FURUKAWA Yuri

NAGANO Hiroaki

TAKAGI Koichiro

UENO Mariko

Tokyo Women’s Medical University

Advanced Endometrial Cancer Arising inAdenomyosis: A Case Report著者名 NAGANO Hiroaki, FURUKAWA Yuri, UENO Mariko,TAKAGI Koichirojournal orpublication titleTokyo Women's Medical University Journalvolume 2page range 40-44year 2018-12-25URL http://hdl.handle.net/10470/00032123doi: 10.24488/twmuj.2018004(https://doi.org/10.24488/twmuj.2018004)40―40―J.TWMU 2: 40-44, 2018Case ReportAdvanced Endometrial Cancer Arising in Adenomyosis: A Case ReportHiroaki NAGANO, Yuri FURUKAWA, Mariko UENO, and Koichiro TAKAGIDepartment of Obstetrics and Gynecology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan(Accepted August 7, 2018)(Advance Publication by J-STAGE October 25, 2018)Endometrial cancer arising in adenomyosis (EC-AIA) is a rare form of uterine cancer. A 53-year-old Japanese postmeno-pausal female was referred to our outpatient clinic for adenomyosis. After the 4-year follow-up, she presented with an in-creased vaginal discharge. Endometrial curettage demonstrated either atypical endometrial hyperplasia or well-differentiatedendometrioid carcinoma. Positron emission tomography/computed tomography revealed multiple pulmonary metastases, pel-vic bone metastases, para-aortic node metastases, and uterine tumor as the primary lesion. She was clinically diagnosed withstage IVB endometrial cancer. Accordingly, total abdominal hysterectomy and bilateral salpingo-oophorectomy were per-formed. Macroscopic findings of the resected uterus were difficult to distinguish from ordinal adenomyosis. Microscopically,diffuse endometrioid carcinoma (grade 2) occupied the entire uterine body, coexisting with adenomyosis. Postoperatively,chemotherapy and zoledronic acid administration were initiated, which are ongoing till date. The case highlights that EC-AIA, a rare but aggressive disease, should be considered when managing patients with adenomyosis.Key Words: endometrial carcinoma, adenomyosis, malignant transformationIntroductionAdenomyosis is one of the most common benign dis-eases of the uterus and is defined as ectopic endometrio-sis invading the uterine myometrium. While endometrialcancer coexisting with adenomyosis (EC-A) is a frequentoccurrence, the malignant transformation of adeno-myosis, that is, endometrial cancer arising in adeno-myosis (EC-AIA), is considered to be a rare event. Here,we report a case of an advanced EC-AIA based on theclinical features of the patient, although it did not fulfillthe classical histological criteria.CaseA 53-year-old Japanese postmenopausal female was re-ferred to our outpatient clinic for adenomyosis. She hadbeen diagnosed with adenomyosis by occasional mag-netic resonance imaging (MRI) at an internal department.Without any interval change, the patient was followed-upat either 6-month or 1-year interval to monitor for anychanges in status. After the 4-year follow-up, she pre-sented with an increased vaginal discharge since 10 days.Endometrial cytology raised a suspicion of adenocarci-noma. Total curettage of the endometrium under anesthe-sia revealed either atypical endometrial hyperplasia orwell-differentiated endometrioid carcinoma. However,Corresponding Author: Hiroaki Nagano, Department of Obstetrics and Gynecology, Tokyo Women’s Medical University Medical Cen-ter East, 2-1-10, Nishiogu, Arakawa-ku, Tokyo 116-8567, JapanE-mail: nagano.hiroaki@twmu.ac.jpdoi: 10.24488/twmuj.2018004CopyrightⒸ 2018 Society of Tokyo Women’s Medical University41―41―Fig.　1　(a) Magnetic resonance imaging (MRI; T2-weighted image) in the sagittal view when the patient was initially referred to the institute; diffusely thickened myometrium with low signal intensity indicates the presence of adenomyosis. (b) MRI under the same condition when the patient was diag-nosed with endometrial cancer. Although uterus size does not show considerable change, the signal intensity in (b) appears higher than that in (a).MRI indicated a suspicious image of the pelvic bone me-tastasis (bilateral pubic and sacral bone) despite no con-siderable change in the uterine size (Fig. 1). After confir-mation using positron emission tomography/computedtomography (PET/CT), which revealed multiple pulmo-nary metastases, pelvic bone (bilateral pubic and sacralbone) metastases, para-aortic node metastases, and uter-ine tumor as primary lesions, she was clinically diag-nosed with