Case report | Open | Published:
Anaplastic carcinoma in ovarian seromucinous cystic tumor of borderline malignancy
Journal of Ovarian Researchvolume 11, Article number: 77 (2018)
The mortality rate of ovarian cancer is the highest among all gynecological malignancies in Japan. Ovarian tumors are classified as benign, borderline malignant, or malignant. Anticipating the histological subtype with imaging only is often difficult because of several histological subtypes of epithelial ovarian tumors (such as serous, mucinous, endometrioid, clear cell, and Brenner tumors). In addition, the majority of mucinous tumors in the ovary are metastatic. Furthermore, mucinous tumors belong to one of the two different subclasses (i.e., intestinal and seromucinous types). Ovarian seromucinous cystic tumors of borderline malignancy are infrequent and only rarely coexist with other malignant tumors.
We have reported a 53-year-old Japanese woman with anaplastic carcinoma in an ovarian seromucinous cystic tumor of borderline malignancy. Her MRI and CT analysis revealed an ovarian tumor with a mural nodule, ascites, and peritoneal dissemination. Enhanced MRI revealed that the mural nodule was enhanced. Enhanced CT analysis revealed that the lymph nodes were not swollen. Intriguingly, the mural nodule crossed the cyst wall into the cavity and onto the surface. Her laboratory data revealed high serum CA 125 level. Cumulatively, these results suggested ovarian malignancy. The patient underwent hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of the disseminated lesions. Lymph node biopsy was omitted because of the suggestion of enhanced CT image findings and palpation during surgery. Her postoperative specimen examination determined FIGO at least stage IIIB, and accordingly, adjuvant chemotherapy was prescribed. After 3 years of the operation, the patient is presently alive without clinical tumor recurrences.
Imaging studies with pathognomonic findings contributed to ovarian cancer diagnosis in this case. To the best of our knowledge, this is the first study in English literature to report detailed classification of mucinous borderline malignancy, seromucinous cystic, and anaplastic carcinoma in an ovarian seromucinous cystic tumor of borderline malignancy.
Ovarian tumors are classified as benign, borderline malignant, or malignant. The mortality rate of ovarian malignancies is the highest among all gynecological malignancies (Fig. 1a, b) . In general, ovarian malignancies display various histological types. The ovarian mucinous borderline malignancies represent 58% and the serous borderline malignancies represent 19% of all borderline malignancies in Japan (Fig. 1c). In contrast, these percent values are 42% and 52.1% of the borderline malignancies, respectively, in the Western countries [2, 3].
Ovarian mucinous borderline malignancies used to be classified earlier into intestinal and endocervical types. However, the World Health Organization changed their name from endocervical to seromucinous type in 2014 . Nakashima reported that ovarian mucinous borderline malignancy in Japan encompasses 38% of intestinal, 36% of seromucinous, and 26% of mixed types . However, Prat reported that 90% of ovarian mucinous borderline malignancies in the Western countries are of the intestinal type .One of the most common ovarian epithelial cancer considered to demonstrate racial group differences is ovarian clear cell carcinoma. Clear cell carcinoma was significantly more prevalent among Asian women (12%) than among any other race (5%) as per the SEER data in the United States . Endometriosis is considered as one of the risk factor associated with clear cell carcinoma . However, the available literature negated that the prevalence of endometriosis is high among Asian women than in other races . High adiposity is reported as a risk factor of ovarian cancer in African–American women . Furthermore, oral contraception, parity, and breastfeeding has been reported to decrease the risk of ovarian cancer . In reference to ovarian borderline malignancy, the incidence rate is high in white women than in black women in the United States . In consideration of these literatures, the difference between the incidence rates for ovarian borderline malignancy among different races may be attributed to the feeding habit, antifertility method used, and economic situation. Furthermore, the genetic differences between races possibly influence the incidence rate of ovarian borderline malignancy. Hence, we need to collect more data and perform further studies to clarify this possibility. Scully reported 7 cases of ovarian mucinous tumors with mural nodules in 1979 . Mural nodules are classified into 6 groups: anaplastic carcinoma, sarcoma, carcinosarcoma, sarcoma-like nodule, mixed nodule, and smooth muscle sarcoma . Some case studies have reported that ovarian seromucinous borderline malignancies can coexist with secondary tumors such as endometrioid carcinoma, clear cell carcinoma, or squamous cell carcinoma [15,16,17]. Indeed, a case of ovarian mucinous borderline malignancy coexisting with anaplastic carcinoma has been reported previously . However, this previous report did not include data on tumor subtyping. To the best of our knowledge, our paper is the first report of an ovarian seromucinous borderline malignancy coexisting with an anaplastic carcinoma.
