The main spread pattern of cervical squamous cell carcinoma is loco-regional invasion, including laterally into the parametrium and distally into the upper vagina, but less often anterior-posteriorly into the bladder or rectum . Spreading to regional pelvic nodes is common, but hematogenous metastases to lungs, liver, brain, etc. is unusual until late in advanced stages of cervical cancer with high grade tumors . Another potential anatomical direction of direct extension in cervical cancer is into the uterine corpus. Retrospective study showed that the uterine corpus tumor invasion is rare in early-stage cervical cancer, especially in squamous histology . A previous study identified 837 (4.9%) cases of uterine corpus invasion in 17074 surgically-treated cervical cancer and found that uterine corpus invasion was independently associated with older age (>50), non-squamous histology, high-grade tumors, large tumor size(>4cm), and nodal metastasis . Non-squamous histology including adenocarcinoma is an independent risk factor for uterine corpus tumor invasion compared to squamous type . The most likely causality of this association is the anatomical proximity to the uterine corpus of the endocervical gland origination of cervical adenocarcinoma. However, cervical squamous carcinoma usually develops at the exocervix and infrequently involves the uterine corpus. Uterine corpus tumor invasion has not been incorporated into the cervical cancer staging system, up to date . Here we reported a case of metastatic uterine corpus cancer that was secondary to a stage IB3 squamous cell cervical cancer. This patient underwent neoadjuvant chemotherapy and laparoscopic radical trachelectomy. She had no surgical-pathological risk factors, but presented a uterine fundus metastasis in a short interval from primary surgery. Pathologic examination confirmed that metastatic squamous carcinoma of uterine fundus was isolated and did not reach the margin of previous surgery, and endometrium was also not involved, suggesting a very low possibility that the lesion of uterine fundus is a direct extension from original cancer of the cervix. One explanation may be that tumor cells in uterine fundus was carried into by uterine manipulator, which is frequently used for retraction and visualization, during minimally invasive surgery. Furthermore, this implantation metastasis in uterine fundus induced the failure of save fertility ultimately. We had modified the CRF and informed consent of NCT02624531 including not to attempt laparoscopic trachelectomy, till its safety was established.
Radical trachelectomy is typically only for stage IB1 patients with tumor 2cm or less in diameter, negative nodes, and non-aggressive histological subtypes . However, some surgeons proposed that neoadjuvant chemotherapy could be used for patients with locally advanced stage to reduce tumor size so that fertility was preserved . Platinum-based neoadjuvant chemotherapy has been shown to improve local control (reduce tumor size and parametrial infiltration) and offer a better control of micro metastases in distant sites as well as in regional lymph nodes . In a previous report, totally 25 cervical cancer staging IB3 (FIGO2018) women underwent neoadjuvant chemotherapy plus conservative surgery, including 10 simples vaginal trachelectomy, 10 vaginal radical trachelectomy, and 5 abdominal radical trachelectomy, among them only 2 (8%) recurred . Considering the limitations of retrospective studies, we are conducting a prospective clinical trial (NCT02624531) about the application of fertility-sparing therapy for patients with cervical cancer staging IB1-IIA2 (FIGO2012). According to the protocol, the patient with stage IB3 (FIGO2018) squamous cell cervical carcinoma is assigned to receive two or three cycles of neoadjuvant chemotherapy followed by radical trachelectomy and further three to four cycles of adjuvant chemotherapy after surgery. The patient we reported presented partial remission (PR) to neoadjuvant chemotherapy, which meant that tumor was still existed in the cervix, though the size was reduced, after neoadjuvant chemotherapy. Accordingly, we have reason to speculate that the tumor cells probably moved from cervix and implanted into uterine fundus by uterine manipulator during surgery. Thus, our special case also suggests that it should be considered to avoid the use of uterine manipulator during minimally invasive fertility-sparing surgery or perform abdominal radical trachelectomy instead.
In summary, we reported a special case of uterine fundus implanted cervical squamous cell carcinoma. The patient was diagnosed with stage IB3 (FIGO 2018) and underwent neoadjuvant chemotherapy plus laparoscopic radical trachelectomy. Pathologic diagnosis was well-differentiated squamous cell carcinoma without pathologic risk factors. The patient suffered from metastatic cancer in uterine fundus later and underwent radical surgery finally. This case with special metastatic manner indicates that the safety of laparoscopic radical trachelectomy is still uncertain for advanced stage cervical cancer even if neoadjuvant and post-surgery chemotherapy is given, and also suggests that it is needed to discuss carefully the benefit and risk of such a strategy with the patient when the fertility preservation is considered.