{"paper_id":"e5c0f1c3-0a55-4732-8ac0-8e8e3e587193","body_text":"Ohira et al. Journal of Medical Case Reports           (2023) 17:36  \nhttps://doi.org/10.1186/s13256-023-03772-w\nCASE REPORT\n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nOpen Access\nJournal of\nMedical Case Reports\nMucinous carcinoma originating \nfrom uterine adenomyosis: a case report\nSatoshi Ohira1*, Ryota Tachibana1, Sayaka Yasaki1, Koji Tsunemi1, Natsuki Uchiyama1, Eri Ikeda1 and Kenji Sano2 \nAbstract \nBackground Uterine adenomyosis is rarely a precursor of malignant tumors, but the most frequent histologi-\ncal subtype is endometrioid carcinoma. We observed a rare case of mucinous carcinoma originating from uterine \nadenomyosis.\nCase presentation A 63-year-old Japanese woman presented to our hospital with lower abdominal pain. She had \nno atypical genital bleeding. Ultrasound demonstrated thickening of the entire uterine wall, but the endometrium \nwas not thick. Magnetic resonance imaging demonstrated an enlarged uterus with thickening of the entire uterine \nwall, suggesting adenomyosis. On the basis of the specimen of endocervical curettage, adenocarcinoma originating \nfrom the endometrium was suspected. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were \nperformed to confirm the diagnosis. Macroscopically, the resected enlarged uterus had no nodules and exudation \nof mucin was observed from the cut surface of the thickened myometrium. The surface of the endometrium was \nsmooth. On histological examination, mucinous carcinoma invaded almost the entire myometrium. Adenomyotic \nlesions were distributed focally in the uterine wall, and transition from adenomyotic glandular epithelium to muci-\nnous carcinoma was detected within several foci. Although adenocarcinoma cells proliferated adjacent to the endo-\nmetrium, the primary endometrial epithelium was atrophic without atypia. Throughout the myometrium, the muci-\nnous carcinoma cells proliferated and floated in dilated lymph vessels with abundant mucin pools. We diagnosed this \ncase as mucinous carcinoma originating from adenomyosis. Although the patient received 11 courses of intravenous \nadjuvant chemotherapy, she died of disease 18 months after the first operation.\nConclusion As only one case of mucinous carcinoma originating from adenomyosis has been reported to date, this \nis the second case report of mucinous carcinoma. Moreover, an abnormal manner of proliferation with marked lym-\nphatic permeation of the tumor cells throughout the myometrium was observed.\nKeywords Mucinous carcinoma, Adenomyosis, Case report\nBackground\nThe ovary is the most common site of endometriosis, and \nendometriosis-associated ovarian cancer accounts for \n0.3–1.0% of endometriosis [1]. The histological types of \nendometriosis-associated ovarian cancers are predomi -\nnantly endometrioid and clear cell carcinoma, whereas \nserous and mucinous carcinoma are rare [2]. Uterine \nadenomyosis, a type of extraovarian endometriosis, is \nrarely a precursor of malignant tumor, but the most fre -\nquent histological subtype is endometrioid carcinoma [3]. \nWe report a rare case of mucinous carcinoma originating \n*Correspondence:\nSatoshi Ohira\nosatoshi@shinshu-u.ac.jp\n1 Department of Obstetrics and Gynecology, Iida Municipal Hospital, 438 \nYawatamachi, Iida 395-8502, Japan\n2 Department of Pathology, Iida Municipal Hospital, 438 Yawatamachi, \nIida 395-8502, Japan\n\nPage 2 of 5Ohira et al. Journal of Medical Case Reports           (2023) 17:36 \nfrom uterine adenomyosis. The current case exhibited an \nabnormal manner of proliferation with marked lymphatic \npermeation of the tumor cells throughout the myome -\ntrium, and this abnormal manner has not been reported \nto our knowledge.