 m g a s In t he a bove c a ses the c l ini ca l situati on w as required. judg ed t o w arrant int ervent ion w ith a s few side- ef fects a s possible. Bo th w om e n w er e i n® r m and reluc t ant t o u nd e rgo r adiot her apy or agg r es sive ch emo t herapy; adverse ef fects of GnR H trea tme n t Discussion wer e t hou g ht t o b e u nl ikely and t reatme nt c o m- Mi xed M u l ler ian tum o u r s are tradi tion a lly di vided me n ce d o n t he ® rst Hippocratic p rincipl e. into t wo g roup s de pen d ing o n w het her t he m e s- Th ere w as con ® rmed c l ini ca l rem i ssion i n b oth en c hymal and e pi thelial e leme n ts a re ut er ine ca ses lasting o ver a yea r with n o s igni ® c a nt s ide- (`ho mo l ogo u s’ , e.g. smoo th m u s cle, e nd o me t rial ef fects. W e s ugge s t that f urther r es ea rch in e luc i da t- stroma ) or no n- uterine ( `he terol ogo us ’ e.g. s triated ing t he r ole o f GnR H analogue s in t he t reatme nt o f mu s cle, ca rtilage , bone ) i n o r igi n ( Ta ble 1 ) . C ar- thes e rare tumo u rs is ind i cated a t b oth a cel lul ar and ci no sarcoma s, con taini ng m a lign a nt c om p one n ts ther apeut ic l evel . from both c el l l ine s, are co mm o n er than the p ure ut erine s arcoma s but s till c o mp rise les s than 2% of 1,2 References ut erine t um o ur s. Th ey a re rare du r ing r epro- du c tive l ife, with a me di an inci de nc e a t a ge 6 5. 1 Salazar O M, Bon ® g lio T A, Patten S F . U t erine sarco- Risk factors ov erlap with e n do m e trial c anc e r ma s: n atur al h istory, treatme nt a nd p rog no sis. Cancer 1978; 42; 1152. (na mely h ypertens ion, diabete s and n u l liparity) but 2 2 Olah K S , G e e H, Blunt S , D unn J A, Ke lly K , Chan to a les ser de gr ee. Th e m o s t reliable r isk factor i s KK . Re trospec tive a nalysi s o f 318 cases o f uterine prev ious pelvic i rradiation , although the t rue i nc i- sarcoma. Eur J Cancer 1991; 27; 1095. de n ce ( betwe e n 5 a nd 3 5 % at t en y ears) is di s- 3 Lur ain J R, Piver MS . U t erine s arcoma s: c linical fe a- puted. tures a nd m a nageme nt. I n: C opples tone M, Ed. Gyne- cologic On cology , Vol I I, 2nd e dition. Edinbur gh: Stage d i n t he s ame m a nner as end o me t rial Chur chill L iving stone, 1992 ; 827. tum o ur s, trea tme n t o f early di sease is by tot al 4 Ro dr igue z J, Hart W . Endo me trial t umo ur s o ccurring abdom i na l hvsterec t omy and b ilateral salpingo - 10 or m o r e years a fter pelvic i rradiati on fo r carcinom a . oo phorect omy with p eritone al c ytolog i ca l sampling . Int J Gy naecol Pa thol 1982; 1; 125. Th e r ole o f lymphaden e ctom y rema ins un c lear. 5 Doss L L, Llorens A S, Henriquez EM. Carcino sar- coma o f the u t erus: a f orty-ye ar experienc e from t he Pr ogn os tic i nd i cators such a s the d e gr ee o f mi totic state o f Mi ssouri. Gy necol On col 1984; 18; 43± 48. act ivity, cel lul ar atypia and c e rvical i nv olveme n t a re 6 Ma rth C , Ko za A , Mu l ler-Ho lzner E , Hetzel H , Fui th less useful t han in e nd o me trial t umo u r s, although LC, Dapunt O . Prognos tically r elevant f actors i n vascular inv olveme nt a nd p ositive c ytolog y are of ma ligna nt m i xed M u l lerian t umo r s o f the u terus . sinister portent . Ge bu rtshilfe Frau enheilk 1990; 50; 605. 