MRI-based morphology of ovarian clear cell carcinomas

Ovarian clear cell carcinoma (CCC) is a distinct histological subtype of epithelial ovarian cancer characterized by unique biological behavior and heterogeneous clinicopathological features. In contrast with other epithelial ovarian malignancies, CCC often presents at an early stage but exhibits significant resistance to conventional platinum-based chemotherapy, underscoring the importance of accurate preoperative identification to optimize surgical management. This review provides a comprehensive overview of the imaging spectrum of CCC, emphasizing correlations between various magnetic resonance imaging (MRI) morphologies and their underlying histopathological architectures. We propose a classification system comprising 9 MRI-based morphological types, ranging from classic unilocular cystic lesions with polypoid mural nodules to entirely solid masses. These imaging patterns are closely linked to two primary pathogenic pathways: the endometriotic cyst pathway and the adenofibromatous pathway. The former typically manifests as cystic lesions with eccentric growth, whereas the latter is more commonly associated with solid or tubulocystic masses exhibiting a characteristic black sponge-like appearance on T2-weighted imaging, reflecting abundant fibrous stroma. The review also highlights emerging and less commonly described imaging signs, including the renal corticomedullary contrast-like appearance associated with stromal edema. Integration of diffusion-weighted imaging and apparent diffusion coefficient values with these morphological signatures may further refine diagnostic accuracy and improve lesion characterization. A thorough understanding of these MRI-based morphological patterns and their radiological-pathological correlations is essential for the accurate preoperative diagnosis of CCC, and has potential implications for patient stratification, surgical planning, and overall clinical outcomes. Similar content being viewed by others

Ovarian clear cell carcinoma (CCC) is a distinct subtype of epithelial ovarian cancer characterized by tumor cells with clear or eosinophilic cytoplasm and hobnail cell morphology [1]. The prevalence of CCC varies considerably by geographic region, accounting for approximately 10% of all ovarian cancers in North America and 20%–25% in Japan [2]. It commonly presents as a large unilateral pelvic mass and is frequently associated with mild-to-moderate elevation in serum carbohydrate antigen 125 (CA 125) levels, typically around 200 IU/mL [3]. Patients with CCC exhibit a higher incidence of paraneoplastic syndromes − particularly hypercalcemia and venous thromboembolism − than those with other histological subtypes [4]. Although more than half of ovarian CCCs have been diagnosed at the International Federation of Gynecology and Obstetrics stage I, CCC is notoriously resistant to conventional chemotherapy, including platinum-based regimens, and clinical outcomes remain poor in the presence of residual disease following primary cytoreductive surgery [5]. Therefore, maximal cytoreductive effort to achieve no gross residual disease is strongly recommended when CCC is suspected, and accurate preoperative identification of CCC may play a critical role in guiding surgical planning and optimizing patient outcomes [6]. Magnetic resonance imaging (MRI) findings in CCC are highly heterogeneous, ranging from predominantly solid to predominantly cystic appearances. This variability reflects the underlying histopathological diversity of the tissue architecture [1, 7]. However, to our knowledge, a comprehensive classification of MRI morphological patterns spanning this solid–cystic spectrum has not been established. This review provides an integrated overview of the pathological basis and pathogenesis of CCC, and systemically characterizes its MRI morphological patterns, with particular emphasis on correlating imaging features with corresponding histopathological findings. Histopathological diversity CCC exhibits marked histopathological heterogeneity, with tumor components arranged in tubulocystic, papillary, and solid architectural patterns that are frequently intermixed within the same lesion [1, 7]. This structural diversity directly contributes to the wide spectrum of MRI appearances observed in CCC (Fig. 1). Two pathogenetic pathways of ovarian CCC Two principal pathogenetic pathways have been proposed for the development of ovarian CCC (Table 1). The endometriotic cyst pathway originates from cystic endometriosis, in which atypical endometriosis develops in the cyst wall and subsequently progresses to CCC [8]. Morphologically, this pathway is typically associated with cystic