Final Diagnosis -- Synchronous Endometrioid Adenocarcinomas of the Endometrium and Right Ovary


Low stage, low grade, synchronous endometrioid adenocarcinomas of the endometrium and right ovary. Background of complex atypical hyperplasia in the endometrium. Numerous foci of atypical endometriosis in the bilateral adnexa. Omentum and appendix involved by endosalpingiosis and benign endometriosis. The patient was screened for mismatch repair defects, but had preserved staining for MLH1, PMS2, MSH2, and MSH6.


The presence of coexistent ovarian and endometrial carcinomas has been identified in 3 to 30% of patients with endometrial carcinoma and 3 to 10% of patients with ovarian carcinoma.[1-5] This condition may arise from ovarian metastasis of endometrial carcinoma, endometrial metastasis of ovarian carcinoma, or synchronous development of independent primary lesions. Various histologic and immunohistochemical criteria have been proposed to differentiate the site or sites of origin. Factors which favor separate primary tumors include histologic dissimilarity, no or superficial myometrial invasion of the endometrial tumor, the presence of atypical endometrial hyperplasia, unilateral ovarian tumor which is located in the parenchyma, lack of vascular invasion, surface implants, or other evidence of endometrial or ovarian tumor spread, and dissimilar findings of molecular genetic, karyotype, or loss of heterozygosity studies.[6-9]

The most common presenting symptom of coexistent tumors, whether metastatic or synchronous primaries, is abnormal uterine bleeding. Abdominal distension, abdominal or pelvic masses, and abdominal or pelvic pain have also been described.[3, 4] Women with coexistent tumors tend to be premenopausal and diagnosed at a younger age (median 41 to 53) than women with either ovarian or endometrial tumors alone.[2-4, 8] This finding is further supported by evidence that young women (age 45 or below) who are diagnosed with endometrial carcinoma are more likely to have synchronous ovarian carcinoma.[10, 11] Other factors which have been associated with coexistent endometrial and ovarian tumors include nulliparity, tobacco use, and increased BMI.[8, 10] These factors were not found to vary significantly between patients with metastatic or synchronous primary lesions.[9] Additionally, endometriosis has been shown to be present in 31% of patients with coexisting ovarian and endometrial carcinomas.[12]

Ovarian tumors which are present concurrently with endometrial tumors have been shown to have multiple histologic types including endometrioid, clear cell, serous, mucinous, and mixed. Interestingly, although the majority of ovarian tumors occurring singly are serous type, up to 90% of patients with coexistent endometrial and ovarian tumors have endometrioid type ovarian carcinoma.[1, 3, 11, 12] In contrast, the frequency of endometrioid carcinoma in endometrial tumors is similar for singly detected and coexistent lesions. Endometrial lesions with clear cell, mucinous, serous, and mixed cell types have also been described in patients with concurrent ovarian tumors.[8, 12] In a series of 74 cases Zaino, et al found the same ovarian and endometrial histologic cell type in 93% of cases despite the fact that only 1-19% had features consistent with metastatic lesions rather than independent primaries.[12]

Patients with carcinomas involving both the ovary and endometrium are more likely to be diagnosed with early stage lesions (FIGO Stage I or II) of low histologic grade (Grade I).[3, 4, 12] They were also shown to have high rates of disease-free and overall survival. In the study by Zaino, et al, recurrence at 5 years was 15% and was dependent on presence of metastases at diagnosis and on histologic grade. In this study, 5 year survival was 85.9% and 10 year survival was 80.3% [2, 4, 12] Further, patients with endometrioid ovarian carcinoma and endometrioid endometrial carcinoma had lower rates of recurrence and higher rates of overall survival than patients with tumors of other histologic cell type.[3, 8, 12]

Given the characteristics of the patient population, as well as the increased presence of concurrent endometriosis, many have suggested that the pathogenesis of synchronous carcinomas could involve a "field effect" whereby hormonal or other stimuli lead to the malignant transformation of multiple similar epithelia.[1, 8, 13] This theory is supported by increasing evidence that endometrioid ovarian carcinomas, the most common form in synchronous lesions, arise from endometriosis.[14, 15] Both endometrioid ovarian and endometrioid endometrial carcinomas have been shown to have mutations in PTEN, PIK3CA, ARID1A, PP2R1A, and CTNNB1, although the frequency of these mutations varies widely based on the organ site.[16] The presence of a mutation in PTEN or CTNNB1 has been proposed as a marker to differentiate metastatic from synchronous primary carcinomas.[17, 18] Other potential genetic markers for differentiation include DNA flow cytometry, loss of heterozygosity, and X-chromosome inactivation.[19-23]

Despite the link between familial ovarian and endometrial cancers with an endometrioid phenotype and diagnosis at a young age, there does not appear to be a strong prevalence of familial cancers in patients who present with synchronous primary malignancies.[24, 25] In a study of 84 cases by Soliman, et al only two patients were identified with familial breast cancer syndromes (one with HPNCC and one with hereditary breast and ovarian cancer syndrome).[8] Another study demonstrated that the prevalence of familial cancers was significantly higher in patients with metastatic lesions than in those with synchronous primary tumors.[9] A third case series found a high likelihood of Lynch syndrome in 7% of patients, all of whom had a personal history of or first degree relative with a Lynch syndrome associated cancer.[25]

In summary, the patient described presented with coexistent lesions of the right ovary and uterus. Although these lesions shared similar histology and immunohistochemical staining patterns multiple features led to the determination that they were independent, synchronous primary tumors. These included the lack of evidence for direct or lymphovascular spread of either the ovarian or the endometrial carcinoma, the presence of a single and unifocal ovarian mass, the presence of extensive endometriosis including some atypical endometriosis, the presence of complex atypical hyperplasia in the endometrium, and the lack of extensive myometrial invasion. The patient also shares many of the clinical findings which were described in the various case reports.