7 Schweizer W, Demopoul os R , Be ller U, Dubin N . Whether to t reat w ith a djuvant r adiot herapy or Prognos tic f actor s f or ma lignant m i xed m e sode rma l ch em o ther apy (and i nd e ed t he o p timu m timi ng a nd/ tumo u rs o f the u terus . Int J Gy naecol Pa thol 1990; or age nt u sed) i s still u n c er tain, with d i stant r ec ur - 9; 129± 33. renc e a per petua l problem . Adv ance d ( stage I II and 8 Chiara S , F o glia G , Odicini F . U t erine s arcoma s: a IV) o r rec ur ren t d isea se has an appalling p rogn o sis clinicop athol ogical s tudy. Oncology 1988; 45; 428± 34. 9 Chegini N , Ron g H , Dou Q , Ki persztok S , Williams rega rdless of trea tme n t. RS . G o na dotrop hin-rel easing h ormo n e a nd G n R H Speci ® c G nR H rec ep tors have bee n d e m o ns trated receptor gene e xpressi on i n h uma n m y om e trium a nd in n or mal my ometrium , lei yomyoma ta, epithelial leiomy om a ta. J Cl in Endocrinol Me tab 1996; 81; 3215± 10± 12 ov arian and e n d om e trial c anc e r c e lls, and a nu m b er of huma n ca ncer c e ll l ine s (MC F- 7, MD A - 10 Emo ns G , Schrode r B, Ortma nn O , Westphal en S , Schultz KD , Sc hally A V . High a f® nity b indi ng a nd MB - 231 , LN C aP) . In vitro inh ibition o f gr owth b y di rect a ntiprol iferative effects of lut einising hormo ne- GnR H analogu es has bee n c lea rly de mo ns trated i n releasing analog ue s i n h uma n e nd ome trial c ancer c ell ov arian tum o ur s and t her e h as been s ome e arly lines. J Cli n Endocrinol M e tab 1993; 77(6); 1458± 64. (and l imi ted ) s ucc es s in t rea ting a dvanced e nd o me - 11 Takagi H , Ima i A , Fu rui T , Horibe S , Fu seya T , 15,16 trial and o v arian canc e r w ith G os erel in. Tama ya T . Evidenc e for tight c oup ling o f go- 200 M. Kat esmark & F . Lawt on na dotrop hin-rel easing h ormo ne r eceptor s t o huma n c ancer c ell l ines. Ca ncer Detect Pr ev 1996; phoshat idylino sitol k inase i n p lasma m e mb rane from 20(2); 146± 52. gynaeco logical c arcinom a s. Gy necol On col 1995; 14 Connor JP, Bu ller R E, Conn P M. Effects of Gn R H 58(1); 110± 5. analog ue s o n s ix o varian c ancer c ell l ine s i n c ulture. 12 Wade K , Quinn M A , Hamm o nd I , Williams K , Gy necol On col 1994; 54(1); 80± 6. Cauc hi M . Ut erine s arcoma : s teroid r eceptor s a nd 15 Va n d er V a nge N , Gr eggi S, B u rger CW, Ke nema ns respons e t o h ormo na l t herapy. Gy necol On col 1990; P, Ve rmo rken J B. E xperience w ith h or mo ne therapy 39; 364. in a dvance d e pithelia l o varian c anc er. Acta Oncol 13 Palvi I , Vinc ze B, Ka lna y A , Turi G , Me zo I , Teplan 1995; 34(6); 813± 20. I, Seprodi J . Effect of gona dotrop hin-rel easing h or- 16 de Vr iese G , Bo ne J. Possibl e r ole o f goserilin , an mo ne a nalog ue s a nd t heir c onjuga tes o n LH-RH agon ist i n t he t reatme nt o f gyna ecol ogical gona dotrop hin-rel easing h ormo ne r eceptor -pos itive cancers. Eur J Gy naecol On col 1993; 14(3); 187± 91. 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Gonadotrophin-Releasing Hormone (GnRH) Analogues in the Treatment of Mixed Mullerian Tumours of the Uterus: Two Case Reports and Review

Katesmark, Michael; Lawton, Frank
Sarcoma , Volume 2 – Jan 1, 1998
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Hindawi Publishing Corporation
Copyright
Copyright © 1998 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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1357-714X
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1369-1643
DOI
10.1080/13577149877975
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Abstract