lesions exhibiting papillary projections. In contrast, the adenofibromatous pathway is thought to arise from non-cystic endometriosis accompanied by fibromatous stromal proliferation, progressing stepwise from clear cell adenofibroma to borderline tumor (Fig. 2) and ultimately carcinoma [9]. This pathway is characteristically associated with solid or tubulocystic masses containing abundant fibrous stroma. Although these two pathways exhibit distinct morphological features, they are not mutually exclusive. In some cases, both endometriotic and adenofibromatous components coexist with a single tumor, suggesting that these pathways may be biologically interconnected and converge during tumorigenesis [9, 10]. Nine types of MRI-based CCC morphology Herein, we propose a classification system comprising nine MRI-based morphological patterns for CCC (Fig. 3), emphasizing the correlation with the underlying histopathological findings shown in Table 2: - 1. Cystic lesion with prominent mural nodules exhibiting a polypoid growth pattern (Fig. 4 and 5) [11,12,13,14] - 2. Cystic lesion with sparse septa and small mural nodules (≥ 3 mm in diameter) (Fig. 6) [11, 15] - 3. Multilocular cystic lesion containing small solid components with intermediate T2-signal intensity and high signal on high b-value diffusion-weighted imaging (DWI) (Fig. 7) [10, 12, 15] - 4. Multilocular cystic lesion with thickened septa exhibiting a black sponge-like appearance, often coexisting with an endometriotic cyst (Fig. 8) [10, 15,16,17] - 5. Multilocular cystic lesion with a black sponge-like appearance accompanied by a small solid component exhibiting intermediate T2-signal and high signal on high b-value DWI (Fig. 9) [10, 15, 19] - 6. Mixed lesion containing a T2-hypointense solid component with a small nodule exhibiting high signal on high b-value DWI (Fig. 10) [15,16,17,18,19,20] - 7. Mixed lesion with multiple mural nodules and solid components exhibiting broad-based or concentric growth patterns surrounding central necrosis (Fig. 11, 12) [13, 15, 21, 22] - 8. Mixed to solid lesion with multiple mural nodules and solid components exhibiting a polypoid growth pattern and projecting into the cystic cavity (Fig. 13) [13, 15, 21, 22] - 9. Solid lesion with central edema exhibiting a renal corticomedullary contrast-like appearance (Fig. 14) [23] Notably, types 7 and 8 both include mixed lesions with multiple mural nodules and solid components; however, the key distinguishing feature is the growth configuration of the solid component. Type 7 is characterized by a broad-based or concentric peripheral solid component surrounding central necrosis, whereas type 8 is characterized by multiple polypoid nodules projecting into the cystic tumor cavity without a dominant concentric peripheral growth pattern. Morphology of MRI findings in CCC MRI findings in CCC have been variably described as multilocular cystic lesions, unilocular lesions with a single nodule, unilocular lesions with multiple nodules, multilocular lesions with a solid component, and solid lesions [10,11,12,13]. CCC arising from endometriosis most commonly appears as a unilocular or multilocular cystic lesion with mural nodules or solid components, typically characterized by a polypoid, focal, or eccentric growth pattern, moderate hyperintensity on T2-weighted imaging (T2WI), and hyperintensity on DWI. Compared with endometriosis-associated endometrioid carcinoma, the mural nodule or solid component tends to be smaller and is more likely to contain internal cysts [13, 14]. CCC often exhibits hyperintense cystic contents on T1-weighted imaging (T1WI), reflecting intralesional hemorrhage (Figs. 4, 5 and 6), and this feature may help to distinguish CCC from endometroid carcinoma and high-grade serous carcinoma [12, 24, 25]. In contrast, CCC arising in association with adenofibroma, which is often associated with cystadenoma, typically presents as a mixed cystic-solid lesion, reflecting its origin from fibrous stromal proliferation. Cystadenoma and adenofibroma are not specific to CCC and can occur across multiple histological subtypes, including serous, mucinous, endometrioid, and clear cell tumors. A characteristic MRI feature described in this context is the black sponge-like appearance on T2WI [16], which is classically associated with ovarian cystadenofibroma, and results from the numerous small hyperintense cysts within the fibrous stroma (Fig. 8, 9). The solid component of adenofibroma exhibits marked hypointensity on T2WI comparable to that of skeletal muscle, due to the presence of dense fibrous stroma (Fig. 10) [17]. Malignant transformation within a clear cell adenofibroma can manifest as focal areas of altered signal