The incidence of ovarian cancer in 2012 was projected to be 230,000 new cases and 151,905 deaths worldwide, representing 4.3 % of all female cancers and 4.2 % of all cancer deaths in women [1]. Ovarian cancer is one of the major causes of death from cancer in women. Ovarian cancer is one of the most chemosensitive solid tumors, with objective responses ranging from 60 to 80 % even in patients with advanced stage. However, most tumors ultimately recur and develop resistance to chemotherapy [2, 3]. Recently, the biological characteristics of ovarian cancer have been clarified [4]. It has long been known that ovarian cancers of serous histology appear to be more sensitive to chemotherapy than other histological subtypes [5–7]. Patients with clear cell carcinoma (CCC) of the ovary showed a significantly worse prognosis in a retrospective review of several Gynecologic Oncology Group (GOG) trials [5]. Several studies also showed that patients with CCC had a poor prognosis and the low response of CCC to conventional platinum-based chemotherapy has been associated with poor survival [8–11].

CCC of the ovary has unique clinical and biological features. The incidence of CCC among epithelial ovarian cancers (EOC) differs among races. In North America and Europe, CCC is the third most common histological subtype of EOC, with an estimated prevalence of 1–12 % [12–15]. CCC comprises more than 20 % of such cancers in Japan [16]. Interestingly, among Asian women living in the United States, CCC was diagnosed twice as frequently (11.1 %) compared to Caucasians (4.8 %) [7, 17].

Several studies have analyzed the risk factors for ovarian cancer by histological subtype. CCC was associated (odds ratio 2.3; 95 % confidence interval 1.2–4.2) with an increased body mass index (BMI ≥30) [18]. However, in the NIH-AARP Diet and Health Study, BMI was correlated only with endometrioid histology [19]. It has long been recognized that CCC often is associated with endometriosis (22–70 %), whereas hobnail cells bear a very strong morphological resemblance to endometrial Arias-Stella cells [20, 21]. Endometriosis frequently shows a sequential change to EOC, including CCC. Therefore, atypical endometriosis is considered to be a precancerous change. Ovarian cancers associated with endometriosis tend to occur in younger women and present 5–6 years earlier, on average, than high-grade serous carcinoma. In National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) data, women with CCC were younger than patients with serous adenocarcinoma (SAC) (55 vs. 64 years; median age) [22].

Ovarian CCC usually presents as a large pelvic mass. The size ranges from 3 to 20 cm, with most tumors detected preoperatively either by clinical examination or imaging [12–14, 23]. Recent reports involving large institutional cohorts compared early-stage (I/II) to advanced-stage ovarian cancers (III/IV) and showed that 57–81 % of CCC were diagnosed at an early stage [9–11]; in SEER data, 56 % of CCC was stage I, compared to 19 % for SAC. Combining the low overall incidence of CCC and their early-stage propensity [24], CCC may make up only 1–5 % of advanced-stage patients in chemotherapy trials, largely due to their overall low incidence and tendency for early-stage distribution at the time of initial diagnosis.

Recently, JGOG/GCIG conducted a clinical trial for CCC, and 652 cases were collected and international central pathological review was performed. This study is the largest yet reported. As a result, several interesting and important histological features of CCC were noted in the process of CPR. It is important to understand typical and unusual histological features of CCC and related tumors for diagnosis.