SEE-FIM Protocol

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SEE-FIM Protocol.jpg
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

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

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

Related Research Articles

<span class="mw-page-title-main">Tubal ligation</span> Surgical clipping,removal or blocking of the fallopian tubes

Tubal ligation is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus the implantation of a fertilized egg. Tubal ligation is considered a permanent method of sterilization and birth control.

Oophorectomy, historically also called ovariotomy is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference to animals, e.g. the surgical removal of ovaries from laboratory animals. Removal of the ovaries of females is the biological equivalent of castration of males; the term castration is only occasionally used in the medical literature to refer to oophorectomy of women. In veterinary medicine, the removal of ovaries and uterus is called ovariohysterectomy (spaying) and is a form of sterilization.

<span class="mw-page-title-main">Endometrial cancer</span> Uterine cancer that is located in tissues lining the uterus

Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

<span class="mw-page-title-main">Ovarian cancer</span> Cancer originating in or on the ovary

Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver.

<span class="mw-page-title-main">Serous tumour</span> Medical condition

A serous tumour is a neoplasm that typically has papillary to solid formations of tumor cells with crowded nuclei, and which typically arises on the modified Müllerian-derived serous membranes that surround the ovaries in females. Such ovarian tumors are part of the surface epithelial-stromal tumour group of ovarian tumors. They are common neoplasms with a strong tendency to occur bilaterally, and they account for approximately a quarter of all ovarian tumors.

<span class="mw-page-title-main">Surface epithelial-stromal tumor</span> Medical condition

Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium or from ectopic endometrial or Fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer; however is mainly only found in postmenopausal women with the exception of the United States where 7% of cases occur in women under the age of 40. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment. 75% of women with epithelial ovarian cancer are found within the advanced-stages; however younger patients are more likely to have better prognoses than older patients.

<span class="mw-page-title-main">Salpingectomy</span> Surgical removal of fallopian tube

Salpingectomy refers to the surgical removal of a fallopian tube. This may be done to treat an ectopic pregnancy or cancer, to prevent cancer, or as a form of contraception.

In medicine, Meigs's syndrome, also Meigs syndrome or Demons–Meigs syndrome, is the triad of ascites, pleural effusion, and benign ovarian tumor. Meigs syndrome resolves after the resection of the tumor. Because the transdiaphragmatic lymphatic channels are larger in diameter on the right, the pleural effusion is classically on the right side. The causes of the ascites and pleural effusion are poorly understood. Atypical Meigs syndrome, characterized by a benign pelvic mass with right-sided pleural effusion but without ascites, can also occur. As in typical Meigs syndrome, pleural effusion resolves after removal of the pelvic mass.

<span class="mw-page-title-main">Primary peritoneal carcinoma</span> Medical condition

Primary peritoneal cancer or carcinoma is also known as serous surface papillary carcinoma, primary peritoneal carcinoma, extra-ovarian serous carcinoma, primary serous papillary carcinoma, and psammomacarcinoma. It was historically classified under "carcinoma of unknown primary" (CUP). Primary peritoneal cancer is a cancer of the cells lining the peritoneum, or abdominal cavity.

In medicine, salpingo-oophorectomy is the removal of an ovary and its Fallopian tube. This procedure is most frequently associated with prophylactic surgery in response to the discovery of a BRCA mutation, particularly those of the normally tumor suppressing BRCA1 gene, which can increase the risk of a woman developing ovarian cancer to as high as 65%.

<span class="mw-page-title-main">Hereditary breast–ovarian cancer syndrome</span> Medical condition

Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families. It accounts for 90% of the hereditary cancers. The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family. The name HBOC may be misleading because it implies that this genetic susceptibility to cancer is mainly in women. In reality, both sexes have the same rates of gene mutations and HBOC can predispose to other cancers including prostate cancer and pancreatic cancer. For this reason, the term "King syndrome" has recently come into use. The new name references Mary-Claire King who identified the genes BRCA1 and BRCA2.

Primary fallopian tube cancer (PFTC), often just tubal cancer, is a malignant neoplasm that originates from the fallopian tube.

Uterine clear-cell carcinoma (CC) is a rare form of endometrial cancer with distinct morphological features on pathology; it is aggressive and has high recurrence rate. Like uterine papillary serous carcinoma CC does not develop from endometrial hyperplasia and is not hormone sensitive, rather it arises from an atrophic endometrium. Such lesions belong to the type II endometrial cancers.

<span class="mw-page-title-main">Olaparib</span> Chemical compound (cancer therapy drug)

Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.

<span class="mw-page-title-main">Fallopian tube</span> Tubes in the human female reproductive system

The fallopian tubes, also known as uterine tubes, oviducts or salpinges, are paired tubes in the human female body that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In other mammals, they are only called oviducts.

A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. It generally refers to such tumors in the ovary but borderline tumors may rarely occur at other locations as well.