intensity appearing as mildly hyperintense regions on T2WI, and marked hyperintensity on DWI with corresponding low apparent diffusion coefficient (ADC) values, and exhibiting intense early and prolonged contrast enhancement on dynamic imaging. These imaging features facilitate early detection of carcinomatous transformation [18]. However, when the malignant component is limited in extent, small or microscopic foci of borderline or invasive carcinoma may be undiscernible on MRI (Fig. 8) [10]. Although the black sponge-like appearance on T2WI has traditionally been regarded as a hallmark of benign ovarian cystadenofibroma, its presence in lesions associated with endometriosis warrants careful interpretation (Fig. 8) because the vast majority of clear cell tumors arising in this setting are malignant [19]. MRI findings of the solid type of CCC have been infrequently reported, with reporting frequencies ranging from 5.7% (3/53 cases) to 6.8% (3/44 cases) [12, 22]. In contrast, in an ultrasound-based study by Pozzati et al. [6], there was a substantially higher prevalence, with 25.0% (19/76) of CCCs without endometriosis and 22.2% (12/54) of CCCs with endometriosis presenting as solid-type lesions. Recent case reports have further expanded the spectrum of solid-type CCC imaging features. Takeyama et al. [23] recently described two cases of entirely solid-type CCC exhibiting a renal corticomedullary appearance, in which peripheral tumor regions showed prominent cancer cell proliferation with increased fibrous stroma, whereas central lesions were characterized predominantly by edematous stroma and fibrosis with relatively sparse tumor cells. Similarly, Wang et al. [26] reported two solid-type CCC cases exhibiting central cystic or necrotic change, while Elsherif et al. [11] described a case of solid-type CCC presenting with heterogeneous hyperintensity on T2WI. In the present 11-case cohort, background ovarian endometriosis was identified in 3 cases, and background adenofibromatous components were observed in 3 cases; however neither background ovarian endometriosis nor adenofibroma was identified in the remaining 5 cases. In pathological reviews, endometriotic cysts have been reported in 50%–74% of patients with CCC [1, 2], whereas the remaining cases presumably originated from adenofibroma. In an MRI-based study of 44 cases, including 4 clear cell adenofibroma-associated, 21 endometriosis-associated, and 19 indeterminate CCCs, solid tumors were observed exclusively in the indeterminate group. These results suggest that indeterminate CCCs may represent an entity distinct from adenofibroma- and endometriosis-associated CCCs [22]. Notably, the imaging and pathological features observed in our 4 indeterminate cases included in Figs. 11, 12, 13, 14 appeared to correspond to the indeterminate form described by Kato et al. [22]. Although this indeterminate group accounted for approximately 45% of our cohort (5/11), it remains uncertain whether these tumors represent a biologically distinct third pathogenetic pathway or whether the precursor lesions were obscured or overgrown by advanced carcinoma. Importantly, the proposed 9-type MRI-based classification system should be considered a preliminary framework because it was derived from a relatively small cohort of 11 cases. Therefore, the proposed categories are intended to provide an educational and hypothesis-generating approach rather than a definitive or fully validated diagnostic system. DWI and ADC value of CCC Tumor microstructure is closely associated with the ADC value (mm2/second), which serves as a potential imaging biomarker [27]. In this case series, the mean (range) ADC value of the solid components in 11 cases was 1.44 (1.08–1.75) × 10–3 mm2/second on 1.5-T MRI. These findings were consistent with previously reported ADC values for CCC using a 1.5-T MRI scanner, which range from 0.98 to 1.87 × 10–3 mm2/second [23, 28, 29]. The observed variability in ADC values likely reflects the underlying histopathological heterogeneity of CCC, characterized by tubulocystic, papillary, and solid architecture patterns. These structural differences influence tumor cellularity and extracellular matrix composition, thereby affecting water diffusivity and resulting in ADC measurement [7, 27,28,29]. Notably, certain individual cases in the present cases, such as the solid lesion with a renal corticomedullary contrast-like appearance (Fig. 14), exhibited ADC values substantially lower than the overall mean ADC value of the solid components (1.44 × 10–3 mm2/second). This variability may be attributable to differences in stromal composition, degree of fibrosis, tumor cellularity, MRI field strength, and lesion subtype.

