{"paper_id":"d9c14f42-fda6-46aa-b28d-ce8e38f315e7","body_text":"Submit Manuscript | http://medcraveonline.com\nAbbreviations: CCC, clear cell carcinoma; IHC, immuno histo \nchemistry; YST, yolk sac tumor; LDH, lactate dehydrogenase;  PAS, \nperiodic acid schiif stain;  EMA, epithelial membrane antigen;  CK, \ncytokeratin; AFP, alpha fetoprotein\nIntroduction\nClear cell carcinoma (CCC) represents 2-10% of all epithelial \novarian cancers. 24-50% of the patients are known to have associated \npelvic endometriosis. Women typically present between the ages of \n40 and 70 with the peak incidence at age 52. CCC is rarely described \nin young females with youngest reported age being 23 years. 1 Risk \nfactors for ovarian cancers include family history, age and nulliparity. \nThe condition is classically associated with dysmenorrhoea, deep \ndyspareunia and infertility. Endometriosis, a common benign \ngynaecologic condition, has been reported in association with certain \nepithelial ovarian tumours. According to a previous report, the rank \norder of the prevalence of endometriosis in each histologic type is \nclear cell (39.2%)>endometrioid (21.2%)>serous (3.3%)>mucinous \ntype (3.0%). 2 Scully and Barlow in 1967 established the close \nassociation between CCC, endometrioid carcinoma of the ovary and \nendometriosis.3 We present a case of CCC associated with endometriosis \nin a 24-year-old young female with immunohistochemistry (IHC). \nCase presentation\nA 24-year-old unmarried female was referred to the Department \nof Obstetrics & Gynaecology in June 2010 with a history of recurrent \nendometriosis-associated pelvic pain and excessive dysmenorrhoea \nfor the last 2years. She was diagnosed to have bilateral ovarian \ncysts measuring 7.4x7cm on right side and 2.5x2cm on left side in \nApril 2008. The symptoms were relieved with oral analgesics and \noral contraceptive pills till 2009. The symptoms recurred in the year \n2010 and on per-abdominal examination; a firm mass was palpable \nin right lower abdomen. Ultrasonography revealed a large complex \ncystic adnexal mass measuring 18x16cm with echogenic nodules and \npapillary excrescences. There was a small cyst in the left ovary about 1 \ncm diameter. α-fetoprotein and β-hCG were normal; however, CA125 \nand LDH were raised. The patient underwent exploratory laparotomy \nwith right salpingo-oophorectomy. Intra-operatively, left ovary was \nseen buried in dense adhesions with gut and sigmoid colon. Ascites \nwas present, was sampled for cytologic examination and was reported \nas negative for malignant cells.\nGrossly, the right ovary was enlarged and was totally replaced by \na tumor measuring 15x13x6cm. The external surface was smooth, \nlobulated and red-grey in colour. On cut section, the tumor was \npredominantly cystic (70%) and showed focal solid areas (30%) \nwith many papillations and polypoid projections. No residual \nnormal ovarian tissue was identifiable. Microscopically, the tumour \nwas composed of papillary and tubule-cystic patterns lined by \npredominantly clear to eosinophilic cells with sharply demarcated cell \nborders, had pleomorphic vesicular nuclei and conspicuous nucleoli \n(Figure 1). Occasional Schiller-Duval body like structures are seen \nalong with numerous Periodic-acid Schiff’s stain (PAS) - positive \ndiastase resistant extracellular hyaline globules (Figure 2A). In \naddition, the serosal aspect of the same side fallopian tube had foci of \nendometriosis. Based on the morphology and age, the possibilities of \nyolk sac tumour and clear cell carcinoma were considered. IHC panel \ncomprising of cytokeratin 7 (CK7), Epithelial membrane antigen \n(EMA), CD15 and α FP was performed. The tumour cells were \nstrongly positive for CK7 and EMA and negative for α FP (Figure \n2). CD15 was non-contributory. Hence, based on the morphology \nand IHC findings, a diagnosis of clear cell carcinoma associated with \nendometriosis was offered. The tumor was stage 1A as per FIGO \novarian cancer staging. She was given five cycles of Cisplatin based \nchemotherapy and she was well after four years and two months of \nfollow-up. \nAdv Cytol Pathol. 