A 53-years-old Japanese woman with ascites and a pelvic tumor was transferred to the Maruyama Memorial General Hospital on the suspicion of ovarian malignancy. A trans-vaginal ultrasound examination confirmed a large ascites volume and approximately 10-cm single ovarian cystic tumor with a mural nodule. The serum level of CA19–9 was 37 IU/L and that of CA125 was increased markedly at 333 IU/L. Magnetic resonance imaging (MRI) revealed ascites and an approximately 10-cm single cystic tumor with a 4-cm mural nodule. T1- and T2-weighted MRI revealed a high-intensity cystic area. In addition, the T1-weighted and fat-suppressed MRI showed the high-intensity cystic area. Therefore, we expected the cyst to contain blood. Moreover, gadorinium-enhanced T1-weighted MRI revealed an enhanced mural nodule (Fig. 2a). Interestingly, the mural nodule crossed the cyst wall into the cavity and onto the surface, which is an extremely rare finding and may be the characteristic of this tumor type. Computed tomography (CT) imaging showed a large ascites volume and tumor dissemination throughout the pelvis (Fig. 2b). On the basis of these examinations, we suspected a malignant tumor. The patient underwent bilateral salpingo-oophorectomy with hysterectomy, omentectomy, resection of disseminated lesions and optimal debulking of the tumor. Lymph node biopsy was omitted because of the suggestion of enhanced CT image findings and palpation during surgery. The content of the left ovarian cyst was chocolate-like. We identified a mural nodule of approximately 4-cm size on the cyst wall (Fig. 3a, b). The histopathological examination revealed columnar tumor cells on the cyst wall. Eosinophilic epithelial cells suggestive of papillary hyperplasia and squamous metaplasia were identified on the endometriosis tissues. The cells showing dysplasia were categorized as borderline malignant. The cyst showed positivity for estrogen receptor and vimentin antibodies, and it was negative for WT-1; therefore, the immunohistochemical staining led to the diagnosis of ovarian seromucinous borderline malignancy (Fig. 4a–e). The mural nodule contained dense hyperplastic polymorphic and eosinophilic undifferentiated cells. The mural nodule was positive for CAM5.2, AE1/AE3, and vimentin and was identified as an anaplastic carcinoma by immunohistochemistry (Fig. 5a–e). A nodule present in the omentum showed the same pathological findings as the mural nodule and was thus diagnosed as a metastasis from the anaplastic carcinoma. The disseminated lesion was < 2 cm in size. We classified the ascites as class I by cytodiagonosis and diagnosed the patient as having an anaplastic carcinoma in the left ovarian seromucinous cystic tumor of borderline malignancy, with a FIGO stage IIIB. She underwent 6 courses of pacritaxel and carboplatin. After 3 years, the patient is still alive without any clinical findings of tumor recurrence.
Ovarian tumors are classified as benign, borderline malignant, or malignant. The most common borderline malignant ovarian tumors are serous and mucinous. Mucinous borderline malignancies can be further subclassified into either intestinal or seromucinous types. Fox et al. reported the first seromucinous-type tumor . Malignancy and recurrences determine the prognosis of seromucinous borderline malignancy tumors . Endometriosis is a pathognomonic sign of approximately 30% of seromucinous type tumors . Approximately 33% of all seromucinous-type tumors present with a mutation in the tumor-suppressor gene ARID1A; therefore, it can be considered as one of the responsible genetic factors . Moreover, ARID1A is believed to be involved in the pathogenesis of endometriosis. In fact, 46% of ovarian clear cell carcinomas and 30% of ovarian endometrioid carcinomas have ARID1A mutations . Mesbah Ardakani et al. compared the molecular profiling of ovarian mucinous tumors with their matched mural carcinomatous nodules by next generation sequencing. They reported a case of KRAS mutation in the mural nodule and paired mucinous borderline malignancy. However, p53 mutation was present in the mural nodule but not in mucinous borderline malignancy . p53 is one of the common tumor-suppressor genes. p53 mutation is the most common and frequent event in high-grade serous ovarian carcinoma . Mackenzie et al. reported that p53 mutation occur more frequently in mucinous carcinoma than in mucinous borderline malignancy . Thus, based on these reports, p53 mutation possibly plays a vital role in the progression of mucinous ovarian tumors. A pathognomonic histological sign of seromucinous borderline malignancies is 100% estrogen receptor positivity by immunohistochemistry; in addition, 65% of cases show progesterone receptor positivity, 92% present show CA125 positivity, and 8% show WT-1 positivity . In our case, we found that the pathological examination of endometriosis was compatible with the results of seromucinous border malignancy after immunohistochemical staining. Mural nodules require differentiation between anaplastic and sarcomatous tumors. Vimentin and CAM5.2 are usually positive in anaplastic tumors by immunohistochemical staining. However, sarcomatous tumors can yield the same immunohistochemistry result. AE1/AE3 can be used to discriminate between these subtypes because it is positive only in anaplastic tumors . In the present case, mural nodule was positive for AE1/AE3; therefore, our patient was diagnosed with anaplastic tumor. Anaplastic tumors occurring in various organs, such as lung, pancreas, kidney, and thyroid, have high malignancy grade. Anaplastic tumor did not involve the prognosis of stage IA seromucinous borderline malignancies . The differential diagnosis between an anaplastic tumor and a sarcomatous tumor is important for their proper treatment, because each tumor has a different prognosis . In summary, we treated an extremely rare case of anaplastic tumor occurring in an ovarian seromucinous borderline malignant cyst. Although the anaplastic tumor had disseminated to the omentum, the conventional ovarian cancer chemotherapy administered to our patient resulted in recurrence-free survival of at least 3 years. To the best of our knowledge, this is the first English language report of an anaplastic tumor occurring in a seromucinous borderline malignancy ovarian cyst. Our study images show that the nodule enlargement in the medial and lateral directions are unusual and may represent a characteristic finding that is useful for the diagnosis of these types of tumor. Finally, our experience suggests that conventional chemotherapy is possibly effective in treating these tumors. However, we need to study more relevant cases to investigate whether conventional chemotherapy is effective.