Subjects/Discussion. Two c ases o f clinical a nd r adiol ogical r esponse of recur rent m i xed M u llerian t um o ur s fo llowing treatme nt w ith e ither n a sal ( Bu s erilin) o r i ntramu scular (Go s erilin) G n RH a nalog ue s a re reported a nd a s hort r eview of the e vide nc e to s up port t his t reatme nt o p tion p resent ed. Key words: mi xe d M u llerian uterine tumours, Gn RH a n alogues. ing o -oophorec tomy and o me n tec tomy . Th ere w as Int roduc tion no e v idenc e o f ex tra-ut er ine s prea d at l aparotom y Mi xed M u l ler ian tumo u r s, de r ived f rom the m e s- and h istology co n® rmed a poor ly di fferentiated c a r- en c hymal remn a nts of the u r ogen i tal r idg e a nd ci no sarcoma with n o m y ome t rial inv asion ( Stage ep ithel ium origi na ting f rom the c o el omi c c avity, are 1a). rare but u s ually rapidly fatal ut erine t um o u r s of De spite t he e a rly stage a t p res en tation , within a post-reprodu ct ive w ome n . Recur ren ce a fter surge ry yea r (Ma rch 19 9 4 ) s he dev elop ed p el vic p ain associ- is co mm o n e ven i n a pparently e arly di sease and ated w ith a palpable v agina l ma ss. A CT s ca n survival de s pite s ubsequen t r adiothe rapy or che mo - co n® rmed a soft tissue m a ss 4 3 5 c m above the the rapy ext rem e ly p oor. vagina l vault ca using p artial righ t u r et eric o b struc- The in vitro ® nd ing o f GnR H rec ep tors on s ome tum o ur lines led u s to t ry treatme nt w ith n a sal GnR H analogu e s in t wo p atient s with s ome sign i ® c ant , a lbeit t emp orary, succ es s. Case 1 A 70 y ear-old m o t her o f ei gh t c hi ldr en, present ed i n April 19 9 3 w ith a short h istory of post me n op ausal- bleed i ng . S he h ad passed thr ough the m e no p ause age d 3 8 a nd h ad nev er taken h ormon e r eplacem e nt the rapy. Her past me di cal h istory inc l ud ed r ec en t ly di agn o sed n o n- insulin d e pe nd e nt d i abetes me l litus with n o thi ng e lse o f relev ance . Th ere w as no e v idenc e o f ut erine e nl argem e nt o n ex a mination , but V a bra cur ettage s ugge s ted a het - er olog ou s ma lign ant m i xed M u l ler ian tumo u r (Ca r- Fig. 1. CT s can (pelvis) o f p at ient (Ca se 1) b e fore treatme nt ci no sarcoma ) and s he s ubsequen t ly u n d e rwe nt a with a G n RH a nalogue de mo nstrating a r ight -side d m a ss o f tot al a bdom i na l hysterec tomy with b ilateral s alp- recurrent tumour (arrowe d) c ausing ureteric obs truction. Co rrespon dence t o: M. Ka tesma rk, D e partme nt o f O b stetrics & G ynaecol ogy, K i ng’ s Co llege H ospital, De nmark H ill, Lo ndon S E5 9RS, UK. The authors w ould w elcome e nquires from r esearch ers able t o o ffer r eliable m eans o f d emo nstratin g G nRH receptor s o n p atholog ical specimens o btained i n t he above c ases. 1357-714X/ 9 8/030197± 04 $9.00 Ó 1998 Ca rfax P ublishing L t d 198 M. Kat esmark & F . Lawt on 19 9 6 . Fr om Fe br ua ry 199 6 t he re w as rapid loc al gr owth i n t he p el vis and s he d i ed f rom ob structive rena l failure in A pril 19 9 6 . Case 2 A 49 y ear-old m o ther of two w as ref erred f rom a me n op ause cl ini c w ith a short h istory of irregu l ar vagina l bleed ing o n c o mb ined h ormon e r eplace me n t ther apy, which she had taken f or ® ve y ears. She h ad a com p lex p ast me di ca l histor y featur ing s ever al op eratio ns for aden o carcin om a of the b owel ( co m- plicati ng p olyposis col i), c ul mi nating i n a panproc- toc olect om y with i leo stomy formation i n 1 98 6 . A Fig. 2. MR I s can (pelvis) o f p a tient (Ca s e 1) t hree mo nths after further o peration f or bowel o bstruc t ion h ad taken comme ncing treatment with a G n RH a n alogue de mo nstrating place i n 1 9 8 9 , w ith n o e vide n ce o f tum o u r recu r - central