  1. van Niekerk, C.C., et al., The Association between Primary Endometrioid Carcinoma of the Ovary and Synchronous Malignancy of the Endometrium. Obstet Gynecol Int, 2010. 2010: p. 465162.
  2. Liu, Y., et al., Clinicopathological characteristics of patients with synchronous primary endometrial and ovarian cancers: A review of 43 cases. Oncol Lett, 2013. 5(1): p. 267-270.
  3. Lim, Y.K., et al., Survival outcome of women with synchronous cancers of endometrium and ovary: a 10 year retrospective cohort study. J Gynecol Oncol, 2011. 22(4): p. 239-43.
  4. Sozen, H., et al., Clinicopathologic and survival analyses of synchronous primary endometrial and epithelial ovarian cancers. J Obstet Gynaecol Res, 2015. 41(11): p. 1813-9.
  5. Gitsch, G., et al., Endometrial cancer in premenopausal women 45 years and younger. Obstet Gynecol, 1995. 85(4): p. 504-8.
  6. Ulbright, T.M. and L.M. Roth, Metastatic and independent cancers of the endometrium and ovary: a clinicopathologic study of 34 cases. Hum Pathol, 1985. 16(1): p. 28-34.
  7. Scully R, Y.R., Clement P, Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament. Atlas of Tumor Pathology, ed. W.A.F.I.o. Pathology. Vol. 23. 1998.
  8. Soliman, P.T., et al., Synchronous primary cancers of the endometrium and ovary: a single institution review of 84 cases. Gynecol Oncol, 2004. 94(2): p. 456-62.
  9. Halperin, R., et al., Simultaneous carcinoma of the endometrium and ovary vs endometrial carcinoma with ovarian metastases: a clinical and immunohistochemical determination. Int J Gynecol Cancer, 2003. 13(1): p. 32-7.
  10. Evans-Metcalf, E.R., et al., Profile of women 45 years of age and younger with endometrial cancer. Obstet Gynecol, 1998. 91(3): p. 349-54.
  11. Walsh, C., et al., Coexisting ovarian malignancy in young women with endometrial cancer. Obstet Gynecol, 2005. 106(4): p. 693-9.
  12. Zaino, R., et al., Simultaneously detected endometrial and ovarian carcinomas--a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study. Gynecol Oncol, 2001. 83(2): p. 355-62.
  13. Chiang, Y.C., et al., Synchronous primary cancers of the endometrium and ovary. Int J Gynecol Cancer, 2008. 18(1): p. 159-64.
  14. Prowse, A.H., et al., Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer, 2006. 119(3): p. 556-62.
  15. Acien, P., et al., Epithelial ovarian cancers and endometriosis. Gynecol Obstet Invest, 2015. 79(2): p. 126-35.
  16. McConechy, M.K., et al., Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Mod Pathol, 2014. 27(1): p. 128-34.
  17. Ricci, R., et al., PTEN as a molecular marker to distinguish metastatic from primary synchronous endometrioid carcinomas of the ovary and uterus. Diagn Mol Pathol, 2003. 12(2): p. 71-8.
  18. Irving, J.A., et al., Synchronous endometrioid carcinomas of the uterine corpus and ovary: alterations in the beta-catenin (CTNNB1) pathway are associated with independent primary tumors and favorable prognosis. Hum Pathol, 2005. 36(6): p. 605-19.
  19. Fujita, M., et al., Application of clonal analysis. Differential diagnosis for synchronous primary ovarian and endometrial cancers and metastatic cancer. Am J Clin Pathol, 1996. 105(3): p. 350-9.
  20. Prat, J., X. Matias-Guiu, and J. Barreto, Simultaneous carcinoma involving the endometrium and the ovary. A clinicopathologic, immunohistochemical, and DNA flow cytometric study of 18 cases. Cancer, 1991. 68(11): p. 2455-9.
  21. Shenson, D.L., et al., Loss of heterozygosity and genomic instability in synchronous endometrioid tumors of the ovary and endometrium. Cancer, 1995. 76(4): p. 650-7.
  22. Lin, W.M., et al., Loss of heterozygosity and mutational analysis of the PTEN/MMAC1 gene in synchronous endometrial and ovarian carcinomas. Clin Cancer Res, 1998. 4(11): p. 2577-83.
  23. Emmert-Buck, M.R., et al., Molecular analysis of synchronous uterine and ovarian endometrioid tumors. Int J Gynecol Pathol, 1997. 16(2): p. 143-8.
  24. Hemminki, K. and C. Granstrom, Familial clustering of ovarian and endometrial cancers. Eur J Cancer, 2004. 40(1): p. 90-5.
  25. Soliman, P.T., et al., Women With Synchronous Primary Cancers of the Endometrium and Ovary: Do They Have Lynch Syndrome? J Clin Oncol, 2005. 23(36): p. 9344-9350.

Contributed by Michelle Heayn, MD, PhD and Jeffery Fine, MD

Case IndexCME Case StudiesFeedbackHome