This current study has several limitations. First, the proposed MRI-based morphological classification was based on a relatively small cohort of 11 cases from limited institutional experience. Therefore, the reproducibility of the 9-type classification and its broader clinical applicability remain uncertain. External validation in larger cohorts, preferably through multicenter studies, would be necessary to determine interobserver agreement, diagnostic performance, and generalizability across different MRI protocols, field strengths, and patient populations. Second, the absence of identifiable precursor lesions in several tumors may reflect either a biologically distinct indeterminate pathway or the overgrowth/obscuration of precursor lesions by advanced carcinoma. Therefore, further radiologic-pathologic and molecular studies are needed. In the present cohort, we consider the latter explanation more plausible, although this interpretation remains provisional and requires validation in future studies.

In this review, we summarized 9 MRI morphological patterns of CCC observed in 11 cases, ranging from early-stage (pT1a) to advanced disease (pT3c), in women aged 40–64 years, with serum CA125 levels ranging from 7.0 to 1766.1 U/mL. Six patients exhibited identifiable precursor lesions (i.e., endometriosis and adenofibroma), whereas the remaining five did not retain lesions with a definable origin. Rather than representing a definitive classification, this preliminary framework could help organize the broad imaging spectrum of CCC and highlight radiologic-pathologic correlations. MRI may provide structural and functional information that supports but does not replace histopathological diagnosis, and may aid the differential diagnosis of epithelial ovarian carcinomas. Further large-scale studies integrating imaging, histopathological, and molecular analyses are required to validate this classification and better elucidate the biological origins and microstructural determinants of CCC. Data availability No datasets were generated or analysed during the current study.

Cheung AN, Ellenson LH, Gilks CB, Kim K-R, Kong CS, Lax SF, et al (2020) Tumours of the ovary. In: WHO classification of tumors editorial board (ed) Female genital tumours, 5th edn. IARC Publications, Lyon, pp 31–167. Okamoto A, Glasspool RM, Mabuchi S, Matsumura N, Nomura H, Itamochi H, et al (2014) Gynecologic Cancer InterGroup (GCIG) consensus review for clear cell carcinoma of the ovary. Int J Gynecol Cancer 24(Suppl 3):S20–25. https://doi.org/10.1097/IGC.0000000000000289 Bennett JA, Dong F, Young RH, Oliva E (2015) Clear cell carcinoma of the ovary: evaluation of prognostic parameters based on a clinicopathological analysis of 100 cases. Histopathology 66:808–815. https://doi.org/10.11111/his.12514 Fadare O, Parkash V (2019) Pathology of endometrioid and clear cell carcinoma of the ovary (2019) Surg Pathol Clin 12:529–564. https://doi.org/10.1016/j.path.2019.01.009 Chen JK, Teoh D, Hu JM, Shin JY, Osann K, Kaoo DS (2008) Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol 109:370–376. https//doi.org/https://doi.org/10.1016/j.ygyno.2008.02.006 Pozzati F, Moro F, Pasciuto T, Gallo C, Ciccarone F, Franchi D, et al (2018) Imaging in gynecological disease (14): clinical and ultrasound characteristics of ovarian clear cell carcinoma. Ultrasound Obstet Gynecol 52:792–800. https://doi.org/10.1002/uog.19171 Ohya A, Fujinaga Y (2022) Magnetic