Ovary

Clear cell neoplasms

Clear cell carcinoma


Editorial Board Member: Carlos Parra-Herran, M.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Gulisa Turashvili, M.D., Ph.D.

Topic Completed: 9 July 2021

Minor changes: 9 July 2021

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PubMed Search: Ovary clear cell carcinoma [title] review [ptyp]

Gulisa Turashvili, M.D., Ph.D.
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Cite this page: Turashvili G. Clear cell carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorclearcell.html. Accessed September 22nd, 2021.
Definition / general
  • Malignant epithelial tumor composed of clear, eosinophilic or hobnail cells with tubulocystic, papillary and solid growth patterns
Essential features
  • Admixture of tubulocystic, papillary and solid growth patterns comprised of cells with uniform nuclear atypia without brisk mitotic figures
  • Usually positive for CK7, PAX8, napsin A and HNF1β and negative for ER, PR and WT1, with aberrant p53 expression in up to 24% of cases
  • May be associated with endometriosis or Lynch syndrome
  • Stage is the most important prognostic factor
ICD coding
  • ICD-O: 8310/3 - clear cell adenocarcinoma, NOS
  • ICD-10: C56 - malignant neoplasm of ovary
  • ICD-11: 2C73.00 - clear cell adenocarcinoma of ovary
Epidemiology
Sites
  • Ovary
  • Any extraovarian site with endometriosis
Pathophysiology
Etiology
Clinical features
Diagnosis
  • Microscopic examination
Laboratory
Radiology description
  • Large unilocular, mainly cystic, smooth marginated mass with 1 or more solid nodular protrusions into the cavity on all imaging modalities
  • High attenuated cystic portion on computed tomography (J Comput Assist Tomogr 2006;30:875)
  • Variable T1 signal, depending on hemorrhagic components on magnetic resonance imaging
  • Blood flow in solid nodules on Doppler ultrasound examination
  • In postmenopausal women, ground glass appearance in a cyst ultrasonographically should be evaluated carefully to rule out a component of clear cell carcinoma (Ultrasonography 2015;34:173)
Radiology images

Images hosted on other servers:

Ovarian mass on ultrasound

Prognostic factors
Case reports
Treatment
Gross description
  • Usually unilateral
  • Mean size 13 cm (range 0.8 - 35 cm) (Histopathology 2015;66:808)
  • Variable appearance on cut surface:
    • Mainly cystic, with fleshy nodules protruding into the cyst lumen
    • Solid and cystic (spongy appearance due to small cysts)
    • Solid (may be arising from clear cell adenofibroma or borderline clear cell tumor)
    • Cyst may contain chocolate brown fluid
    • Pale yellow to brown appearance
    • Necrosis or hemorrhage
  • Ovarian surface involvement in 11% of cases (Histopathology 2015;66:808)
Gross images

Contributed by Ayse Ayhan, M.D. and AFIP images
External surface

External surface

Cut surface Cut surface

Cut surface

External surface


Cut surface Cut surface

Cut surface

Polypoid areas in a cyst

Frozen section description
  • Admixure of characteristic tubulocystic, papillary and solid growth patterns
  • Uniformly atypical cells with clear to eosinophilic cytoplasm, no brisk mitoses
Frozen section images

