Epithelial ovarian tumors classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]

Overview

Ovarian epithelial tumors can be classified on several bases depending on the morphology, histopathological behavior and clinical characteristics. The general classification of benign, borderline and malignant tumors is supplemented by classification systems augmented by molecular and clinico-pathological behavior of the tumors. This section also contains WHO classification of ovarian tumors to allow differentiation between epithelial tumors and other ovarian tumors.

Classification

General Classification

  • Table below provides a summary of this classification:
Epithelial Ovarian Tumors
Benign Borderline Malignant
  • Serous cystadenoma
  • Mucinous cystadenoma
  • Endometrioid cystadenoma
  • Clear cell tumor
  • Brenner tumor
  • Serous borderline tumor
  • Mucinous borderline tumor
  • Endometrioid borderline tumors
  • Clear cell tumor
  • Brenner tumor of borderline malignancy
  • Serous adenocarcinoma
  • Mucinous adenocarcinoma
  • Endometrioid adenocarcinoma
  • Clear cell adenocarcinoma
  • Malignant Brenner tumor
  • Carcinosarcoma

WHO Classification of Ovarian Epithelial Tumors

  • WHO classifies epithelial ovarian tumors on the basis of histology as follows:[2][3][4][5][6]
    • Serous tumors:
      • Benign (cystadenoma)
      • Borderline tumors (serous borderline tumor)
      • Malignant (serous adenocarcinoma)
    • Mucinous tumors:
      • Benign (cystadenoma)
      • Borderline tumors (mucinous borderline tumor)
      • Malignant (mucinous adenocarcinoma)
    • Endometrioid tumors:
      • Benign (cystadenoma)
      • Borderline tumors (endometrioid borderline tumor)
      • Malignant (endometrioid adenocarcinoma)
    • Clear cell tumors:
      • Benign
      • Borderline tumors
      • Malignant (clear cell adenocarcinoma)
    • Transitional cell tumors:
      • Brenner tumor
      • Brenner tumor of borderline malignancy
      • Malignant Brenner tumor
      • Transitional cell carcinoma (non-Brenner type)
    • Epithelial-stromal:
      • Adenosarcoma
      • Carcinosarcoma (formerly mixed Müllerian tumors)
Ovarian Epithelial Tumors
Serous Tumors Mucinous Tumors Endometrioid Tumors Clear Cell Tumors Transitional Cell Tumors Epithelial-Stromal
  • Benign (cystadenoma)
  • Borderline tumors (serous borderline tumor)
  • Malignant (serous adenocarcinoma)
  • Benign (cystadenoma)
  • Borderline tumors (mucinous borderline tumor)
  • Malignant (mucinous adenocarcinoma)
  • Benign (cystadenoma)
  • Borderline tumors (endometrioid borderline tumor)
  • Malignant (endometrioid adenocarcinoma)
  • Benign
  • Borderline tumors
  • Malignant (clear cell adenocarcinoma)
  • Brenner tumor
  • Brenner tumor of borderline malignancy
  • Malignant Brenner tumor
  • Transitional cell carcinoma (non-Brenner type)
  • Adenosarcoma
  • Carcinosarcoma (formerly mixed Müllerian tumors)

International Agency for Research on Cancer Histologic Groups of Ovarian Tumors

Classification from International agency for research on cancer is summarized in the table: [4][5][7]

Ovarian Tumors
  • Carcinoma
    • Serous carcinoma
    • Mucinous carcinomac
    • Endometrioid carcinoma
    • Clear cell carcinoma
    • Adenocarcinoma NOS
    • Other specified carcinomas
    • Unspecified carcinoma
  • Sex cord-stromal tumors
  • Germ cell tumors
  • Other specified cancers (including malignant Brenner tumor, mullerian mixed tumor, and carcinosarcoma)
  • Unspecified cancer

Epithelial Ovarian Cancer Classification Based on Clinicopathologic and Molecular Evidence