stage IVB endometrial cancer (Fig. 2). Ac-cordingly, total abdominal hysterectomy and bilateralsalpingo-oophorectomy were performed. The surgicalfindings revealed small amount of serous ascites, overnewborn-head-sized enlarged uterus with smooth surfacewithout adhesion, normal appearance of the ovaries andtubes, and no apparent peritoneal dissemination. Macro-scopically, the resected uterus exhibited a diffuse-thickness myometrium (4-5 cm in thickness), which wasdifficult to distinguish from ordinal adenomyosis, and aminimal endometrial lesion at the fundus of the uterus (5mm) (Fig. 3). Histologically, the resected specimens re-vealed that diffuse-type endometrioid carcinoma occu-pied the entire uterine body (depth of the invasion, 45mm/45 mm). The endometrium appears thin and incon-spicuous and is mostly replaced by intraepithelial carci-noma, except for the lesion observed at the funduswherein aberrant glands with eosinophilic papillary nestin the lumen were predominantly observed, along withsmall foci of the solid growth component with eosino-philic cytoplasm and milder nuclear atypia (Fig. 4 ) .Myometrial lesions were diffuse and primarily comprisedtwo patterns: in situ lesions that replaced the glands ofadenomyosis and invasive lesions with microcystic, elon-gated, and fragmented pattern (accompanied with psam-moma bodies). The depth of myometrial invasion wasmostly just beneath the serosa, although partly exposedmicroscopically. Further, small parts of benign adeno-myosis coexisted (Fig. 5). Furthermore, the cervical inva-sion and lymphatic spread in the adnexa were observed.The immnohistochemical staining for vimentin was fo-cally positive, whereas it was negative for p53 (wild-type), estrogen receptor, and progesterone receptor.The patient’s postoperative course was uneventful.Chemotherapy with paclitaxel plus carboplatin was initi-ated on postoperative day 13 at the 3-week interval forsix cycles; no major adverse events were observed duringthe chemotherapy. In addition, she was administeredzoledronic acid (4 mg/body) every 4 weeks. After six cy-cles of chemotherapy, PET/CT revealed a reduced size ofpulmonary metastases (partial response). Subsequently,three additional cycles of the same regimen were admin-istered. Chest CT for reevaluation revealed small residuallesions of pulmonary metastases. Finally, the chemother-apy regimen was changed to doxorubicin combined withcisplatin, and the treatment is ongoing till date.42―42―Fig.　2　Positron emission tomography/computed tomographydemonstrates multiple pulmonary metastases (a), para-aortic node metastases (b), and pelvic bone metastases (c). Arrows: each le-sion.Fig.　3　The macroscopic view of the resected uterus (a) and its sagittal section (b). The uterus shows the diffuse-thickness myometrium, which is difficult to distinguish from ordinal adenomyosis. The en-dometrium was thin, except for a minimal lesion observed at the fundus (arrow).Fig.　4　A high power view of the neoplastic glands show floating eosinophilic cancer nests (H&E; magnification, ×100).DiscussionThe malignant transformation of endometriosis is well-established carcinogenesis in ovarian cancer, especiallyfor clear cell and endometrioid types. Reportedly, themalignant transformation occurs in approximately 1 %of ovarian endometriosis cases１）. However, the malignanttransformation of adenomyosis into endometrial carci-noma is considered to be an extremely rare occurrence.Till date, only a limited number of case reports have beendocumented sporadically. In 1959, Colman proposed adiagnostic criteria for EC-AIA, which was a modificationof that for the malignant transformation of endometriosis,as follows: (1) cancer must not be located in the en-dometrium or any other place in the pelvis, (2) cancer43―43―Fig.　5　Microscopic findings reveal that (a) diffuse-type carcinoma occupied the complete uterine body, partly coexisting with adenomyosis (arrow) in a loupe image; (b) a nest of cancer adjacent to adenomyosis in the left portion (H&E; magnification, ×40); (c) in situ lesion surrounded by the endo-metrial stromal cells that are stained with CD-10 (immunohistochemical staining for CD-10; magnifi-cation, ×40); and (d) invasive lesion with microcystic, elongated, and fragmented pattern accompanied with a psammoma body (H&E; magnification, ×100).arises from the epithelium of adenomyosis and shouldnot invade from another