resonance imaging findings of cystic ovarian tumors: major differential diagnoses in five types frequently encountered in daily clinical practice. Jpn J Radiol 40:1213–1234. https://doi.org/10.1007/s11604-022-01321-x Yamamoto S, Tsuda H, Suzuki K, Takano M, Tamai S, Matsubara O (2009) An allelotype analysis indicating the presence of two distinct ovarian clear-cell carcinogenic pathways: endometriosis-associated pathway vs. clear-cell adenofibroma-associated pathway. Virchows Arch 455:261–270. https//doi.org/https://doi.org/10.1007/s00428-009-0816-9 Zhao C, Wu LS, Barner R (2011) Pathogenesis of ovarian clear cell adenofibroma, atypical Proliferative (borderline) tumor, and carcinoma: clinicopathologic features of tumors with endometriosis or adenofibromatous components support two related pathways of tumor development. J Cancer 2:94–106. https://doi.org/10.7150/jca.2.94 Takeuchi M, Matsuzaki K, Harada M (2024) Endometriosis, a common but enigmatic disease with many faces: current concept of pathophysiology, and diagnostic strategy. Jpn J Radiol 428:801–819. https://doi.org/10.1007/s11604-024-01569-5 Elsherif SB, Bhosale PR, Lall C, Menias CO, Itani M, Butler KA, et al (2021) Current update on malignant epithelial ovarian tumors. Abdom Radiol (NY) 46:2264–2280. https//doi.org/https://doi.org/10.1007/s00261-021-0381-0 Tanaka YO, Okada S, Satoh T, Matsumoto K, Oki A, Saida T, et al (2016) Differentiation of epithelial ovarian cancer subtypes by use of imaging and clinical data: a detailed analysis. Cancer Imaging 16:3. https://doi.org/10.1186/s40644-016-0061-9 Morioka S, Kawaguchi R, Yamada Y, Iwai K, Yoshimoto C, Kobayashi H (2019) Magnetic resonance imaging findings for discriminating clear cell carcinoma and endometrioid carcinoma of the ovary. J Ovarian Res 12:20. https:// doi.org/https://doi.org/10.1186/s13048-019-0497-1 Manabe T, Hirose Y, Kiryu T, Koudo H, Hoshi H (2007) Magnetic resonance imaging of endometrial cancer and clear cell cancer. J Comput Assist Tomogr 31:229–235. https://doi.org/10.1097/01.rct.0000238005.42129.64. Reinhold C, Rockall A, Sadowski EA, Siegelman ES, Maturen KE, Vagas HA, et al (2021) Ovarian-adnexal reporting lexicon for MRI: a white paper of the ACR ovarian-adnexal reporting and data systems MRI committee. J Am Coll Radiol 18:713–729. https://doi.org/10.1016/j.jacr.2020.12.022 Takeuchi M, Matsuzaki K, Kusama M, Shimazu H, Yoshida S, Nishitani H, et al (2003) Ovarian cystadenofibromas: characteristic magnetic resonance findings with pathologic correlation. J Comput Assist Tomogr 27:871–873. https://doi.org/10.1097/00004728-200311000-00007 Takeuchi M, Harada M, Matsuzaki K (2017) Black sponge-like appearance. Japanese Journal of Imaging Diagnosis 37:886 (Japanese) Takeuchi M, Matsuzaki K, Uehara H, Furumoto H, Harada M (2013) Clear cell adenocarcinoma arising from clear cell adenofibroma of the ovary: value of DWI and DCE-MRI. Magn Reson Med Sci 12:305–308. https://doi.org/10.2463/mrms.2013-0001 Tsuboyama T (2020) Chapter TT8 Ovarian superficial epithelial and stromal tumor. CASE 8. Clear cell carcinoma derived from endometriotic cyst. Imaging of Obstetrical and Gynecological Disease (Japanese): A Case-Based approach. 