Epithelial ovarian tumors origin of neoplasia

Jump to navigation Jump to search


Epithelial ovarian tumors Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Epithelial Ovarian Tumors from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Epithelial ovarian tumors origin of neoplasia On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Epithelial ovarian tumors origin of neoplasia

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Epithelial ovarian tumors origin of neoplasia

CDC on Epithelial ovarian tumors origin of neoplasia

Epithelial ovarian tumors origin of neoplasia in the news

Blogs on Epithelial ovarian tumors origin of neoplasia

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Epithelial ovarian tumors origin of neoplasia

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

The origin of neoplasia in epithelial ovarian cancer: A mystery to solve

  • The previous proposition regarding the origin of epithelial ovarian cancers was that these tumors originated from surface epithelium of the ovaries and the neoplastic and metaplastic changes led to their differentiation into various histological subtypes such as serous tumors, clear cell carcinoma and endometrioid tumors.[1][2][3][4][5]
  • However the surface epithelium of ovaries is derived from mesothelium and ovarian carcinoma resembled more closely to tissues derived from Mullerian ducts rather than ovarian mesothelium derived surface epithelium. For example serous cancer histology resembles fallopian tube epithelium and that of transitional cells tumor resembles urinary bladder. Likewise endometrioid, and sero-mucinous carcinomas are thought to have their origin in endometriosis, and Walthard nests potentially give rise to mucinous and Brenner malignant tumors, at least partially. All of these precursors are Müllerian system derivatives.[1][2][3][4][5][6]
  • Secondly the genetic profile also overcasts shadows of doubt about origin of these neoplasms from ovarian surface epithelium. The presence of identical TP53 mutations in serous tubal intra-epithelial tumors and ovarian serous tumors puts a question mark on ovarian origin theory. Gene expression profiling also demonstrated the presence of similarities between serous tubal intra-epithelial tumors and ovarian serous tumors. The various theories of origin of epithelial ovarian cancers have been discussed below.[3][4][5][7][8]

Ovarian origin of ovarian epithelial tumors

  • This simple theory states that ovarian epithelial tumors simply originate from surface epithelium of ovaries through various neoplastic changes. But recent data has highlighted the numerous inconsistencies in the theory that was once highly regarded as accurate.[3][4][5]
  • Firstly surface epithelium of ovaries is derived from mesothelium and ovarian carcinoma resembled more closely to tissues derived from Mullerian ducts rather than ovarian mesothelium derived surface epithelium. For example serous cancer histology resembles fallopian tube epithelium and that of transitional cells tumor resembles urinary bladder. Likewise endometrioid, and sero-mucinous carcinomas are thought to have their origin in endometriosis, and Walthard nests potentially give rise to mucinous and Brenner malignant tumors, at least partially. All of these precursors are Müllerian system derivatives.[1][2][3][4][5][6]
  • Secondly the presence of identical TP53 mutations in serous tubal intra-epithelial tumors and ovarian serous tumors puts a question mark on ovarian origin theory. Gene expression profiling also demonstrated the presence of similarities between serous tubal intra-epithelial tumors and ovarian serous tumors.[3][4][5][7][8]
  • The expression of PAX8 and absence of calretinin in high grade serous tumors presents another problem with theory of ovarian origin because PAX8 is a Müllerian marker and calretinin is a mesothelium marker.[4][5]
  • In 2001, a Dutch study revealed the presence of high grade serous carcinomas in fallopian tubes of women with genetic susceptibility to hereditary ovarian cancers with no evidence of such lesions in ovaries of same women. These lesions were termed as serous tubal intra-epithelial tumors.[3][4][5][9][7][10]
  • Additional studies demonstrated the presence of similar lesions in fallopian tubes of women without genetic susceptibility to ovarian cancer. In cases when fallopian tubes were removed carefully along with ovarian and/or peritoneal serous cancer, the involvement of mucosa of the tubes were found to be involved in about 70% of the cases.[3][4][5][9][7][10]
  • In an attempt to explain these apparent discrepancies it was postulated that invagination of ovarian epithelium into ovarian stroma creates “cortical inclusion cysts”. These cysts then undergo various metaplastic changes (coelomic metaplasia hypothesis) due to hormonal influence and repair mechanisms to give rise to ovarian epithelial cancer. Although these cysts are present but no such neoplastic and metaplastic transformation has been reported or observed until now. Additionally the observed cysts could dimply be the transplants from the fallopian tubes.[3][4][5][11]
  • Another proposed theory is the implantation of tubal epithelium from fimbria into ovarian inclusion cysts due to their close contact during the ovulation process. This may explain the origin of serous tumor of the ovaries but unable to explain other tumor sub-types.[3][4][5]

