Ovary
Clear cell neoplasms
Clear cell carcinoma
Authors: Sonali Lanjewar, M.B.B.S., Raavi Gupta, M.D.
Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 1 April 2018
Minor changes: 19 October 2020
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: Ovary tumor clear cell carcinoma [title] AND (free full text[sb] AND Humans[Mesh])
Table of Contents
Definition / general | Epidemiology | Diagrams / tables | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Lanjewar S, Gupta R. Clear cell carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorclearcell.html. Accessed January 18th, 2021.
Definition / general
- Malignant tumor of clear, hobnail and eosinophilic cells in a tubulocystic, papillary and solid configuration
- Mean age is 55 years (Gynecol Oncol 2008;109:370)
- Associated with endometriosis in up to 70% of cases (Gynecol Oncol 2000;77:298)
- Can be associated with Lynch syndrome (Eur J Cancer 2016;55:65)
- Stage is the single most important prognostic factor (Kurman: WHO Classification of Tumours of Female Reproductive Organs, 4th Edition, 2014)
Epidemiology
- Highest incidence in Japan (25% of ovarian carcinomas), compared to Western countries (J Obstet Gynaecol Res 2014;40:338)
- Distribution in United States is 48% whites, 31% blacks and 11.1% Asians (Gynecol Oncol 2011;121:407)
Diagrams / tables
Contributed by Ayse Ayhan, M.D.
Clear cell carcinoma, case 1: Schema
Clinical features
- Frequent association with ovarian or pelvic endometriosis (Gynecol Oncol 2010;116:374)
- Commonly associated with paraneoplastic hypercalcemia and venous thromboembolism
Radiology description
- Clear cell carcinomas are commonly identified on USG by the presence of a single large cystic mass with smooth marginated solid component
- Presence of ground glass appearance in a cyst suggests an endometrioma, which in postmenopausal women should be evaluated carefully to rule out a component of clear cell carcinoma (Ultrasonography 2015;34:173)
Prognostic factors
- When confined to the pelvis, clear cell carcinoma has much better prognosis than high grade serous carcinoma
- However, advanced stage clear cell carcinoma has a worse prognosis (Am J Surg Pathol 2011;35:36)
- Presence of GPC3 is associated with poor prognosis (J Clin Pathol 2010;63:962),
Case reports
- 40 year old woman with bilateral ovarian clear cell carcinoma (Iran J Pathol 2016;11:478)
- 56 year old women with clear cell carcinoma of ovary (Gynecol Oncol Case Rep 2013;6:25)
Treatment
- Comprehensive surgical staging is required in early stage clear cell carcinoma, which includes bilateral salpingo-oophorectomy, total hysterectomy, lymph node dissection and omental biopsies
- At an advanced stage standard treatment of paclitaxel plus carboplatin is recommended (Ann Oncol 2016;27:i50)
- Clear cell carcinoma is resistant to platinum based chemotherapy, making metastatic disease difficult to treat (Am J Surg Pathol 2011;35:36)
Gross description
- Commonly unilateral with a size up to 30 cm (mean 15 cm)
- Cut surface is thick walled unilocular cyst with multiple yellow-beige fleshy nodules protruding into the lumen, these nodules may be lined by an endometriotic cyst which typically contains chocolate–brown fluid
Gross images
Contributed by Ayse Ayhan, M.D.
Clear cell carcinoma, case 1:
Outer appearance
Cut surface
Fixed pictures of surgical material
Clear cell carcinoma, case 2:
Outer appearance
Cut surface
Fixed cut surface
AFIP images
Polypoid tumor
arising in
endometriotic cyst
Microscopic (histologic) description
- Tubulocystic, papillary and solid patterns
- Papillae are small, regular and frequently hyalinized
- Tumor cells are polygonal to cuboidal and flattened with clear to eosinophilic cytoplasm; may have hobnail morphology
- Tubules and cysts contain dense eosinophilic "targetoid" secretions
- Intracytoplasmic mucin can give signet ring appearance
- Eosinophilic hyaline bodies can be seen (Am J Surg Pathol 2011;35:36, Adv Anat Pathol 2012;19:296)
Microscopic (histologic) images
Contributed by Sonali Lanjewar, M.D., M.B.B.S.
Clear cell carcinoma
Contributed by Semir Vranić, M.D., Ph.D.
Clear cell carcinoma of the ovary
AFIP images
Left: cystic pattern; right: lined by atypical hobnail cells
Poorly differentiated
With adenofibroma component
With extensive round cell infiltration
Numerous intracytoplasmic hyaline bodies
Mucicarmine
Positive stains
- Keratin, LeuM1 (90%), hyaline globules are PAS+ diastase resistant but AFP- (Am J Clin Pathol 1989;91:511)
- VHL gene product (90%, Am J Clin Pathol 2008;129:592), HNF-1beta (Mod Pathol 2006;19:83)
- Napsin A (Mod Pathol 2015;28:111)
Negative stains
Molecular / cytogenetics description
- Most common mutations are ARID1A (46 - 57%), PIK3CA (40%) and PTEN (J Gynecol Oncol 2016;27:e31)
- Can be seen with Lynch syndrome, most commonly with germline mutations in MSH2 (Int J Gynecol Pathol 2012;31:524)
Differential diagnosis
- Dysgerminoma: Oct3/4+, CK7-, to focal rare positivity
- Endometrioid carcinoma with clear cell features: columnar cell morphology, squamoid differentiation, cribriform architecture with IHC phenotype of ER/PR+, napsin A- and HNF1beta- favor endometrioid carcinoma
- High grade serous carcinoma: p53+, WT1+, HNF1beta-
- Metastatic clear cell renal carcinoma: commonly CK7-, ER-, PR-, RCC+, CD10+, carbonic anhydrase IX+ (Am J Surg Pathol 2008;32:377)
- Yolk sac tumor: AFP+, GPC3+
Board review style question #1
- When associated with Lynch syndrome, most common germline mutation seen in clear cell carcinoma is:
- BRAF mutation
- Methylation of MLH1 promoter
- MSH2 mutation
- All of the above
Board review style answer #1