  • Recent advances in histopathology and a better understanding of clinicopathologic characteristics have led to a classification system that correlates histology and clinical characteristics.
  • This classification subdivides malignant ovarian tumors in two types.
  • Type I tumors generally arise from endometriosis or fallopian tubal related serous epithelium. They exhibit less aggressive clinical course and a different genetic profile relative to Type II.[1][3]
  • Type II tumors generally arise from fallopian tubal epithelium. They exhibit more aggressive clinical course and a different genetic profile relative to Type I.[1][3]
  • Type I tumors are generally characterized by chromosomal stability and somatic mutations that may include KRAS, BRAF, PTEN, PIK3CA, CTNNB1, ARID1A and PPP2R1A. BRCA1 mutation, on the other hand, has not been observed and TP53 mutation is very rare.[8][9][10]
  • Type II tumors are characterized by chromosomal instability. The mutations characteristic of high grade tumors, especially TP53 are common. TP53 has been reported in more than 90% of these tumors and a high proportion contains either BRCA mutations or BRCA related mutations such as RAD51, PALB2.[8][11][12]
Epithelial Ovarian Cancer
Type I Type II
  • Low-grade serous carcinoma
  • Endometrioid carcinoma
  • Clear cell carcinoma
  • Mucinous carcinoma
  • Malignant Brenner tumor
  • Seromucinous carcinoma
  • High-grade serous carcinoma
  • Undifferentiated carcinoma
  • Carcinosarcoma

WHO Classification of Ovarian Tumors

WHO classifies ovarian tumors as follows:[1][2][3][4][5][6]

Ovarian Cancer
Epithelial Sex-Cord Stromal Germ Cell Others
  • Serous tumors:
    • Benign (cystadenoma)
    • Borderline tumors (serous borderline tumor)
    • Malignant (serous adenocarcinoma)
  • Mucinous tumors:
    • Benign (cystadenoma)
    • Borderline tumors (mucinous borderline tumor)
    • Malignant (mucinous adenocarcinoma)
  • Endometrioid tumors:
    • Benign (cystadenoma)
    • Borderline tumors (endometrioid borderline tumor)
    • Malignant (endometrioid adenocarcinoma)
  • Clear cell tumors:
    • Benign
    • Borderline tumors
    • Malignant (clear cell adenocarcinoma)
  • Transitional cell tumors:
    • Brenner tumor
    • Brenner tumor of borderline malignancy
    • Malignant Brenner tumor
    • Transitional cell carcinoma (non-Brenner type)
  • Epithelial-stromal:
    • Adenosarcoma
    • Carcinosarcoma (formerly mixed Müllerian tumors)
  • Pure stromal tumors:
    • Fibroma
    • Cellular fibroma
    • Thecoma
    • Luteinized thecoma associated with sclerosing peritonitis
    • Fibrosarcoma
    • Sclerosing stromal tumor
    • Signet-ring stromal tumor
    • Microcystic stromal tumor
    • Leydig cell tumor
    • Steroid cell tumor
    • Steroid cell tumor, malignant
  • Pure sex cord tumors:
    • Adult granulosa cell tumor
    • Juvenile granulosa cell tumor
    • Sertoli cell tumor
    • Sex cord tumor with annular tubules
  • Mixed sex cord-stromal tumors
    • Sertoli-Leydig cell tumors
      • - Well-differentiated
      • - Moderately differentiated with heterologous elements
      • - Poorly differentiated with heterologous elements
      • - Retiform with heterologous elements
    • Sex cord-stromal tumours, NOS*
  • Teratoma
    • Immature
    • Mature
    • Solid
    • Cystic (dermoid cyst)
  • Dysgerminoma
  • Endometrial Sinus tumors
  • Embryonal carcinoma
  • Polyembryoma
  • Choriocarcinoma
  • Mixed germ cell tumors tumors
  • Gonadoblastoma
  • Germ cell sex cord-stromal tumor of nongonadoblastoma type
  • Tumors of rete ovarii
  • Mesothelial tumors
  • Tumors of uncertain origin and miscellaneous tumors
  • Gestational trophoblastic diseases
  • Soft tissue tumors not specific to ovary
  • Malignant lymphomas leukemias, and plasmacytomas
  • Unclassified tumors
  • Secondary (metastatic) tumors
  • Tumor-like lesions

