Case Report Serous Tubal Intraepithelial Carcinoma: .Serous Tubal Intraepithelial Carcinoma: An...

Case Report Serous Tubal Intraepithelial Carcinoma: .Serous Tubal Intraepithelial Carcinoma: An Incidental
Case Report Serous Tubal Intraepithelial Carcinoma: .Serous Tubal Intraepithelial Carcinoma: An Incidental
Case Report Serous Tubal Intraepithelial Carcinoma: .Serous Tubal Intraepithelial Carcinoma: An Incidental
Case Report Serous Tubal Intraepithelial Carcinoma: .Serous Tubal Intraepithelial Carcinoma: An Incidental
Case Report Serous Tubal Intraepithelial Carcinoma: .Serous Tubal Intraepithelial Carcinoma: An Incidental
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  • Case ReportSerous Tubal Intraepithelial Carcinoma: An Incidental Findingat the Time of Prophylactic Bilateral Salpingo-Oophorectomy

    Monique Hiersoux Vaughan,1 Susan C. Modesitt,2 Yunchuan Mo,3 and Elisa R. Trowbridge4

    1Department of Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, VA, USA2Thornton Gynecologic Oncology Division, Department of Obstetrics and Gynecology, University of Virginia Health System,Charlottesville, VA, USA3Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA4Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology,University of Virginia Health System, Charlottesville, VA, USA

    Correspondence should be addressed to Elisa R. Trowbridge; etrowbridge@virginia.edu

    Received 23 November 2014; Revised 7 February 2015; Accepted 7 February 2015

    Academic Editor: Yoshio Yoshida

    Copyright 2015 Monique Hiersoux Vaughan et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

    Background. Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion for high-grade pelvic serous carcinoma. Theincidence of STIC is estimated to occur in 0.6% to 6% of women who are BRCA positive or have a strong family history of breast orovarian cancer. Case. A 56-year-old woman underwent robotic-assisted sacrocolpopexy, rectocele repair, and concurrent bilateralsalpingo-oophorectomy for recurrent stage 3 pelvic organ prolapse and reported family history of ovarian cancer. Histopathologicexamination of her left fallopian tube revealed STIC. Conclusion. We report this rare occurrence of STIC in a patient undergoingsurgery primarily for pelvic organ prolapse and having a family history of ovarian cancer. Possible management options includeobservation with annual physical exam and CA-125, surgical staging, or empiric chemotherapy. However, due to the lack ofconsensus regarding management options, referral to a gynecologic oncologist is recommended.

    1. Introduction

    Serous tubal intraepithelial carcinoma (STIC) is a rare patho-logic finding at the time of benign gynecologic surgery.It arises in the distal fimbriated end of the fallopian tubeand likely represents a precursor lesion to high-grade pelvicserous carcinoma. In this case report, we describe a patientwho was unexpectedly found to have STIC at the time ofbenign gynecologic surgery. We discuss the diagnosis, impli-cations, management options, and prevention strategies forSTIC.

    2. Case Presentation

    In March 2013, a 56-year-old G4P4 presented with recurrentstage 3 pelvic organ prolapse (apical and posterior) after totalvaginal hysterectomy, transobturator TVT sling, and anterior

    colporrhaphy with Gynecare Prolift (Ethicon, Somerville,New Jersey) mesh in 2007. On presentation, the patientcomplained of a one-year history of vaginal bulge, obstructeddefecation, and symptoms of urge incontinence. She wasotherwise healthy with body mass index of 20 kg/m2 buthad a 15-pack-year smoking history. On pelvic exam, shehad a normal bimanual exam with no tenderness or adnexalmasses. Her pelvic organ prolapse quantification system(POPQ) exam revealed apical prolapse with the vaginal cufflocated 3 cm above the hymen and posterior vaginal walldefect to 3 cm below the hymen. Additionally, the patientreported a family history of ovarian cancer in amaternal auntin her 30s as well as possible ovarian cancer in a maternalcousin in her 30s, both still living. These family membershad not undergone genetic testing. She had two healthyreproductive-age daughters. A robotic-assisted laparoscopicsacrocolpopexy, rectocele repair, and risk-reducing bilateral

    Hindawi Publishing CorporationCase Reports in Obstetrics and GynecologyVolume 2015, Article ID 760429, 4 pageshttp://dx.doi.org/10.1155/2015/760429

  • 2 Case Reports in Obstetrics and Gynecology

    salpingo-oophorectomy (RRSO) were recommended. Due toher strong family history of ovarian cancer, she was offeredreferral to the High Risk Breast and Ovarian Cancer Clinicpreoperatively, but she declined.

    At the time of laparoscopy, her abdominal and pelvicsurveys were normal with atrophic appearing ovaries. Herbilateral fallopian tubes and ovaries were sent for histopatho-logic examination. Given her family history of ovarian carci-noma, the protocol for sectioning and extensively examiningthe fimbria (SEE-FIM) was utilized in this case (please see adescription of the SEE-FIMprotocol in the discussion below).Both ovaries were also serially sectioned along the longitu-dinal axis and submitted in their entirety. No abnormalitieswere noted in either of the salpingo-oophorectomy speci-mens at the time of gross examination.

