Are histomorphologic changes in the fimbrial ends more to blame for primary epithelial ovarian carcinomas than initially thought?

Objective: To investigate the relationship between primary epithelial ovarian tumors and histomorphologic changes in the fimbrial ends (FEs) of the fallopian tubes. Materials and Methods: Twenty-eight serous carcinomas (SCs) and 12 non-serous carcinomas (NSC) were studied. Ovarian and concomitant invasive tumors in FEs were labeled with PAX8, WT-1 and Calretinin. Results: Eighty-six percent of SCs were high grade (HG), 14% of were low grade (LG). 71% of SCs (85% HG, 15% LG) had concomitant invasive tumors in FEs. Serous tubal intraepithelial carcinoma (STIC) was seen in 29% (75% HG, 25% LG), all had concomitant invasive tumors in FEs. The presence of tumors in FEs was statistically significant in SCs (p=0.03). 33% of NSCs had concomitantly invasive tumors in FEs. 67% of endometrioid tumors, 33% of clear cell carcinomas had endometriosis. 50% of mucinous tumors, 67% of endometrioid tumors, 50% of benign Brenner tumors had Walthard nest. Except for mucinous carcinomas, ovarian and concomitant invasive tumors in FEs displayed tubal phenotype (Calretinin-/PAX8+). Conclusion: The results of our study suggest that, invasive tumors and STIC in FEs are not only limited to HGSCs, but can also be seen in LGs. FEs could also be a site of origin for NSCs, however, future studies with more cases are needed.