necrosis of t umour with no signi® cant enlargeme nt rence. (arrowed). Va bra cur et tings ob taine d o n 5 J uly 1 9 9 3 d e mo n- strated a pparent ly p oor ly differen t iated a deno - ca rcino ma of en d o me trial o r igin, b ut imm u n o cy toc he mi stry of the s ubsequent h yster- ec tomy specime n c on ® rmed a heter ologo u s ma lig- na nt m i xed m e sode rma l tum o u r . Tu m o ur volume was small and i n® ltration c on ® ne d t o t he s uper® c ial my omet rium on l y (St age 1 b ). After some i nitial c om p lica tions arising f rom her previous ext ens ive pelvic s urger y, she r em a ined w el l un t il D e c em b er 19 9 4 , when s he dev eloped p el vic pain and h aematur ia associated w ith a pel vic m a ss. MR I sca nni ng c o n® rmed a 5 3 5 c m vault ma ss ex ten di ng t o S 3, with n o p elvic l ymphaden o pathy. Sub sequent c y stoscop y ex c lud e d i nvasive t um o u r i n Fig. 3. MR I s can (pelvis) o f p a tient (Ca s e 1) t hree mo nths after the b ladde r. compl eting treatme nt with a G n RH a n alogue. Post-treatme nt She w as com m e n c ed o n G os erelin a ce tate 3 . 6 evide nce of e nlargeme nt is now present (arrowe d) b u t areas of central necrosis pe rsist and t here is compression rathe r t han mg / 2 8 d a ys in F e b ruary 19 9 4 . Th er e w as rapid invasion of l ocal structures. cl ini ca l regr ession, and b oth a CT s ca n and M R I per formed i n J un e 1 99 4 s howed n o e v idenc e o f tum o ur progr es sion. After co mp let ing s ix c y cles o f Goserilin s he tion a nd r ight -sided p elvic l ymphadeno pathy rema ined i n r em i ssion un til N o v emb er 19 9 4 , when ex t en d ing t o t he p ara caval regi on ( Fi g. 1) . inc r ea sing p elvic a nd l ow back pain was found t o b e In v iew of her pain and t he r apid retur n o f di sea se associated w ith r adiol og ical r ec ur ren ce . S he w as she was com m e n c ed o n G osereli n a ce tate 3 . 6 m g / 2 8 co mm e nc e d o n s alvage r adiother apy (Mi d p lain da ys (Zo l adex , ICI, UK) w ith r apid resolut ion o f do se o f 40 G y in 2 0 d a ily fractions); de s pite s ome symptoms . Pe lvic e x ami nation w as no rmal in J une ini tial s ucces s in s ymptom red uc t ion, she dev elop ed 19 9 4 a nd m a gne t ic r es ona nce i ma gi ng ( MR I) p er - recu rrent s mall bowel o b struction a ssociated w ith formed t he s ame m o nt h s howed n o s ign i ® c ant progressive l eft i liac l ymphadeno pathy. Th e fo rmer incr ea se in t um o u r s ize o r progressio n o f the p el vic was thou gh t m o r e l ikely t o b e d u e t o s urgi cal a dhe- lymphadeno pathy (Fi g. 2) . sions rather than tumo u r , and w ith c a reful d i etary She r em a ined i n b oth r adiol ogi ca l and c lini cal adjustment a nd p ain con t rol s he r ema ined r ea son- remi ssion and c o mp leted t he s ix- mont h c o ur se of ably well u n t il A pril 199 6 . treatme nt . F u rther MR I assessmen t i n D e ce mb er Inc reasing b ack pain was associated w ith t um o ur 19 9 4 s howe d e vide nc e o f ce nt ral ne c rosis in t he re-gr owth a nd w as treated w ith t hree c ycles o f tum o ur ma ss and n o l ymphaden op athy (Fi g. 3 ) . Cycl op hosphamide ( Fa rmitalia, UK) a nd C isplatin In M a rch 19 9 5 a further e pi sode o f vagina l bleed - (Fa rmitalia, UK) i n e arly 19 9 6 ; cl ini cally ther e w as ing h eralded t he r etur n o f progressiv e t um o ur . An a partial res ponse, but r adiol og ical c o n® rmation w as of fensive polypoid t umo u r arising f rom the v aginal di f® cul t b eca use of her prev ious surge r y. Inc on tro- vault w as exc