Clear cell neoplasms
Clear cell carcinoma

Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Sonali Lanjewar, M.B.B.S.
Raavi Gupta, 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])

Sonali Lanjewar, M.B.B.S.
Raavi Gupta, M.D.
Page views in 2020: 24,669
Page views in 2021 to date: 1,461
Cite 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
Diagrams / tables

Contributed by Ayse Ayhan, M.D.
Missing Image

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
  • 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


Positive stains
Negative stains
Molecular / cytogenetics description
Differential diagnosis
Board review style question #1
    When associated with Lynch syndrome, most common germline mutation seen in clear cell carcinoma is:

  1. BRAF mutation
  2. Methylation of MLH1 promoter
  3. MSH2 mutation
  4. All of the above
Board review style answer #1
C. MSH2 mutation

Comment Here

Reference: Clear cell carcinoma
Back to top
Image 01 Image 02