SEE-FIM Protocol

Short description: Pathology protocol to assess cancer risk

Schematic of the components of the fallopian tube (upper right). Below are microscopic images taken from cross sections of the ampulla (left) and longitudinal sections of the infundibulum and fimbria (center right). A focus of early high grade serous carcinoma discovered in the fimbria is seen at the far right. The left panel illustrates the SEE-FIM protocol.

The SEE-FIM protocol is a pathology dissection protocol for Sectioning and Extensively Examining the Fimbria (SEE-FIM). This protocol is intended to provide for the optimal microscopic examination of the distal fallopian tube (fimbria) to identify either cancerous or precancerous conditions in this organ.[1][2]

## Contents

* 1 Background
* 2 Introduction of the SEE-FIM protocol
* 2.1 Conception
* 2.2 Method
* 3 Acceptance in pathology practice
* 4 Indications for the Protocol
* 4.1 Prophylactic salpingectomy
* 4.2 Opportunistic salpingectomy
* 4.3 Surgical excision specimens from women with HGSC
* 5 See also
* 6 Abbreviations
* 7 References

## Background

Women with either a strong family history of breast and ovarian cancer or a documented inherited (germline) mutation in a BRCA gene are encouraged to consider risk reduction salpingo-oophorectomy (RRSO). The surgery is ideally conducted prior to the time that the risk of developing HGSC became too great to defer the procedure, which was age 35 for women with BRCA1 and 45 for BRCA2 mutations. Removal of both tubes and ovaries has reduced the risk of subsequent HGSC by 85% [see BRCA mutation].[3]

Beginning in 2000, pathologists began to encounter early, often non-invasive HGSCs (serous tubal intraepithelial carcinomas or STICs) in the fallopian tubes of women with germ line BRCA mutation who underwent RRSO.[4][5][6][7]

## Introduction of the SEE-FIM protocol

### Conception

The SEE-FIM protocol was introduced in 2005 and required examining all of the fallopian tube, specifically the sectioning and examination of the distal one-third (infundibulum and fimbria).[1] Early HGSCs of the fallopian tube, once considered rare, were encountered frequently in this portion of the tube once the SEE-FIM protocol was adopted. Based on this information, the distal fallopian tube was cited as an origin for many HGSCs formerly classified as ovarian cancers. The SEE-FIM protocol was adopted by many to identify or exclude these tumors during pathologic examination of the fallopian tubes in risk reduction salpingo-oophorectomies.[8][9]

### Method

The SEE-FIM protocol consists of five steps (See Figure):

1. The tube is fixed for at least 2 hours in laboratory fixative.
2. The distal one third is amputated.
3. The distal one third is sectioned in the longitudinal (sagittal) plane as thinly as possible and submitted for processing.
4. The remainder of the tube is sectioned in the transverse (cross section) plane every 1-2 millimeters and submitted for processing.
5. Sections are stained with hematoxylin and eosin and are examined by the pathologist with attention to the epithelial cells and the presence of any evidence of a malignancy or precancerous condition.[1]

## Acceptance in pathology practice

As of 2018, the SEE-FIM protocol was being used by 85% of academic pathology practices and 65% of private practices in the United States and elsewhere in the World.[8][10][11][12][13] Routine use of the SEE-FIM protocol has been recommended by the College of American Pathologists and the International Society of Gynecologic Pathologists when processing fallopian tubes in risk reduction surgeries, and cases of ovarian and uterine serous cancer.[14][15] It is also recommended in the reporting guidelines for gynecologic cancer sponsored by the British Gynecologic Cancer Society.[16] It is also part of routine protocols in academic institutions and was employed to ascertain the frequency of STIC in a large population-based study.[17][18]

## Indications for the Protocol

The primary purpose of the SEE-FIM protocol is to detect small cancers in the fallopian tube that are not visible to the naked eye. It is used most often in the following scenarios.

### Prophylactic salpingectomy

In RRSO specimens from healthy women at increased risk for HGSC, the protocol is used to confirm or exclude the presence of an early HGSC (STIC). If a malignancy is discovered there is a significant risk of a later recurrence, computed at 10% and 27% at 5 and 10 years. In contrast, if no abnormality is found the risk is less than 1%.[19]

### Opportunistic salpingectomy

This procedure has been introduced to remove the fallopian tubes when convenient after the cessation of childbearing. The protocol is used to exclude occult cancer. A recent study of over 25,000 women who underwent this procedure reported no cases of HGSC in follow-up if no cancer was found.[see Prophylactic salpingectomy].[20]

### Surgical excision specimens from women with HGSC

In cases with advanced HGSC, the SEE-FIM protocol provides a detailed assessment of the fallopian tube to determine if the tumor arose in the fallopian tube. If pathologic examination confirmed the presence of HGSC in the tubal epithelium, the tumor would be classified as a primary fallopian tube malignancy. This information is also helpful in ascertaining the extent (or stage) of tumor involvement, which in turn influences choice of therapy. .[21]

## See also

* High grade serous carcinoma
* BRCA mutation
* Fallopian tube cancer
* Ovarian cancer
* Ovarian Cancer Research Alliance
* Prophylactic salpingectomy

## Abbreviations

BRCA – Breast cancer associated tumor suppressor genes, including BRCA1 and BRCA2. Inherited (germline) loss of a BRCA gene imposes an increased risk of breast and ovarian cancer.

