Clear cell carcinomas of the mullerian system: does the pathogenesis vary depending on their nuclear grade and their association with endometriosis? An immunohistochemical analysis.

Ahmad Alduaij,Tahreem A Karim,W Dwayne Lawrence,M Ruhul Quddus,Katrine Hansen,Cunxian Zhang,Michelle M Lomme,C James Sung

doi:10.1155/2012/674748

Abstract

Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.

Highlights

While the pathogenesis of mullerian serous and endometrioid carcinomas has been linked to p53 and PTEN mutations, respectively, the pathogenesis of clear cell carcinoma remains largely speculative
Adequate tissue material was available in all 41 cases; of which 24 cases were assigned as high nuclear grade and 17 were low nuclear grade tumors (Tables 1 and 2)
Proliferative index marker (Ki67) showed brisk positivity in both low and high nuclear grade tumors irrespective of their association with endometriosis (Figure 1)

Summary

Introduction

While the pathogenesis of mullerian serous and endometrioid carcinomas has been linked to p53 and PTEN mutations, respectively, the pathogenesis of clear cell carcinoma remains largely speculative. CCCs of the mullerian system are largely found in the endometrium and ovary, but primary peritoneal clear cell carcinoma has been reported. It is known that many clear cell carcinomas arise in endometriosis. Recent studies have speculated that ovarian clear cell carcinoma may develop along two pathways, both of which are related to endometriosis [5]. The epithelial atypia arises within an endometriotic cyst and progresses to carcinoma. Endometriosis induces fibromatosis resulting in the formation of an adenofibroma. In this second pathway, adenofibromas progress to atypical adenofibroma and subsequently to CCC. Studies have shown that cystic CCCs and adenofibromatous CCCs have different clinicopathologic features. Cystic CCC is often diagnosed at an early stage while adenofibromatous CCCs are found

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