Clear Cell Carcinoma of the Ovary Arising in a Mucinous Cystadenoma

938 J Clin Pathol 2000;53:938–939

Clear cell carcinoma of the ovary arising in a J Clin Pathol: first published as 10.1136/jcp.53.12.938 on 1 December 2000. Downloaded from mucinous cystadenoma

N Dutt, D M Berney

Abstract Case report A 57 year old woman presented complain- A 57 year old woman presented with abdomi- ing of increasing abdominal swelling of six nal swelling, which had been increasing for the months duration. A mixed solid cystic left past six months. There was no evidence of ovarian tumour measuring 24 cm in di- ascites or tumour cachexia. Ultrasonography ameter was excised. Histology showed revealed an enlarged left ovary, which had a numerous cysts lined by benign mucinous solid cystic echotexture. The contralateral epithelium blending imperceptibly into ovary was of normal size. Hysterectomy with borderline clear cell and mucinous areas bilateral salpingo-oophorectomy was per- that in turn merged with an invasive clear formed. cell carcinoma. To the best of our knowledge, this is the first reported case of clear cell carcinoma arising in a mucinous cys- Pathological findings tadenoma. The implications for the previ- A left ovarian tumour was removed that × × ously postulated pathogenesis of these measured 24 15 8 cm and weighed 1750 g. tumours are discussed. No breaches of the ovarian capsule or omental (J Clin Pathol 2000;53:938–939) deposits were seen at the time of surgery. The right ovary was of normal size. The cut surface Keywords: ovary; clear cell carcinoma; mucinous revealed multiple cysts filled with mucinous cystadenoma brown coloured fluid and solid areas that com- prised approximately 30% of the tumour volume. Microscopically the tumour was com- The pathogenesis of clear cell carcinomas has posed of numerous cysts lined by a single layer been in dispute ever since their description in of tall columnar mucus containing cells with 1939.1 Whereas some authors have suggested regular basal nuclei. There was a gradual tran- that they show a specific type of diVerentiation sition to cystic areas that were lined by cells that mimics a population of normal cells, other showing clear cell change, but which showed authors have stressed their association with little pleomorphism or nuclear stratification. serous and endometrioid carcinomas. Other areas showed multilayered atypical cuboidal cells with hyperchromatic and pleo- We describe here, to the best of our http://jcp.bmj.com/ knowledge, the first case of a clear cell morphic nuclei. “Hobnailing” of the nucleus carcinoma arising in a mucinous cystadenoma. was seen (fig 1). Extensive areas of the tumour Within this lesion clear cell carcinoma was seen showed complex papillae lined by clear and contiguous with borderline forms and benign hobnail cells (fig 2). These areas again merged mucinous epithelium. This case, together with with more complex and eventually solid areas the previously reported finding of mucinous composed of sheets of clear cells and hobnail inclusions in clear cell carcinomas, indicates cells with bulbous dark nuclei (fig 3). Several that clear cell carcinomas might arise more cyst lumina contained eosinophilic material on October 2, 2021 by guest. Protected copyright. commonly from mucinous tumours than had and several of the atypical cells showed intra- been previously supposed, and we suggest that cytoplasmic lumina. Special staining was car- these findings add weight to the theory that ried out using periodic acid SchiV (PAS), with clear cell carcinoma is an end stage appearance and without diastase and Alcian blue. This of many epithelial ovarian tumours. revealed diastase resistant PAS staining of the benign mucinous cells, and many of the clear

Department of Morbid Anatomy and Histopathology, St Bartholomew’s Hospital, West Smithﬁeld, London EC1A 7BE, UK N Dutt D M Berney

Correspondence to: Dr Berney

Accepted for publication Figure 1 Cyst wall lined by a single layer of benign Figure 2 Borderline areas of clear cells showing 12 April 2000 mucinous cells blending into multilayered cells with stratiﬁcation and mildly pleomorphic hobnailed and [email protected] hobnailed nuclei. hyperchromatic nuclei.

