Clinicopathological analysis of mullerian adenosarcoma of the uterus

756_Chin Med J 2010:123(6);756-759Clinical experienceClinicopathological analysis of mullerian adenosarcoma of theuterusHAN Xiao-yan, XIANG Yang, GUO Li-na, SHEN Keng, WAN Xi-run, HUANG Hui-fang and PAN Ling-yaKeywords: mullerian adenosarcoma; uterine tumor; clinicopathology[ Tterine mllerian adenosarcoma is a very rare tumorcriteria for endometrial cancer and cervical cancer. Of the, clinically. Shi et al' has reported 9 uterinesix uterine endometrial adenosarcoma, there were oneadenosarcomas among 116 uterine sarcomas during 11stage Ia, two stage Ib, one stage Ic and two stage HI.years in West China Second Hospital. It consists ofThree cervical adenosarcoma patients were all stage Ibenign or atypical neoplastic glands within a sarcomatous(Table).stroma and represents only 8% of uterine sarcomas. Itshistological features are intermediate between the benignPrimary diagnosis and pathological findingsadenofibroma and the highly malignant carcinosarcomaSix patients were diagnosed correctly before surgeryand biologic behaviors show low malignant potential.' Inthrough histologic examinations of resected lesions orthis report, we analyzed nine cases of uterine mullerianreviewing of pathological slides from other hospitals; twoadenosarcoma, and the clinical characteristics, diagnosis,patients were interpreted as endometrial stromal tumors;treatment and prognosis of this tumor were discussed.and the other one was considered to be endometrioma-like polypus.CLINICAL DATAThe pathologic features were summarized in Table. OnBetween January 2003 and February 2009, nine patientsgross examination, maximum tumor size ranged from 1.0diagnosed as uterine mullerian adenosarcoma in surgicalto 12.0 cm (mean, 6.1 cm). Tumors exhibited polypoid,pathology files were treated in Peking Union Medicalpapillary or bulbous growth pattern and they had theCollege Hospital. Of the nine cases, six were located inappearance of grayish pink, grayish white or dark tan inthe endometrium and the remaining three were originatedcolor. The cutting surface was commonly solid andfrom cervix. This original research was approved by thejelly-like cyst fluid was noted in two cases.local institutional review board.Microscopically, the tumors were composed of benign orClinical findingsatypical-appearing neoplastic glands within aThe patients ranged in age from 18 to 47 years (averagesarcomatous stroma which appeared as periglandular33.8 years, median 31 years). Six women were <40 yearscuffs or intraglandular polypoid projections of increasedof age. Two patients were postmenopausal. The meancellular structure (Figure 1). The mitotic rate was 5-15gravity and parity were 1.2 and 0.6 (range 0 4 and 0 -2). per 10 high-power fields. No muscular invasion wasrespectively. Six women were nulligravida.found in four patients and superficial muscular invasionin two patients; deep muscular invasion existed in twoThe chief complaints of 6 uterine endometrial mullerianpatients. Sarcomatous overgrowth in which a pureadenosarcomas were abnormal vaginal bleeding (5 cases);sarcomatous component occupied at least 25% of thepelvic pain (3 cases) and abnormal vaginal discharge (onetumor was present in three cases (Figure 2, Table).case). These tumors tended to appear as exophyticHeterologous elements which were striated muscle andpolypoid masses growing inside the uterine cavity andchondrometaplasia were identified in two patients.occasionally extended from the uterus via cervical orifice.Immunohistochemically, the stromal cells were negativePhysical examinations showed enlarged uterus (3 cases),with CD10 in four out of six cases. The other two casescervical neoplasm protruding from the extemnal cervicalwere focally positive with CD10.os or palpable pelvic mass (2 cases, each) and vaginalDOI: 0.760cmj.is.0366-6999.2010.06.022mass (one case).Department of Obstetrics and Gynecology (Han XY, Xiang )Shen K Wan XR Hunano HF and Pan LY), DepartmentThe presenting manifestations of cervical adenosarcomaPatholo中国煤化工ical College Hospital,included iregular menstruation, repeating vaginalPekingc Academy of