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Year : 2014  |  Volume : 57  |  Issue : 4  |  Page : 623-625
Bilateral synchronous high-grade serous carcinoma and clear cell carcinoma in right and left ovaries with immunohistochemical confirmation: An exceptional finding

1 Department of Pathology, KGMU, Lucknow, Uttar Pradesh, India
2 Department of Obstetrics and Gynaecology, KGMU, Lucknow, Uttar Pradesh, India

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Date of Web Publication11-Oct-2014


Synchronous epithelial or mixed epithelial and germ cells tumors in the same ovary is a recognized event, however, having two different surface epithelial tumors in contra lateral ovaries is a rare occurrence; prognosis and pathogenesis of which is still not clear. We came across similar finding in a 60-year-old female with different types of surface epithelial neoplasm in right and left ovaries at the same time; both of which were malignant. Clinicoradiologically only the left ovary revealed tumor, right ovary was atrophic. To our surprise, left ovary revealed high grade serous carcinoma and the right ovary displayed clear cell carcinoma. We performed immunohistochemistry to rule out the possibility of clear cell variant of serous papillary carcinoma. On literature search, we found; only single case with synchronous presentation of two different surface epithelial ovarian tumors in the same patient, both of which were benign.

Keywords: Clear cell carcinoma, high-grade serous carcinoma, immunohistochemistry, ovarian tumors, surface epithelial neoplasm

How to cite this article:
Preeti A, Arunachalam KA, Pradeep Y, Mati GM. Bilateral synchronous high-grade serous carcinoma and clear cell carcinoma in right and left ovaries with immunohistochemical confirmation: An exceptional finding . Indian J Pathol Microbiol 2014;57:623-5

How to cite this URL:
Preeti A, Arunachalam KA, Pradeep Y, Mati GM. Bilateral synchronous high-grade serous carcinoma and clear cell carcinoma in right and left ovaries with immunohistochemical confirmation: An exceptional finding . Indian J Pathol Microbiol [serial online] 2014 [cited 2023 Nov 30];57:623-5. Available from:

   Introduction Top

Ovarian carcinoma accounts for a great number of deaths from malignancies and is the leading cause of cancer fatalities in women. [1] Approximately, 60% of all ovarian tumors are epithelial, arising from the ovarian surface epithelium or small epithelial inclusion cysts. Surface epithelium is capable of differentiating into serous, mucinous, endometrioid, clear cell or transitional epithelium. Serous and mucinous tumors are the most common epithelial tumors. [1]

Cases with the ovary showing a mixed pattern of epithelial differentiation is on record, these patients having mixed pattern have poor clinical outcome when compared with pure epithelial tumor. [2],[3] However, the simultaneous occurrence of different histological patterns in bilateral ovaries is a rare entity and only a single case with bilateral benign tumors has been reported. [4] Synchronous presentation of dissimilar malignant surface epithelial neoplasm in different ovaries has never been reported in the literature, and this is the first one to be discussed to best of our knowledge.

   Case report Top

A 60-year-old postmenopausal female, P 5 L 5 A 0, presented with complaints of persistent pain in abdomen, for t 1-month. There was no associated bleeding per vaginum. Bimanual examination revealed a normal sized uterus and a cystic mass was felt laterally on the left side near the posterior fornix.

On ultrasonography enlarged left ovary with a hypoechoic and septate cyst of size 61.9 mm × 64.9 mm × 34.7 mm was seen along with moderate ascites (++). The right ovary and uterus were reported as atrophied.

Ultrasound guided fine-needle aspiration cytology smears from left ovarian cyst showed papillary fragments of crowded atypical glandular cells with large overlapping pleomorphic nuclei with prominent nucleoli and were diagnosed as serous papillary adenocarcinoma.

Total abdominal hysterectomy and bilateral salphingo-opeherectomy along with omentectomy was done. Intra-operatively, surfaces of both the ovaries were nodular. No mass was detected surgically in the omentum.

