High-grade serous carcinoma (HGSC) is the most common type of pelvic cancer among women. Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion of HGSC. Herein, we report a rare occurrence of STIC in patients undergoing surgery for benign indications without a family history of ovarian cancer. A 77-year-old woman underwent total laparoscopic hysterectomy and bilateral salpingo-oophorectomy for uterine prolapse. Pathological examination revealed bilateral STIC without ovarian abnormalities, and no other abnormal findings were noted. Another patient, a 49-year-old woman, underwent laparoscopic total hysterectomy and bilateral salpingectomy for uterine fibroids. STIC lesions were observed in both fallopian tubes. Subsequently, a staging was performed. No additional lesions were found, and the patient was followedup through imaging and blood tests. As reports of STIC lesions are rare, data on their clinical outcomes and management strategies are limited. In this report, we present cases of incidental STIC in benign surgery and discuss its proper interpretation and management. Through the early detection of STIC lesions, patients with risk factors can be identified in advance, which will allow prevention and early detection of ovarian cancer. Opportunistic salpingectomy was also actively discussed in this regard.
High-grade serous carcinoma (HGSC) is the most common type of pelvic cancer among women and is responsible for most epithelial ovarian cancer-related deaths [
Our understanding of HGSC pathogenesis has substantially improved over the past few decades. Serous cancers are conventionally considered to originate from the ovarian surface epithelium or cortical inclusion cysts. The fallopian tubes have not been examined because ovarian carcinoma precursors are expected to arise from the ovaries. However, no ovarian precursor lesions have been identified. A hypothesis of malignant cell migration from the fallopian tube to the ovary has been proposed [
With the discovery of HGSC originating from the fallopian tubes, alternative preventive strategies have emerged. In particular, prophylactic oophorectomy is performed in women at risk of ovarian cancer, and preventive measures involving the tube are now being considered. Thirteen members of the International Federation of Obstetrics and Gynecology society have stated guidelines regarding opportunistic salpingectomy, with the majority supporting this practice [
A STIC diagnosis is rare in women undergoing salpingectomy for benign indications (<0.01%) [
In this report, we present two cases of isolated STIC incidentally found during benign gynecological surgery, along with a brief literature review.
In the first case, the STIC was incidentally discovered during laparoscopic total hysterectomy and bilateral salpingo-oophorectomy for uterine prolapse correction.
A 77-year-old woman, gravida 4 para 4 (all delivered vaginally), presented to a hospital complaining of a recurrent vaginal bulge lasting 1 year. Pelvic organ prolapse quantification examination revealed stage-3 apical prolapse. No other unusual findings were observed on transvaginal ultrasonography. The patient had no significant medical or familial history of cancer. Total laparoscopic hysterectomy and bilateral salpingo-oophorectomy with sacral colopexy were performed. No significant intra-operative findings were observed. The uterus, bilateral tubes, and ovaries were sent for histopathological examination, and no gross abnormalities were noted in either specimen. The postoperative course was uneventful, and the patient was discharged on postoperative day 3. Pathological examination of the specimen revealed bilateral STIC (
In the second case, the STIC was discovered after laparoscopic total hysterectomy and bilateral salpingectomy for uterine fibroids. A 49-year-old woman, gravida 1 para 1 (all delivered vaginally), was followed-up for multiple uterine fibroids on an outpatient basis. The patient underwent surgery, and three doses of gonadotropin-releasing hormone agonists were administered. The patient had no significant medical or familial history of cancer. Preoperative ultrasonography revealed no specific findings, other than the presence of uterine fibroids. Total laparoscopic hysterectomy and bilateral salpingectomy were performed; however, no significant intraoperative findings were observed. Pathological examination of the resected tissue revealed STIC in both fallopian tubes. Immunohistochemical staining revealed focal p53 positivity. These results were discussed with the patient; considering the potential risk, a staging operation was performed with bilateral oophorectomy. No specific findings were observed on the postoperative abdominopelvic computed tomography or positron emission tomography-computed tomography. The CA-125 level was 21.90, which was within the normal range. Laparoscopic bilateral oophorectomy, partial omentectomy, and right-sided round ligament resection were performed. Pathological examination revealed that the specimens were benign. The patient was discharged without complications, and follow-up imaging and blood tests were performed at an outpatient clinic.
This is a case report; therefore, the approval of the ethics committee and institutional review board was not required.
Approximately 20 years of progressive data accumulation has established that the distal fallopian tube is an origin site for HGSC, which was evident when STIC was identified as a precursor lesion in the tubal epithelium. Additionally, the concurrent presence of identical somatic TP53 mutations in STIC and pelvic HGSC lesions support this establishment. Furthermore, gene expression in HGSC is more closely related to fallopian tube morphology than to the ovarian surface epithelium. HGSC expresses a Müllerian marker (PAX8), not a mesothelial marker (calretinin) [
The incidence of STIC ranges from 0.6–6% [
In our cases, the patients were not examined for BRCA mutations because they had no familial history of cancer. Few reports have described incidental STIC in patients with unknown BRCA mutation status. Although its prevalence has not been established in large studies, the STIC frequency in these women is 0.6–1.1% [
There are no standardized criteria for STIC diagnosis because the histopathological spectrum is very wide. Currently, most STIC lesions are diagnosed using a combination of histopathological and immunohistochemical staining [
As reports of STIC lesions are rare, data on the clinical outcomes and management strategies are limited. Wethington et al. [
Epithelial ovarian cancer is a leading cause of death, with the most fatal subtype being HGSC. As 80% of ovarian cancers occur in women with no known family history, the risk of fallopian tube and ovarian cancers should be considered in all gynecological surgeries. To date, no functional screening methods have been developed. Current modalities such as gynecological examination, transvaginal ultrasound, and serum CA-125 and HE4 biomarkers have not yielded satisfactory results [
In response to the gradually accumulating STIC studies, several providers have expanded the role of routine salpingectomy, hysterectomy, and sterilization procedures [
Various studies have improved our understanding of the association between STIC and HGSC. This recent paradigm shift in the understanding of extrauterine pelvic cancer has clinical implications for its screening, prevention, diagnosis, and management [
Currently, no clear guidelines exist for the management of incidentally identified STIC. Patients should be evaluated for risk factors including BRCA1 and BRCA2 mutations. Careful decisions should be made regarding additional surgery, adjuvant treatment, and follow-up plans considering individual patient factors.
This work was supported by the education, research and student guidance grant funded by Jeju National University
Histopathological findings of the specimen from the distal fallopian tube. (A) Stratified and thickened epithelial layer, focal loss of polarity and ciliated cells, lack of stromal invasion, enlarged nuclei, and hyperchromatic chromatin are visualized. Hematoxylin and eosin staining (×200). (B) Total negative expression of p53 was observed (in the yellow circle). Scattered nuclear stain (×200).