MedicalSciencedischarge and evacuation of tssues from vagina. CervicalHCNMHGpolypoid neoplasms were the presenting sign in all theCorrespondence to: Dr. XIANG Yang, Department of Obstetricsand Gynecology, Peking Union Medical College Hospital, Pekingthree paticents with an enlarged uterus in one patient.Union Medical College and Chinese Academy of MedicalSciences, Beijing 100730, China (Fax: 86- 10-65124875. Email:The patients were staged according to FIGO stagingxiangyang65@ gmail.com)Chinese Medical Jourmal 2010;123(6):756-759757Table. Clinicopathological features of 9 cases of uterine mullerian adenosarcomaCase Age SizeMIscHeterologousStageOperationAdjuvantFollow-up RecurrenceNo. (years) (cm)treatment(years)_ (years)Chemotherapy147 7.slaTAHNED,3.33 None(DDP. four courses)RH+BSO+pelvic28 7.0 SuperficialnNED,5.08 Nonelymphadenectomy(PEI, four courses)3° 4:10.Unknown+ Striated musleπCRS (excision of tumors inDOD, 1.250.17vagina and pelvis)(PEL, two courses) HT1.LEChemoherapy6.SupericialAlive,3.08 2.332.LH(PEL, three courses) HTChermotberapy31 12.0 Dep +TAH+RSONED, 1.00None .(PEL, three courses)CRS (TAH+BSO+excision of40 6.DeepIbNED, 1.33 Nonebulk tumors in pelvic)(PL, one course), radiation, HT3.2LAVH+BSONoneNED.0.50ChondrmetaplasiaNED, 1.671.E'The patient underwent TAH and RSO due to "uterine leiomyoma" in local hospital. MI: myometrial invasion; SO: sarcomatous overgrowth; TAH: total abdominalhysterectomy, LH: laparoscopic hysterectomy; LAVH: laparoscopic asted vaginal hysterectomy; RH: radical hysterectomy, LE: local excision; CRS: cytoreductivesurgery; BSO: bilateral sapingoophorectomy; RSO: rgh-sided salpingo oprecomy, DDP: cisplatin; PEL: csplain, pharmorubicin and fofanide; P: cisplatin andifosfamide; HT: bormone therapy; NED: no evidence of disease; DOD: dead of disease.cytoreductive surgery in two patients. Conservation ofunilateral or bilateral ovaries was performed in five cases.After surgery, seven patients received chemotherapy; onewas treated with radiotherapy; and three patients weregiven hormone therapy (methyl acetoxyprogesterone).Follow-up data were available for all the patients with amean interval of 2.64 years (range, 0.50 to 6.50 years). .Seven patients were alive and well with no evidence ofrecurrence. One patient of clinical stage I containingsarcomatous overgrowth died from recurrence 1.25 yearsafer surgery (case 3). The other one developed arecurrent tumor 2.33 years after local excision of thetumor in uterine cavity and she remained healthy sincehysterectomy (case 4, Table).DISCUSSIONMullerian adenosarcoma is a rare tumor first described byClement and Scully in 1974. It exhibits a benignglandular element and a malignant stroma. This tumormost commonly occurs in the endometrium and lessfrequently in the extrauterine genital tract. Uterineendometrial adenosarcomas were typically found inpostmenopausal women with the median age in extensiveseries 58 years.’ Compared with them, cervicalFigure 1. Low-power view of cervical adenosarcoma showingcondensation of a byperellar stroma forming periglandularadenosarcomas tended to appear more often in youngercuffs around cervical glands (case 9, bhematoxylin and eosin,women with the average age at presentation 31 years."original magnification x35).Our study covered younger women with the median ageFigure 2* High-powerver view of areas of sarcomatous overgrowthof 31 years. Six women were <40 years of age. Twoshowing stromai cells displaying obvious cytologic atypia andnulligravida with cervical adenosarcoma were only 18increased mitotic figures.A cervical glandular tube lined bymucinous epithelium can be scen in the picture (arrow) (case 9,and 23 years. In comparison to other uterine malignanthematoxylin and ecosin, original magnification x150).tumors, uterine mullerian adenosarcomas presented withnonspecific symptoms and signs. The most commonTreatment and prognosisclinical nresentations were ahnormal vaginal bleeding andThree patients were managed by complete local excisionpelvic中国煤化工mors might protrudeof the tumors in cervix or uterine cavity for fertilitythrougand vagina/cervicalsparing but unfortunately one of them recurred more