Stage IV malignant transformation of mature cystic teratoma palliatively treated with concurrent chemoradiotherapy: A case report

Abstract

BACKGROUND

Malignant transformation (MT) of mature cystic teratoma (MCT) has a poor prognosis, especially in advanced cases. Concurrent chemoradiotherapy (CCRT) has an inhibitory effect on MT.

CASE SUMMARY

Herein, we present a case in which CCRT had a reduction effect preoperatively. A 73-year-old woman with pyelonephritis was referred to our hospital. Computed tomography revealed right hydronephrosis and a 6-cm pelvic mass. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) revealed squamous cell carcinoma. The patient was diagnosed with MT of MCT. Due to her poor general condition and renal malfunction, we selected CCRT, expecting fewer adverse effects. After CCRT, her performance status improved, and the tumor size was reduced; surgery was performed. Five months postoperatively, the patient developed dissemination and lymph node metastases. Palliative chemotherapy was ineffective. She died 18 months after treatment initiation.

CONCLUSION

EUS-FNB was useful in the diagnosis of MT of MCT; CCRT suppressed the disease and improved quality of life.

Key Words: Mature cystic teratoma; Malignant transformation; Squamous cell carcinoma; Concurrent chemoradiotherapy; Endoscopic ultrasound-guided fine-needle biopsy; Case report

Core Tip: Malignant transformation (MT) of mature cystic teratoma (MCT) is uncommon and has a poor prognosis, especially in advanced cases. Surgery and chemotherapy are selected in accordance with ovarian cancer, but the prognosis is typically poor due to the high degree of malignancy, making treatment often challenging. We present a case of stage IV MT of MCT in which concurrent chemoradiotherapy (CCRT) had a reduction effect preoperatively. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was used for diagnosis due to the patient’s poor general condition. EUS-FNB was useful in diagnosing MT of MCT; CCRT suppressed the disease and improved the patient’s quality of life.

INTRODUCTION

Malignant transformation (MT) of mature cystic teratoma (MCT) is uncommon, occurring in 0.17%-2% of MCTs[1]. There is no established treatment method; debulking surgery and multidrug chemotherapy are performed in accordance with epithelial ovarian cancer. However, the prognosis of advanced cancer is poor: the 2-year survival rate is approximately 30% for stage III and 0% for stage IV[2]. In some cases, due to systemic conditions or complications, adequate treatment is not available. We present a case of stage IV MT of MCT that was diagnosed using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and palliatively treated with concurrent chemoradiotherapy (CCRT).

CASE PRESENTATION

Chief complaints

A 73-year-old multiparous woman was referred to the emergency department of our hospital with fever and right lower back pain.

History of present illness

Symptoms started 2 weeks before presentation.

History of past illness

She had a medical history of cerebral infarction, hypertension, hyperlipidemia, and benign left ovarian tumor.

Personal and family history

She denied any family history of malignancy.

Physical examination

On physical examination, the vital signs were as follows: Body temperature, 38.5 °C; blood pressure, 120/68 mmHg; heart rate, 82 beats per minute; respiratory rate, 20 breaths per minute. Internal examination revealed that the tumor was adhered to the pelvic wall and had poor mobility.

Laboratory examinations

The serum squamous cell carcinoma antigen level was 5.7 ng/mL, carcinoembryonic antigen level was 0.9 ng/mL, CA19-9 level was 26 U/mL, and CA125 level was 10.8 U/mL. The white blood cell count was 18200/μL, C-reactive protein level was 9.62 mg/dL, serum creatine level was 1.17 mg/dL, and the estimated glomerular filtration rate was 35 mL/min.

Imaging examinations

Ultrasonography revealed an irregular solid pattern and a small amount of ascitic fluid. Computed tomography (CT) revealed right hydronephrosis and a 68 cm × 64 cm × 45 mm solid cystic mass with fat and calcification densities in the right pelvic cavity. Chest CT showed multiple grain-sized nodules in both lungs. Magnetic resonance imaging (MRI) showed that the tumor was adhered to both the uterus and rectum, with a 1.5 cm peritoneal dissemination at the right pelvic wall near the ureter (Figure 1).

Figure 1 Computed tomography and magnetic resonance imaging findings. A-C: Computed tomography revealed right hydronephrosis, a 6-cm solid cystic mass with fat and calcification densities, and multiple nodules in the lungs (orange circles); D-F: Magnetic resonance imaging showed that the tumor was adhering to the uterus and rectum. There was suspected dissemination near the right ureter (orange circle).

MULTIDISCIPLINARY EXPERT CONSULTATION

Cervical cytology was negative for intraepithelial lesions or malignancy, and there were no findings suggestive of human papillomavirus infection. We suspected MT of the MCT from CT and MRI findings. Paracentesis or laparoscopic biopsy are usually considered for diagnosis; however, as there was some ascites, and the tumor was located deep in the pelvis and invaded surrounding organs, we concluded that both were difficult. Therefore, we performed EUS-FNB based on the location of the tumor and its adhesion to the rectum. Pathological examination revealed squamous cell carcinoma (Figure 2).

Figure 2 Pathological diagnosis using endoscopic ultrasound-guided fine-needle biopsy was squamous cell carcinoma.

FINAL DIAGNOSIS

The patient was diagnosed with stage IV MT of the MCT.

