Zeeshan-ud-din  ( Department of Pathology & Microbiology, The Aga Khan University Hospital, Karachi. )
Nausheen Yaqoob  ( Department of Pathology & Microbiology, The Aga Khan University Hospital, Karachi. )
Naila Kayani  ( Department of Pathology & Microbiology, The Aga Khan University Hospital, Karachi. )
Sheema H Hasan   ( Department of Pathology & Microbiology, The Aga Khan University Hospital, Karachi. )

A 45 year old woman presented with right side dovarian mass with multiple omental deposits and liver metastases. The right ovary was enlarged and showed apartly cystic partly solid cut surface. Histological picture showed clear cell carcinoma with areas of mucinouscystadenoma and endometriosis. Clear cell carcinoma is known to be associated with endometriosis. To the best of author's knowledge, it's association with mucinouscystadenoma has been described only once in the literature,where clear cell carcinoma was shown to be associated with mucinous cystadenoma without any evidence of endometriosis.

Clear cell carcinoma is a relatively uncommon typeof ovarian tumour which comprises 2.4% of ovarianepithelial neoplasms.1Although they were initially calledmesonephromas and mesonephric carcinomas, their epithelial nature is now accepted due to their high association with pelvic endometriosis.2,3We describe a case of clear cell carcinoma of the ovary in association with mucinous cystadenoma andendometriosis. To the best of our knowledge, only one suchcase has been published previously in the literature by NDutt et al4, in which clear cell carcinoma was described associated with mucinous cystadenoma without anyevidence of endometriosis.4This association was criticizedby WG Mccluggage as according to him the mucinousareas represented mucinous metaplasia of the endometriotic cyst of ovary.5However in our case, therewere separate foci of mucinous cystadenoma and endometriosis coexisting with areas of clear cellcarcinoma, supporting the case of N Dutt et al.

A45 year old woman presented to the clinician with abdominal pain and distension since one month. Ultrasound examination revealed a right-sided ovarian mass with multiple omental deposits and liver metastases. Per-operatively, in addition to the enlarged right ovary, the left ovary was also found to be enlarged, and the omentum studded with tumour deposits. Bilateral salpingo-ophorectomy was performed along with an omental biopsy which was sent for histological evaluation.Grossly the right ovary was enlarged, measuring 9.5x 9 x 6 cm. with ruptured capsule and a partly cystic, partly solid cut surface. The solid areas were pale brown, soft,necrotic and spongy. The cystic spaces were filled with mucinous secretions and included a haemorrhagic cyst. The left ovary measured 6 x 6 x 4 cm. and showed cystic spacesfilled with dark brown haemorrhagic material.Histological examination of the right ovary revealedan infiltrating neoplasm composed of solid sheets and nests of  large polyhedral clear cells having pleomorphic nuclei with clumped chromatin and prominent nucleoli (Figure 1).In some areas multiple layers of these cells were seen liningthe cystic spaces with hob nail appearance focally (Figure2). Tumour cells showed cytoplasmic glycogen on special staining and immuno histochemically, they were shown tobe positive for cytokeratin CAM 5.2 and AE1/AE3 and were negative for alphafeto protein. Cystic spaces lined by asingle layer of tall columnar mucinous cells were seen inclose proximity to the tumour. There was no cytologicalatypia or complexity of architecture in these areas. Therewere foci of endometriosis in the adjacent ovarian tissue.Based on the features, described a diagnosis of clear cellcarcinoma of the ovary associated with benign mucinouscystadenoma and endometriosis was made. The right ovaryshowed features consistent with mucinous cystadenomaalong with areas of endometriosis. Deposits of clear cellcarcinoma were identified in the omental biopsy.

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Clear cell carcinoma was first described in 1939 by Schiller, who called it a "mesonephroma" of ovary due to its presumptive origin from the mesonephric rests in the femalegenital tract.3,4 In view of their association with pelvicendometriosis and endometriotic cysts, the frequentad mixture with typical endometroid carcinoma, andultra structural similarities with mullerian epithelial cells,their epithelial origin is now generally accepted.2,6 Clearcell carcinoma comprises 2.4% of ovarian epithelial neoplasms and 7.4% of ovarian carcinomas.1The patientsare usually in their fifth or sixth decades of life.1,7 Interestingly, they are the most common epithelial ovarian neoplasms to be associated with paraneoplastic hypercalcaemia.1Clear cell carcinoma has an incidence of associated pelvic endometriosis in 50% and endometriosisin the same ovary in 24% of the cases.2,4,8Some authors believe that this incidence of association may be much higher if ovarian clear cell carcinomas are extensively sampled because of the possible obliteration of endometriosis by the tumour.5,8Benign and borderline clearcell tumours of ovary  are very rare and most are malignant with a 5 year survival rate ranging from 37-47%.4,7,9Histologically different patterns have been described out of which solid and tubulopapillary are most common.1,7,9,10 The cells are polygonal with abundant clear cytoplasm separated by delicate fibrovascular septae with papillarycores often exhibiting hyalinization. In the tubulopapillary pattern, the cells show a hobnail appearance. Cytoplasmic glycogen in the favour of PAS positive, diastase resistanthyaline globules is seen.1,7Immuno histochemically, the tumour cells are positive for cytokeratins, epithelial membrane antigen and vimentin and are negative for alpha-fetoprotein. The differential diagnosis includes yolk sactumour, dysgerminoma and metastatic renal cellcarcinoma.1The presence of intracytoplasmic lumina with mucinous inclusions are described in clear cell carcinoma which, according to some authors, support the hypothesis that clear cell carcinoma should be regarded as an end stage transformation, which may arise from any of the other epithelial tumours.4Association of clear cellcarcinoma with mucinous lesions has been described only infrequently. One such case was described by N Dutt et al.where clear cell carcinoma was seen associated with mucinous cystadenoma.4 This association was criticizedby WG Mccluggage, according to whom the mucinous areas were in fact reproductive mucinous metaplasia ofthe endometriotic cyst of ovary.5According to him,mucinous metaplasia in endometriotic cysts can be soextensive that a diagnosis of mucinous cystadenoma may be considered.5However, in our case there were separatefoci of mucinous cystadenoma and endometriosiscoexisting with areas of clear cell carcinoma. There was no continuity between the areas of endometriosis andmucinous cystadenoma in our case. This favours the caseof  N Dutt et al who suggested the origin of clear cellcarcinoma in a background of mucinous cystadenoma.