thanmasseYHCN MH Gexaminations. Sometwo years later and underwent hysterectomy eventually.patients had an enlarged uterus or palpable pelvic mass.Other patients' treatment consisted of hysterectomy inPatients with cervical adenosarcoma often presented withthree patients, radical hysterectomy in one patient andpolypoid neoplasms and might be confused with benignChin Med J 2010;123(6):756-759appearing cervical polyps.thus, alowing conservation of reproductive function.39.10Geisler et al' reported that a young woman with stage IB1Diagnosis of uterine mullerian adenosarcoma depends oncervical adenosarcoma was succsfully treated by apathological examination of removed tumors from uterineroboticallyassisted totallaparoscopicradicalcavity or cervix. Some researchers' have recommendedtrachelectomy with cerclage as well as pelvic andthat diagnosis of adenosarcoma be made when one orpara-aortic lymphadenectomy for fertility sparing. Inmore of the following are present: 1) stromal mitoticcontrast to cervical adenosarcoma, however, in uterinecount of two or more per ten high-power fields; 2)endometrial adenosarcoma, recurrence rates as high asmarked stromal cellularity; and 3) more than a mild50%- -85% have been reported after conservativedegree of stromal nuclear atypia. The stromal componentsurgery.. This may be related to the incomplete removalmay consist of homologous elements and less frequently,of tumors. In this study, a young patient with uterineheterologous elements can be found such as cartilage andendometrial adenosarcoma underwent local excision andstriated muscle.' The differential diagnosis includesthen was placed on three courses of PEI chemotherapybenign lesions such as adenofibroma, adenomyoma,and hormone therapy. More than two years later thepolyp in uterine cavity or cervix and malignant lesionstumor recurred and hysterectomy was carried out.such as low grade endometrial stromal sarcoma,Pathology indicated that the disease had infiltratedmalignant mixed mullerian tumors and embryonalsuperficial myometrium. Now the patient is disease-free.thabdomyosarcoma, etc. Carefully observing component,structure, heteromorphism and nuclear mitosis of theIn this research, conservation of unilateral or bilateraltumor may be helpful to reach a definite pathologicalovaries was performed in five women and no onediagnosis. As the lesions are not well-ditributed andrecurred in the regular follow-up. Of the four patientsoften overlap with benign areas, it is important to dowho underwent bilateral salpingo-oothectomy, only onebiopsy from diseased regions thoroughly. In this study sixpatient of stage M suffered from ovarian metastasis.out of nine patients were diagnosed clearly and correctlyOzmen et alk reported conservation of both ovaries alongbefore operations. Two patients were considered to bewithdefinitivestaging surgery and adjuvant“endometrial stromal sarcoma” and the remaining onechemotherapy was performed in a 14-year-old girl withpatient was suspected of“endometrioma-like polypus".uterine adenosarcoma. After 30 months, she had noevidence of disease. Michener et al' indicated that theThis study demonstrated that most uterine mullerianrisk of ovarian involvement at initial surgery was rareadenosarcomas were generally of low-grade malignancy.(2%). The author also suggested the reliability of ovarianSeven out of nine cases were stage I patients. Definitiveconservation in young patients with disease confined tostaging surgery for uterine endometrial adenosarcomathe uterus. Then biopsy of bilateral ovaries was necessarycomprises total abdominal hysterectomy, bilateralto exclude tumor infilration.salpingo oophorectomy, pelvic lymph node sampling,omentectomy and peritoneal washing. As for cervicalUterine mullerian adenosarcoma is generally regarded asadenosarcoma, the relative rarity has made the assessmentbeing low malignant potential. Distant metastases are rare,of the most effective management difficult. Most authorswhereas local recurrences are more common. Clementrecommend total abdominal hysterectomy, usuallyand Scully reported 100 patients with uterine mullerianaccompanied by bilateral salpingo-oophorectomy.adenosarcoma. Recurrent tumor developed in 23 casesOpinions upon the practical value of staging byind approximately one third of whom recurred five orlymphadenectomy during primary surgery divergemore years after hysterectomy. Recurrent tumor wasbetween gynecologists. Those with poor prognosticalmost always confined to the vagina, pelvis, or abdomen.factors such as deep myometrial invasion or sarcomatousDistant blood-borme metastases occured in only twoovergrowth may benefit from adjuvant chemotherapy andcases.Risk factors associated with recurrence anradiotherapy.