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 22nd, 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)
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
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.
Contributed by Semir Vranić, M.D., Ph.D.
AFIP images
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