Synchronous serous carcinoma arising in adenomyosis and small cell carcinoma of ovary-pulmonary type (SCCOPT): a case report and literature review

Serous carcinoma arising in adenomyosis is rare, with only 8 cases reported in the literature. Primary small cell carcinoma of the ovary-the pulmonary type (SCCOPT) is a rare and aggressive entity associated with poor outcomes and limited treatment options. The presence of two malignant tumors synchronously happening in one patient has never been reported before. In this study, we summarized and analyzed the clinicopathological features of a serous carcinoma arising in adenomyosis synchronous with SCCOPT and reviewed the corresponding literature. A 60-year-old postmenopausal woman presented to our hospital with abdominal distension, abdominal pain, and constipation. A colonoscopy and lung computed tomography (CT) scan showed no abnormalities. Ultrasonography and CT scans revealed a solid-cystic mass in the pelvic cavity, with a slightly thickened uterine myometrium at the fundus with heterogeneous echo. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic and para-aortic lymphadenectomy, and the final pathology showed serous carcinoma originating from adenomyosis, while the eutopic endometrium and both fallopian epithelia had no cancer infiltrations. The solid-cystic mass in the right ovary was diagnosed with SCCOPT, which was found to metastasize to the uterine myometrium. The prognosis of previously reported cancers of adenomyosis origin and SCCOPT were poor, while our case was alive without disease during an 18-month follow-up. Findings from this case report could expand our recognition on the coexistence of serous carcinoma arising in adenomyosis with small cell carcinoma of the ovary-pulmonary type.

Serous carcinoma; Adenomyosis; Malignant transformation; Small cell carcinoma of the ovary; Pulmonary type; Immunohistochemistry

[1] Rolly F. Ueber einen Fall von Adenomyoma uteri mit Uebergang in Carcinom und Metastasenbildung. Virchows Arch Pathol Anat. 1897; 150: 555–582.

[2] Sampson JA. Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. American Journal of Obstetrics & Gynecology. 1925; 9: 111–114.

[3] Abushahin N, Zhang T, Chiang S, Zhang X, Hatch K, Zheng W. Serous endometrial intraepithelial carcinoma arising in adenomyosis: a report of 5 cases. International Journal of Gynecological Pathology. 2011; 30: 271–281.

[4] Ismiil ND, Rasty G, Ghorab Z, Nofech-Mozes S, Bernardini M, Thomas G, et al. Adenomyosis is associated with myometrial invasion by FIGO 1 endometrial adenocarcinoma. International Journal of Gynecological Pathology. 2007; 26: 278–283.

[5] Yuan H, Zhang S. Malignant transformation of adenomyosis: literature review and meta-analysis. Archives of Gynecology and Obstetrics. 2019; 299: 47–53.

[6] Liu C, Chang W, Liu W, Wang P. Serous carcinoma arising from adenomyosis. Taiwanese Journal of Obstetrics and Gynecology. 2017; 56: 706–707.

[7] Griffin M, Parai S, Ghatage P, Dimakulangan A. Papillary serous carcinoma of the uterus arising in an adenomyoma. Acta Cytologica. 1996; 40: 849–850.

[8] Koshiyama M, Suzuki A, Ozawa M, Fujita K, Sakakibara A, Kawamura M, et al. Adenocarcinomas arising from uterine adenomyosis: a report of four cases. International Journal of Gynecological Pathology. 2002; 21: 239–245.

[9] Izadi-Mood N, Samadi N, Sarmadi S, Eftekhar Z. Papillary serous car-cinoma arising from adenomyosis presenting as intramural leiomyoma. Archives of Iranian Medicine. 2007; 10: 258–260.

[10] Lu B, Chen Q, Zhang X, Cheng L. Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases. Diagnostic Pathology. 2016; 11: 46.

[11] Matsuo K, Moeini A, Machida H, Scannell CA, Casabar JK, Kakuda M, et al. Tumor characteristics and survival outcome of endometrial cancer arising in adenomyosis: an exploratory analysis. Annals of Surgical Oncology. 2016; 23: 959–967.

[12] Atienza-Amores M, Guerini-Rocco E, Soslow RA, Park KJ, Weigelt B. Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions. Gynecologic Oncology. 2014; 134: 410–418.

[13] World Health Organization. Female Genital Tumours. 5th edn. International Agency for Research: CancerLyon, France. 2020.

[14] Reed NS, Pautier P, Åvall-Lundqvist E, Choi C, du Bois A, Friedlander M, et al. Gynecologic cancer intergroup (GCIG) consensus review for ovarian small cell cancers. International Journal of Gynecologic Cancer. 2014; 24: S30–S34.

[15] Koshiyama M, Okamoto T, Ueta M. The relationship between endometrial carcinoma and coexistent adenomyosis uteri, endometriosis externa and myoma uteri. Cancer Detection and Prevention. 2004; 28: 94–98.

[16] Hsu M, Chou S, Lin S, Liang S, Chiu H, Hsu C. Very early stage adenocarcinoma arising from adenomyosis in the uterus. Taiwanese Journal of Obstetrics and Gynecology. 2006; 45: 346–349.

[17] Baba A, Yamazoe S, Dogru M, Ogawa M, Takamatsu K, Miyauchi J. Clear cell adenocarcinoma arising from adenomyotic cyst: a case report and literature review. Journal of Obstetrics and Gynaecology Research. 2016; 42: 217–223.