Secondary Müllerian system

  • This theory tries to explain this apparent enigma of existence of Müllerian epithelial lesions in locations not derived from Müllerian ducts such as ovaries and peritoneal cavity. Secondary Müllerian system consists of müllerian-type tissue lined cysts that are located in close proximity to the ovaries.[12][3][4][5]
  • According to this hypothesis Müllerian tissues, considered by some as vestigial, are found in locations such as para-tubal and para-ovarian locations and these tissues or cysts, not the ovarian epithelium itself, give rise to epithelial ovarian neoplasms. These tumors, arising outside ovaries, then enlarge and become implants/or compress ovaries and present as ovarian tumors.[1][3][4][5]
  • But there are number of problems this theory fails to explain. For example mucinous epithelial tumors of ovaries resemble intestinal epithelium rather than endocervical epithelium. Also transitional cell tumor resemble morphologically to bladder epithelium that is not a derivative of Müllerian system.[3][4][5][6]
  • Another apparent flaw is that transition of these cysts lined by Müllerian-type epithelium, although present, to carcinoma has been very rare.[3][4][5]

The origin of epithelial ovarian tumors from fallopian tubes and endometrium, and not from ovaries

  • The evidence from recent studies indicate that majority of epithelial ovarian cancers have their origin outside ovaries, especially from fallopian tubes and endometrium. This idea is supported by several observations in a number of studies.[3][4][5]
  • The histology of serous, endometrioid and clear cell carcinoma demonstrates that their morphology is similar to that fallopian tubes, and endometrium rather than ovarian epithelium.[3][4][5][13][14]
  • Presence of PAX8, a Müllerian marker, and absence of calretinin, a mestothelial marker, further supports the theory. Moreover the genetic profile expression similarities and presence of similar TP53 mutation signatures in serous tubal intra-epithelial tumors and epithelial ovarian cancers also supports the extra-ovarian origin of epithelial ovarian cancer.[3][4][5][7][8].
  • In 2001, a Dutch study revealed the presence of high grade serous carcinomas in fallopian tubes of women with genetic susceptibility to hereditary ovarian cancers with no evidence of such lesions in ovaries of same women. These lesions were termed as serous tubal intra-epithelial tumors.[3][4][5][7][10][9]
  • Additional studies demonstrated the presence of similar lesions in fallopian tubes of women without genetic susceptibility to ovarian cancer. In cases when fallopian tubes were removed carefully along with ovarian and/or peritoneal serous cancer, the involvement of mucosa of the tubes were found to be involved in about 70% of the cases.[3][4][5][7][10][9]
  • These tubal serous lesions were located in fimbria in almost all of the cases, giving rise to the proposition that serous tumors originated in fallopian tubes and then implantation into ovaries.[3][4][5][15][7][16]
  • The association between adnexal malignant mixed mesodermal tumors and serous tubal intraepithelial tumors pints further in direction of tubal origin of these epithelial ovarian tumors.[3][4][5][17][18]
  • Similarly morphologic and molecular studies have indicated that endometrioid and clear cell carcinoma of the ovaries have their origin in endometriosis. These studies suggest that these tumors arise from endometriomas, the endometriotic cysts that are present outside the normal endometrium.[3][4][5][13][14]
  • This theory regarding the origin of endometrioid and clear cell carcinoma of the ovary is supported by the fact that tubal ligation that prevents endometriotic implants into ovary and peritoneum in endometriosis has a protective effect on endometrioid and clear cell type cancers but not on the serous cancer of the ovary because it doesn't occlude the connection between fimbria and the ovaries.[3][4][5][19][20]

