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Abstract

Cervical cancer is one of the most common malignant tumours of female reproductive system. Concurrent chemoradiotherapy is the standard treatment for locally advanced cervical cancer and brachytherapy is an irreplaceable part of cervical cancer radiotherapy. However, bilateral cervical cancer in a complete septate is extremely rare. There is no standard consensus on the therapeutic management or follow-up owing to the rarity of this condition. This current case report presents an unusual case of a 25-year-old female patient with a double vagina and double uterus combined with a stage IIIC1r moderately differentiated squamous cell carcinoma in both cervices. This report introduces a treatment plan involving concurrent chemoradiotherapy for this rare and interesting case, focusing on a novel brachytherapy method, in which an intrauterine applicator, an applicator and an implantation needle were used. The tumours shrank significantly after chemotherapy and the novel brachytherapy.

Keywords

Double vagina double cervix double uterus cancer case report

Introduction

Uterine cervical cancer is the most common gynaecological malignancy worldwide and remains a leading cause of cancer-related deaths in women, especially among women living in under-developed countries with poor sanitation and low income.^1,2 Cervical cancer treatment in China is guided by the National Comprehensive Cancer Network (NCCN) guidelines.³ Three-dimensional brachytherapy is a relatively advanced brachytherapy method, and the combination of a uterine tube applicator and a vaginal oval applicator is the most common technique used for cervical cancer without surgery; and these advanced technologies are described in detail in the ICRU REPORT No. 89.⁴ Uterus didelphys is a type of uterine malformation that presents as a double uterus and double cervix, which arises due to non-fusion of the Müllerian duct system. A complete septate vagina is seldom observed.⁵ In addition, a double vagina and double uterus combined with bilateral cervical cancer is an infrequent occurrence. Therefore, there are few brachytherapy models for this rare cervical cancer. This current case report describes a female patient with a double vagina and double uterus combined with squamous cell carcinoma of both cervices.

Case report

In June 2020, a 25-year-old unmarried woman visited the Department of Gynaecology, Yulin First Hospital, Yulin, Shaanxi Province, China, after experiencing irregular menstruation and low waist pain for 6 months and aggravating symptoms for 1 month. Whilst there, she was found to have a human papilloma virus 16/18 infection and was preliminarily diagnosed with cervical cancer using gynaecological B-ultrasound. Subsequently, she underwent a cervical biopsy, which revealed a malignant tumour, suggesting a moderately differentiated squamous cell carcinoma, but the local hospital could not give her better treatment due to medical conditions. In early July 2020, she presented to the Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China for professional and effective treatment.

In this current case, there was a septum between the two cervices. Both cervices had tumours, but the septum was complete. The two tumours were thought to be double primary tumours and not metastatic tumours. Her body surface area was 1.55 m², her body weight was 50 kg and she had a body mass index of 17.5 kg/m². She had menarche at the age of 14 years, with regular cycles, severe dysmenorrhoea and dyspareunia. She had her first sexual intercourse at the age of 19 and had an abortion at the age of 21. She was informed by doctors at that time that she had complete septate uterus with cervical and vaginal duplication. She was born in an underdeveloped rural area, did not receive a good education and her father died of myocardial infarction, so the economic situation was worrying. There were no congenital defects in her family history, including reproductive malformations. Gynaecological examination revealed a complete septate uterus with a double vagina and cervix, and both cervices had tumours larger than 4 cm in diameter, contact bleeding reaching the pelvic sidewall and a normal rectum. Pelvic magnetic resonance imaging (MRI) revealed invasion of the upper vaginal wall and several muscles of the pelvis and positive pelvic lymph nodes (Figures 1a and 1b). The findings were consistent with FIGO 2018 stage IIIC1r.⁶ The principle of therapy (pelvic external beam radiation therapy [EBRT] + concurrent platinum-containing chemotherapy + brachytherapy) for stage IIIC1r is recommended as a standard treatment according to the NCCN guidelines.³ Therefore, intensity-modulated radiation therapy was performed for this patient. The clinical target volume (CTV) included the double cervix, double uterus, upper vaginal 1/2 and pelvic lymphatic drainage area (total iliac, internal iliac, external iliac, anterior sacral and deep inguinal lymphatic drainage area). The planned target volume (PTV) was defined as CTV margins of 0.7 cm, planning gross tumour volume-lymph node (PGTVn) was the pelvic lymph node visible in imaging and the completed median dose for 95% PGTVn and 95% PTV was 60 Gy and 50 Gy, respectively. The tandem applicator was inserted into the right uterine cavity and two vaginal ovals were fixed in each cervix during the first three intracavitary brachytherapy insertions. The D90 values for the CTV (high-risk clinical target volume [HR-CTV]) and D2cc values for the bladder, bowel and rectum were determined. The dose of CTV (HR-CTV) was 6 Gy for each fraction, for a total of three times. In the last three intracavitary brachytherapy, a tube was inserted into one uterus, two needles were fixed in each cervix and the dose of CTV (HR-CTV) was 7 Gy in each fraction. Furthermore, two cycles of systematic treatments (8 mg/kg bevacizumab intravenous [i.v.] drip on day 1, 175 mg/m² liposomal paclitaxel i.v. drip on day 1, 80 mg/m² nedaplatin paclitaxel i.v. drip on day 1; and in order to reduce adverse reactions, the dose of the liposomal paclitaxel and nedaplatin was reduced by 20%; 3 weeks per cycle) were combined with external irradiation and iridium-192 intracavitary brachytherapy, as well as four sequential cycles of the same systematic treatments were administered. After radiotherapy and chemotherapy, the size of the tumours decreased significantly (Figures 1c and 1d). The 90% dose curve covered 90.77% of the HR-CTV volume and the D2cc doses in the bladder and rectum were 94.27% and 95.97%, respectively (Figure 1e). During treatment, there was a grade II bone marrow suppression reaction dominated by leukocyte and haemoglobin reduction and a grade I intestinal reaction dominated by diarrhoea. After treatment, the patient returned to her place of residence. Follow-up discovered that she had severe anaemia caused by vaginal bleeding after 5 months and suffered from unbearable abdominal pain, which required oral morphine for pain relief. The patient died of multiple organ failure 3 months later.