-8 Six patients in this study were treatedmetastasis in literatures included deep myometrialwith hysterectomy while the other three underwent localinvasion, lymph-vascular space invasion, sarcomatousexcision of the tumors in cervix or uterine cavity. Afterovergrowth, spread outside the uterus and the presence ofsurgery, seven patients were placed on chemotherapy,heterologous elements in primary tumor, etc.t4 Thisradiotherapy or hormone therapy.study revealed that the presence of late clinical stage andsarcomatousovergrowth were unfavorable factorsIn this study, more conservative surgical management hasaffecting recurrence and prognosis. Recurrent tumorbeen employed in young patients who are willing todeveloped in two of the nine cases and one patient diedpreserve fertilities. Two patients withcervicalotient on stage 1I withadenosarcoma underwent local complete excision of thesarco中国煤化工d a very agesivetumors and pathology demonstrated no residual in theclinicC N M H Gnonths after surgery,cutting edge. Follow-up showed no evidence oShe picacilou wun 4 upiwy giuwung mass in vagina andrecurrence for 1.67 and 6.50 years separately. Localdied from recurrence eventually. The other patient ofexcision may be an alternative in young patients withearly stage disease underwent removal of the mass inpedunculated cervical adenosarcomas and involved stalks,uterine cavity which did not show sarcomatousChinese Medical Jourmal 2010;123(6);:756-759759overgrowth. The tumor recurred 2.33 years later and6. Kaku T, Silverberg SG Major FI, Miller A, Fetter B, Bradypresented with occupation in uterine cavity and cervicalMF. Adenosarcoma of the uterus: a Gynecologic Oncologycanal. Then hysterectomy was performed and pathologyGroup clinicopathologic study of 31 cases. Int J Gynecolshowing superficial myometrium was involved. To ourPathol 1992; 11: 75-88.knowledge the recurrence might be associated with7. Geisler JP, Oπr CI, Manahan KJ. Robotically asisted totalincomplete removal of the mass in uterine cavity duringlaparoscopic radical trachelectomy for fertility sparing in stagethe primary operation. After bysterectomy she remainedIB1 adenosarcoma of the cervix. J Laparoendosc Adv Surgin good health.TechA 2008; 18: 727-729.. Park HM, Park MH, Kim YJ, ChunH, Ahn JI, Kim CI.In conclusion, uterine mullerian adenosarcoma is a rareMullerian adenosarcoma with sarcomatous overgrowth of thetumor without specific clinical symptoms and signs. Thecervix presenting as cervical polyp: a case report and reviewdiagnosis depends on pathomorphologic observation. Theof the literature. Int J Gynecol Cancer 2004; 14: 1024-1029.tumors show low malignant potential and the vast. Ramos P, Ruis A, Carabias E, Pinero I, Garzon A, Alvarez Imajority are at early stage. Surgical excision is the mainMulrian adenosarcoma of the cervix with heterologoustreatment strategy with a good prognosis in early stageelements: report of a case and review of the literature.disease by complete removal of tumors. The prognosis isGynecol Oncol 2002; 84: 161-166.poor in advanced adenosarcoma with sarcomatous10. Gal D, Kemer H, Beck D, Peretz BA, Eyal A. Paldi E.overgrowth. Fertility-sparing surgery is feasible in thoseMullerian adenosarcoma of the uterine cervix. Gynecol Oncolyoung patients with superficial cervical adenosarcoma or1988; 31: 445-453.tumors confined to a local area of cervix. Due to the11. Baker TR, Piver MS, Lele SB, Tsukada Y. Stage I uterinerelatively high rate of recurrence, long-term follow-up isadenosarcoma: a report of six cases. 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