Incidental Serous Tubal Intraepithelial Carcinoma Detected by a Surgery for Ectopic Pregnancy

Serous tubal intraepithelial carcinoma is a putative precursor of high-grade serous carcinoma, which is the most common histological type of ovarian or pelvic peritoneal cancer. Serous tubal intraepithelial carcinoma is commonly found in patients with breast cancer susceptibility gene mutations who undergo risk-reducing salpingo-oophorectomy. Incidental serous tubal intraepithelial carcinoma found by a non-prophylactic surgery is rare. A 33-year-old woman referred to our hospital for a diagnosis of ectopic pregnancy. She underwent a laparoscopic right salpingectomy. Pathologically, ectopic pregnancy in the ampulla of the right fallopian tube was confirmed and serous tubal intraepithelial carcinoma was observed in the fallopian tube. Subsequently, she underwent a laparoscopic hysterectomy, bilateral oophorectomy, and left salpingectomy as additional treatment. She has experienced no recurrence thus far for 37 months since the surgery.


Introduction
Serous tubal intraepithelial carcinoma (STIC) is a putative precursor of high-grade serous carcinoma (HGSC), which is the most common histological type of ovarian or pelvic peritoneal cancer. STIC is commonly found in patients with breast cancer susceptibility gene (BRCA) mutations who undergo risk-reducing salpingo-oophorectomy (RRSO). Incidental STIC found by a non-prophylactic surgery is rare. Here, we present a case of STIC incidentally found by a surgery How to cite this paper: Yamamoto, T., Shimura, K., Sugahara, T., Ogiso, N. and Okubo, T. (

Case Presentation
A 33-year-old woman, gravida 7 para 2 (5 artificial abortions and 2 vaginal labors), presented to a hospital complaining of irregular genital bleeding and lower abdominal pain, with a positive gestational test. She was suspected of having an ectopic pregnancy. She referred to our hospital for a diagnosis and surgery.
She was in 5 weeks and 5 days of gestation, based on the date of her last menstrual period. She had no family history of cancer. Upon the first clinical examination, genital bleeding and lower abdominal tenderness with peritoneal irritation were present. Transvaginal sonography revealed a moderate to large intra-abdominal hemorrhage in the Douglas' pouch and a cystic region that appeared to be the gestational sac in the right fallopian tube. The results of biochemical blood examination were almost within normal limits, except for a lower hemoglobin concentration and elevated β human chorionic gonadotropin (1209.4 mIU/mL). Accordingly, she was diagnosed of having a right fallopian tube rupture due to ectopic pregnancy, and a laparoscopic right salpingectomy was performed. There were no significant intraoperative findings, except for the ectopic pregnancy. She was pathologically diagnosed with ectopic pregnancy at the ampulla of the right fallopian tube and STIC. We suggested either follow-up or additional treatment to the patient. She and her husband decided to undergo a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. During the surgery, cytology results of the peritoneal washings were negative for malignancy. There was no residual tumor pathologically in the uterus or adnexa. She has been followed up for recurrence by examining level of serum CA125 and using computed tomography. She received estrogen replacement therapy using estradiol transdermal gel (1 mg/day). At the time of this report, she has no evidence of disease 37 months after the surgery.

Pathological Findings
A rupture of the ampulla of the right fallopian tube was observed. Villi were present in the fallopian tube. In addition, epithelial tube thickness was partially increased. There was increased epithelial cell stratification, enlarged nuclei and nuclear rounding, and hyperchromasia (Figure 1(a)). Immunohistochemical staining was highly positive for MIB1 and p53 (Figure 1 [4]. In our case, although she was not examined BRCA mutation status, she did not have a family history of ovarian or breast cancer.

Discussion
She was accidentally diagnosed as STIC at 33 years old.
There are no common criteria for absolute diagnosis of STIC. Currently, most STICs have been diagnosed using a combination of morphology and immunohistochemical analysis for p53 and Ki-67. Morphologic features of STIC include at least 1 mitotic figure, epithelial stratification (more than 2 cell layers), apoptotic bodies, nuclear enlargement and/or nuclear rounding, marked pleomorphism, abnormal chromatin and nuclear molding [9]. TP53 mutation is assumed when positive immunohistochemical staining for p53 is noted for more than 75% of cells or completely negative. Using a Ki-67 labeling index threshold of 10% to differentiate between STIC and normal fallopian tube epithelium, the sensitivity and specificity were 100% and 96.4%, respectively [10]. MIB-1 and Ki-67 labeling were used to diagnose this case. We diagnosed this case as STIC by the pathological findings of the morphology, TP53 mutation, and high Ki-67 labeling index. was no residual tumor. However, she was in her 30s, and estrogen replacement therapy was needed.
In conclusion, this is the first report of STIC diagnosed in a patient with an ectopic pregnancy in her early 30s. STIC might cause dysfunction of the ciliated epithelium in the fallopian tube. Therefore, the fallopian tube of patients with ectopic pregnancy should be closely observed, even for patients with no family history of ovarian or breast cancer.

Consent
Written informed consent was obtained from the patient for publication of this case report.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this paper.