This is an extremely rare case that suggests that mural nodule of anaplastic tumor possibly has a characteristic finding from the study of imaging that the mural nodule crossed the cyst wall into the cavity and onto the surface. To the best of our knowledge, this is the first English language report of an anaplastic tumor occurring in a seromucinous borderline malignancy ovarian cyst.
AT-Rich Interaction Domain 1A
Center for Cancer Control and Information Service, National Cancer Center, Japan. https://ganjoho.jp/reg_stat/statistics/dl/index.html.
Buttin BM, Herzog TJ, Powell MA, Rader JS, Mutch DG. Epithelial ovarian tumors of low malignant potential: the role of microinvasion. Obstet Gynecol. 2002;99(1):11–7. PubMed PMID: 11777503
Rice LW, Berkowitz RS, Mark SD, Yavner DL, Lage JM. Epithelial ovarian tumors of borderline malignancy. Gynecol Oncol. 1990;39(2):195–8. PubMed PMID: 2227595
Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO Classification of Tumours of Female Reproductive Organs. In: WHO Classification of Tumours. 4. Aufl. Lyon: WHO Press; 2014.
Nakashima N, Nagasaka T, Oiwa N, Nara Y, Fukata S, Fukatsu T, Takeuchi J. Ovarian epithelial tumors of borderline malignancy in Japan. Gynecol Oncol. 1990;38(1):90–8. PubMed PMID: 2162318
Prat J. Pathology of the ovary. Philadelphia: Saunders; 2004.
Park HK, Ruterbusch JJ, Cote ML. Recent trends in ovarian Cancer incidence and relative survival in the United States by race/ethnicity and histologic subtypes. Cancer Epidemiol Biomark Prev. 2017;26(10):1511–8. PubMed PMID: 28751475
Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A, Ovarian Cancer Association Consortium. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol. 2012;13(4):385–94. PubMed PMID: 22361336
Jacoby VL, Fujimoto VY, Giudice LC, Kuppermann M, Washington AE. Racial and ethnic disparities in benign gynecologic conditions and associated surgeries. Am J Obstet Gynecol. 2010;202(6):514–21. PubMed PMID: 20430357
Bandera EV, Qin B, Moorman PG, Alberg AJ, Barnholtz-Sloan JS, Bondy M, Cote ML, Funkhouser E, Peters ES, Schwartz AG, Terry P, Schildkraut JM. Obesity, weight gain, and ovarian cancer risk in African American women. Int J Cancer. 2016;139(3):593–600. PubMed PMID: 27038123
Moorman PG, Alberg AJ, Bandera EV, Barnholtz-Sloan J, Bondy M, Cote ML, Funkhouser E, Peters ES, Schwartz AG, Terry P, Crankshaw S, Wang F, Schildkraut JM. Reproductive factors and ovarian cancer risk in African-American women. Ann Epidemiol. 2016;26(9):654–62. PubMed PMID: 27528178
Mink PJ, Sherman ME, Devesa SS. Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States. Results from the SEER Program, 1978–1998. Cancer. 2002;95(11):2380–9. PubMed PMID: 12436446
Prat J, Scully RE. Ovarian mucinous tumors with sarcoma-like mural nodules: a report of seven cases. Cancer. 1979;44(4):1332–44. PubMed PMID: 498014
Scully RE, Young RH, Clement PB. Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament. Int J Gynecol Pathol. 1999;18(3):228.