We received a hysterectomy with bilateral salphingo-opeherectomy and omentectomy specimen [Figure 1]a. Left ovary was enlarged and nodular, measuring 4 cm × 2.5 cm × 2 cm with solid and cystic areas. Solid areas displayed few surface papillary projections with intervening grey white, hemorrhagic and necrotic portions [Figure 1]c. Right ovary, was nodular measuring 3 cm × 2.8 cm × 1.4 cm. On opening, it was white spongy on gross examination [Figure 1]b. Both the fallopian tubes, uterus and omentum, were unremarkable.
Figure 1: Gross photomicrograph of uterus with bilateral adnexa (a), cut surface of right ovary is solid gray-white spongy (b), and left ovary shows solid cystic areas with papillary configuration (c)

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Representative tissue pieces were embedded, processed, stained with hematoxylin and eosin and examined microscopically. Sections from the left ovary displayed a tumor arranged predominantly in branched papillary architecture with central fibrovascular core, lined by atypical tumor cells displaying nuclear stratification surrounded by desmoplastic stroma. The tumor cells were pleomorphic, with vesicular nucleus, prominent nucleoli and a moderate amount of eosinophilic cytoplasm. Mitotic figures were prominent [Figure 2] a and c. Few psammomatous calcifications were seen.
Figure 2: Microscopic images of left ovary displaying a malignant neoplasm disposed in papillary configuration (H and E, scanner view) (a), tumor cells have vesicular nuclei and scant cytoplasm (H and E, ×100) (c). Right ovary tumor was predominantly disposed in solid sheets (H and E, scanner view) (b). The tumor cells are large with small hyperchromatic nuclei and abundant clear cytoplasm (H and E, ×100) (d)

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The sections from the right ovary showed tumor cells arranged predominantly in solid sheets with focal abortive acinar and papillary configuration. The tumor cells were large with small hyperchromatic nuclei and abundant clear cytoplasm [Figure 2]b and d. Provisional diagnoses of serous papillary cystadenocarcinoma in left ovary with a possibility of either primary clear cell carcinoma or clear cell variant of serous papillary carcinoma in right ovary were considered.

A detailed panel of immunohistochemistry (IHC) markers was used as per review of the literature [Table 1]. The tumor cells in the left ovary displayed strong membranous for CK7 and nuclear positivity for WT1, ER and p53; however CK20, CEA and CD15, were negative [Figure 3]a, c, e, g, i. Whilst the tumor cells in right ovary were positive for CK7, CEA, CD15 and nuclear positivity for WT1 was noted in a small number of tumor cells [Figure 3]b, d, f, h, j. Clear cells were negative for CK20, ER and p53, thereby suggesting that the right ovary harbored clear cell carcinoma which was phenotypically and on IHC different from the tumor of left ovary (serous papillary carcinoma).
Table 1: IHC panel performed on the right and left ovarian tumor with controls

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Figure 3: Immunohistochemistry panel: Clear cell carcinoma (right ovary) on right and papillary serous cystadenocarcinoma (left ovary) on left side displaying CK7, CK20, ER, p53 and CD15 immunoexpression (×100). Both the tumors are positive for CK7 (a and b) and negative for CK 20 (c and d). Clear cell carcinoma is negative for ER (f) and p53 (h) and is positive for CD15 (j). Whereas serous papillary carcinoma shows strong nuclear postivity for ER and p53 (e and g). CD15 is negative (i)

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The patient was given four cycles of chemotherapy and was presently asymptomatic till last follow-up postsurgery of 4 months.

   Discussion Top

Benign ovarian neoplasms can occur in all age groups whereas malignant ovarian neoplasms are more commonly seen in the elderly. Serous tumors being most common around one-fourth of all and clear cell tumors are comparatively rare 2-5% of all ovarian tumors and having poorer prognosis compared with serous tumors. Clear cell carcinoma of the ovary differs not only on histology, but also vary in their clinical, molecular and immunohistochemical properties. [4],[5]

Almost all primary ovarian neoplasms, except mucinous tumors, exhibit typical CK7+/CK20 - keratin profile. Serous carcinomas are also strongly reactive for p53, WT1, ER, E-cadherin and also express CK5/6, CK8, CK18, EMA, S-100 and PAX-8. [6],[7] Markers of diagnostic significance in clear cell carcinoma include CEA, HNF-1 β, CD15, EMA, Ber-EP4, Bcl2, CA-125 and PAX 8. [8]

