Unilateral ovarian recurrence 5 years after hysterectomy for microinvasive squamous cervical cancer stage IA1: a rare case report

Previous studies have shown a good prognosis for microinvasive squamous cervical cancer [1]. The standard treatment the National Comprehensive Cancer Network recommends is a simple hysterectomy or cervical conization for patients with microinvasive squamous cervical cancer without LVSI if there is no fertility requirement. The ovarian metastasis (OM) incidence is relatively low in patients with squamous cell carcinoma (SCC). Ovarian preservation can be safely performed in young patients [2]. Primary ovarian SCC is extremely rare. Most cases are caused by cystic teratoma malignancy, and very few cases are caused by Brenner tumor or endometriosis. A review of the published literature revealed only one case of ovarian SCC recurred 8 years after fertility-conserving surgery for early microinvasive SCC [3]. This was the second case of unilateral ovarian recurrence 5 years after a hysterectomy for microinvasive squamous cervical cancer stage IA1.

A 49-year-old female patient suffered from a 3-month history of dull pain in the left lower abdomen. And she had laparoscopic hysterectomy for the microinvasive SCC stage IA1 in 2018. Five years ago, the patient was admitted to our hospital with postcoital vaginal bleeding. The cervical biopsy pathology indicated grade III cervical intraepithelial neoplasia (CIN III) with the involvement of glands and human papillomavirus (HPV) type 16 DNA positive. The cervical conical resection was performed. The postoperative examination indicated extensive CIN III with glandular involvement. The microscopic invasive SCC (both width and depth less than 1 mm) was found in the focal area, without lymph vascular space invasion (LVSI) (Fig. 1). Because the patient had no fertility requirement, laparoscopic total hysterectomy and bilateral salpingectomy were performed, and no more severe lesions were found on the postoperative pathological examination.

The patient was followed up regularly after surgery, and no abnormalities were found in cervical cytology, HPV infection, and squamous cell carcinoma antigen (SCC-Ag) during an annual review. Five years after surgery, she complained of a 3-month history of dull pain in the left lower abdomen. Physical examination showed a palpable mass on the left side of the pelvic cavity, and examination of the vulva, vagina, and vaginal stump was normal. The cytology and HPV test results of vaginal stump exfoliation were negative. The levels of the tumor marker of SCC-Ag in serum showed marked elevation (10.60 ng/mL), and the carbohydrate antigen 125 was normal. The sonographic examination demonstrated a left ovarian solid mass measuring 4.2 × 3.4 × 3.6 cm. Pelvic MRI demonstrated a left ovarian solid tumor measuring 5.5 × 3.9 × 5.6 cm with heterogeneous enhancement (Fig. 2a and b), and increased left pelvic lymph nodes were also demonstrated. The positron emission tomography-computed tomography (PET-CT) did not reveal the possibility of metastatic tumors or tumors derived from other origins. Therefore, an exploratory laparotomy was performed. During laparotomy, a left ovarian tumor measuring about 5.0 × 4.5 × 3.0 cm seemed densely adherent to the posterior peritoneal wall, including the left ureter, which was resected completely. Pelvic lymph nodes were suboptimal resection due to the tumor adhering closely to the pelvic sidewall. Postoperative anatomy revealed a solid mass with a greyish-white section (Fig. 3). The right ovarian was resected, and no abnormal appearance was observed. Postoperative pathology showed moderately differentiated SCC with negative pelvic lymph nodes (Fig. 4a). Immunohistochemistry showed that the tumor cells were positive for P16, P63, P40, and CK5/6 markers, and the positive rate of Ki67 was about 80% (Fig. 4b-f). No endometriosis or teratoma components were found. The possibility of primary ovarian SCC could not be completely ruled out; however, the ovarian tumor was considered to be derived from the microinvasive SCC of the cervix stage IA1 in combination with the patient's medical history and immunohistochemical examination. Following surgery, the serum SCC-Ag decreased to 3.8 ng/mL on postoperative day 7. The patient was supplemented with radiotherapy and chemotherapy after surgery, there was no sign of tumor recurrence, and long-term follow up will be conducted to observe the prognosis.

The OM of cervical cancer is rare. A recent systematic review showed that the incidence of OM in stage IA to IIB cervical carcinoma was 1.46% [4]. For patients with microinvasive squamous cervical cancer without LVSI, the standard treatment is a simple hysterectomy or cervical conization if there is no fertility requirement. Ovary preservation is reasonable and appropriate in young patients because oophorectomy seriously affects their long-term quality of life and increases the risk of osteoporosis and cardiovascular diseases.

The recurrence rates of different stages of cervical cancer were about 10% for FIGO Stage IB, 17% for IIA stage, 23% for IIB stage, 42% for III stage and 74% for IVA stage [5]. The recurrence rate for tumors ≤ 2 cm has an estimated recurrence risk of only 1.2% while for tumors larger than 2 cm the recurrence rate is as high as 21% [6, 7]. The symptoms of cervical cancer recurrence are usually insidious, including recurrence of local pelvic disease, para-aortic lymph nodes, and distant recurrence. Previous studies reported that distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump;10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence [8]. There has been considerable controversy regarding ovarian preservation in patients with cervical adenocarcinoma. Current studies have shown that ovarian preservation in young women with early-stage cervical AC might be safe [9]. Ovarian recurrence is extremely rare for microinvasive squamous cervical cancer. A review of the published literature revealed only one case of ovarian SCC recurred 8 years after fertility-conserving surgery for early microinvasive SCC with positive lymphovascular involvement [3]; this was the second case of unilateral ovarian recurrence 5 years after hysterectomy for the microinvasive squamous cervical cancer stage IA1 without LVSI.

Follow-up visits should include a complete physical examination, history, and pelvic rectal examination, and necessary laboratory and imaging tests as indicated by clinical symptoms. The serum SCC-Ag is consistently associated with the recurrence and mortality of newly diagnosed cervical cancer, and this marker can be used to monitor disease progression in patients with cervical cancer [10, 11]. The patient's treatment history, recurrence/metastasis site, and lesion degree should be comprehensively evaluated, combined with the general condition of the patient. The organic combination of multiple treatment modes, such as radical radiotherapy, pelvic dissection, palliative chemotherapy, and targeted therapy, should be given selectively. Patients with metastatic recurrent cervical cancer have a poor prognosis despite salvage therapy. The patient in the case reports of Takao underwent debulking surgery and was treated with adjuvant chemotherapy consisting of paclitaxel and carboplatin, followed by radiotherapy, but the patient showed progressive disease [3].

In conclusion, we reported a case of ovarian recurrence 5 years after hysterectomy for the microinvasive SCC stage IA1 without LVSI. Our findings suggested that although ovarian recurrence for the microinvasive SCC stage IA1 was rare, gynecological oncologists should not overlook its possibility.