Abstract
Purpose
Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube.
Methods
Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes.
Results
The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology.
Conclusion
The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.
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References
ACOG Committee Opinion No. 774 Summary: opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention (2019). Obstetr Gynecol 133(4):842–843
Chen F, Gaitskell K, Garcia MJ, Albukhari A, Tsaltas J, Ahmed AA (2017) Serous tubal intraepithelial carcinomas associated with high-grade serous ovarian carcinomas: a systematic review. BJOG Int J Obstetr Gynaecol 124(6):872–878. https://doi.org/10.1111/1471-0528.14543
Coleman MP, Forman D, Bryant H, Butler J, Rachet B, Maringe C et al (2011) Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 377(9760):127–138. https://doi.org/10.1016/S0140-6736(10)62231-3
Committee opinion no. 620: Salpingectomy for ovarian cancer prevention (2015). Obstetr Gynecol 125 (1):S. 279–281
Crum CP, Drapkin R, Miron A, Ince TA, Muto M, Kindelberger DW, Lee Y (2007) The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 19(1):3–9. https://doi.org/10.1097/GCO.0b013e328011a21f
Daya D, Cheung ANY, Khunamornpong S, Kim KR, Prat J, Young RH (2014) Epithelial Tumors of the Müllerian type of the Peritoneum. In: WHO classification of tumours of female reproductive organs, S. 92–93. Available online: https://gbv.eblib.com/patron/FullRecord.aspx?p=4661027. Accessed 20.08.2020
Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA J Am Med Assoc 304(9):967–975. https://doi.org/10.1001/jama.2010.1237
Falconer H, Yin L, Grönberg H, Altman D (2015) Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst. https://doi.org/10.1093/jnci/dju410
Goff B (2012) Symptoms associated with ovarian cancer. Clin Obstet Gynecol 55(1):36–42. https://doi.org/10.1097/GRF.0b013e3182480523
Goodman MT, Shvetsov YB (2009) Incidence of ovarian, peritoneal, and fallopian tube carcinomas in the United States, 1995–2004. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 18(1):132–139. https://doi.org/10.1158/1055-9965.EPI-08-0771
Gottschau M, Mellemkjaer L, Hannibal CG, Kjaer SK (2016) Ovarian and tubal cancer in Denmark: an update on incidence and survival. Acta Obstet Gynecol Scand 95(10):1181–1189. https://doi.org/10.1111/aogs.12948
Gramlich T, Austin RM, Lutz M (1990) Histologic sampling requirements in ovarian carcinoma: a review of 51 tumors. Gynecol Oncol 38(2):249–256. https://doi.org/10.1016/0090-8258(90)90050-u
Hanley GE, Kwon JS, Finlayson SJ, Huntsman DG, Miller D, McAlpine JN (2018) Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada. Am J Obstet Gynecol 219(2):172.e1–172.e8. https://doi.org/10.1016/j.ajog.2018.05.019
Harao M, Ando J, Kamata H, Hoshi N, Igarashi S, Sekiguchi R, Sugano K (2018) Peritoneal cancer arising after total abdominal hysterectomy and bilateral salpingo-oophorectomy for cervical cancer in a patient with right breast cancer and germline mutation of BRCA1 gene: a case report and literature review. Breast Cancer (Tokyo, Japan) 25(2):243–249. https://doi.org/10.1007/s12282-017-0813-9
Hicks-Courant KD (2016) Growth in salpingectomy rates in the United States since 2000. Am J Obstet Gynecol 215(5):666–667. https://doi.org/10.1016/j.ajog.2016.07.055
Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG (2017) The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer 17(1):65–74. https://doi.org/10.1038/nrc.2016.113
Kulac I, Usubutun A (2013) Microscopic lesions of fallopian tubes in endometrioid carcinoma of the endometrium: how effective are the macroscopic tubal sampling techniques? J Gynecol Oncol 24(2):114–119. https://doi.org/10.3802/jgo.2013.24.2.114
Kurman RJ, Shih I-M (2016) The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded. Am J Pathol 186(4):733–747. https://doi.org/10.1016/j.ajpath.2015.11.011
