Indian Journal of Pathology and Microbiology

: 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

Agarwal Preeti1, Kumar Arun Arunachalam1, Yashodhara Pradeep2, Goel Madhu Mati1,  
1 Department of Pathology, KGMU, Lucknow, Uttar Pradesh, India
2 Department of Obstetrics and Gynaecology, KGMU, Lucknow, Uttar Pradesh, India

Correspondence Address:
Agarwal Preeti
Department of Pathology, KGMU, Lucknow - 226 003, Uttar Pradesh


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.

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;57:623-625

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 2021 Dec 2 ];57:623-625
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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.


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}

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}

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}{Figure 3}

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


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.


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