TP53 – A tumor suppressor gene that is mutated in High grade serous carcinoma.

RRSO – Risk reduction salpingo-oophorectomy.

RRS – Risk reduction salpingectomy.

HGSC – Extrauterine high grade serous carcinoma.

STIC – Serous tubal intraepithelial carcinoma, a non-invasive precursor to high grade serous carcinoma

## References

1. ↑ 1.0 1.1 1.2 Medeiros, Fabiola; Muto, Michael G.; Lee, Yonghee; Elvin, Julia A.; Callahan, Michael J.; Feltmate, Colleen; Garber, Judy E.; Cramer, Daniel W. et al. (February 2006). "The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome". The American Journal of Surgical Pathology 30 (2): 230–236. doi:10.1097/01.pas.0000180854.28831.77. ISSN 0147-5185. PMID 16434898. https://pubmed.ncbi.nlm.nih.gov/16434898.
2. ↑ Cass, Ilana; Holschneider, Christine; Datta, Nandini; Barbuto, Denise; Walts, Ann E.; Karlan, Beth Y. (December 2005). "BRCA-mutation-associated fallopian tube carcinoma: a distinct clinical phenotype?". Obstetrics and Gynecology 106 (6): 1327–1334. doi:10.1097/01.AOG.0000187892.78392.3f. ISSN 0029-7844. PMID 16319259. https://pubmed.ncbi.nlm.nih.gov/16319259.
3. ↑ Rebbeck, Timothy R.; Lynch, Henry T.; Neuhausen, Susan L.; Narod, Steven A.; Van't Veer, Laura; Garber, Judy E.; Evans, Gareth; Isaacs, Claudine et al. (2002-05-23). "Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations". The New England Journal of Medicine 346 (21): 1616–1622. doi:10.1056/NEJMoa012158. ISSN 1533-4406. PMID 12023993. https://pubmed.ncbi.nlm.nih.gov/12023993.
4. ↑ Zweemer, R. P.; van Diest, P. J.; Verheijen, R. H.; Ryan, A.; Gille, J. J.; Sijmons, R. H.; Jacobs, I. J.; Menko, F. H. et al. (January 2000). "Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations". Gynecologic Oncology 76 (1): 45–50. doi:10.1006/gyno.1999.5623. ISSN 0090-8258. PMID 10620440. https://pubmed.ncbi.nlm.nih.gov/10620440.
5. ↑ Rose, P. G.; Shrigley, R.; Wiesner, G. L. (May 2000). "Germline BRCA2 mutation in a patient with fallopian tube carcinoma: a case report". Gynecologic Oncology 77 (2): 319–320. doi:10.1006/gyno.2000.5740. ISSN 0090-8258. PMID 10785486. https://pubmed.ncbi.nlm.nih.gov/10785486.
6. ↑ Paley, P. J.; Swisher, E. M.; Garcia, R. L.; Agoff, S. N.; Greer, B. E.; Peters, K. L.; Goff, B. A. (February 2001). "Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis". Gynecologic Oncology 80 (2): 176–180. doi:10.1006/gyno.2000.6071. ISSN 0090-8258. PMID 11161856. https://pubmed.ncbi.nlm.nih.gov/11161856.
7. ↑ Colgan, T. J.; Murphy, J.; Cole, D. E.; Narod, S.; Rosen, B. (October 2001). "Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status". The American Journal of Surgical Pathology 25 (10): 1283–1289. doi:10.1097/00000478-200110000-00009. ISSN 0147-5185. PMID 11688463. https://pubmed.ncbi.nlm.nih.gov/11688463.
8. ↑ 8.0 8.1 Samimi, Goli; Trabert, Britton; Duggan, Máire A.; Robinson, Jennifer L.; Coa, Kisha I.; Waibel, Elizabeth; Garcia, Edna; Minasian, Lori M. et al. (March 2018). "Processing of fallopian tube, ovary, and endometrial surgical pathology specimens: A survey of U.S. laboratory practices". Gynecologic Oncology 148 (3): 515–520. doi:10.1016/j.ygyno.2018.01.016. ISSN 1095-6859. PMID 29395311.
9. ↑ Kurman, Robert J.; Shih, Ie-Ming (July 2011). "Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm". Human Pathology 42 (7): 918–931. doi:10.1016/j.humpath.2011.03.003. ISSN 1532-8392. PMID 21683865.
10. ↑ Koc, Nermin; Ayas, Selçuk; Arinkan, Sevcan Arzu (January 2018). "Comparison of the Classical Method and SEE-FIM Protocol in Detecting Microscopic Lesions in Fallopian Tubes with Gynecological Lesions". Journal of Pathology and Translational Medicine 52 (1): 21–27. doi:10.4132/jptm.2016.06.17. ISSN 2383-7837. PMID 27539290.
