Ovary

• Typically, unilateral solid or solid and cystic mass with friable, necrotic / hemorrhagic cut surface (Am J Surg Pathol 2012;36:831)
  • Typically unilateral, only 10% bilateral (Clin Case Rep 2021;9:e05160)
• Typically large mass; mean size: 13.6 cm (Am J Surg Pathol 2012;36:831)
• Often spread beyond the ovary and over peritoneal surfaces (Crit Rev Oncol Hematol 2019;134:46)

Contributed by Mona Kandil, M.D., Ph.D.

• High grade malignant carcinomatous and sarcomatous elements admixed
• Carcinomatous element
  • Most common carcinomatous element is high serous adenocarcinoma; the second most common is endometrioid (Am J Surg Pathol 2012;36:831)
    • Serous > endometrioid > clear cell > squamous > mixed > undifferentiated carcinoma
  • Can also be mucinous, mixed high grade serous and endometrioid carcinoma, mixed high grade serous and clear cell carcinoma, or undifferentiated adenocarcinoma (Gynecol Oncol 2016;142:248)
• Sarcomatous element: can be homologous (50%) or heterologous (50%)
  • Homologous
    • Typically nonspecific malignant mesenchymal cells but may resemble fibrosarcoma, leiomyosarcoma or other sarcomas native to Müllerian organs (Clin Case Rep 2021;9:e05160)
  • Heterologous
    • Specific malignant elements of a non-Müllerian tissue including cartilaginous, osteosarcomatous or rhabdomyoblastic elements (J Ovarian Res 2020;13:129)
    • Incidence of sarcomatous types: chondrosarcoma > rhabdomyosarcoma > osteosarcoma and liposarcoma > neuroectodermal elements
    • Most often only 1 type of heterologous sarcoma
• Lymphovascular invasion common
• High grade cytologic atypia and brisk mitotic activity
• Intracytoplasmic hyaline globules in sarcomatous component are frequently seen

Contributed by Hatem Kaseb, M.D., Ph.D., M.P.H. and Mona Kandil, M.D., Ph.D.

• Shown to have mutations in genes commonly associated with uterine and ovarian carcinomas, such as TP53, KRAS and PIK3CA (most commonly observed mutations); others reported include CDKN1B, CTNNB1, FBXW7, PPP2R1A, CDH4, PTEN, PIK3CA, CCNE1, TERT, ARID1A, ARID1B, SPOP, BAZ1A, MLL3 and BCOR (Proc Natl Acad Sci U S A 2016;113:12238, Nat Commun 2014;5:5006)
• TP53 (Am J Clin Oncol 2023;46:572, Histopathology 2000;37:427, Proc Natl Acad Sci U S A 2016;113:12238, Obstet Gynecol 1994;83:118)
  • Mutations in TP53 are the most common in OCS, found in > 50% of cases
  • Often associated with tumorigenesis, advanced stage and worse survival, though not necessarily prognostic
  • Commonly deleted and frequently present in the serous epithelial component (> 50%)
• PIK3CA
  • ~40% of OCS exhibit PIK3CA missense mutations; these mutations show no prognostic significance (Nat Commun 2014;5:5006, Histopathology 2000;37:427, J Cancer Res Ther 2015;11:1022, Front Oncol 2023;13:1278300)
• EGFR or KIT
  • Overexpression of EGFR or KIT proteins may occur in OCS (Cancer Sci 2003;94:986)
• Mismatch repair (MMR)
  • Alterations or losses in MMR proteins are observed in some OCS, with defects more common in uterine than ovarian carcinosarcomas (Nat Commun 2014;5:5006, Am J Clin Oncol 2023;46:572)
• HER2 / Neu, MYC and VEGFA
  • Amplification of HER2, MYC and VEGFA genes may be present, potentially impacting tumor growth and progression (Am J Clin Oncol 2023;46:572)
• BRCA1 / BRCA2
  • BRCA1 / BRCA2 mutations and associated deficiencies in DNA double strand break repair have been reported, especially in cases where the carcinomatous component is serous carcinoma (Am J Clin Oncol 2023;46:572)
• Tumor mutational burden (TMB)
  • TMB in OCS and ovarian tumors is typically low (Am J Clin Oncol 2023;46:572)

A 55 year old woman presents with an abdominal mass, which is represented in the microscopic image above. She denies any accompanying symptoms. Which of the following immunohistochemical staining results will fit this patient profile?

1. CK7+, vimentin-
2. CK7-, vimentin-
3. CK7+, vimentin+
4. CK7-, vimentin+

C. CK7+, vimentin+. In ovarian carcinosarcoma, the carcinomatous component (demonstrated here on the right) will be positive for CK7, while the sarcomatous component (on the left) will be positive for vimentin. Answer B is incorrect because at least one component should be positive for CK7 and the other for vimentin. Answers A and D are incorrect because as mentioned above, the carcinomatous component is positive for CK7 and the sarcomatous component is typically positive for vimentin, therefore, the tumor overall should show positivity for CK7 and vimentin in at least one component.

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Reference: Carcinosarcoma

A 65 year old woman presents with a 15 cm solid cystic mass of the ovary. An excisional biopsy is performed. Microscopic images of 2 distinct areas are shown above. Which of the following genes is the most likely to be mutated?

1. EGFR
2. HER2
3. KRAS
4. TP53

D. TP53 is the most common mutation (> 50%) in carcinosarcomas of the ovary. Answer B is incorrect because HER2 is amplified in only a small fraction of ovarian carcinosarcoma cases. Answer C is incorrect because KRAS is commonly mutated in ovarian carcinosarcoma cases; however, TP53 is the most commonly reported mutation in ovarian carcinosarcoma. Answer A is incorrect because EGFR is rarely mutated / overexpressed in ovarian carcinosarcoma cases.

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Reference: Carcinosarcoma