www.jclinpath.com Short report 939

Clear cell elements have been reported admixed with every type of primary carcinoma J Clin Pathol: first published as 10.1136/jcp.53.12.938 on 1 December 2000. Downloaded from of the ovary, although endometrioid and serous tumours were the most common.78 The association of clear cell carcinomas with mucinous lesions has been reported only infre- quently. One case was a clear cell carcinoma admixed with mucinous components compris- ing less than 50% of the tumour. The case was part of a series and it is not known whether the mucinous component was benign, borderline, or malignant.7 The same authors also reported Figure 3 Pure clear cell carcinomatous areas featuring a case of clear cell change in “more than focal multilayered pleomorphic clear cells. areas” in a mucinous cystadenocarcinoma. Thus, our present case appears to be the first cells showed intracytoplasmic lumina with blue that unequivocally shows clear cell carcinoma staining and purple red central mucoid inclusions. arising from a benign mucinous tumour. This assumes epidemiological relevance because Discussion mucinous cystadenocarcinomas have not been Clear cell tumours are epithelial tumours that found in intimate association with endometrio- can possess several characteristic cell types. sis, which is frequently found with other ovar- Clear cells and hobnail cells are the most com- ian neoplasms such as endometrioid and clear mon, followed by cuboidal, flat, and oxyphil cell carcinomas.389 cell types.2 Clear cell carcinoma was first No definite genetic association has been described in 1939,3 when the typical features identified for clear cell carcinomas. Several were described. The term mesonephroma was genes, such as BRCA1, p53, and HER-2/neu, coined to describe its presumptive origin from have been implicated in the origin of ovarian mesonephric rests in the female reproductive surface epithelial tumours in general, and system. Others have suggested a mullerian ori- K-ras and chromosome 17 alterations have gin,4 citing a study group in which 50% of the been found to be associated specifically with cases had associated pelvic endometriosis mucinous and serous carcinomas.10 Our find- against a 7.6% incidence of endometriosis ings, the presence of mucinous inclusions, and given for cases of ovarian carcinoma in general. a lack of a genetic association all add weight to More recently, a study of 17 cases of clear 5 the hypothesis that clear cell carcinomas cell tumours categorised them as benign, low should be regarded as an end stage transforma- malignant potential, and invasive. The benign tion, which may arise from any of the other lesions were lined by a single layer of predomi- epithelial tumours. nantly hobnail shaped cells with little or no

atypia, separated from each other by a http://jcp.bmj.com/ prominent ovarian type stroma. Tumours of 1 Schiller W. Mesonephroma ovarii. Am J Cancer 1939;35:1– low malignant potential showed moderate to 21. 2 Scully RE, Young RH, Clement PB. Tumours of the ovary, pronounced nuclear atypia, including variation maldeveloped gonads, fallopian tube and broad ligament. in size, chromatin clumping, irregular nuclear Clear cell tumours, 3rd ed. Armed Forces Institute of contours, and prominent nucleoli. Additional Pathology, 1998:141–51. 3 Scully RE. Recent progress in ovarian carcinoma. Hum architectural irregularities consisted of layer- Pathol 1970;1:73–98. ing, budding, and crowding of the tubular epi- 4 Scully RE, Barlow JF. “Mesonephroma” of ovary. Tumour on October 2, 2021 by guest. Protected copyright. thelium. These non-invasive variants have of mullerian nature related to endometrioid carcinoma. Cancer 1967;20:1405–16. always been much more rare than their malig- 5 Roth MC, Langley FA, Fox H, et al. Ovarian clear cell nant counterparts, especially when compared adenoﬁbromatous tumors. Cancer 1984;53:1156–63. with other common benign ovarian tumours. 6 O’Donnell M, Al-Nafussi AI. Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas. Histopathology The presence of intracytoplasmic lumina 1995;26:181–4. with mucinous inclusions and microcyst for- 7 Kurman RJ, Craig JM. Endometrioid and clear cell carcinoma of the ovary. Cancer 1972;29:1653–64. mation was described as part of the morphol- 8 Corner GW, Jr, Hu CY, Hertig AT. Ovarian carcinoma aris- 6 ogy of clear cell carcinomas. However, this ing in endometriosis. Am J Obstest Gynecol 1950;59:760– ﬁnding did not lead the authors to hypothesise 74. 9 Willis R A. The pathology of tumours, 4th ed. London: Butter- that this indicated a link with mucinous worths, New York: Appleton Century Crofts, 1967:517– tumours, but rather that the presence of intra- 18. 10 Riopel MA, Ronnett BM, Kurman RJ. Evaluation of cytoplasmic lumina and mucoid inclusions diagnostic criteria and behaviour of ovarian intestinal-type might indicate end stage morphology. mucinous tumours. Am J Surg Pathol 1999;23:617–35.