\nCase presentation\nA 63-year-old postmenopausal Japanese woman (gravida \n2, para 2) presented to the internal medicine of our hos -\npital with a 2-month history of lower abdominal pain. \nAlthough uterine adenomyosis was noted in her forties, \nit was not followed up. She had no atypical genital bleed -\ning. As the serum carbohydrate antigen 19-9 (CA19-9) \nlevel was high at 64,868  U/mL, close inspection of the \npancreas, gallbladder, liver, and gastrointestinal tract was \nperformed. Although gallbladder adenomyomatosis was \ndetected, no malignant diseases were observed in these \norgans. Abdominal computed tomography (CT) revealed \nan enlarged uterus; therefore, she was referred to the \ndepartment of gynecology. Ultrasound demonstrated \nthickening of the entire uterine wall, but the endome -\ntrium was not thick. Cytological testing of the endocer -\nvix revealed atypical glandular cells. Although it was \nnot possible to pass the probe beyond the cervix, owing \nto the specimen of endocervical curettage, adenocarci -\nnoma originating from the endometrium was suspected. \nMagnetic resonance imaging (MRI) demonstrated an \nenlarged uterus with thickening of the entire uterine \nwall, suggesting adenomyosis. Both T1- and T2-weighted \nimaging revealed no uterine nodules (Fig. 1). Three weeks \nlater from the measurement with internal medicine, the \nserum CA19-9 level was markedly high at 115,950 U/mL. \nThe serum cancer antigen 125 (CA125) level was high at \n113.7 U/mL, whereas the carcinoembryonic antigen level \nwas normal. No metastatic lesions were found on chest \nand abdominal CT.\nTotal abdominal hysterectomy and bilateral salpingo-\noophorectomy were performed to confirm the diagno -\nsis. Intraoperative ascitic cytology was negative, and \nthere was no peritoneal dissemination. Macroscopically, \nthe resected enlarged uterus had no nodules and exuda -\ntion of mucin was observed from the cut surface of the \nthickened myometrium. The surface of the endometrium \nwas smooth, and the bilateral ovaries were unremarkable \n(Fig. 2).\nOn histological examination, mucinous carcinoma \n(not otherwise specified; NOS) invaded almost the entire \nmyometrium (Fig.  3a). The tumor cells had a cribriform \npattern composed of mucin-producing columnar epithe -\nlium. The nuclei of the tumor cells were hyperchromatic; \nmitotic figures were sporadically observed. Adenomy -\notic lesions were distributed focally in the uterine wall, \nFig. 1 Magnetic resonance imaging demonstrated an enlarged uterus with thickening of the entire uterine wall, suggesting adenomyosis. Both \nT1-weighted (a) and T2-weighted (b) imaging revealed no uterine nodules\n\nPage 3 of 5\nOhira et al. Journal of Medical Case Reports           (2023) 17:36 \n \nand transition from adenomyotic glandular epithelium \nto mucinous carcinoma was detected within several \nfoci (Fig.  3b). Although adenocarcinoma cells prolifer -\nated adjacent to the endometrium, the primary endo -\nmetrial epithelium was atrophic without atypia (Fig.  3c). \nThroughout the myometrium, the mucinous carcinoma \ncells proliferated and floated in dilated lymph vessels \nwith abundant mucin pools (Fig.  3d). Microscopic meta -\nstatic lesions were observed in both ovaries. Endocervi -\ncal epithelium and stroma of the uterine cervix were free \nof malignancy. Immunohistochemically, the adenocarci -\nnoma cells were positive for p53 and CA19-9, but nega -\ntive for estrogen receptor and p16.\nAccording to the International Federation of Gynecol -\nogy and Obstetrics (FIGO 2008) staging, we diagnosed \nthis case as stage IIIA mucinous carcinoma originating \nfrom adenomyosis, pT3aN0MX. The patient received \nintravenous adjuvant chemotherapy (paclitaxel 175  mg/\nm2 and carboplatin AUC6). After six courses of chemo -\ntherapy, the serum CA19-9 and CA125 levels decreased \nto 36 U/mL and 7.4 U/mL, respectively.