Contributed by Gulisa Turashvili, M.D., Ph.D.
Epithelial neoplasm

Epithelial neoplasm

Uniform cytologic atypia

Uniform cytologic atypia

Microscopic (histologic) description
  • 3 classic growth patterns, frequently admixed but 1 pattern (usually papillary or tubulocystic) may predominate (Am J Surg Pathol 2011;35:36, Adv Anat Pathol 2012;19:296, Am J Surg Pathol 2016;40:656, Histopathology 2015;66:808):
    • Papillary:
      • Most frequent (70%)
      • Usually small, round, simple, nonbranching papillae with fibrous / hyalinized, edematous / myxoid or empty (open tumor rings) stromal cores
      • Lined by 1 - 2 layers of cuboidal, flattened or hobnail cells
      • Micropapillary tufts may be seen
      • Rarely irregular, broad papillae with or without hierarchical branching and micropapillae (Am J Surg Pathol 2008;32:269)
    • Tubulocystic:
      • Frequent (65%)
      • Variably sized tubules and cysts, with or without intraluminal dense eosinophilic secretions and outpouchings
      • Lined by a single layer of hobnail, cuboidal or flattened cells
      • Often associated with an adenofibromatous background
    • Solid:
      • Least common (62%)
      • Diffuse sheets or nested clusters of polyhedral cells separated by delicate septa exhibiting clear to eosinophilic cytoplasm
  • General features:
    • Low cuboidal, polyhedral, hobnail or flattened cells with uniform nuclear atypia, prominent nucleoli and variable mitotic activity (usually low at < 6 per 10 high power fields)
    • Hobnail cells have hyperchromatic nuclei protruding into lumina of tubulocystic structures or lining papillae
    • Focal nuclear pleomorphism may be present in 40%
    • Eosinophilic hyaline globules (Am J Surg Pathol 2011;35:36, Adv Anat Pathol 2012;19:296)
    • Nuclear pseudoinclusions
    • Peritumoural or diffuse lymphoplasmacytic infiltrate may be present
    • May be associated with clear cell adenofibroma, clear cell borderline tumor, endometriosis or endometrioid adenocarcinoma
    • Not graded (high grade by definition)
    • Oxyphilic variant of clear cell carcinoma is composed of tumor cells with variable amounts of clear to granular eosinophilic cytoplasm (oxyphil cells), especially in nested, solid or trabecular growths (Am J Surg Pathol 1987;11:661)
  • Rare features:
    • Multinucleated cells
    • Psammoma bodies
    • Diastase resistant intracytoplasmic material imparting a signet ring appearance (so called targetoid cells)
    • Intraglandular cellular sloughing mimicking high grade serous carcinoma
    • Uncommon growth patterns include glandular, nested, trabecular and reticular-like (myxoid stroma)
Microscopic (histologic) images

Contributed by Gulisa Turashvili, M.D., Ph.D., Sonali Lanjewar, M.D., M.B.B.S., Semir Vranić, M.D., Ph.D. and AFIP images
Variable architecture Variable architecture

Variable architecture

Papillary architecture Papillary architecture Papillary architecture

Papillary architecture


Tubulocystic architecture

Tubulocystic architecture

Tubulocystic and papillary architecture

Tubulocystic and papillary architecture

Solid pattern

Solid architecture

Solid architecture Targetoid cells

Targetoid cells


Left: cystic pattern; right: hobnail cells

Adenofibroma component

Hyaline bodies

HNF1β

HNF1β

Napsin A

Napsin A

Cytology description
  • Round to oval nuclei with fine chromatin
  • Abundant, pale, finely granular to vacuolated cytoplasm and indistinct cytoplasmic membranes
  • Hyaline extracellular material forming so called raspberry bodies or globule-like structures (Cytopathology 2016;27:427)
  • Psammoma bodies in ascitic fluid (Acta Cytol 2000;44:1005)
Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Uterus with cervix, fallopian tubes and ovaries, total hysterectomy and bilateral salpingo-oophorectomy:
    • Right ovary: clear cell carcinoma, positive for ovarian surface involvement (see synoptic report)
    • Left ovary and fallopian tubes: benign
    • Endometrium: inactive
    • Myometrium: leiomyomata
    • Uterine serosa and cervix: benign
Differential diagnosis
Board review style question #1

    Which of the following germline mutations is more common in Lynch syndrome associated clear cell carcinoma?

  1. ARID1A mutation
  2. BRAF mutation
  3. MSH2 mutation
  4. PMS2 mutation
  5. PTEN mutation
Board review style answer #1
C. MSH2 mutation

Comment Here

Reference: Clear cell carcinoma
Board review style question #2
    Which of the following is the most useful immunohistochemical panel for distinguishing between clear cell carcinoma and high grade carcinoma with clear cell features?

  1. ER, PR, WT1 and p53
  2. ER, PR, WT1 and SALL4
  3. PAX8, p16, napsin A and HNF1β
  4. WT1, ER, napsin A and HNF1β
  5. WT1, napsin A, p16 and SALL4
Board review style answer #2
D. WT1, ER, napsin A and HNF1β

Comment Here

Reference: Clear cell carcinoma
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