Leonhardt K, Einenkel J, Sohr S, Engeland K, Horn L-C (2011) p53 signature and serous tubal in-situ carcinoma in cases of primary tubal and peritoneal carcinomas and serous borderline tumors of the ovary. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 30(5):417–424. https://doi.org/10.1097/PGP.0b013e318216d447
Liao C-I, Chow S, Chen L-M, Kapp DS, Mann A, Chan JK (2018) Trends in the incidence of serous fallopian tube, ovarian, and peritoneal cancer in the US. Gynecol Oncol 149(2):S. 318–323. https://doi.org/10.1016/j.ygyno.2018.01.030
Malpica AE, Elizabeth D, Hecht JL, Ali-Fehmi R, Quick CM, Singh N et al (2018) Endometrial carcinoma, grossing and processing issues: recommendations of the international society of gynecologic pathologists. Int J Gynecol Pathol 38(Iss 1 Suppl 1):S9–S24. https://doi.org/10.1097/PGP.0000000000000552
McCluggage WG, Judge MJ, Clarke BA, Davidson B, Gilks CB, Hollema H et al (2015) Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Mod Pathol Off J US Can Acad Pathol Inc 28(8):S. 1101–1122. https://doi.org/10.1038/modpathol.2015.77
McCluggage WG, Hirschowitz L, Gilks CB, Wilkinson N, Singh N (2017) The Fallopian tube origin and primary site assignment in extrauterine high-grade serous carcinoma: findings of a survey of pathologists and clinicians. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 36(3):S. 230–239. https://doi.org/10.1097/PGP.0000000000000336
Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C et al (2006) The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 30(2):230–236. https://doi.org/10.1097/01.pas.0000180854.28831.77
Meserve EEK, Brouwer J, Crum CP (2017) Serous tubal intraepithelial neoplasia: the concept and its application. Mod Pathol Off J US Can Acad Pathol 30(5):S. 710–721. https://doi.org/10.1038/modpathol.2016.238
Morrison JC, Blanco LZ, Vang R, Ronnett BM (2015) Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series. Am J Surg Pathol 39(4):442–453. https://doi.org/10.1097/PAS.0000000000000352
Moss EL, Evans T, Pearmain P, Askew S, Singh K, Chan KK et al (2015) Should all cases of high-grade serous ovarian, tubal, and primary peritoneal carcinomas be reclassified as tubo-ovarian serous carcinoma? Int J Gynecol Cancer Off J Int Gynecol Cancer Soc 25(7):S1201–1207. https://doi.org/10.1097/IGC.0000000000000477
Perets R, Drapkin R (2016) It's totally tubula. Riding the new wave of ovarian cancer research. Can Res 76(1):10–17. https://doi.org/10.1158/0008-5472.CAN-15-1382
Perrone ME, Reder NP, Agoff SN, Garcia RL, Agnew KJ, Norquist BM et al (2020) An alternate diagnostic algorithm for the diagnosis of intraepithelial fallopian tube lesions. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 39(3):261–269. https://doi.org/10.1097/PGP.0000000000000604
Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH et al (2001) Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. J Pathol 195(4):451–456. https://doi.org/10.1002/path.1000
Przybycin CG, Kurman RJ, Ronnett BM, Shih I-M, Vang R (2010) Are all pelvic (nonuterine) serous carcinomas of tubal origin? Am J Surg Pathol 34(10):1407–1416. https://doi.org/10.1097/PAS.0b013e3181ef7b16
Rabban JT, Krasik E, Chen L-M, Powell CB, Crawford B, Zaloudek CJ (2009) Multistep level sections to detect occult fallopian tube carcinoma in risk-reducing salpingo-oophorectomies from women with BRCA mutations: implications for defining an optimal specimen dissection protocol. Am J Surg Pathol 33(12):1878–1885. https://doi.org/10.1097/PAS.0b013e3181bc6059
Rabban JT, Garg K, Crawford B, Chen L-M, Zaloudek CJ (2014) Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery. Am J Surg Pathol 38(6):729–742. https://doi.org/10.1097/PAS.0000000000000199
Rottmann M, Burges A, Mahner S, Anthuber C, Beck T, Grab D et al (2017) Cancer of the ovary, fallopian tube, and peritoneum: a population-based comparison of the prognostic factors and outcomes. J Cancer Res Clin Oncol 143(9):1833–1844. https://doi.org/10.1007/s00432-017-2422-6
