Ovarian Endometriosis with Borderline Serous Tumor: A Rare Occurrence

The endometriosis term was first described by Carl Freiherr Von in 1860 and it is defined as the presence of endometrial-like glands and stroma outside the uterus. Endometriosis is a prevalent benign condition arising from the female reproductive system and affects about 7%–10% of females.[] The association of endometriosis with serous borderline ovarian tumors has been a matter of interest in gynecology. Sampson[] first described the association between endometriosis and carcinoma. Later, numerous studies have reported this association. Endometriosis-associated ovarian tumors have a more favorable prognosis and better survival than nonendometriosis-associated ovarian cancer.[] The endometriosis-associated ovarian malignancies are clear cell adenocarcinoma and endometrioid adenocarcinoma, whereas serous and mucinous are rare malignancies associated with endometriosis. Here, we present a case report in which endometriosis was associated with a borderline serous tumor. CASE REPORT Here, we present the case report of a forty five year old female who had clinically presented with complaints of painful and heavy menstrual bleeding for the last 6 months. The patient was advised radiological investigations and showed multiple fibroids of the uterus varying in size from 0.5 to 5 cm along with a left side adnexal (tubo-ovarian) mass measuring 15 cm × 10 cm. Following this, CA125 was advised and showed increased levels. In view of all these findings, the patient underwent a total abdominal hysterectomy under general anesthesia. During surgery, frozen sections were taken and the whole left-sided tubo-ovarian mass was sent for histopathological review. Grossly, a globular, partially capsulated cyst was received, measuring 7.5 cm × 7 cm × 3 cm. The external surface was hemorrhagic, and multiple septations were seen; the lumen was seen filled with dark-colored blood. The cut surface of the tissue shows irregular papillary growth measuring 4 cm × 4 cm × 2.5 cm and the inner surface shows gray, white solid areas [Figure 1b]. On microscopy of frozen sections of a specimen, atypical epithelial cells were seen arranged in solid sheets and trabeculae and a diagnosis of an atypical proliferative ovarian tumor was given. Surgery was further conducted, and the whole radical hysterectomy specimen with various lymph nodes, i.e., bilateral left external iliac, internal iliac, and right obturator lymph node, with omental and peritoneal tissue was sent to histopathology along with peritoneal fluids for cytopathology. The cut section of the uterus showed a large fibroid protruding from the serosal surface measuring 6 cm × 6 cm × 5 cm and another fibroid on the anterior surface m/s 3 cm × 3 cm and a few intramural fibroids measuring 0.5 cm. The endometrial cavity showed a polyp protruding into the lumen measuring 1 cm in diameter [Figure 1a]. Sections were taken from the different locations of the uterus and cervix with ovary, and thin sections were prepared from formalin-fixed paraffin-embedded tissue blocks and then subjected to hematoxylin and eosin staining. A few more sections were taken from the left side tubo-ovarian mass also. On microscopy of the uterus, leiomyomatous polyp with multiple leiomyomas with hyaline changes was seen. All lymph nodes sent were found to be uninvolved by the tumor. Sections of the left tubo-ovarian mass revealed florid spindle cell proliferation arranged in fascicles and whorls with dense fibrocollagenous stroma. The cyst wall was lined by single to stratified squamous epithelium which showed minimal atypia and areas of tufting [Figure 2]. Sheets of hemosiderin laden macrophages [Figure 3] and foci of benign looking endometrial glands and scant stroma were also seen Figure showed minimal atypia and areas of tufting [Figure 3]. Sheets of hemosiderin laden macrophages [Figure 2a] and foci of benign looking endometrial glands and scant stroma were also seen [Figure 2b]. Following all these features, the diagnosis of ovarian endometriosis with serous borderline tumor was given and peritoneal fluid sent for cytopathology was found to be negative for malignant cells.