\nThree months after the last course of chemotherapy, \nthe serum CA19-9 level increased to 455  U/mL, and \npelvic CT revealed swelling of left common iliac lymph \nnode. Although the progressive disease was noted, the \npatient underwent five more courses of intravenous \nchemotherapy (paclitaxel 175  mg/m 2 and carboplatin \nAUC6) in consideration of the patient’s desire. However, \nthe degree of swelling of the lymph node on CT did not \ndecrease and the left pelvic lymph nodes were resected. \nFig. 2 Macroscopically, the resected enlarged uterus had no nodules \nand the surface of the endometrium was smooth\nFig. 3 Histological findings of the resected uterus (hematoxylin and eosin staining). a Mucinous carcinoma invaded the myometrium and the \ntumor cells had a cribriform pattern composed of mucin-producing columnar epithelium. b Adenomyotic lesions were distributed focally in the \nuterine wall, and the transition from adenomyotic glandular epithelium to mucinous carcinoma was detected within several foci. c Although \nadenocarcinoma cells proliferated adjacent to the endometrium, the primary endometrial epithelium was atrophic without atypia. d The mucinous \ncarcinoma cells proliferated and floated in dilated lymph vessels with abundant mucin pools\n\nPage 4 of 5Ohira et al. Journal of Medical Case Reports           (2023) 17:36 \nMicroscopically, metastasis of adenocarcinoma was \nobserved in the left common iliac lymph nodes. After a \nmonth of the second operation, CT revealed large swell -\ning of paraaortic and mediastinal lymph nodes. The \npatient died of disease 18 months after the first operation.\nDiscussion\nMalignant neoplasms originating from uterine adenomy -\nosis are rare. Koshiyama et al. reported that adenocarci -\nnoma originating from adenomyosis accounted for 0.7% \nof all uterine body carcinomas treated by hysterectomy \n[4]. The most frequent histological subtype of malignant \nlesions is endometrioid carcinoma [3]. In our literature \nreview, we found 23 well-documented cases of other \nhistological subtypes as follows: 4 clear cell carcinomas \n[3–6], 4 serous carcinomas [4, 7, 8], 6 serous endome -\ntrial intraepithelial carcinomas [8, 9], 6 adenosarcomas \n[10–15], and 1 case each of adenosquamous carcinoma \n[16], carcinosarcoma [17], and mucinous carcinoma \n(minimal deviation adenocarcinoma; MDA) [18]. There -\nfore, the current case is the second case of mucinous car -\ncinoma originating from uterine adenomyosis. Moreover, \nthe current case (mucinous carcinoma, NOS) is distin -\nguished from the reported case of mucinous carcinoma, \ngastric type (MDA).\nThe diagnostic criteria for carcinoma developing from \nadenomyosis were proposed by Colman and Rosenthal \nas follows [19]: (i) the carcinoma should be absent from \nthe endometrium and elsewhere in the pelvis; (ii) the car-\ncinoma should be observed arising from the epithelium \nof the areas of adenomyosis and not invading it from \nanother source; and (iii) endometrial stromal cells should \nbe surrounding the aberrant glands to support the diag -\nnosis of adenomyosis. Our case does not strictly meet \nColman’s criteria because the specimen of preoperative \nendocervical curettage suggested adenocarcinoma origi -\nnating from the endometrium. However, we consider the \ndiagnosis consistent with that of mucinous carcinoma \noriginating from adenomyosis because of the observ -\nable transitions between adenomyosis and mucinous \ncarcinoma.\nIn the current case, the tumor cells exhibited an abnor -\nmal manner of proliferation, that is, the mucinous car -\ncinoma cells diffusely proliferated and floated in dilated \nlymph vessels with abundant mucin pools throughout the \nmyometrium. Demarcated nodules were not observed on \npreoperative MRI or included in macroscopic findings of \nthe resected uterus. Many cases of malignant tumors origi-\nnating from adenomyosis exhibited demarcated lesions \nin the myometrium [6 , 7, 15, 17, 20], and abnormal pro -\nliferation, as observed in our case, has not been reported \nto our knowledge. Moreover, the preoperative serum \nCA19-9 level in our case was markedly high at 115,950 U/\nmL. One reason for the high serum CA19-9 level was the \nmarked mucin production from carcinoma cells. Although \nour patient underwent intravenous chemotherapy for the \nrecurrent tumor in the pelvis, the treatment option might \nbe radiotherapy in a case of recurrent mucinous carcinoma \n[21].