    She had an uneventful postoperative course and was dis-charged home on postoperative day number 2. Histopatho-logic examination of the specimen returned with serous tubalintraepithelial carcinoma of the fimbriated portion of the leftfallopian tube. The left ovary along with the right fallopiantube and right ovary revealed no pathologic abnormality.Figure 1 depicts the histologic findings of STIC, includingnuclear atypia, loss of polarity, increasedmitoses, and positivep53 staining.

    These findings were discussed with the patient and shewas referred for gynecologic oncology consultation, wheremanagement options were discussed. These included obser-vation with close follow-up, repeated surgery with biopsiesand staging, or empiric chemotherapy. She chose to proceedwith observation and is followed up every 6 months withpelvic exam and CA-125. Her last CA-125 was normal at5 u/mL. At her initial visit with gynecologic oncology, thepatient was very fearful of genetic testing due to concerns thatit was experimental. She subsequently met with a geneticcounselor but continues to decline genetic testing.

    3. Discussion

    The incidence of STIC has primarily been studied in patientswith known BRCA mutations or a strong family historyof breast or ovarian cancer and is estimated to be in therange of 0.6% to 6% [13]. Wethington et al. [2] found theincidence of STIC in women undergoing risk-reducingsalpingo-oophorectomy (RRSO) at a single institution to be2%. All of the patients in that study had a known BRCAmutation or high-risk personal or family history. Rabban et al.[4] performed a pathologic evaluation of the fallopian tubesof women at low risk for hereditary breast and ovarian cancerundergoing benign gynecologic surgery. STIC lesions wereidentified in 4 out of 522 cases (0.76%). STIC is a pathologicfinding of unclear clinical significance, but it appears tobe a precursor lesion for high-grade pelvic (tubal, ovarian,or primary peritoneal) serous carcinoma arising in the distalfimbriated end of the fallopian tube [5, 6]. Evidence support-ing this theory includes the following: approximately 1015%of fallopian tube STIC cases are detected in women under-going RRSO for BRCA 1 and 2 mutations [1] and STIC isdetected in approximately 5060% of cases of sporadic pelvic

    high-grade serous carcinoma [7]. Additionally, patients withconcurrent pelvic serous tumors and STIC have been shownto have identical TP53mutations in both themetastatic tumorand the fallopian tube precursor, suggesting clonality [8].Finally, there have been compelling studies in recent yearsdemonstrating that many high-grade serous ovarian can-cers actually originate in the fallopian tube mucosa. Evidencesupporting this theory came originally fromRRSOs in BRCAmutation carriers, where many occult ovarian cancers werefound to have tubal involvement. Given this new data, thefallopian tubes of high-risk women are now more closelyscrutinized (see below regarding the SEE-FIM protocol) [9,10].

    There are currently no standardized criteria for diag-nosis of STIC lesions, as the histopathologic spectrum isvery wide and no two STICs appear exactly the same.However, STIC is traditionally diagnosed with a combina-tion of histopathologic and morphologic evaluation withimmunohistochemical staining. Histopathologic features ofSTIC include a variable combination of epithelial stratifi-cation (including loss of cellular polarity and exfoliation ofcells into the lumen), intraepithelial fracture lines, irregularluminal surface, pleomorphism, loss of ciliation, irregularchromatin pattern, nuclear rounding, nuclear molding,increased nuclear-to-cytoplasmic ratio, mitotic figures, andapoptotic bodies [11]. Morphologic features evident from lowpower include architectural disarray and increased nuclearstratification of the tubal epithelium without evidence ofstromal invasion. High-power examination demonstratesindividual cells with enlarged nuclei resulting in an increasednuclear to cytoplasmic ratio, prominent nucleoli, loss ofpolarity, and lack of ciliated cells. Immunohistochemicalstaining usually is positive for TP53 andKi-67 [2, 4]. TP53 is atumor suppressor gene that is typically mutated in STIC andpelvic serous tumors. The overexpressed, nonfunctional P53protein accumulates, leading to strong, nuclear reactivity in aconfluent distribution. Conversely, Ki-67 is a protein markerof cellular proliferation and is typically overexpressed in STICand pelvic serous tumors. Finally, immunohistochemicalstaining for STIC may reveal overexpression of phosphory-lated histone H2AX (-H2AX), which is an early cellularresponse to DNA double stand breaks, as well as overexpres-sion of Bcl-2 (an antiapoptotic protein) that may indicatea change to a secretory phenotype, with complete loss ofciliated cells in the fallopian tube [12].

    Given this patients reported family history, the SEE-FIMprotocol was utilized for histologic examination of her fallop-ian tubes. Initially implemented in patients with documented