Uterus
Carcinoma
Clear cell carcinoma

Editorial Board Member: Jennifer Bennett, M.D.
Editor-in-Chief: Debra Zynger, M.D.
Jutta Huvila, M.D.
C. Blake Gilks, M.D.

Topic Completed: 21 April 2020

Minor changes: 7 May 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed search: Clear cell carcinoma[TI] uterus

Jutta Huvila, M.D.
C. Blake Gilks, M.D.
Page views in 2019: 11,938
Page views in 2020 to date: 8,283
Cite this page: Huvila J, Gilks CB. Clear cell carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusclearcell.html. Accessed August 8th, 2020.
Definition / general
  • Tumor of postmenopausal patients that histologically resembles ovarian clear cell carcinoma with clear, oxyphil or hobnail cells
Essential features
  • Diagnosed based on characteristic morphology
  • Solid architecture more common than papillary
  • HNF-1B, NapsinA and AMACR positive
  • Can be any of the 4 molecular subtypes of endometrial carcinoma but most common is no specific molecular profile (p53, mismatch repair and POLE wild type, estrogen receptor negative)
Terminology
  • Also called clear cell adenocarcinoma
ICD coding
  • ICD-O: 8310/3 - clear cell adenocarcinoma, NOS
  • ICD-10: C54.1 - malignant neoplasm of endometrium
Epidemiology
Sites
  • Uterus
Pathophysiology
  • Heterogeneity of molecular pathogenesis (Histopathology 2015;66:664)
  • All 4 molecular subtypes can be seen (p53 abnormal, mismatch repair deficient, POLE mutant and no specific molecular profile) (Histopathology 2015;66:664)
  • p53 abnormal (serous-like) are aggressive, similar to other p53 abnormal endometrial carcinomas (Histopathology 2015;66:664)
  • Mismatch repair deficient often shows mixed morphology, with clear cell and endometrioid components (J Natl Cancer Inst 2016;108:djv427)
  • Only no specific molecular profile (p53, POLE and mismatch repair wild type) fit the classic clinical profile of clear cell carcinoma
Etiology
  • Unknown
Clinical features
Diagnosis
  • Diagnosis is based on characteristic findings on an endometrial biopsy or curettage, which is typically performed for postmenopausal bleeding
  • Abdominal and pelvic imaging can be performed for the purpose of clinical staging
Prognostic factors
Case reports
Treatment
  • Total hysterectomy and bilateral salpingo-oophorectomy
  • Radiation therapy may be considered
Clinical images

Images hosted on other servers:

Endometrial mass

Microscopic (histologic) description
  • Diagnosis should be based on the presence of prototypical morphologic (both architectural and cytological) features (Int J Gynecol Pathol 2019;38:S40)
  • Cytological features (Am J Cancer Res 2013;3:70, Int J Gynecol Pathol 2019;38:S40)
    • Polygonal cells with moderate to abundant clear or eosinophilic cytoplasm
    • Hobnail cells and flat cells
    • Occasional enlarged irregular nucleoli
    • Variable cytological atypia
    • Relatively low mitotic index
    • High mitotic index or pleomorphic nuclei does not rule out clear cell carcinoma in an otherwise typical tumor
    • Occasionally targetoid bodies, eosinophilic globules or psammoma bodies
  • Architectural features (Am J Cancer Res 2013;3:70, Int J Gynecol Pathol 2019;38:S40)
    • Solid, glandular or papillary architecture or a combination of these
    • Stromal hyalinization (uncommon)
    • No diffuse nuclear stratification in the papillary areas or diffuse columnar cell changes
Microscopic (histologic) images

Contributed by Jutta Huvila, M.D.

Solid architecture

Glandular architecture

Glandular pattern

Papillary and glandular architecture

Papillary architecture


Hyalinized stroma

Clear cell cytology

Clear and hobnail cells

Oxyphilic cells

Clear and hobnail cells


Targetoid bodies

Psammoma bodies

ER

NapsinA

MSH6

Molecular / cytogenetics description
  • ~50% are related to p53 abnormal, mismatch repair deficient or POLE mutant
  • Remaining cases show occasional KRAS or PIK3CA mutations, without PTEN or TP53 abnormalities (Hum Pathol 2019;92:10)
Sample pathology report
  • Endometrium, biopsy:
    • Clear cell carcinoma of the endometrium (MMR intact, p53 wild type) (see comment)
    • Comment: There is intact expression of mismatch repair proteins (PMS2 and MSH6) and wild type expression of p53, i.e. staining of variable intensity in < 80% of tumor cell nuclei.
Differential diagnosis
Board review style question #1



Which of the following is true about clear cell carcinoma of the endometrium (shown in the image)?

  1. It is associated with a favorable prognosis
  2. It is associated with high levels of estrogen exposure (endogenous or exogenous)
  3. There is molecular heterogeneity
  4. There is no association with Lynch syndrome
Board review answer #1
C. There is molecular heterogeneity. Clear cell carcinomas of the endometrium can be associated with mutations in POLE (in which case they have a very favorable prognosis), mismatch repair deficiency (which may be a result of Lynch syndrome), mutations in TP53 (poor prognosis) or none of the above.

Comment Here

Reference: Clear cell carcinoma
Board review style question #2
The immunoprofile of most endometrial clear cell carcinomas includes

  1. Immunonegativity for AMACR
  2. Immunopositivity for progesterone receptor
  3. Immunoreactivity for NapsinA
  4. Mutant pattern staining for p53
Board review answer #2
C. Immunoreactivity for NapsinA. The immunophenotype of a majority of endometrial clear cell carcinomas is positivity for NapsinA and AMACR, negativity for progesterone receptor and wild type staining pattern for p53.

Comment Here

Reference: Clear cell carcinoma
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