Endometriosis is characterized by the presence of endometriotic tissue outside the uterus and is associated with pelvic pain and subfertility. The exact pathology of endometriosis is, however, unknown, but according to some, reflux of endometrial tissue through the fallopian tube during menstruation, coelomic metaplasia, embryonic cell rest, lymphatic and vascular spread are considered.[] Many factors like genetic, hormonal as well as immune system have a role to play.[] The ovary is the most common site of endometriosis followed by pelvic structures. While endometriosis is a benign condition, it has some resemblance with malignancy, including metastatic-like behavior, tissue invasion, proliferation, angiogenesis, and decreased apoptosis.[] Clear cell ovarian carcinoma and endometrioid carcinoma are most strongly and reproducibly associated with endometriosis.[] Borderline tumors of low malignant potential also exist, most typically with serous or mucinous differentiation. Endometriosis has its malignant potential due to high estrogen concentration which leads to malignant proliferation of endometriotic cysts or since there is a mutation in the AR1D1A gene and consequent loss of BAF250a expression. ARID1A is a tumor suppressor gene, and the loss of ARID1A expression is considered to be responsible for the activation of early carcinogenic mechanisms.[] Mutations of this gene are closely associated with atypical endometriosis. However, in distal nonatypical endometriotic tissue, no alterations in ARID1A have been reported. At present, miRNAs’ role as a biomarker has been under investigation, as it is found to be dysregulated in both endometriosis and ovarian cancer,[] thus demonstrating the molecular association between these two entities. The iron produced in endometriotic cysts also causes oxidative stress, which leads to genetic mutation and progression to malignancy.[]

The actual prevalence of endometriosis-associated ovarian tumors is often underestimated. Since there is a lack of enough confident criteria for diagnosing endometriosis associated ovarian tumors, such small or destructive foci of endometriosis might be missed if extensive sampling is not done. Thus, it is important to study endometriosis associated borderline or malignant ovarian epithelial tumors and to analyze clinical, histopathological feature their survival and immunohistochemical data and also to compare it with tumors without any association with endometriosis. 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 understands that her 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.

1 Sarmadi S, Mood NI, Hajeer P, Motevalli D, Masoomian M. The association between endometriosis and surface epithelial ovarian tumors: A review of pathological data. Int J Cancer Manag 2018; 11:e96102 Sampson JA. Endometrial carcinoma of the ovary arisisng in endometrial tissue in that organ. Arch Surg 1925; 10:1–723 Gorp TV, Amant F, Neven P, Vergote I, Moerman P. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol 2004; 18:349–714 Worley MJ, Welch WR, Berkowitz RS, Ng SW. Endometriosis-associated ovarian cancer: A review of pathogenesis. Int J Mol Sci 2013; 14:5367–795 Giudice LC, Kao LC. Endometriosis. Lancet 2004; 364:1789–996 Giudice LC. Clinical practice: Endometriosis. New Engl J Med 2010; 362:2389–987 Rossing MA, Cushing-Haugen KL, Wicklund KG, Doherty JA, Weiss NS. Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery. Cancer Causes Control 2008; 19:13578 Grandi G, Toss A, Cortesi L, Botticelli L, Volpe A, Cagnacci A. The association between endometriomas and ovarian cancer: Preventive effect of inhibiting ovulation and menstruation during reproductive life. Biomed Res Int 2015; 2015:751571. Epub 2015 Aug 309 Agrawal S, Tapmeier T, Rahmioglu N, Kirtley S, Zondervan K, Becker C. The miRNA mirage: How close are we to finding a non-invasive diagnostic biomarker in endometriosis?A systematic review. Int J Mol Sci 2018; 19:59910 Moris Brilhante AV, Augusto KL, Portela MC, Gabriele Sucupira LC, Freistas Oliveira LA, Verissimo Pouchaim AJ, et al. Endometriosis and ovarian cancer: An integrative review (Endometriosis and ovarian cancer). Asian Pac J Cancer Prev 2017; 18:11–6