11. ↑ Minig, L.; Cabrera, S.; Oliver, R.; Couso, A.; Rubio, M. J.; Iacoponi, S.; Martin-Salamanca, M. B.; Carballo-Rastrilla, S. et al. (October 2018). "Pathology findings and clinical outcomes after risk reduction salpingo-oophorectomy in BRCA mutation carriers: a multicenter Spanish study". Clinical & Translational Oncology 20 (10): 1337–1344. doi:10.1007/s12094-018-1865-9. ISSN 1699-3055. PMID 29623583. https://pubmed.ncbi.nlm.nih.gov/29623583.
12. ↑ Zhao, R. J.; Wang, Y. Y.; Li, Z.; Wu, K. Y.; Kong, L. F.; Zheng, W. X. (2017-08-08). "[Morphologic features of fallopian tubal epithelium in pelvic high-grade serous carcinoma"]. Zhonghua Bing Li Xue Za Zhi = Chinese Journal of Pathology 46 (8): 542–547. doi:10.3760/cma.j.issn.0529-5807.2017.08.005. ISSN 0529-5807. PMID 28810294. https://pubmed.ncbi.nlm.nih.gov/28810294.
13. ↑ Reitsma, Welmoed; de Bock, Geertruida H.; Oosterwijk, Jan C.; Bart, Joost; Hollema, Harry; Mourits, Marian J. E. (January 2013). "Support of the 'fallopian tube hypothesis' in a prospective series of risk-reducing salpingo-oophorectomy specimens". European Journal of Cancer 49 (1): 132–141. doi:10.1016/j.ejca.2012.07.021. ISSN 1879-0852. PMID 22921157. https://pubmed.ncbi.nlm.nih.gov/22921157.
14. ↑ Movahedi-Lankarani, Saeid; Krishnamurti, Uma; Bell, Debra A.; Birdsong, George G.; Biscotti, Charles V.; Chapman, Christopher N.; Klepeis, Veronica; Otis, Christopher N. (August 2018). "Protocol for the Examination of Specimens From Patients With Primary Tumors of the Ovary, Fallopian Tube, or Peritoneum.". https://documents.cap.org/protocols/cp-femalereproductive-ovary-fallopian-18protocol-1100.pdf.
15. ↑ Malpica, Anais; Euscher, Elizabeth D.; Hecht, Jonathan L.; Ali-Fehmi, Rouba; Quick, Charles M.; Singh, Naveena; Horn, Lars-Christian; Alvarado-Cabrero, Isabel et al. (January 2019). "Endometrial Carcinoma, Grossing and Processing Issues: Recommendations of the International Society of Gynecologic Pathologists". International Journal of Gynecological Pathology 38 (1 Suppl 1): S9–S24. doi:10.1097/PGP.0000000000000552. ISSN 1538-7151. PMID 30550481.
16. ↑ "Ovary, Fallopian Tube and Primary Peritoneal Carcinoma Histopathology Reporting Guide.". May 2019. https://www.bgcs.org.uk/wp-content/uploads/2019/05/ICCR-ovary-ft-pps-bookmarked-guide.pdf.
17. ↑ "Gynecologic Pathology Grossing Guidelines Specimen Type.". April 2023. https://www.uclahealth.org/sites/default/files/documents/UterusNeoplastic091119.pdf.
18. ↑ Samimi, Goli; Trabert, Britton; Geczik, Ashley M.; Duggan, Máire A.; Sherman, Mark E. (October 2018). "Population Frequency of Serous Tubal Intraepithelial Carcinoma (STIC) in Clinical Practice Using SEE-Fim Protocol". JNCI Cancer Spectrum 2 (4): pky061. doi:10.1093/jncics/pky061. ISSN 2515-5091. PMID 31360879.
19. ↑ Steenbeek, Miranda P.; van Bommel, Majke H. D.; Bulten, Johan; Hulsmann, Julia A.; Bogaerts, Joep; Garcia, Christine; Cun, Han T.; Lu, Karen H. et al. (2022-06-10). "Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis". Journal of Clinical Oncology 40 (17): 1879–1891. doi:10.1200/JCO.21.02016. ISSN 1527-7755. PMID 35302882.
20. ↑ Hanley, Gillian E.; Pearce, Celeste L.; Talhouk, Aline; Kwon, Janice S.; Finlayson, Sarah J.; McAlpine, Jessica N.; Huntsman, David G.; Miller, Dianne (2022). "Outcomes from opportunistic salpingectomy for ovarian cancer prevention". JAMA Netw Open 5 (2): e2147343. doi:10.1001/jamanetworkopen.2021.47343. ISSN 2291-0026. PMID 35138400.
21. ↑ Kindelberger, David W.; Lee, Yonghee; Miron, Alexander; Hirsch, Michelle S.; Feltmate, Colleen; Medeiros, Fabiola; Callahan, Michael J.; Garner, Elizabeth O. et al. (February 2007). "Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship". The American Journal of Surgical Pathology 31 (2): 161–169. doi:10.1097/01.pas.0000213335.40358.47. ISSN 0147-5185. PMID 17255760. https://pubmed.ncbi.nlm.nih.gov/17255760.

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