Salvador S, Scott S, Francis JA, Agrawal A, Giede C (2017) No. 344-Opportunistic salpingectomy and other methods of risk reduction for ovarian/fallopian tube/peritoneal cancer in the general population. J Obstetr Gynaecol Canada JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 39(6):S. 480–493. https://doi.org/10.1016/j.jogc.2016.12.005
Samimi G, Trabert B, Duggan MA, Robinson JL, Coa KI, Waibel E et al (2018a) Processing of fallopian tube, ovary, and endometrial surgical pathology specimens: a survey of U.S. laboratory practices. Gynecol Oncol 148(3):S. 515–520. https://doi.org/10.1016/j.ygyno.2018.01.016
Samimi G, Trabert B, Geczik AM, Duggan MA, Sherman ME (2018b) Population frequency of serous tubal intraepithelial carcinoma (STIC) in clinical practice using SEE-fim protocol. JNCI Cancer Spectr 2(4):pky061. https://doi.org/10.1093/jncics/pky061
Seidman JD (2015) Serous tubal intraepithelial carcinoma localizes to the tubal-peritoneal junction: a pivotal clue to the site of origin of extrauterine high-grade serous carcinoma (ovarian cancer). Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 34(2):112–120. https://doi.org/10.1097/PGP.0000000000000123
Seidman JD, Zhao Po, Yemelyanova A (2011) “Primary peritoneal” high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer. Gynecol Oncol 120(3):470–473. https://doi.org/10.1016/j.ygyno.2010.11.020
Siegel RL, Miller KD, Jemal A (2020) Cancer statistics. CA Cancer J Clin 70(1):S. 7–30. https://doi.org/10.3322/caac.21590
Singh N, Gilks CB, Wilkinson N, McCluggage WG (2015) Assessment of a new system for primary site assignment in high-grade serous carcinoma of the fallopian tube, ovary, and peritoneum. Histopathology 67(3):S. 331–337. https://doi.org/10.1111/his.12651
Singh N, Gilks CB, Hirschowitz L, Kehoe S, McNeish IA, Miller D et al (2016a) Primary site assignment in tubo-ovarian high-grade serous carcinoma: consensus statement on unifying practice worldwide. Gynecol Oncol 141(2):S. 195–198. https://doi.org/10.1016/j.ygyno.2015.10.022
Singh N, Gilks CB, Hirshowitz L, Wilkinson N, McCluggage WG (2016b) Adopting a uniform approach to site assignment in tubo-ovarian high-grade serous carcinoma: the time has come. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 35(3):S. 230–237. https://doi.org/10.1097/PGP.0000000000000270
Singh N, McCluggage WG, Gilks CB (2017) High-grade serous carcinoma of tubo-ovarian origin: recent developments. Histopathology 71(3):S. 339–356. https://doi.org/10.1111/his.13248
Soong TR, Kolin DL, Teschan NJ, Crum CP (2018) Back to the future? The fallopian tube, precursor escape and a dualistic model of high-grade serous carcinogenesis. Cancers. https://doi.org/10.3390/cancers10120468
Sørensen RD, Schnack TH, Karlsen MA, Høgdall CK (2015) Serous ovarian, fallopian tube and primary peritoneal cancers: a common disease or separate entities—a systematic review. Gynecol Oncol 136(3):571–581. https://doi.org/10.1016/j.ygyno.2015.01.534
Trabert B, Coburn SB, Mariani A, Yang HP, Rosenberg PS, Gierach GL et al (2018) Reported incidence and survival of fallopian tube carcinomas: a population-based analysis from the North American association of central cancer registries. J Natl Cancer Inst 110(7):750–757. https://doi.org/10.1093/jnci/djx263
Visvanathan K, Shaw P, May BJ, Bahadirli-Talbott A, Kaushiva A, Risch H et al (2018a) Fallopian tube lesions in women at high risk for ovarian cancer: a multicenter study. Cancer Prev Res (Philadelphia, Pa.) 11(11):S697–706. https://doi.org/10.1158/1940-6207.CAPR-18-0009
Visvanathan K, Wang T-L, Shih I-M (2018b) Precancerous lesions of ovarian cancer—a US perspective. J Natl Cancer Inst 110(7):692–693. https://doi.org/10.1093/jnci/djx269
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Höhn, A.K., Klagges, S., Gläser, A. et al. Increase of fallopian tube and decrease of ovarian carcinoma: fact or fake?. J Cancer Res Clin Oncol 147, 911–925 (2021). https://doi.org/10.1007/s00432-020-03387-4
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DOI: https://doi.org/10.1007/s00432-020-03387-4