References

  1. 1.0 1.1 1.2 1.3 Rojas V, Hirshfield KM, Ganesan S, Rodriguez-Rodriguez L (December 2016). "Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment". Int J Mol Sci. 17 (12). doi:10.3390/ijms17122113. PMC 5187913. PMID 27983698.
  2. 2.0 2.1 2.2 Horta M, Cunha TM (2015). "Sex cord-stromal tumors of the ovary: a comprehensive review and update for radiologists". Diagn Interv Radiol. 21 (4): 277–86. doi:10.5152/dir.2015.34414. PMC 4498422. PMID 26054417.
  3. 3.0 3.1 3.2 3.3 3.4 McCluggage WG (August 2011). "Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis". Pathology. 43 (5): 420–32. doi:10.1097/PAT.0b013e328348a6e7. PMID 21716157.
  4. 4.0 4.1 4.2 4.3 Meinhold-Heerlein I, Fotopoulou C, Harter P, Kurzeder C, Mustea A, Wimberger P, Hauptmann S, Sehouli J (April 2016). "The new WHO classification of ovarian, fallopian tube, and primary peritoneal cancer and its clinical implications". Arch. Gynecol. Obstet. 293 (4): 695–700. doi:10.1007/s00404-016-4035-8. PMID 26894303.
  5. 5.0 5.1 5.2 5.3 "onlinelibrary.wiley.com".
  6. 6.0 6.1 6.2 Kurman RJ, Shih I (March 2010). "The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory". Am. J. Surg. Pathol. 34 (3): 433–43. doi:10.1097/PAS.0b013e3181cf3d79. PMC 2841791. PMID 20154587. Vancouver style error: initials (help)
  7. Meinhold-Heerlein I, Fotopoulou C, Harter P, Kurzeder C, Mustea A, Wimberger P, Hauptmann S, Sehouli J (October 2015). "Statement by the Kommission Ovar of the AGO: The New FIGO and WHO Classifications of Ovarian, Fallopian Tube and Primary Peritoneal Cancer". Geburtshilfe Frauenheilkd. 75 (10): 1021–1027. doi:10.1055/s-0035-1558079. PMC 4629993. PMID 26556905.
  8. 8.0 8.1 Kurman RJ, Shih I (July 2011). "Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm". Hum. Pathol. 42 (7): 918–31. doi:10.1016/j.humpath.2011.03.003. PMID 21683865. Vancouver style error: initials (help)
  9. Shih I, Kurman RJ (May 2004). "Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis". Am. J. Pathol. 164 (5): 1511–8. PMID 15111296. Vancouver style error: initials (help)
  10. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih I, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG (October 2010). "ARID1A mutations in endometriosis-associated ovarian carcinomas". N. Engl. J. Med. 363 (16): 1532–43. doi:10.1056/NEJMoa1008433. PMC 2976679. PMID 20942669. Vancouver style error: initials (help)
  11. Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, Stewart C, Fereday S, Caldas C, Defazio A, Bowtell D, Brenton JD (May 2010). "Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary". J. Pathol. 221 (1): 49–56. doi:10.1002/path.2696. PMC 3262968. PMID 20229506.
  12. Senturk E, Cohen S, Dottino PR, Martignetti JA (November 2010). "A critical re-appraisal of BRCA1 methylation studies in ovarian cancer". Gynecol. Oncol. 119 (2): 376–83. doi:10.1016/j.ygyno.2010.07.026. PMID 20797776.

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