i sed a nd c o mb ined r adiother apy and ver tible e v iden c e o f tum o u r progression w as, how- na sal Bu s er el in a ce tate 1 5 0 m g T D S (Su prec ur , ev er, shown o n P E T s canning i n M a rch 19 9 7 , and Hoes ch st, UK) s uppressed h er d i sease un til e arly she is cu rrent ly m a naged o n M S T 3 0 0 m g b d, Gn RH a n alogues i n treat ment of mixed M u llerian tumours 199 Table 1. Cl assi® cation of m i xed M u llerian tumours Epithelial Epithelial component component Me senc hyma l component Benign Malignant Tumour type Benign Ad eno® b roma Ad enosar com a H om o log ou s Un d escribe d Ad enosar com a H eterolo g ous Malignant Carcino® broma Carcino sarcom a H om o log ou s Carcinom e senchym o ma C arcino sarcom a H eterolo g ous Ami triptyl ine 1 0 m g n o ct e a nd O r omo r ph 40 m g a s In t he a bove c a ses the c l ini ca l situati on w as required. judg ed t o w arrant int ervent ion w ith a s few side- ef fects a s possible. Bo th w om e n w er e i n® r m and reluc t ant t o u nd e rgo r adiot her apy or agg r es sive ch emo t herapy; adverse ef fects of GnR H trea tme n t Discussion wer e t hou g ht t o b e u nl ikely and t reatme nt c o m- Mi xed M u l ler ian tum o u r s are tradi tion a lly di vided me n ce d o n t he ® rst Hippocratic p rincipl e. into t wo g roup s de pen d ing o n w het her t he m e s- Th ere w as con ® rmed c l ini ca l rem i ssion i n b oth en c hymal and e pi thelial e leme n ts a re ut er ine ca ses lasting o ver a yea r with n o s igni ® c a nt s ide- (`ho mo l ogo u s’ , e.g. smoo th m u s cle, e nd o me t rial ef fects. W e s ugge s t that f urther r es ea rch in e luc i da t- stroma ) or no n- uterine ( `he terol ogo us ’ e.g. s triated ing t he r ole o f GnR H analogue s in t he t reatme nt o f mu s cle, ca rtilage , bone ) i n o r igi n ( Ta ble 1 ) . C ar- thes e rare tumo u rs is ind i cated a t b oth a cel lul ar and ci no sarcoma s, con taini ng m a lign a nt c om p one n ts ther apeut ic l evel . from both c el l l ine s, are co mm o n er than the p ure ut erine s arcoma s but s till c o mp rise les s than 2% of 1,2 References ut erine t um o ur s. Th ey a re rare du r ing r epro- du c tive l ife, with a me di an inci de nc e a t a ge 6 5. 1 Salazar O M, Bon ® g lio T A, Patten S F . U t erine sarco- Risk factors ov erlap with e n do m e trial c anc e r ma s: n atur al h istory, treatme nt a nd p rog no sis. Cancer 1978; 42; 1152. (na mely h ypertens ion, diabete s and n u l liparity) but 2 2 Olah K S , G e e H, Blunt S , D unn J A, Ke lly K , Chan to a les ser de gr ee. Th e m o s t reliable r isk factor i s KK . Re trospec tive a nalysi s o f 318 cases o f uterine prev ious pelvic i rradiation , although the t rue i nc i- sarcoma. Eur J Cancer 1991; 27; 1095. de n ce ( betwe e n 5 a nd 3 5 % at t en y ears) is di s- 3 Lur ain J R, Piver MS . U t erine s arcoma s: c linical fe a- puted. tures a nd m a nageme nt. I n: C opples tone M, Ed. Gyne- cologic On cology , Vol I I, 2nd e dition. Edinbur gh: Stage d i n t he s ame m a nner as end o me t rial Chur chill L iving stone, 1992 ; 827. tum o ur s, trea tme n t o f early di sease is by tot al 4 Ro dr igue z J, Hart W . Endo me trial t umo ur s o ccurring abdom i na l hvsterec t omy and b ilateral salpingo - 10 or m o r e years a fter pelvic i rradiati on fo r carcinom a . oo phorect omy with p eritone al c ytolog i ca l sampling . Int J Gy naecol Pa thol 1982; 1; 125. Th e r ole o f lymphaden e ctom y rema ins un c lear. 5 Doss L L, Llorens A S, Henriquez EM. Carcino sar- coma o f the u t erus: a f orty-ye ar experienc