___

  • Kurman R. In: Hedrick Ellenson L, Ronnett, Brigitte M, eds. Blaustein`s Pathology of The Female Genital Tract: Springer, 2019.
  • Kurman RJ. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma. Ann Oncol 2013;24 (Suppl 10):x16-21. doi:10.1093/annonc/mdt463.
  • Nik NN, Vang R, Shih Ie M, Kurman RJ. Origin and pathogenesis of pelvic (ovarian, tubal, and primary peritoneal) serous carcinoma. Annu Rev Pathol 2014;9:27-45. doi:10.1146/annurev-pathol-020712-163949.
  • McCluggage WG. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology 2011;43:420-32. doi: 10.1097/PAT.0b013e328348a6e7.
  • Kurman RJ. In: WHO Classification of Tumours Editorial Board eds. WHO Classification of Tumours of the Female Genital Tumors, 5th ed, Vol. 4: World Health Organization, 2020.
  • Conic I, Dimov I, Tasic-Dimov D, Djordjevic B, and Stefanovic V. Ovarian epithelial cancer stem cells. Scientific World Journal 2011;11:1243-69. doi: 10.1100/tsw.2011.112.
  • Reichman ME, Altekruse S, Li CI, et al. Feasibility study for collection of HER2 data by National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program central cancer registries. Cancer Epidemiol Biomarkers Prev 2010;19:144-47. doi: 10.1158/1055-9965.EPI-09-0807.
  • Gershenson DM. Low-grade serous carcinoma of the ovary or peritoneum. Ann Oncol 2016;27(Suppl 1):i45-i49. doi:10.1093/annonc/mdw085.
  • Vang R, Shih Ie M, and Kurman RJ. Fallopian tube precursors of ovarian low- and high-grade serous neoplasms. Histopathology 2013;62:44-58. doi:10.1111/his.12046.
  • Crum CP. Intercepting pelvic cancer in the distal fallopian tube: theories and realities. Mol Oncol 2009;3:165-70. doi:10.1016/j.molonc.2009.01.004.
  • Carlson JW, Miron A, Jarboe EA, et al. Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention. J Clin Oncol 2008;26:4160-65. doi:10.1200/JCO.2008.16.4814.
  • Rabban JT, Krasik E, Chen LM, Powell CB, Crawford B, and Zaloudek CJ. 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 2009;33:1878-85. doi:10.1097/PAS.0b013e3181bc6059.
  • Kurman RJ and Shih Ie M. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010;34:433-43. doi: 10.1097/PAS.0b013e3181cf3d79.
  • Laury AR, Ning G, Quick CM, et al. Fallopian tube correlates of ovarian serous borderline tumors. Am J Surg Pathol 2011;35:1759-65. doi: 10.1097/PAS.0b013e318233b0f7.
  • Li J, Abushahin N, Pang S, et al. Tubal origin of 'ovarian' low-grade serous carcinoma. Mod Pathol 2011;24:1488-99. doi: 10.1038/modpathol.2011.106.
  • Wang Y, Hong S, Mu J, et al. Tubal Origin of "Ovarian" Low-Grade Serous Carcinoma: A Gene Expression Profile Study. J Oncol 2019:2019:1-9. doi: 10.1155/2019/8659754.
  • Malpica A, Deavers MT, Lu K, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004;28:496-504. doi: 10.1097/00000478-200404000-00009.
  • Arora S, Yelikar BR, Karigoudar MH. Evaluation of SEE-FIM (Sectioning and Extensively Examining the Fimbriated End) protocol in identifying fallopian tube precursor lesions in women with ovarian tumors. J Obstet Gynaecol 2019;69:153-59. doi: 10.1007/s13224-018-1155-z.
  • Nomura H, Ikki A, Fusegi A, et al. Clinical and pathological outcomes of risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer. Int J Clin Oncol 2021. doi: 10.1007/s10147-021-02020-9.
  • Cheng A, Li L, Wu M, et al., Pathological findings following risk-reducing salpingo-oophorectomy in BRCA mutation carriers: A systematic review and meta-analysis. Eur J Surg Oncol 2020;46:139-47. doi: 10.1016/j.ejso.2019.09.002.
  • Medeiros F, Muto MG, Lee Y, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006;30:230-36. doi: 10.1097/01.pas.0000180854.28831.77.
  • Mehra KK, Chang MC, Folkins AK, et al. The impact of tissue block sampling on the detection of p53 signatures in fallopian tubes from women with BRCA 1 or 2 mutations (BRCA+) and controls. Mod Pathol 2011;24:152-56. doi: 10.1038/modpathol.2010.171.
  • Salvador S, Gilks B, Kobel M, Huntsman D, Rosen B, and Miller D. The fallopian tube: primary site of most pelvic high-grade serous carcinomas. Int J Gynecol Cancer 2009;19:58-64. doi: 10.1111/IGC.0b013e318199009c.
  • Lynch HT, Casey MJ, Snyder CL, et al. Hereditary ovarian carcinoma: heterogeneity, molecular genetics, pathology, and management. Mol Oncol 2009;3:97-137. doi:10.1016/j.molonc.2009.02.004.
  • Kurman RJ, McConnell TG. Precursors of endometrial and ovarian carcinoma. Virchows Arch 2010;456:1-12. doi:10.1007/s00428-009-0824-9.
  • Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 2007;19:3-9. doi: 10.1097/GCO.0b013e328011a21f.
  • Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A 2011;108:18032-37. doi: 10.1073/pnas.1115052108.
  • Soslow R. In: Goldblum J eds. Current Concepts in Gynecologic Pathology: Epithelial Tumors of the Gynecologic Tract, An Issue of Surgical Pathology Clinics. 1st ed,. Vol. 4; Saunders, 2011.
  • Cuatrecasas M, Catasus L, Palacios J, Prat J. Transitional cell tumors of the ovary: a comparative clinicopathologic, immunohistochemical, and molecular genetic analysis of Brenner tumors and transitional cell carcinomas. Am J Surg Pathol 2009;33:556-67. doi: 10.1097/PAS.0b013e318188b84c.
  • Adler E, Mhawech-Fauceglia P, Gayther SA, and Lawrenson K. PAX8 expression in ovarian surface epithelial cells. Hum Pathol 2015;46:948-56. doi: 10.1016/j.humpath.2015.03.017.
  • Alvarado-Cabrero I, Navani SS, Young RH, Scully RE. Tumors of the fimbriated end of the fallopian tube: a clinicopathologic analysis of 20 cases, including nine carcinomas. Int J Gynecol Pathol 1997;16:189-96. doi: 10.1097/00004347-199707000-00001.
  • Maeda D, Ota S, Takazawa Y, et al. Mucosal carcinoma of the fallopian tube coexists with ovarian cancer of serous subtype only: a study of Japanese cases. Virchows Arch 2010;457:597-608. doi: 10.1007/s00428-010-0979-4. Epub 2010 Sep 25.
  • Seidman JD, Zhao P, Yemelyanova A."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 2011;120:470-73. doi: 10.1016/j.ygyno.2010.11.020.
  • Liu F, Wei J, Shen D, Liu J. Mucinous borderline tumor involving fallopian tube: case report and review of the literature. Int J Clin Exp Pathol 2013;6:962-65.
  • Kobayashi H, Kajiwara H, Kanayama S, et al. Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review). Oncol Rep 2009;22: 233-40. doi: 10.3892/or 00000429.