1. Clear cell carcinoma of the ovary
Jan Laco
The Fingerland Department of Pathology
Charles University Faculty of Medicine
and University Hospital
Hradec Kralove, Czech Republic

2. Ovarian cancer High grade serous Clear cell Endometrioid Mucinous
Low grade serous

3. Novel classification Type I Type II Low-grade serous Mucinous
Low-grade endometrioid
Clear cell
High-grade serous
High-grade endometrioid
Undifferentiated carcinoma
Carcinosarcoma
Early stage
Advanced stage
From precursors
De novo
KRAS, BRAF, PTEN, PIK3CA, ARID1A
TP53, BRCA
Indolent (?)
Aggressive
Chemoresistant
Initially chemosensitive
Favourable prognosis
Poor prognosis

4. Clinical features 2nd to 3rd most common OC … 5 – 25 %
Japan … 15 – 25 % … ↑↑↑
USA + Europe … 1 – 12 %
median age … 55 years
thromboembolic events (40 %)
hypercalcemia
Lynch syndrome (MSH2)

5. 50 – 70 % prognosis ??? + endometriosis x + adenofibroma/BT
Kurman et al.: Molecular pathogenesis … . Hum Pathol, 2011, 42,

6. Gross features Stage I … 35 – 60 % Stage II … 10 – 22 %
Rupture of capsule … 40 % … pT1c
Unilocular cystic tumor + solid areas
Mean size … 15 cm

7. Microscopy
“a malignant tumor composed of clear, eosinophilic and hobnail cells, displaying a combination of tubulo-cystic, papillary and solid patterns“ (WHO 2014)
Grade 3 (WHO 2014)

8. Immunohistochemistry
CK7+/CK20-
PAX8+
Triple negative – WT-1/ER/p53wt
± CA125/p16

9. Hepatocyte nuclear factor-1β
CCC ovary … %
Endometrioid Ca ovary … 25 %
Mucinous Ca ovary + Krukenberg … 50 %
Serous Ca ovary … 0-5 %
adenoCa cervix … 75 %
CCC of kidney, urinary bladder, pancreas, …

10. Napsin A CCC ovary … 85-100 % Endometrioid Ca ovary … 0-10 %
Mucinous Ca ovary … negative
Serous Ca ovary … negative
CCC endometrium … 65 %
Ca of lung, kidney, thyroid

11. Molecular genetics Inactivating mutation ARID1A (40-60 %)
Stress response, glucose metabolism, coagulation
Inactivating mutation ARID1A (40-60 %)
Activating mutation PIK3CA (40 %)
Amplification MET (30-40 %)
Deletion PTEN (20 %)

12. CCC vs high grade serous Ca
HG Serous Ca
Papillae
Hyalinized
Non-hyalinized
Cytoplasm
Clear/eosinophilic
Basophilic
Mitotic rate
Low
High
WT-1/ER
Negative
Positive
HNF-1β/napsin A

13. CCC vs dysgerminoma CCC dysgerminoma Age Older Younger Cells
Rounded, central nuclei
Polygonal, eccentric nuclei
Lymphocytes/granulomas
Absent
Present
SALL4/OCT3/PLAP/c-kit
Negative
Positive
CK7/EMA/PAX8

14. Schiller-Duval bodies
CCC vs yolk sac tumor
CCC
Yolk sac tumor
Age
Older
Younger
Papillae
Schiller-Duval bodies
Hyalinized
Absent
Non-hyalinized
Present
Hyaline bodies
SALL4/glypican-3
Negative
Positive
CK7/EMA/PAX8
HNF-1β

15. CCC vs metastatic clear cell RCC
Personal history
Imaging methods
---
Positive
β-catenin/CD10/adipophilin
Negative
CK7

16. Prognosis
Stage
Nodal status
Adenofibroma/BT ???
Various IHC markers

17. Biologic behaviour 5 year survival Stage I … 69 % Stage II … 55 %
Stage III … 14 %
Stage IV … 4 %
Recurrence rate
Stage I/II … 30 %
Stage III/IV … 75 %

18. Biologic behaviour Resistance to platinum-based chemotherapy
Sunitinib + PIK3/AKT/mTOR inhibitors