Dubé V, Roy M, Plante M, Renaud MC, Têtu B. Mucinous ovarian tumors of Mullerian-type: an analysis of 17 cases including borderline tumors and intraepithelial, microinvasive, and invasive carcinomas. Int J Gynecol Pathol. 2005;24(2):138–46. Review. PubMed PMID: 15782070
Nakamura E, Sato Y, Moriguchi S, Yamashita A, Higo T, Asada Y. Ovarian Seromucinous borderline tumor and clear cell carcinoma: an unusual combination. Case Rep Obstet Gynecol. 2015;2015:690891. https://doi.org/10.1155/2015/690891. Epub 2015 May 13. PubMed PMID: 26075120; PubMed Central PMCID: PMC4444562
D'Angelo E, Dadmanesh F, Pecorelli S, Prat J. Squamous cell carcinoma of the ovary arising from a mucinous cystic tumor of endocervical (müllerian) type. Int J Gynecol Pathol. 2010;29(6):529–32. https://doi.org/10.1097/PGP.0b013e3181e4b7ae. PubMed PMID: 20881861
Yamazaki H, Matsuzawa A, Shoda T, Iguchi H, Kyushima N. Ovarian mucinous cystic tumor of borderline malignancy with a mural nodule of anaplastic spindle cell carcinoma: a case report. J Ovarian Res. 2013;6(1):86. https://doi.org/10.1186/1757-2215-6-86. PubMed PMID: 24305620; PubMed Central PMCID: PMC4176295
Fox H, Langley FA. Tumors of the Ovary. Chicago: William Heinemann/Year Book; 1976.
Shappell HW, Riopel MA, Smith Sehdev AE, Ronnett BM, Kurman RJ. Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas. Am J Surg Pathol. 2002;26(12):1529–41. Review. PubMed PMID: 12459620
Rutgers JL, Scully RE. Ovarian mullerian mucinous papillary cystadenomas of borderline malignancy. A clinicopathologic analysis. Cancer. 1988;61(2):340–8. PubMed PMID: 3334969
Wu CH, Mao TL, Vang R, Ayhan A, Wang TL, Kurman RJ, IeM S. Endocervical-type mucinous borderline tumors are related to endometrioid tumors based on mutation and loss of expression of ARID1A. Int J Gynecol Pathol. 2012;31(4):297–303. https://doi.org/10.1097/PGP.0b013e31823f8482. PubMed PMID: 22653341; PubMed Central PMCID: PMC3501990
Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, IeM S, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG, et al. N Engl J Med. 2010;363(16):1532–43. https://doi.org/10.1056/NEJMoa1008433. Epub 2010 Sep 8. PubMed PMID: 20942669; PubMed Central PMCID: PMC2976679
Mesbah Ardakani N, Giardina T, Amanuel B, Stewart CJ. Molecular profiling reveals a clonal relationship between ovarian mucinous tumors and corresponding mural carcinomatous nodules. Am J Surg Pathol. 2017;41(9):1261–6. PubMed PMID: 28498287
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15. PubMed PMID: 21720365
Mackenzie R, Kommoss S, Winterhoff BJ, Kipp BR, Garcia JJ, Voss J, Halling K, Karnezis A, Senz J, Yang W, Prigge ES, Reuschenbach M, Doeberitz MV, Gilks BC, Huntsman DG, Bakkum-Gamez J, McAlpine JN, Anglesio MS. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms. BMC Cancer. 2015;15:415. PubMed PMID: 25986173
Vang R, Gown AM, Barry TS, Wheeler DT, Ronnett BM. Immunohistochemistry for estrogen and progesterone receptors in the distinction of primary and metastatic mucinous tumors in the ovary: an analysis of 124 cases. Mod Pathol. 2006;19(1):97–105. PubMed PMID: 16294196
Matias-Guiu X, Aranda I, Prat J. Immunohistochemical study of sarcoma-like mural nodules in a mucinous cystadenocarcinoma of the ovary. Virchows Arch A Pathol Anat Histopathol. 1991;419(2):89–92. PubMed PMID: 1714661
Provenza C, Young RH, Prat J. Anaplastic carcinoma in mucinous ovarian tumors: a clinicopathologic study of 34 cases emphasizing the crucial impact of stage on prognosis, their histologic spectrum, and overlap with sarcomalike mural nodules. Am J Surg Pathol. 2008;32(3):383–9. PubMed PMID: 18300813
Hillesheim PB, Farghaly H. Anaplastic spindle cell carcinoma, arising in a background of an ovarian mucinous cystic tumor: a case report with clinical follow up, review of the literature. Int J Clin Exp Pathol. 2010;3(8):808–11. Review. PubMed PMID: 21151395; PubMed Central PMCID: PMC2993232
Availability of data and materials
The data supporting the findings of this study are available within the article.
Ethics approval and consent to participate
This report was approved by the Ethics Committee of Maruyama Memorial General Hospital (No. 2017–2).
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.