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CASE REPORT
Year : 2022  |  Volume : 49  |  Issue : 2  |  Page : 213-216

A case report – Synchronous endometrial and ovarian cancer


1 Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College, KAHER, Belagavi, Karnataka, India
2 Department of Pathology, Jawaharlal Nehru Medical College, KAHER, Belagavi, Karnataka, India
3 Department of Haematooncology, Dr. Prabhakar Kore Hospital, Belagavi, Karnataka, India

Date of Submission28-Jan-2022
Date of Acceptance22-Jun-2022
Date of Web Publication23-Aug-2022

Correspondence Address:
Mrityunjay Metgud
Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College, KAHER, Belagavi - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.jss_14_22

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  Abstract 


Synchronous malignancies of the female genital tract are a very rare entities. Synchronous endometrial and ovarian cancer (SEOC's) is defined as simultaneous presence of these two cancers at the time of diagnosis as opposed to the metachronous cancer where these two cancers are diagnosed at different chronologic time points. Clinical presentation of these women is indistinct, and due to the different management and the favorable prognosis of SEOC's, an extensive pathological evaluation is required to distinguish SEOC's from the metastatic disease. Synchronous and Metachronous malignant tumours are the two components of multiple primary malignant tumours (MPMT's). The distinction between the independent primary tumors and metastatic tumours is clinically significant and complicated. Synchronous endometrial and ovarian carcinoma is a rare entity. SEOC's are more frequently undiagnosed. Henceforth, the diagnostic dilemma of SEOC's versus metastatic disease is challenging and therefore separating the two groups is important as the prognosis is different.

Keywords: Endometrial carcinoma, ovarian carcinoma, synchronous cancer


How to cite this article:
Metgud M, Srivani T, Patil KP, Savanur M, Malli R, Sanikop A, Bhise R. A case report – Synchronous endometrial and ovarian cancer. J Sci Soc 2022;49:213-6

How to cite this URL:
Metgud M, Srivani T, Patil KP, Savanur M, Malli R, Sanikop A, Bhise R. A case report – Synchronous endometrial and ovarian cancer. J Sci Soc [serial online] 2022 [cited 2022 Oct 3];49:213-6. Available from: https://www.jscisociety.com/text.asp?2022/49/2/213/354260




  Introduction Top


Synchronous malignancies of the female genital tract are very rare entities (0.5%–1.7%).[1] Among them, synchronous endometrial and ovarian cancers (SEOCs) are the most common types of malignancy and account for 50%–70% of all synchronous female genital tract tumors with a frequency of 5% among endometrial and 10% among ovarian primary tumors.[2] SEOCs are defined as the simultaneous presence of these two cancers at the time of diagnosis as opposed to metachronous cancer where these two cancers are diagnosed at different chronologic time points.[2] Due to the different management and the favorable prognosis of SEOCs, it is important to separate SEOCs from a metastatic disease.[2] The clinical presentation of these women is indistinct, and due to the different management and the favorable prognosis of SEOCs, an extensive pathological evaluation is required to distinguish SEOCs from metastatic disease.[1]


  Case Report Top


A 60-year-old female presented with postmenopausal bleeding for 2 months. She did not have any other gynecologic problems. She did not have any history of breast or colon malignancy in the past. The patient was a known diabetic and on treatment. There was no family history of breast or colon malignancy. Abdominopelvic examination revealed a paraumbilical hernia and an enlarged uterus of 24 weeks size with a smooth surface and firm in consistency. A separate mass was also appreciated in the right iliac fossa which was firm in consistency. A pelvic examination too revealed 24 weeks size uterus with a smooth surface and firm consistency. A right adnexal mass was also appreciated of 10 cm × 8 cm in size which was firm in consistency. The abdominal CT scan confirmed an enlarged uterus of size 14 cm × 13 cm × 12.5 cm and a right adnexal mass of 9 cm × 9.4 cm, with the likelihood of gastrointestinal stromal or a solid ovarian neoplasm. Serum CA-125 concentration was 24.6 U/mL (normal range <35 U/mL). Her chest X-ray also did not reveal any features suggestive of metastasis.