\nThe prognosis of endometrial carcinoma originating \nfrom adenomyosis remains controversial. Machida et  al. \ndescribed that endometrial carcinoma arising in adenomy-\nosis (EC-AIA) group (n = 46) had a significantly decreased \n5-year disease-free survival (DFS) rates compared with \nendometrial cancer coexisting with adenomyosis (EC-A) \ngroup (n = 350) (72.2% versus 85.5%, p = 0.001) [22]. Mean-\nwhile, Chao et  al. studied a population with endometrial \nendometrioid carcinoma and described that the 5-year \nDFS rates were 96% in the group of EC without adenomyo-\nsis (n = 1043), 91% in the EC-A group (n = 230), and 100% \nin the EC-AIA group (n = 28) (p = 0.045) [23].\nConclusions\nWe described a rare case of mucinous carcinoma originat-\ning from uterine adenomyosis. This case demonstrated an \nabnormal manner of proliferation with marked lymphatic \npermeation of the tumor cells throughout the myome -\ntrium. Further accumulation of cases is needed to clarify \nthe pathogenesis and behavior of mucinous carcinoma \noriginating from adenomyosis.\nAbbreviations\nCA19-9  Carbohydrate antigen 19-9\nCT  Computed tomography\nMRI  Magnetic resonance imaging\nCA125  Cancer antigen 125\nNOS  Not otherwise specified\nMDA  Minimal deviation adenocarcinoma\nEC-AIA  Endometrial carcinoma arising in adenomyosis\nEC-A  Endometrial cancer coexisting with adenomyosis\nDFS  Disease-free survival\nAcknowledgements\nThe authors are grateful to Tomofumi Watanabe (Department of Radiology, \nIida Municipal Hospital) for the radiodiagnosis in this case.\nAuthor contributions\nSO, RT, SY, KT, NU, and EI were in charge of this patient. KS performed \nhistological examination in this case. All authors read and approved the final \nmanuscript.\nFunding\nNot applicable.\nAvailability of data and materials\nAll data presented in this report are included in this article.\nDeclarations\nEthics approval and consent to participate\nThe study was sent to the ethical committee of Iida Municipal Hospital, and \nneed for approval was waived.\n\nPage 5 of 5\nOhira et al. Journal of Medical Case Reports           (2023) 17:36 \n \n•\n \nfast, convenient online submission\n •\n  \nthorough peer review by experienced researchers in your field\n• \n \nrapid publication on acceptance\n• \n \nsupport for research data, including large and complex data types\n•\n  \ngold Open Access which fosters wider collaboration and increased citations \n \nmaximum visibility for your research: over 100M website views per year •\n  At BMC, research is always in progress.\nLearn more biomedcentral.com/submissions\nReady to submit y our researc hReady to submit y our researc h  ?  Choose BMC and benefit fr om: ?  Choose BMC and benefit fr om: \nConsent for publication\nWritten informed consent was obtained from the patient for publication of \nthis case report. A copy of the written consent is available for review by the \nEditor-in-Chief of this journal.\nCompeting interests\nThe authors declare that they have no competing interests.\nReceived: 15 February 2022   Accepted: 12 January 2023\nReferences\n 1. Munksgaard PS, Blaakaer J. The association between endometriosis and \novarian cancer: a review of histological, genetic and molecular altera-\ntions. Gynecol Oncol. 2012;124:164–9.\n 2. Yoshikawa H, Jimbo H, Okada S, Matsumoto K, Onda T, Yasugi T, et al. \nPrevalence of endometriosis in ovarian cancer. Gynecol Obstet Invest. \n2000;50(suppl 1):11–7.\n 3. Baba A, Yamazoe S, Dogru M, Ogawa M, Takamatsu K, Miyauchi J. Clear \ncell adenocarcinoma arising from adenomyotic cyst: a case report and \nliterature review. J Obstet Gynaecol Res. 2016;42:217–23.\n 4. 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The clinicopathological \ncharacteristics and survival outcomes of endometrial carcinoma coexist-\ning with or arising in adenomyosis: a pilot study. Sci Rep. 2020;10:5984. \nhttps:// doi. org/ 10. 1038/ s41598- 020- 63065-w.\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in pub-\nlished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}