[18] Scott RB. Malignant changes in endometriosis. Obstetrics and Gynecology. 1953; 2: 283–289.

[19] Colman HI, Rosenthal AH. Carcinoma developing in areas of adenomyosis. Obstetrics and Gynecology. 1959; 14: 342–348.

[20] Machida H, Maeda M, Cahoon SS, Scannell CA, Garcia-Sayre J, Roman LD, et al. Endometrial cancer arising in adenomyosis versus endometrial cancer coexisting with adenomyosis: are these two different entities?Archives of Gynecology and Obstetrics. 2017; 295: 1459–1468.

[21] Mao X, Zheng W, Mao W. Malignant changes in adenomyosis in patients with endometrial adenocarcinoma: a case series. Medicine. 2017; 96: e8336.

[22] Zouzoulas OD, Tsolakidis D, Efstratiou I, Pervana S, Pazarli E, Grimbizis G. Correlation between Adenomyosis and Endometrial cancer: 6-year experience of a single center. Facts, Views & Vision in ObGyn. 2018; 10: 147–152.

[23] Woodruff JD, Erozan YS, Genadry R. Adenocarcinoma arising in adenomyosis detected by atypical cytology. Obstetrics and Gynecology. 1986; 67: 145–148.

[24] Koike N, Tsunemi T, Uekuri C, Akasaka J, Ito F, Shigemitsu A, et al. Pathogenesis and malignant transformation of adenomyosis (Review). Oncology Reports. 2013; 29: 861–867.

[25] Lee EK, Fader AN, Santin AD, Liu JF. Uterine serous carcinoma: molecular features, clinical management, and new and future therapies. Gynecologic Oncology. 2021; 160: 322–332.

[26] Jones RK, Searle RF, Bulmer JN. Apoptosis and bcl-2 expression in normal human endometrium, endometriosis and adenomyosis. Human Reproduction. 1998; 13: 3496–3502.

[27] Nie J, Liu X, Guo S. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in adenomyosis and its rectification by a histone deacetylase inhibitor and a demethylation agent. Reproductive Sciences. 2010; 17: 995–1005.

[28] Goumenou AG, Arvanitis DA, Matalliotakis IM, Koumantakis EE, Spandidos DA. Loss of heterozygosity in adenomyosis on hMSH2, hMLH1, p16Ink4 and GALT loci. International Journal of Molecular Medicine. 2000; 6: 667–671.

[29] Yin L, Li J, Wei Y, Ma D, Sun Y, Sun Y. Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: a case report and literature review. Medicine. 2018; 97: e10900.

[30] Young RH, Oliva E, Scully RE. Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathological analysis of 150 cases. The American Journal of Surgical Pathology. 1994; 18: 1102–1116.

[31] Bing Z, Adegboyega PA. Metastasis of small cell carcinoma of lung into an ovarian mucinous neoplasm: immunohistochemistry as a useful ancillary technique for diagnosis and classification of rare tumors. Applied Immunohistochemistry & Molecular Morphology. 2005; 13: 104–107.

[32] Oneda E, Zorzi F, Gorio A, Quaglia F, Abeni C, Rota L, et al. Diagnosis of small cell carcinoma of the ovary or ovarian metastases of small cell carcinoma of the lung: a case report and review of the literature. Case Reports in Oncology. 2020; 13: 822–828.

[33] Callegaro-Filho D, Gershenson DM, Nick AM, Munsell MF, Ramirez PT, Eifel PJ, et al. Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT): a review of 47 cases. Gynecologic Oncology. 2016; 140: 53–57.

[34] Conlon N, Silva A, Guerra E, Jelinic P, Schlappe BA, Olvera N, et al. Loss of SMARCA4 expression is both sensitive and specific for the diagnosis of small cell carcinoma of ovary, hypercalcemic type. The American Journal of Surgical Pathology. 2016; 40: 395–403.

[35] Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N, Tomiak E, et al. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nature Genetics. 2014; 46: 438–443.

[36] Eichhorn JH, Young RH, Scully RE. Primary ovarian small cell carcinoma of pulmonary type. A clinicopathologic, immunohistologic, and flow cytometric analysis of 11 cases. The American Journal of Surgical Pathology. 1992; 16: 926–938.

[37] Ramos P, Karnezis AN, Craig DW, Sekulic A, Russell ML, Hendricks WPD, et al. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4. Nature Genetics. 2014; 46: 427–429.

[38] Jelinic P, Mueller JJ, Olvera N, Dao F, Scott SN, Shah R, et al. Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nature Genetics. 2014; 46: 424–426.

[39] Yaghmour G, Prouet P, Wiedower E, Jamy OH, Feldman R, Chandler JC, et al. Genomic alterations in neuroendocrine cancers of the ovary. Journal of Ovarian Research. 2016; 9: 52.

[40] Walenkamp AME, Sonke GS, Sleijfer DT. Clinical and therapeutic aspects of extrapulmonary small cell carcinoma. Cancer Treatment Reviews. 2009; 35: 228–236.

[41] Brennan SM, Gregory DL, Stillie A, Herschtal A, Mac Manus M, Ball DL. Should extrapulmonary small cell cancer be managed like small cell lung cancer? Cancer. 2010; 116: 888–895.