A laparotomy was performed. Intraoperatively, the uterus was uniformly enlarged around 24–26 weeks size with a smooth surface and firm in consistency and an enlarged right ovary of approximately 10 cm × 9 cm in size with firm to hard in consistency. The left ovary and Fallopian tube were normal [Figure 1]. The ascitic fluid for cytology was obtained and total abdominal hysterectomy with bilateral salpingo-oophorectomy with omentectomy was done. A paraumbilical hernia repair was performed. The intraoperative and postoperative period was uneventful. The ascitic fluid cytology showed a negative for malignant cells.
Figure 1: Right ovarian tumor with enlarged uterus intraoperatively

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Pathologically, the tumors were histologically dissimilar, unilateral ovarian tumor, no myometrial invasion, no vascular space invasion of endometrial and ovarian cancer, and absence of other evidence of spread. The histopathological report of the specimen sent revealed clear-cell carcinoma of the right ovary with endometrioid carcinoma of the endometrium Grade 1. There were adenomyotic changes seen in the myometrium. The left ovary and cervix were unremarkable. A histological diagnosis of endometrial endometrioid carcinoma Stage 1A, Grade 1 with right ovary clear-cell carcinoma Stage 1A, Grade 3 was made [Figure 2] and [Figure 3]. Based on the above findings, a diagnosis of SEOCs was made.
Figure 2: Endometrial endometrioid adenocarcinoma

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Figure 3: Clear-cell carcinoma of right ovary – sheets of large cells with clear cytoplasm and large pleomorphic vesicular nucleus with prominent nucleoli

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The patient had a regular follow-up and received six cycles of adjuvant chemotherapy.


  Discussion Top


Synchronous and metachronous malignant tumors are the two components of multiple primary malignant tumors.[3] When the second primary cancer is diagnosed simultaneously or within 6 months of primary cancer, it is termed as synchronous tumors and when diagnosed after 6 months of primary cancer, it is defined as metachronous tumors.[3] The dilemma continues, as to how to differentiate the primary from metastatic tumors and consequently the management strategies.[3] In the past, the pathological criteria laid down by Ulbright and Roth, were later refined by Scully et al. to distinguish synchronous primary tumors from metastatic tumors.[1],[2] Scully et al. have classified them into three groups (a) primary endometrial tumors with ovarian metastasis, (b) primary ovarian tumors with endometrial dissemination, and (c) synchronous endometrial and ovarian malignancies.[1] The published literature has reported better outcomes in the synchronous disease category as compared to the other groups.[1] The differential diagnosis between synchronous and metastatic diseases in the endometrium and ovary do have prognostic and therapeutic implications, and is often misdiagnosed as Stage III endometrial carcinoma or Stage II ovarian carcinoma.[3]

The pathogenesis is explained by the theories – “Estrogenic environment, Microenvironment restriction and a hormonal field effect” in the development of SEOCs.[3] Several molecular studies have shown that 95% of SEOCs share clonal origin irrespective of their clinicopathological features.[3] The most common mutation identified is a PTEN (over 75% of cases), followed by ARID 1A. Other less commonly identified mutations were PIK3CA, HNF1B, KRAS, and CTNNB110.[3] SEOCs are a disease of middle-aged women. One hypothesis to link this association is the possibility of Lynch syndrome.[3] The patients with HNPCC also develop endometrial or ovarian cancer.[4] The incidence of SEOC among women with Lynch syndrome is reported as 21.5%.[3] The results of studies suggest that patients with endometrioid or clear-cell ovarian cancer under the age of 53 are at higher risk for loss of MMR (MLH1, MSH2, and MSH6) expression and Lynch syndrome.[5],[6] However, the majority of SEOCs are sporadic cancers.[7] All sporadic SEOCs share nonsynonymous mutations in at least one cancer driver gene of EEC and/or EOC.[3]

The simultaneous detection of malignancy at the endometrial and ovary is often challenging to both the clinicians and the pathologists to arrive at a correct diagnosis and for the appropriate management. The distinction between independent primary tumors and metastatic tumors is clinically significant and is complicated as well. These tumors can be distinguished only after histopathological examination of the surgical specimen, utilization of criteria set by Ulbright and Roth, later modified by Scully et al., and immunohistochemical studies.[3]

It is observed that the histologic subtype of both primary tumors is endometrioid in 50%–70% of cases with SEOCs. However, synchronous primary endometrial and ovarian cancers may have a similar appearance or may be of different histologic types.[3] SEOCs are characterized by histological dissimilarity of the tumors, no or only superficial myometrial invasion of endometrial cancer, no vascular space invasion of endometrial and ovarian tumor, absence of other evidence of spread, ovarian unilateral tumor, ovarian tumor in the parenchyma, and without the involvement of the surface of the ovary, dissimilarity of molecular genetics or karyotypic abnormalities in the tumors, and different ploidy of DNA of the tumors.[3]

