Ovary

Other surface epithelial tumors

Undifferentiated / dedifferentiated carcinoma (ovary / endometrium)


Editorial Board Member: Gulisa Turashvili, M.D., Ph.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Basile Tessier-Cloutier, M.D.

Last author update: 17 February 2022
Last staff update: 25 August 2022

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PubMed Search: Undifferentiated carcinoma [TIAB] ovary

Basile Tessier-Cloutier, M.D.
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Cite this page: Tessier-Cloutier B. Undifferentiated / dedifferentiated carcinoma (ovary / endometrium). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorundifferentiated.html. Accessed December 7th, 2022.
Definition / general
Essential features
  • At least focal sheet-like growth pattern with lack of glandular or papillary differentiation
  • High mitotic and proliferation indices
  • Absence or significantly diminished expression of markers of differentiation (e.g. CK7, PAX8, ER and claudin4)
  • Presence of a differentiated component (usually low grade endometrioid adenocarcinoma) is necessary for the diagnosis of dedifferentiated carcinoma
  • Loss of a core SWI / SNF protein is helpful in confirming the diagnosis but not essential to make the diagnosis
ICD coding
  • ICD-O:
    • 8020/3 - carcinoma, undifferentiated, NOS
    • 8020/3 - dedifferentiated carcinoma
  • ICD-11:
    • 2C73.Y & XH1YY4 - other specified malignant neoplasms of the ovary & carcinoma, undifferentiated, NOS
    • 2C73.Y & XH5R16 - other specified malignant neoplasms of the ovary & dedifferentiated carcinoma
    • 2C76.Y & XH1YY4 - other specified malignant neoplasms of the corpus uteri & carcinoma, undifferentiated, NOS
    • 2C76.Y & XH5R16 - other specified malignant neoplasms of the corpus uteri & dedifferentiated carcinoma
Epidemiology
Sites
  • Endometrium
  • Ovary
Pathophysiology
  • Likely evolves from a differentiated endometrial or ovarian carcinoma secondary to disrupted epigenetic modulation
  • Inactivation of the SWI / SNF chromatin remodeling complex is common
  • Often associated with mismatch repair deficiency
Etiology
  • No associated environmental risk factors
Clinical features
  • Usually presents at advanced stage
  • Abdominal pain and swelling
Diagnosis
  • There are no established tests to screen for endometrial and ovarian malignancies where the vast majority of undifferentiated and dedifferentiated carcinomas occur
  • When clinical suspicion arises, abdominal ultrasound and computed tomography scans are useful adjunct
  • Definitive diagnosis requires biopsy tissue
Radiology description
  • Large, solid adnexal mass with variable hemorrhage and necrosis
Prognostic factors
Case reports
Treatment
  • Primary ovarian tumor treated primarily with chemotherapy followed by surgery
  • Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH BSO) with or without lymphadenectomy
  • Emerging evidence supports that SWI / SNF deficient undifferentiated and dedifferentiated carcinoma does not respond to the conventional platinum based regimens (J Pathol Clin Res 2021;7:144)
Gross description
  • Large, solid mass with extensive tumor necrosis
Gross images

Images hosted on other servers:
Surgical specimen

Surgical specimen

Microscopic (histologic) description
  • Undifferentiated component:
    • Diffuse, sheet-like growth pattern with lack of glandular or papillary architecture (occasionally glandular or papillary structures from the differentiated component may be entrapped)
    • Comprised of a proliferation of monomorphic, medium sized cells
    • Abrupt keratinization may be seen
    • Cells frequently show discohesion (at least focally)
    • Variable amount of cytoplasm, sometimes with rhabdoid features
    • Brisk mitoses
    • Necrosis frequently present
    • Some cases may show focal spindling and myxoid changes
  • Differentiated component:
    • Typically low grade endometrioid adenocarcinoma
    • Rarely high grade endometrioid adenocarcinoma, high grade serous carcinoma or clear cell carcinoma
Microscopic (histologic) images

Contributed by Basile Tessier-Cloutier, M.D.
Dedifferentiated ovarian carcinoma

Undifferentiated and differentiated components

Undifferentiated ovarian carcinoma

Solid architecture

Undifferentiated ovarian carcinoma

Discohesive rhabdoid cells

ARID1B

ARID1B

Positive stains
Negative stains
  • In the differentiated component (if present):
    • p53 wild type pattern (patchy negative to intermediate nuclear staining)
      • Uncommonly the differentiated component may be high grade, which can be associated with a mutant p53 IHC pattern
    • p16 (patchy negative to weak nuclear and cytoplasmic staining)
      • Uncommonly the differentiated component may be high grade, which can be associated with a diffuse p16 IHC pattern
    • Mismatch repair deficiency (MLH1, PMS2, MSH2, MSH6) is common (~50%)
  • In the undifferentiated component:
    • CK7, PAX8, ER, WT1, claudin4 (may have weak or focal expression)
    • SWI / SNF complex loss of protein expression (BRG1, INI1 or co-loss of ARID1A and ARID1B)
    • Usually p53 wild type (negative to patchy intermediate nuclear staining)
    • p16 (negative to patchy weak nuclear and cytoplasmic staining)
    • Mismatch repair deficiency (MLH1, PMS2, MSH2, MSH6) is common (~50%)
Molecular / cytogenetics description
  • Commonly shows an inactivating mutation in one of the core SWI / SNF complex genes, resulting in the loss of expression of BRG1 (SMARCA4 gene), INI1 (SMARCB1 gene) or co-loss of ARID1A and ARID1B
  • Most cases are associated with mismatch repair deficiency and of those with MLH1 deficiency, almost all show MLH1 promoter hypermethylation
  • Mutations in other genes associated with endometrioid carcinoma, such as PTEN, PIK3CA, KRAS and CTNNB1, are often reported
Sample pathology report
  • Uterus, fallopian tubes and ovaries, hysterectomy and bilateral salpingo-oophorectomy:
    • Endometrial dedifferentiated carcinoma (see synoptic report)
    • Associated with an endometrioid adenocarcinoma FIGO grade 1
    • Mismatch repair status: abnormal (MLH1 lost)
  • Uterus, fallopian tubes and ovaries, hysterectomy and bilateral salpingo-oophorectomy:
    • Undifferentiated carcinoma of the ovary (see synoptic report)
    • Mismatch repair status: abnormal (MLH1 lost)
Differential diagnosis
Additional references
Board review style question #1

This is a representative image from a solitary ovarian tumor in a 75 year old woman. The tumor shows absent INI1 immunohistochemistry expression. What is the most likely diagnosis?

  1. Carcinosarcoma
  2. High grade serous carcinoma of the ovary
  3. Primary diffuse large B cell lymphoma of the ovary
  4. Small cell carcinoma of the ovary hypercalcemic type
  5. Undifferentiated carcinoma of the ovary
Board review style answer #1
E. Undifferentiated carcinoma of the ovary

Comment Here

Reference: Undifferentiated carcinoma of the ovary
Board review style question #2

This is a representative image from an endometrial tumor in a 75 year old woman. What is the most likely diagnosis?

  1. Carcinosarcoma of the ovary
  2. Collision tumor
  3. Endometrial dedifferentiated carcinoma
  4. High grade endometrioid adenocarcinoma of the ovary
  5. High grade serous carcinoma of the ovary
Board review style answer #2
C. Endometrial dedifferentiated carcinoma

Comment Here

Reference: Undifferentiated carcinoma of the ovary
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