Figure 1.

Magnetic resonance imaging (MRI) scans of a 25-year-old female patient that presented with irregular menstruation and low waist pain for 6 months and aggravating symptoms for 1 month who was subsequently found to have a double vagina and double uterus combined with squamous cell carcinoma of both cervices: (a & b): MRI scans showing the presence of the tumours (white arrows) invading both cervices with thickened walls before treatment; (c & d) MRI scans showing the tumours (white arrows) in both cervices were significantly reduced after chemotherapy and radiotherapy treatment and (e) the dose–volume histogram of the clinical target volume (high-risk clinical target volume), rectum and bladder dose during brachytherapy. The colour version of this figure is available at: http://imr.sagepub.com.

All procedures performed in this current case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. The reporting of this study conforms to CARE guidelines.⁷

Discussion

Concurrent chemoradiotherapy (CCRT) is the standard treatment strategy for locally advanced cervical cancer.⁸ Radiotherapy, which includes external irradiation and intracavitary brachytherapy, has always been considered an important form of treatment for cervical cancer.⁹ In particular, it is worth noting that brachytherapy plays an extremely important role in the treatment of cervical cancer.¹⁰ The current case received both radiotherapy and chemotherapy, which significantly decreased the size of the tumours (Figure 1). The patient tolerated the treatment without serious adverse reactions. The current case innovatively received tandem and implant needle applicators during brachytherapy. Brachytherapy is usually guided by the ICRU REPORT No. 89,⁴ but almost all of the criteria are based on normal tissues and organs. None of the criteria mention the brachytherapy of malformed female reproductive systems.⁴ The prevalence of congenital malformations in the female reproductive system is approximately 2–3%, and among infertile women, the prevalence is approximately 9.8%.^5,11 Several classifications have been published for female congenital genital anomalies, also known as Müllerian anomalies, which are based on the extent of Müllerian duct development and fusion.¹² A septate uterus is the most common congenital uterine duplication anomaly, representing approximately 49.1%.¹³ This is caused by incomplete fusion of the Müllerian ducts, resulting in two uterine cavities with a single fundus, cervix and vagina, which can also be separated. Only scattered reports of complete septate uterus, duplicated cervix and vaginal septum have been reported worldwide.^14–20 The first case of double cervical carcinoma in a case of double uterus and subseptate vagina was reported in 1955.¹⁴ Shortly afterwards, a study reported that of 20 patients with cervical carcinoma associated with an anomalous uterus, only two cases were found to involve both cervices.¹⁵ In 1968, a case of double cervical carcinoma in situ was published.²¹ The case of a 56-year-old female with a double vagina and double cervix was reported in 1982.¹⁶ While the left cervix was normal, the right cervix showed a poorly differentiated squamous cell carcinoma.¹⁶ The patient in this rare case received a total dose of 1500 cGy (rad) to Manchester point A and surgery was performed 3 weeks later.¹⁶ To the best of our knowledge, the current case report is the first to describe the use of brachytherapy for a patient with cervical cancer with a double vagina and double cervix. Two cases of cervical cancer with Mullerian malformations were reported in 1986 and 1992, respectively.^17,18 Both of these cases involved single vagina and double cervix with carcinoma in situ; and both patients eventually underwent cold knife conization treatment or surgery.^17,18 A previous report described a case of congenital double uterus and the pathology after surgery showed cervical intraepithelial neoplasia (CIN3) in the right cervix and a poorly differentiated squamous cell carcinoma in the left cervix.¹⁹ This was the second case in which a double uterus deformity was treated using brachytherapy.¹⁹ Another report described a case of cervical cancer and uterine malformations diagnosed by MRI in 2016, but no treatment was reported.²⁰ A summary of the symptoms, histopathology and treatment for these cases is shown in Table 1.^15–20 For this particular type of cervical cancer, there remains a large difference between the brachytherapy that was used in the current case and the method mentioned in Table 1.^16,19 Instead of using a Manchester A point prescription dose, the current case was treated with image-guided three-dimensional brachytherapy, using two needles, one in each cervix. The intrauterine applicator was used in one of the uterine cavities and the prescription dose of CTV was 6–7 Gy. The 90% dose curve covered 90.77% of the CTV-HR volume; and the D2cc doses in the bladder and rectum were 94.27% and 95.97%, respectively (Figure 1).