Clear cell carcinomas are usually negative for WT1 and ER-α [Table 1]; though, few studies have reported a proportion of clear cell carcinoma cases being positive for WT1, the percentage of reactive tumor cells are much less when compared with serous carcinomas. [7] In our case, WT1 was positive in tumor cells with a clear morphology, but the expression was weak and limited to few areas.

p53 expression is weak or negative in clear cell carcinoma compared with the strong positivity in a serous carcinoma, which was coherently found in right ovary tumor in our case when compared to left. [9]

Divergent differentiation at other sites are always associated with poor prognosis, so careful histological examination and appropriate panel of IHC to diagnose and differentiate between malignant ovarian surface epithelial neoplasms should always be performed in cases with even small focus of diverse histopathology. [10]

It is postulated that synchronous two different morphologies of ovarian epithelial neoplasm can occur in the same ovary because of divergent differentiation of single malignant clone. As far as our case is concerned possible explanation could be either that there were two different primaries occurring at same time or phenotypic differentiation of a single tumor occurred on metastasis to the other ovary.

Our case is unique as it is the first report of its kind showing simultaneous occurrence of two different histological types of ovarian carcinoma in contra lateral ovaries.

Further it was also unusual that right ovarian tumor was not picked up on ultrasonography perhaps because of almost normal size of right ovary and the clear cell carcinoma was an incidental finding on histopathological examination.

   References Top

Dhillon PK, Yeole BB, Dikshit R, Kurkure AP, Bray F. Trends in breast, ovarian and cervical cancer incidence in Mumbai, India over a 30-year period, 1976-2005 : a0 n age-period-cohort analysis. Br J Cancer 2011;105:723-30.  Back to cited text no. 1
Moid FY, Jones RV. Granulosa cell tumor and mucinous cystadenoma arising in a mature cystic teratoma of the ovary : A0 unique case report and review of literature. Ann Diagn Pathol 2004;8:96-101.  Back to cited text no. 2
McKenna M, Kenny B, Dorman G, McCluggage WG. Combined adult granulosa cell tumor and mucinous cystadenoma of the ovary : g0 ranulosa cell tumor with heterologous mucinous elements. Int J Gynecol Pathol 2005;24:224-7.  Back to cited text no. 3
Sethi D, Ahluvalia C, Sharma U, Khetarpal S. A synchronous presentation of two different ovarian tumors : a0 rare occurrence. Ann Med Health Sci Res 2013;3:268-70.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
Eltabbakh GH, Mount SL, Beatty B, Simmons-Arnold L, Cooper K. Clinical and molecular differences between clear cell and papillary serous ovarian carcinoma. J Surg Oncol 2006;93:379-86.  Back to cited text no. 5
Nofech-Mozes S, Khalifa MA, Ismiil N, Saad RS, Hanna WM, Covens A, et al. Immunophenotyping of serous carcinoma of the female genital tract. Mod Pathol 2008;21:1147-55.  Back to cited text no. 6
Acs G, Pasha T, Zhang PJ. WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium. Int J Gynecol Pathol 2004;23:110-8.  Back to cited text no. 7
Ueda H, Watanabe Y, Nakai H, Hemmi H, Koi M, Hoshiai H. Microsatellite status and immunohistochemical features of ovarian clear-cell carcinoma. Anticancer Res 2005;25:2785-8.  Back to cited text no. 8
Shimizu M, Nikaido T, Toki T, Shiozawa T, Fujii S. Clear cell carcinoma has an expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas. Cancer 1999;85:669-77.  Back to cited text no. 9
Köbel M, Kalloger SE, Carrick J, Huntsman D, Asad H, Oliva E, et al. A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am J Surg Pathol 2009;33:14-21.  Back to cited text no. 10

Correspondence Address:
Agarwal Preeti
Department of Pathology, KGMU, Lucknow - 226 003, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.142706

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

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