TREATMENT

We were hesitant to perform debulking surgery because her Eastern Cooperative Oncology Group performance status (PS) score was 2. In addition, multidrug chemotherapy has side effects that could exacerbate renal dysfunction. Since CCRT is performed in hospital, it is possible even if the PS is 2 or higher, and we considered that side effects can be observed and dealt with in detail. In addition, the amount of cisplatin used in combination can be reduced according to renal function, and the treatment results are better than those with radiation alone. Therefore, we selected CCRT. The patient received 50 Gy of radiotherapy in 25 fractions to the lower pelvis with 30 mg/m² cisplatin for 4 weeks. The side effects included loss of appetite and weight, fever, and diarrhea, all grade 1 according to the Common Terminology Criteria for Adverse Events v5.0. Medication was given for fever and diarrhea, and the patient quickly recovered. After CCRT, the tumor size was reduced by 7.3%, mobility improved, and the PS score improved from 2 to 1. Total abdominal hysterectomy, right salpingo-oophorectomy, and removal of the dissemination were performed. The ascites cytology was positive. No tumors remained in the abdomen postoperatively. The patient was asymptomatic but requested follow-up.

Five months postoperatively, edema was observed in the right lower leg. Positron emission tomography showed peritoneal dissemination in the right pelvic wall, multiple lymph node metastases, and increased lung metastases. The patient requested palliative chemotherapy to reduce the edema. We administered doxorubicin hydrochloride liposome 40 mg/m² on day 1 but had to stop treatment due to a decrease in blood pressure and generalized rashes that could indicate an allergic reaction. We then administered three courses of gemcitabine 1000 mg/day, on days 1, 8, and 15, but discontinued due to disease progression.

OUTCOME AND FOLLOW-UP

The patient died 18 months after treatment initiation due to multiple organ failure. Information from this case report organized into timeline (Figure 3).

Figure 3 Timeline of this case. CCRT: Concurrent chemoradiotherapy.

The patient and her family were satisfied with the treatment and its progress.

DISCUSSION

This case demonstrates the following two points: CCRT had a preoperative reduction effect in MT of MCT, and EUS-FNB is useful for diagnosing MT of MCT.

CCRT reduced the MT of MCT. Table 1 shows previous cases in which CCRT was administered for MT of MCT[3-8]. The advanced cases survived with no evidence of disease. However, all of these cases had CCRTs administered postoperatively. To our knowledge, this is the first case report of preoperative CCRT. Similar to the postoperative cases, CCRT showed a reduction in the MT of MCT, and the side effects were tolerable. According to the literature, cases of long-term survival even in advanced stages have been completely removed by surgery. However, in cases such as this case, where the general condition is poor or the patient is elderly or has complications, treatment that prolongs the prognosis without causing complications is necessary, and CCRT can be said to be a treatment that satisfies such needs. Of course, CCRT also has side effects such as intestinal perforation, radiation enteritis, and cystitis, which may be necessary to treat, but these can be avoided to some extent by narrowing the irradiation field with intensity-modulated radiation therapy. Another long-term disadvantage is that it is difficult to use angiogenesis inhibitors such as bevacizumab because of the increased possibility of intestinal perforation. Although preoperative CCRT for ovarian cancer is currently uncommon, preoperative radiotherapy is often used for colorectal cancer. Recent reports have shown that patients with recurrent MT of MCT have been treated with a combination of surgery, chemotherapy, and CCRT to achieve long-term survival[9,10]. More definitive conclusions can be drawn as more cases accumulate in the future.

Table 1 Summary of patients with malignant transformation of mature cystic teratomas who received concurrent chemoradiotherapy.

Ref.	Age	Stage	Surgery	Adjuvant therapy	Follow-up (months)	Outcome
Rose et al[3], 1993	42	III C	RSO, retroperitoneal dissection, PAN	CCRT (cisplatin)	11	DOD
Do et al[4], 2001	44	II B	LSO	CCRT (5-FU, leucovorin)	36	NED
Park et al[5], 2008	43	III C	PLN, PAN, total omentectomy, Appe	CCRT, TP	13	NED
Yoshida et al[6], 2016	37	II B	TAH, BSO	CCRT (cisplatin, 5-FU)	27	NED
Tokunaga et al[7], 2016	49	III A	TAH, BSO, pOM, PLN, PAN	CCRT	?	NED
Tokunaga et al[7], 2016	40	III C	TAH, BSO, pOM, PLN, PAN	CCRT	?	NED
Bacalbasa et al[8], 2020	47	I A	TAH, LSO	CCRT (cisplatin)	24	NED

Appe: Appendectomy; BSO: Bilateral salpingo-oophorectomy; DOD: Died of disease; LSO: Left salpingo-oophorectomy; NED: No evidence of disease; Pom: Partial omentectomy; PLN: Pelvic lymphadenectomy; PAN: Para-aortic lymphadenectomy; TAH: Total abdominal hysterectomy; TP: Paclitaxel, cisplatin; CCRT: Concurrent chemoradiotherapy.

EUS-FNB is useful for diagnosis. Paracentesis or endoscopic biopsy are the usual methods for ovarian cancer biopsy; however, in the present case, there were minimal ascites, the tumor was adhered to the rectum and pelvic wall and had poor mobility, and dissemination was deep in the pelvis. EUS-FNB is a minimally invasive rapid diagnostic technique. At our hospital, EUS-FNB is used for lymph node biopsies and histological examination of intestinal submucosal tumors. Other cases of MT of MCT that were incidentally diagnosed on colonic biopsy have been reported[11]. Advanced MT of MCT may directly invade adjacent organs; however, investigation of further cases is required.

The effects of immune checkpoint inhibitors for recurrence or chemo-resistant cases have been reported in recent years[12-14]. We hope to collect data from additional cases and develop effective treatments.

CONCLUSION

EUS-FNB is a useful method of diagnosing MT of MCT. Although advanced-stage patients have poor prognosis, CCRT has the potential to suppress the disease temporarily and improve the patient’s quality of life with few adverse effects.