e from t he Pr ogn os tic i nd i cators such a s the d e gr ee o f mi totic state o f Mi ssouri. Gy necol On col 1984; 18; 43± 48. act ivity, cel lul ar atypia and c e rvical i nv olveme n t a re 6 Ma rth C , Ko za A , Mu l ler-Ho lzner E , Hetzel H , Fui th less useful t han in e nd o me trial t umo u r s, although LC, Dapunt O . Prognos tically r elevant f actors i n vascular inv olveme nt a nd p ositive c ytolog y are of ma ligna nt m i xed M u l lerian t umo r s o f the u terus . sinister portent . Ge bu rtshilfe Frau enheilk 1990; 50; 605. 7 Schweizer W, Demopoul os R , Be ller U, Dubin N . Whether to t reat w ith a djuvant r adiot herapy or Prognos tic f actor s f or ma lignant m i xed m e sode rma l ch em o ther apy (and i nd e ed t he o p timu m timi ng a nd/ tumo u rs o f the u terus . Int J Gy naecol Pa thol 1990; or age nt u sed) i s still u n c er tain, with d i stant r ec ur - 9; 129± 33. renc e a per petua l problem . Adv ance d ( stage I II and 8 Chiara S , F o glia G , Odicini F . U t erine s arcoma s: a IV) o r rec ur ren t d isea se has an appalling p rogn o sis clinicop athol ogical s tudy. Oncology 1988; 45; 428± 34. 9 Chegini N , Ron g H , Dou Q , Ki persztok S , Williams rega rdless of trea tme n t. RS . G o na dotrop hin-rel easing h ormo n e a nd G n R H Speci ® c G nR H rec ep tors have bee n d e m o ns trated receptor gene e xpressi on i n h uma n m y om e trium a nd in n or mal my ometrium , lei yomyoma ta, epithelial leiomy om a ta. J Cl in Endocrinol Me tab 1996; 81; 3215± 10± 12 ov arian and e n d om e trial c anc e r c e lls, and a nu m b er of huma n ca ncer c e ll l ine s (MC F- 7, MD A - 10 Emo ns G , Schrode r B, Ortma nn O , Westphal en S , Schultz KD , Sc hally A V . High a f® nity b indi ng a nd MB - 231 , LN C aP) . In vitro inh ibition o f gr owth b y di rect a ntiprol iferative effects of lut einising hormo ne- GnR H analogu es has bee n c lea rly de mo ns trated i n releasing analog ue s i n h uma n e nd ome trial c ancer c ell ov arian tum o ur s and t her e h as been s ome e arly lines. J Cli n Endocrinol M e tab 1993; 77(6); 1458± 64. (and l imi ted ) s ucc es s in t rea ting a dvanced e nd o me - 11 Takagi H , Ima i A , Fu rui T , Horibe S , Fu seya T , 15,16 trial and o v arian canc e r w ith G os erel in. Tama ya T . Evidenc e for tight c oup ling o f go- 200 M. Kat esmark & F . Lawt on na dotrop hin-rel easing h ormo ne r eceptor s t o huma n c ancer c ell l ines. Ca ncer Detect Pr ev 1996; phoshat idylino sitol k inase i n p lasma m e mb rane from 20(2); 146± 52. gynaeco logical c arcinom a s. Gy necol On col 1995; 14 Connor JP, Bu ller R E, Conn P M. Effects of Gn R H 58(1); 110± 5. analog ue s o n s ix o varian c ancer c ell l ine s i n c ulture. 12 Wade K , Quinn M A , Hamm o nd I , Williams K , Gy necol On col 1994; 54(1); 80± 6. Cauc hi M . Ut erine s arcoma : s teroid r eceptor s a nd 15 Va n d er V a nge N , Gr eggi S, B u rger CW, Ke nema ns respons e t o h ormo na l t herapy. Gy necol On col 1990; P, Ve rmo rken J B. E xperience w ith h or mo ne therapy 39; 364. in a dvance d e pithelia l o varian c anc er. Acta Oncol 13 Palvi I , Vinc ze B, Ka lna y A , Turi G , Me zo I , Teplan 1995; 34(6); 813± 20. I, Seprodi J . Effect of gona dotrop hin-rel easing h or- 16 de Vr iese G , Bo ne J. Possibl e r ole o f goserilin , an mo ne a nalog ue s a nd t heir c onjuga tes o n LH-RH agon ist i n t he t reatme nt o f gyna ecol ogical gona dotrop hin-rel easing h ormo ne r eceptor -pos itive cancers. Eur J Gy naecol On col 1993; 14(3); 187± 91. 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