Ovary tumor
Clear cell carcinoma
Clear cell carcinoma

Author: Sonali Lanjewar, M.D., MBBS
Editor: Raavi Gupta, M.D.

Revised: 2 April 2018, last major update April 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Ovary tumor clear cell carcinoma [title] AND (free full text[sb] AND Humans[Mesh])

Related topics: Oxyphilic variant
Cite this page: Lanjewar, S. Clear cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/ovarytumorclearcell.html. Accessed May 26th, 2018.
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
  • Can be associated with Lynch syndrome
  • Stage is the single most important prognostic factor
Diagrams / tables

Images hosted on PathOut server, contributed by Ayse Ayhan, M.D.:

Clear cell carcinoma, case 1 - Schema

Clinical features
  • Frequent association with ovarian or pelvic endometriosis
  • Commonly associated with paraneoplastic hypercalcemia and venous thromboembolism
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)
  • 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 mean size of 15 cm
  • Solid to cystic
  • Fleshy pale yellow nodules lining an endometriotic cyst
Gross images
Images hosted on PathOut server, 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

Contributed by AFIP

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; including hobnail morphology
  • Tubules and cyst 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
Images hosted on PathOut server, contributed by AFIP:

Clear cell and endometrioid adenocarcinoma, mixed

Papillary pattern

Hobnail and flat cells

Left: cystic pattern; right: lined by atypical hobnail cells

Solid pattern

Papillae lined by hobnail cells and have hyalinized cores

Targetoid appearance

Mucicarmine stain

Poorly differentiated

Complex glomeruloid papilla

With adenofibroma component

With extensive round cell infiltration

Numerous intracytoplasmic hyaline bodies

Images hosted on other servers:

Contributed by Dr. Semir Vranic

Positive stains
Negative stains
Molecular / cytogenetics description
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 and PR- while being RCC and CD10+
  • Yolk sac tumor: AFP+, GPC3+
Board review 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 answer #1
C. MSH2 mutation