The origin of mucinous tumors of gastrointestinal type and transitional cell (Brenner) tumors: Still a mystery to solve

  • Mucinous and the transitional tumors of ovaries are two of the least common types of the epithelial ovarian tumors. In fact, most of the mucinous tumors in ovaries are secondary and primary tumors only form about 3% of all epithelial ovarian cancers. Mucinous epithelium in mucinous tumors of ovaries resemble more to intestinal mucinous epithelium rather than that of endocervix as was previously argued. Transitional cell tumors, on the other hand, are closer to bladder epithelium in histological studies.[5][3][4][6][21][22]
  • Another study demonstrated the presence of Brenner tumor foci in mucinous cystadenoma in almost one fifth of the cases. Alternatively the association of mucinous tumors with Walthard cell nests, which are composed of transitional-type epithelium, also indicates the connection between mucinous and transitional tumors.[5][3][4][21][22]


References

  1. ↑ 1.0 1.1 1.2 1.3 Devouassoux-Shisheboran M, Genestie C (January 2015). "Pathobiology of ovarian carcinomas". Chin J Cancer. 34 (1): 50–5. doi:10.5732/cjc.014.10273. PMC 4302089. PMID 25556618.
  2. ↑ 2.0 2.1 2.2 Lauchlan SC (July 1984). "Metaplasias and neoplasias of Müllerian epithelium". Histopathology. 8 (4): 543–57. PMID 6090303.
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 3.24 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. PMC 3148026. PMID 21683865. Vancouver style error: initials (help)
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 4.24 4.25 Dubeau L (December 2008). "The cell of origin of ovarian epithelial tumours". Lancet Oncol. 9 (12): 1191–7. doi:10.1016/S1470-2045(08)70308-5. PMC 4176875. PMID 19038766.
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 Kurman RJ, Shih I (April 2008). "Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications". Int. J. Gynecol. Pathol. 27 (2): 151–60. doi:10.1097/PGP.0b013e318161e4f5. PMC 2794425. PMID 18317228. Vancouver style error: initials (help)
  6. ↑ 6.0 6.1 6.2 6.3 Riopel MA, Ronnett BM, Kurman RJ (June 1999). "Evaluation of diagnostic criteria and behavior of ovarian intestinal-type mucinous tumors: atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas". Am. J. Surg. Pathol. 23 (6): 617–35. PMID 10366144.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP (February 2007). "Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship". Am. J. Surg. Pathol. 31 (2): 161–9. doi:10.1097/01.pas.0000213335.40358.47. PMID 17255760.
  8. ↑ 8.0 8.1 8.2 Marquez RT, Baggerly KA, Patterson AP, Liu J, Broaddus R, Frumovitz M, Atkinson EN, Smith DI, Hartmann L, Fishman D, Berchuck A, Whitaker R, Gershenson DM, Mills GB, Bast RC, Lu KH (September 2005). "Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon". Clin. Cancer Res. 11 (17): 6116–26. doi:10.1158/1078-0432.CCR-04-2509. PMID 16144910.
  9. ↑ 9.0 9.1 9.2 9.3 Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, Feltmate CM, Berkowitz RS, Muto MG (September 2007). "Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction". J. Clin. Oncol. 25 (25): 3985–90. doi:10.1200/JCO.2007.12.2622. PMID 17761984.