2017;2(1):1‒3 1\n© 2017 Gupta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nClear cell carcinoma of the ovary in a 24-year-old \nfemale associated with endometriosis\nVolume 2 Issue 1 - 2017\nNalini Gupta,1 Arvind Rajwanshi,1 Vanita Suri2\n1Department of Cytology and Gynaecologic Pathology, \nPostgraduate Institute of Medical Education and Research, India \n2Department of Obstetrics and Gynaecology, Postgraduate \nInstitute of Medical Education and Research, India\nCorrespondence: Nalini Gupta, Department of Cytology \nand Gynecological Pathology, Postgraduate Institute of Medical \nEducation and research, Chandigarh, India, T el +91-172-2755114, \nFax +91-172-2744401, Email nalini203@gmail.com\nReceived: November 12, 2016 | Published: January 02, 2017\nAbstract\nClear cell carcinoma (CCC) of the ovary comprises about 7.4% of ovarian carcinomas \nand 2.4% of ovarian epithelial neoplasms. The average age at the time of diagnosis \nranges from 48 to 58 years. A close association between CCC and endometriosis \nhas been documented in the previous series with documentation of transition from \nendometriosis to CCC in few series. Fifty percent of cases of CCC are stage I at the \ntime of diagnosis, and 15% are stage II. Yolk sac tumor (YST) can have a variety of \nmorphologic patterns, some of which can resemble CCC. The distinction between YST \nand CCC is important for the clinical management of patients. Immunohistochemistry \n(IHC) may be mandatory for differentiating these tumors in cases with diagnostic \ndifficulty. We report a case of a 24-year-old female diagnosed to have CCC associated \nwith endometriosis. We wish to highlight the role of IHC in such diagnostically \ndifficult cases. \nKeywords: clear cell carcinoma, immunohistochemistry, ovary, yolk sac tumor\nAdvances in Cytology & Pathology\nCase Report\n Open Access\n\n\nClear cell carcinoma of the ovary in a 24-year-old female associated with endometriosis\n2\nCopyright:\n©2017 Gupta et al.\nCitation: Gupta N, Rajwanshi A, Suri V.  Clear cell carcinoma of the ovary in a 24-year-old female associated with endometriosis. Adv Cytol Pathol. \n2017;2(1):1‒3. DOI: 10.15406/acp.2017.02.00006\nFigure 1 Clear cell carcinoma ovary. \n(A) Gross of the cystic ovarian tumor with smooth external surface and solid \nareas having polypoid projections\n(B) Cystic spaces lined by multilayered clear cell to tall columnar epithelium \n(H&Ex10X).\n(C) Papillary to tubule-cystic pattern of tumor cells (H&Ex10X).\n(D) Clear to eosinophilic cells with sharply demarcated cell borders and \npleomorphic vesicular nuclei with numerous extracellular hyaline globules \n(H&Ex40X).\nFigure 2 Clear cell carcinoma ovary.\n(A) Many PAS positive hyaline globules (PASx40X).\n(B) T umour cells positive for epithelial membrane antigen (Immunostainx40X).\n(C) T umor cells positive for cytokeratin7 (Immunostainx40X).\n(D) T umor cells negative for α-fetoprotein (Immunostainx40X).\nDiscussion\nClear cell carcinoma (CCC) was first described in 1939,4 and was \nclassified as a subgroup of epithelial ovarian carcinoma. The clinical \nfeatures include abdominal or pelvic mass, abdominal distension or \npain. Women typically present between the ages of 40 and 70 with the \npeak incidence at age 52. We presented this case in a young 24-year-\nold unmarried female. Takano M et al. 1 analyzed 254 cases of CCC \nwith a mean age of 52.3years (range 23-73 years). Ryu SY et al., 5 \nanalyzed 150 cases of CCC with a median age of 46.8 years. Malignant \ntransformation of endometriosis in gonadal and extra gonadal sites has \nbeen well documented since Sampson4 reported the first case in 1925. \nAn interesting point in the present case is that clear cell carcinoma \nwas detected within two years of diagnosis of endometriosis. On \nmicroscopic examination, yolk sac tumor was considered a strong \npossibility based on the presence of PAS positive hyaline globules \nas well as Schiller-Duval like bodies. Cytohistomorphological \ndifferences between CCC and YST have been enlisted in Table 1.6 This \ncase also highlights importance of IHC in such difficult cases. Table 2 \nshows immunohistochemical markers helpful to differentiate between \nCCC of the ovary and YST.7–10 Clear cell carcinoma of the ovary are \nknown to be positive for CK7, EMA and Leu M1/ CD15 as compared \nto yolk sac tumor. CK and EMA were positive in the present case; \nhowever CD15 was non-contributory due to technical error. Napsin \nA has been identified as a newer marker, which shows positivity in \napproximately 85% CCC of the ovary. 