Table 1.

A summary of the symptoms, histopathology and treatment of female patients with malformed reproductive systems with cervical cancer.^15–20

Author	Mullerian malformation	Diseased cervix	Age, years	Reproductive history	Symptoms	Survival	Treatment
Wall RL, 1958¹⁵	DV + DC	L: CISR: CIS	35	Delivered 2	Bleeding	N/A	Surgery
Corbett PJ & Crompton AC, 1982¹⁶	DV + DC	L: NR: PDSCC	56	Nulliparous	Bleeding	N/A	BT ^a + surgery
Fox S et al., 1986¹⁷	OV + DC	L: CISR: CIS	30	Abortion; delivered 2	Abdominal pain	N/A	Surgery
Bakri Y et al., 1992¹⁸	OV + DC	L: CISR: CIS	29	Nulligravida	Asymptomatic	At least 2 years	CKC
Lee CD et al., 2000¹⁹	DV + DC	L: PDSCCR: CIN3	45	Delivered 1	Bleeding	4 years	EBRT^b + BT^c
Gu CH & Zheng LP, 2016²⁰	DV + DC	L: NR: SCC	47	Abortion 9; delivered 2	Abdominal pain	N/A	N/A
Current case, 2023	DV + DC	L: MDSCCR: MDSCC	25	Abortion 1	Waist pain, irregular menstruation	8 months	CCRT

^aDose 15 Gy/3F; ^bdose of 8-MV 45 Gy/25F; ^cdose of 6.5 Gy/F*2.

DV, double vagina; DC, double cervix; L, left; R, right; CIS, carcinoma in situ; N/A, not available in the original article; N, normal; PDSCC, poorly differentiated squamous cell carcinoma; BT, brachytherapy; OV, one vagina; CKC, cold knife conization; CIN, cervical intraepithelial neoplasia; EBRT, external beam radiation therapy; SCC, squamous cell carcinoma; MDSCC, moderately differentiated squamous cell carcinoma; CCRT, concurrent chemoradiotherapy.

Currently, there is no standard consensus on the therapeutic management or follow-up of female patients with malformed reproductive systems with cervical cancer owing to the rarity of this condition. For this uncommon clinical situation, standard brachytherapy might need to be modified to obtain better efficacy and minimize the occurrence of adverse reactions. The method used in the current case might not have been perfect, but it was a suitable alternative for such rare and unusual cases.

Research Data

Research Data for Bilateral cervical cancer in a complete septate uterus with a double cervix and vagina: a case report

Research Data for Bilateral cervical cancer in a complete septate uterus with a double cervix and vagina: a case report by Li Wang and Zi Liu in Journal of International Medical Research

Footnotes

Author contributions

Li Wang wrote the paper and Zi Liu provided the research data.

Declaration of conflicting interests

The authors declare that there are no conflicts of interest.

Funding

The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Hospital Level Project of Xi'an International Medical Centre, Xi’an, Shaanxi Province, China (no. 2021QN023).

ORCID iD

Zi Liu

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