1st edn. Supervised by Narumi Y, Takahama J, Yamamoto K (eds). Medical Sciences International, Ltd., Tokyo Avesani G, Caliolo G, Gui B, Petta F, Panico C, Manna VL, et al (2021) Pearls and potential pitfalls for correct diagnosis of ovarian cystadenofibroma in MRI: A pictorial essay. Korean J Radiol 22:1809–1821. https://doi.org/10.3348/kjr.2020.1312 Takeyama N, Sasaki Y, Ueda Y, Tashiro Y, Tanaka E, Nagai K, et al (2024) Magnetic resonance imaging-based radiomics analysis of the differential diagnosis of ovarian clear cell carcinoma and endometrioid carcinoma: a retrospective study. Jpn J Radiol 42:731–43. https://doi.org/10.1007/s11604-024-01545-z Kato H, Hatano Y, Makino H, Furui T, Morishige KI, Matsuo M (2016) Clear cell carcinoma of the ovary: comparison of MR findings of histological subtypes. Abdom Radiol (NY) 41:2476–2483. https://doi.org/10.1007/s00261-016-0777-9 Takeyama N, Ueda Y, Omatsu M, Nemoto T, Ogawa T, Miyamoto S, et al (2025) Two case reports of ovarian clear cell carcinoma: atypical MRI findings with a renal corticomedullary contrast-like appearance. Radiol Case Rep 20:2513–2520. https://doi.org/10.1016/j.radcr.2025.01.091 Li HM, Qiang JW, Xia GL, Zhao SH, Ma FH, Cai SQ, et al (2015) MRI for differentiating ovarian endometrioid adenocarcinoma from high-grade serous adenocarcinoma. J Ovarian Res 8:26. https://doi.org/10.1186/s13048-015-0154-2 Ma FH, Qiang JW, Zhang GZ, Li HM, Cai SQ, Rao YM (2016) Magnetic resonance imaging for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma. J Ovarian Res 9:40. https://doi.org/10.1186/s13048-016-0251-x Wang W, Ding J, Zhu X, Li Y, Gu Y, Peng W (2015) Magnetic resonance imaging characteristics of ovarian clear cell carcinoma. PLOS One 10:e0132406. https://doi.org/10.1371/journal.pone.0132406 Winfield JM, Wakefield JC, Doling D, Hall M, Freeman S, Bren- ton JD, et al (2019) Diffusion-weighted MRI in advanced epithelial ovarian cancer: apparent diffusion coefficient as a response marker. Radiology 293:374–383. https://doi.org/10.1148/radiol.2019190545 Ono T, Kishimoto K, Tajima S, Maeda I, Takagi M, Suzuki N, et al (2020) Apparent diffusion coefficient (ADC) values of serous, endometrioid, and clear cell carcinoma of the ovary: pathological correlation. Acta Radiol 61:992–1000. https://doi.org/10.1177/0284185119883392 Lin L, Fu L, Wu H, Cheng S, Chen G, Chen L, et al (2025) The value of MRI in differentiating ovarian clear cell carcinoma from other adnexal masses with O-RADS MRI scores of 4–5. Insights into Imaging 16:22. https://doi.org/10.1186/s13244-024-01860-z

The authors would like to thank Masahiro Hoshikawa, MD, PhD. from department of Pathology, Machida Municipal Hospital for kindly providing pathological images in Fig. 14. Funding Open Access funding provided by SHOWA Medical University Author information Authors and Affiliations Contributions N.T took the lead in writing the manuscript. Parts of the content were also requested from Y.T, J.M, M.K, R.H, and Y.O. The pathological images in Figs. 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, and 13 were prepared by Y.U after individual discussions between T.O regarding the cases. N.T, Y.T, J.M, M.K, R.H, and Y.O discussed together to determine the overall concept. M.K provided the pathological images for Figs. 2 and 7 and the explanation of gross anatomy. Finally, all members reviewed the manuscript and approved its submission. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Takeyama, N., Tashiro, Y., Ueda, Y. et al. MRI-based morphology of ovarian clear cell carcinomas. Abdom Radiol (2026). https://doi.org/10.1007/s00261-026-05611-0 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00261-026-05611-0