<i>BRCA</i> mutation Medical condition

A BRCA mutation is a mutation in either of the BRCA1 and BRCA2 genes, which are tumour suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, while others have no proven impact. Harmful mutations in these genes may produce a hereditary breast–ovarian cancer syndrome in affected persons. Only 5–10% of breast cancer cases in women are attributed to BRCA1 and BRCA2 mutations, but the impact on women with the gene mutation is more profound. Women with harmful mutations in either BRCA1 or BRCA2 have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal. The risk of breast and ovarian cancer is higher for women with a high-risk BRCA1 mutation than with a BRCA2 mutation. Having a high-risk mutation does not guarantee that the woman will develop any type of cancer, or imply that any cancer that appears was actually caused by the mutation, rather than some other factor.

<span class="mw-page-title-main">High-grade serous carcinoma</span> Medical condition

High-grade serous carcinoma (HGSC) is a type of tumour that arises from the serous epithelial layer in the abdominopelvic cavity and is mainly found in the ovary. HGSCs make up the majority of ovarian cancer cases and have the lowest survival rates. HGSC is distinct from low-grade serous carcinoma (LGSC) which arises from ovarian tissue, is less aggressive and is present in stage I ovarian cancer where tumours are localised to the ovary.

<span class="mw-page-title-main">Prophylactic salpingectomy</span> Surgical technique

Prophylactic salpingectomy is a preventative surgical technique performed on patients who are at higher risk of having ovarian cancer, such as individuals who may have pathogenic variants of the BRCA1 or BRCA2 gene. Originally salpingectomy was used in cases of ectopic pregnancies. As a preventative surgery however, it involves the removal of the fallopian tubes. By not removing the ovaries this procedure is advantageous to individuals who are still of child bearing age. It also reduces risks such as cardiovascular disease and osteoporosis which are associated with removal of the ovaries.

Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma.

References

  1. 1 2 3 Medeiros, Fabiola; Muto, Michael G.; Lee, Yonghee; Elvin, Julia A.; Callahan, Michael J.; Feltmate, Colleen; Garber, Judy E.; Cramer, Daniel W.; Crum, Christopher P. (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. S2CID   20695412.
  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. S2CID   36569900.
  3. ↑ Rebbeck, Timothy R.; Lynch, Henry T.; Neuhausen, Susan L.; Narod, Steven A.; Van't Veer, Laura; Garber, Judy E.; Evans, Gareth; Isaacs, Claudine; Daly, Mary B.; Matloff, Ellen; Olopade, Olufunmilayo I.; Weber, Barbara L.; Prevention and Observation of Surgical End Points Study Group (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.
  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.; Kenemans, P. (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.
  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.
  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.
  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. S2CID   29496482.
  8. 1 2 Samimi, Goli; Trabert, Britton; Duggan, Máire A.; Robinson, Jennifer L.; Coa, Kisha I.; Waibel, Elizabeth; Garcia, Edna; Minasian, Lori M.; Sherman, Mark E. (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. PMC   5829019 . 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. PMC   3148026 . 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. PMC   5784219 . PMID   27539290.
  11. ↑ Minig, L.; Cabrera, S.; Oliver, R.; Couso, A.; Rubio, M. J.; Iacoponi, S.; Martin-Salamanca, M. B.; Carballo-Rastrilla, S.; Cádenas-Rebollo, J. M.; García-Garcia, A.; Gil-Ibáñez, B.; Juan-Fita, M. J.; Patrono, M. G. (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. S2CID   4606980.
  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.
  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.
  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" (PDF). College of American Pathologists.
  15. ↑ Malpica, Anais; Euscher, Elizabeth D.; Hecht, Jonathan L.; Ali-Fehmi, Rouba; Quick, Charles M.; Singh, Naveena; Horn, Lars-Christian; Alvarado-Cabrero, Isabel; Matias-Guiu, Xavier; Hirschowitz, Lynn; Duggan, Máire; Ordi, Jaume; Parkash, Vinita; Mikami, Yoshiki; Ruhul Quddus, M. (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. PMC   6296844 . PMID   30550481.
  16. ↑ "Ovary, Fallopian Tube and Primary Peritoneal Carcinoma Histopathology Reporting Guide" (PDF). May 2019.
  17. ↑ "Gynecologic Pathology Grossing Guidelines Specimen Type" (PDF). April 2023.
  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. PMC   6649708 . 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.; van Beekhuizen, Heleen J.; Minig, Lucas; Gaarenstroom, Katja N.; Nobbenhuis, Marielle; Krajc, Mateja; Rudaitis, Vilius; Norquist, Barbara M. (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. PMC   9851686 . 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. PMC   8829665 . PMID   35138400.
  21. ↑ Kindelberger, David W.; Lee, Yonghee; Miron, Alexander; Hirsch, Michelle S.; Feltmate, Colleen; Medeiros, Fabiola; Callahan, Michael J.; Garner, Elizabeth O.; Gordon, Robert W.; Birch, Chandler; Berkowitz, Ross S.; Muto, Michael G.; Crum, Christopher P. (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. S2CID   86662.
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