  10. ↑ 10.0 10.1 10.2 10.3 Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH (November 2001). "Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer". J. Pathol. 195 (4): 451–6. doi:10.1002/path.1000. PMID 11745677.
  11. ↑ Pothuri B, Leitao MM, Levine DA, Viale A, Olshen AB, Arroyo C, Bogomolniy F, Olvera N, Lin O, Soslow RA, Robson ME, Offit K, Barakat RR, Boyd J (April 2010). "Genetic analysis of the early natural history of epithelial ovarian carcinoma". PLoS ONE. 5 (4): e10358. doi:10.1371/journal.pone.0010358. PMC 2859950. PMID 20436685.
  12. ↑ Devouassoux-Shisheboran M, Genestie C (January 2015). "Pathobiology of ovarian carcinomas". Chin J Cancer. 34 (1): 50–5. doi:10.5732/cjc.014.10273. PMC 4302089. PMID 25556618.
  13. ↑ 13.0 13.1 Veras E, Mao TL, Ayhan A, Ueda S, Lai H, Hayran M, Shih I, Kurman RJ (June 2009). "Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases". Am. J. Surg. Pathol. 33 (6): 844–53. doi:10.1097/PAS.0b013e31819c4271. PMID 19342944. Vancouver style error: initials (help)
  14. ↑ 14.0 14.1 Martin DC (1997). "Cancer and endometriosis: do we need to be concerned?". Semin. Reprod. Endocrinol. 15 (3): 319–24. doi:10.1055/s-2008-1068762. PMID 9383841.
  15. ↑ Piek JM, Verheijen RH, Kenemans P, Massuger LF, Bulten H, van Diest PJ (August 2003). "BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis". Gynecol. Oncol. 90 (2): 491. PMID 12893227.
  16. ↑ Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP (February 2006). "The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome". Am. J. Surg. Pathol. 30 (2): 230–6. PMID 16434898.
  17. ↑ Lee TY, Lee C, Choi WJ, Lee JY, Kim HY (July 2013). "Synchronous occurrence of primary malignant mixed müllerian tumor in ovary and uterus". Obstet Gynecol Sci. 56 (4): 269–72. doi:10.5468/ogs.2013.56.4.269. PMC 3784138. PMID 24328014.
  18. ↑ Gupta AJ, Singh M, Rani P, Jain S, Khurana N, Sahu L (2017). "Malignant mixed mullerian tumor of ovary-scrape cytology: Findings with review of literature". J Cytol. 34 (2): 125–126. doi:10.4103/0970-9371.203568. PMC 5398022. PMID 28469326.
  19. ↑ Piek JM, van Diest PJ, Zweemer RP, Kenemans P, Verheijen RH (September 2001). "Tubal ligation and risk of ovarian cancer". Lancet. 358 (9284): 844. doi:10.1016/S0140-6736(01)05992-X. PMID 11570411.
  20. ↑ Rosenblatt KA, Thomas DB (November 1996). "Reduced risk of ovarian cancer in women with a tubal ligation or hysterectomy. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives". Cancer Epidemiol. Biomarkers Prev. 5 (11): 933–5. PMID 8922304.
  21. ↑ 21.0 21.1 Vang R, Gown AM, Zhao C, Barry TS, Isacson C, Richardson MS, Ronnett BM (June 2007). "Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary". Am. J. Surg. Pathol. 31 (6): 854–69. doi:10.1097/PAS.0b013e31802efb45. PMID 17527072.
  22. ↑ 22.0 22.1 Seidman JD, Khedmati F (November 2008). "Exploring the histogenesis of ovarian mucinous and transitional cell (Brenner) neoplasms and their relationship with Walthard cell nests: a study of 120 tumors". Arch. Pathol. Lab. Med. 132 (11): 1753–60. doi:10.1043/1543-2165-132.11.1753. PMID 18976011.
Retrieved from "https://www.wikidoc.org/index.php?title=Epithelial_ovarian_tumors_origin_of_neoplasia&oldid=1555070"