The majority of women with SEOCs are 41–54 years of age, of which 40% are nulliparous, 2/3 premenopausal, and 1/3 obese.[2] The risk factors with SEOCs are those associated with hyperestrogenic state – obesity, perimenopause, chronic anovulation, polycystic ovarian disease, estrogen-producing ovarian tumors, and estrogen replacement therapy.[1],[4] The most common presentation is Abnormal uterine bleeding (AUB) in about 46% of cases and few with postmenopausal bleeding. About 17% of patients with pelvic pain and 13% with a palpable abdominal and pelvic mass.[2],[3] In our case, however, the female was 60-year-old, postmenopausal, multiparous with normal body mass index (BMI) who presented to us with postmenopausal bleeding.

Therapy is governed by stage and grade of ovarian tumor because the ovarian tumor has a worse prognosis and higher risk of recurrence.[8] The treatment of choice in SEOCs is systematic surgical staging. The procedure includes total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, pelvic and para-aortic lymphadenectomy ± appendicectomy, and complete resection of all disease after collecting ascitic fluid/saline wash fluid for cytology.[2],[3] This allows a more clear decision for stage-related postoperative adjuvant therapy.[3] The main adjuvant treatment is chemotherapy, followed by radiotherapy.[3]

Prognostic factors

Prognostic factors include young age, premenopausal status, normal BMI, low FIGO stage, low grade, and low-risk histology, low level of cancer antigen CA-125, complete staging or debulking surgery.[8] High CA-125 level is an independent risk factor of the disease.[8] Several studies have shown that patients with synchronous primary cancers have a good overall prognosis. The women with SEOCs had a 10-year survival similar to those who did not have synchronous ovarian cancer (79.4% vs. 80.7%).


  Conclusion Top


Synchronous endometrial and ovarian carcinoma is a rare entity.[1] The gynecologic oncology group study found that women with SEOCs had an overall prognosis of 86% of 5-year survival and 80% of 10-year survival.[3] SEOCs are more frequently undiagnosed or understaged due to limited preoperative workup and also intraoperative assessment of ovarian pathology, especially with occult disease.[3] Henceforth, the diagnostic dilemma of SEOCs versus metastatic disease is challenging and therefore separating the two groups is important as the prognosis is different.

Statement of consent

Informed consent was obtained.

Details of ethics approval

Institutional ethic approval was obtained for the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Khalid N, Ullah F, Zafar H, Anwer AW, Abbas T, Shakeel O, et al. Synchronous primary endometrial and ovarian cancers: Trends and outcomes of the rare disease at a South Asian Tertiary Care Cancer Center. Cureus 2020;12:e9163.  Back to cited text no. 1
    
2.
Makris GM, Manousopoulou G, Battista MJ, Salloum I, Chrelias G, Chrelias C. Synchronous endometrial and ovarian carcinoma: A case series. Case Rep Oncol 2017;10:732-6.  Back to cited text no. 2
    
3.
FOGSI Oncology Committee Volume :1 Issue: 1, October 3rd 2020 – Synchronous VS Metastatic Endometrial And Ovarian Cancer – A Diagnostic and Management Dilemma.  Back to cited text no. 3
    
4.
Guerra F, Girolimetti G, Perrone AM, Procaccini M, Kurelac I, Ceccarelli C, et al. Mitochondrial DNA genotyping efficiently reveals clonality of synchronous endometrial and ovarian cancers. Mod Pathol 2014;27:1412-20.  Back to cited text no. 4
    
5.
Drake AC, Campbell H, Porteous ME, Dunlop MG. The contribution of DNA mismatch repair gene defects to the burden of gynecological cancer. Int J Gynaecol Cancer 2003;13:262-77.  Back to cited text no. 5
    
6.
Vierkoetter KR, Ayabe AR, VanDrunen M, Ahn HJ, Shimizu DM. Lynch syndrome in patients with clear cell and endometrioid cancers of the ovary. J Gynaecol Oncol 2014;135:81-4.  Back to cited text no. 6
    
7.
Kobayashi Y, Nakamura K, Nomura H, Banno K, Irie H, Adachi M, et al. Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers. Int J Gynecol Cancer 2015;25:440-6.  Back to cited text no. 7
    
8.
Heitz F, Amant F, Fotopoulou C, Battista MJ, Wimberger P, Traut A, et al. Synchronous ovarian and endometrial cancer – An international multicenter case-control study. Int J Gynecol Cancer 2014;24:54-60.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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