9 SALL4 is another sensitive \nimmunohistochemical marker, which is useful to differentiate YST \nfrom CCC. Glypican-3 is an oncofetal protein, which is expressed in \ngerm cell tumors, particularly YST. Based on age and morphology, a \ndifferential diagnosis of YST and CCC of the ovary was considered in \nthe present case and IHC was useful to clinch the diagnosis as CCC \nof the ovary. Dysgerminoma, Krukenberg tumor, metastatic renal cell \ncarcinoma, and struma ovarii are less common entities that may cause \ndiagnostic difficulty at times. \nT able 1 Pathologic features to differentiate clear cell carcinoma of the ovary \nfrom yolk sac tumor\nPathologic features Clear cell \ncarcinoma Y olk sac tumor\nT umor pattern T ubulo-papillary, \nsolid\nVarious patterns \ndescribed\nFibro-vascular septae Delicate, Hyalinized -/+\nCellular cohesion ++ +\nSchiller-duval like \nbodies - ++\nNuclear pleomorphism + ++\nCytoplasmic outlines Better preserved Faint and delicate\nNuclear membrane Smooth thickened Not thickened\nNucleoli + +++\nMulti nucleation + ++\nCytoplasmic \nvacuolation + ++\nHob-nailing of tumor \ncells + ++\nPAS positive hyaline \nglobules ++ +\nT able 2 Immunohistochemical markers to differentiate clear cell carcinoma of \nthe ovary from yolk sac tumor\nIHC markers Clear cell carcinoma Y olk sac tumor\nCK7 + -\nEMA + -\nCD15/Leu M1 + -\nNapsin A + -\nAFP - +/-\nGlypican3 - ++\nSALL4 - ++\n\n\nClear cell carcinoma of the ovary in a 24-year-old female associated with endometriosis\n3\nCopyright:\n©2017 Gupta et al.\nCitation:  Gupta N, Rajwanshi A, Suri V.  Clear cell carcinoma of the ovary in a 24-year-old female associated with endometriosis. Adv Cytol Pathol. \n2017;2(1):1‒3. DOI: 10.15406/acp.2017.02.00006\nConclusion\nIn conclusion, the association of endometriosis and clear cell \ncarcinoma of the ovary should be kept in mind, mainly in patients \nwith a persistent ovarian cyst irrespective of the age.\nAcknowledgements\nNone.\nConflict of interest\nThe author declares no conflict of interest.\nReferences\n1. Takano M, Kikuchi Y , Yaegashi N, et al. Clear cell carcinoma of the \novary: a retrospective multicentre experience of 254 patients with com -\nplete surgical staging. Br J Cancer. 2006;94(10):1369–1374.\n2. Hiroyuki Yoshikawa, Haruko Jimbo, Satoshi Okada, et al. Prevalence of \nendometriosis in ovarian cancer. Gynecol Obstet Invest. 2000;50(Suppl \n1):11–17.\n3. Sampson JA. Endometrial carcinoma of ovary, arising endometrial tis -\nsue in that organ. Arch Surg. 1925;10(1):1–72. \n4. Scully RE. Recent progress in ovarian cancer. Hum Pathol . \n1970;1(1):73–98.\n5. Ryu SY , Park SI, Nam BH, et al. Prognostic significance of histological \ngrade in clear-cell carcinoma of the ovary: a retrospective study of Ko -\nrean Gynecologic Oncology Group. Ann Oncol. 2009;20(6):1032–1036. \n6. Kuwashima Y , Uehara T, Kurosumi M, et al. Cytological distinction \nbetween clear cell carcinoma and yolk sac tumor of the ovary. Eur J \nGynaecol Oncol. 1996;17(5):345–350.\n7. Ramalingam P, Malpica A, Silva EG, et al. The use of cytokeratin 7 and \nEMA in differentiating ovarian yolk sac tumors from endometrioid and \nclear cell carcinomas. Am J Surg Pathol. 2004;28(11):1499–505.\n8. Cao D, Guo S, Allan RW, Molberg KH, et al. SALL4 is a novel sensitive \nand specific marker of ovarian primitive germ cell tumors and is particu-\nlarly useful in distinguishing yolk sac tumor from clear cell carcinoma.  \nAm J Surg Pathol. 2009;33(6):894–904.\n9. Yamashita Y , Nagasaka T, Naiki-Ito A, et al. Napsin A is a specific marker \nfor ovarian clear cell adenocarcinoma. Mod Pathol. 2015;28(1):111–117.\n10. Esheba GE, Pate LL, Longacre TA. Oncofetal protein glypican-3 distin-\nguishes yolk sac tumor from clear cell carcinoma of the ovary. Am J Surg \nPathol. 2008;32(4):600–607.","source_license":"CC0","license_restricted":false}