source, and (3) endometrial stro-mal cells surround the aberrant glands to support the di-agnosis of adenomyosis２）. Since then, most case serieshave referred these criteria. Nevertheless, the first crite-rion “cancer must not be located in the endometrium orother place in the pelvis” seems to inconsistently corre-spond to the relatively aggressive nature of EC-AIA. Ithas been pointed out that the prevalence of EC-AIA haspossibly been underestimated because to fulfill all theaforementioned criteria, advanced cases of adenomyosishave to be excluded.Machida et al. examined 46 patients with EC-AIA in24 studies, which were extracted from the systematicEnglish literature searched through web-based search en-gines３）. They adapted the modified criteria supported bythe immunostaining results based on previous reports, al-though the details were not explained. EC-AIA-involved-endometrium was defined as a continuous transition fromthe adenomyotic epithelium in the myometrium to adeno-carcinoma, which extended to the endometrium. Theycompared 16 patients with EC-AIA with tumors extend-ing into the endometrium with the remaining 28 patientswith EC-AIA with tumors confined to the myometrium(excluded 2 patients with data missing). No differenceswere observed in demographics and tumor characteristics(e.g., age, symptoms, grade, histology, and stage) andsurvival outcome of the patients between the two groups.Seventy-six percent of EC-AIA cases demonstrated en-dometroid histology, most of which comprised grade 1 or2 tumor.In addition, they assessed the histopathological find-ings and prognosis of EC-AIA compared with the controlgroup of EC-A and reported that EC-AIA correlated withpoor prognosis and tended to have aggressive tumor fea-tures, including deep myometrial invasion, advanced44―44―stage, and nodal metastasis. Furthermore, most cases ofEC-AIA were negative for estrogen receptors contrary toEC-A３）. Notably, our case demonstrated almost all theaforementioned features corresponding EC-AIA. Diffi-culty in early-stage detection may be one of the possiblefactors for the aggressive tumor feature of EC-AIA. Inthe present case, MRI image of the uterine body revealeda higher signal intensity, which is not typical for adeno-myosis, compared with that captured 4 years prior.Therefore, meticulous observation for change in signalintensity of MRI images may facilitate an early diagnosisof EC-AIA.Till date, the oncogenic mechanism underlying themalignant transformation of adenomyosis remains un-clear. The incidence of genetic mutations, includingthose in the AT-rich interactive domain 1A gene(ARDIA ) , which is often observed in endometriosis-associated ovarian cancer, has not been reported in theliterature on EC-AIA４）. Thus, further molecular genetics-based studies of EC-AIA are warranted to elucidate thepathogenesis and, hopefully, develop more individual-ized treatment strategy for this endometrial cancer sub-type in the future.ConclusionIn conclusion, we reported a case of advanced EC-AIAbased on the clinical and histopathological characteris-tics. The criteria for diagnosing EC-AIA requires revi-sion to precisely define advanced EC-AIA. Overall, thiscase highlights the necessity of considering aggressivediseases, such as EC-AIA, when following up on patientswith adenomyosis.AcknowledgementsThe authors would like to show their greatest appreciation forProfessor Mariko Fujibayashi whose comments and sugges-tions were of inestimable value in this study.Conflicts of Interest: The authors declare that they haveno conflict of interest.References1）Kobayashi H: Ovarian cancer in endometriosis: epidemi-ology, natural history, and clinical diagnosis. Int J ClinOncol 14: 378―382, 20092）Colman HI, Rosenthal AH: Carcinoma developing in ar-eas of adenomyosis. Obstet Gynecol 14: 342―348, 19593）Machida H, Maeda M, Cahoon SS et al: Endometrialcancer arising in adenomyosis versus endometrial cancercoexisting with adenomyosis: are these two different en-tities? Arch Gynecol Obstet 295: 1459―1468, 20174）Wiegand KC, Shah SP, Al-Agha OM et al: ARID1Amutations in endometriosis-associated ovarian carcino-mas. N Engl J Med 363: 1532―1543, 2010

Advanced Endometrial Cancer Arising in Adenomyosis: A Case Report

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Advanced Endometrial Cancer Arising in Adenomyosis: A Case Report

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