Growing teratoma syndrome: a surgical conundrum

Abstract

Growing teratoma syndrome (GTS) is a tumour growth, which contains mature teratomatous elements during or after chemotherapy for malignant germ cell tumours. Surgery is the only potential treatment option for GTS because these growing teratomas are resistant to chemotherapy and radiation therapy. Extensive surgeries may be needed in GTS with multivisceral resections to achieve no residual disease status. This report presents a case of GTS treated with multiple surgical resections in a woman with malignant immature teratoma ovary in her early thirties; she is disease free after 1 year of treatment.

Background

Growing teratoma syndrome (GTS) is an overgrowth of benign teratomatous elements following chemotherapy and normalisation of tumour markers.^{1 2} The incidence of GTS after testicular cancer is 1.9%–7.6% and after ovarian cancer is 12%.¹ The persistent growth of tumour tissue causes pressure symptoms and leads to a lot of distress to the patient. Surgery is the only potential therapeutic option in such patients. Our case report describes the extensive surgical resections needed in a case of GTS involving multiple vital organs of the abdominal cavity.

Case presentation

A nulliparous woman in her early 30s reported to our hospital with abdominal distension and pain. She had a history of two previous laparotomies for pelvic mass with gross ascites at a local hospital and reported to us 3 months after the second surgery. Her histopathology report was grade III immature teratoma of the ovary. She was cachexic with Eastern Cooperative Oncology Group performance status 3, had tense ascites and an ill-defined fixed pelvic mass measuring 10×10 cm. Tumour markers were markedly elevated; alpha-fetoprotein (AFP) 9872.7 ng/mL, lactate dehydrogenase (LDH) 990.5 U/L, beta human chorionic gonadotropin (β hCG) 21.39 mIU/mL, cancer antigen (CA) 19.9 180.66 IU/mL, Carcino Embryonic Antigen (CEA) 3.25 ng/mL and CA125 - 132.2 U/mL. Contrast-enhanced CT (CECT) scan of the abdomen, pelvis and chest (figure 1) showed a large heterogeneously enhancing pelvic mass measuring 9×5.8×7.4 cm, involving bilateral adnexa with multiple large peritoneal deposits and a deposit in the right subdiaphragmatic location of size 31×36 mm. On the left side, there was a deposit of size 43×26 mm, which was causing mass effect on the spleen with loss of planes. Three large deposits (10×7.6 cm, 6×6.3 cm, 11×7 cm) were seen in infrahepatic location with infiltration into segments VI, IV, V, II and III of the liver along with gross ascites and nodularity of omentum and peritoneum. Omental biopsy showed metastatic immature teratoma (figure 2). The patient received two cycles of BEP (bleomycin, etoposide and cisplatin) chemotherapy. Before third cycle of chemotherapy, she developed pain abdomen and distension. On the examination, a well-defined, non-tender, firm mass measuring 15×10 cm was palpable in the lower abdomen with restricted mobility. Another firm mass of size 15×10 cm was also palpable in the epigastrium and right hypochondrium.

Figure 1.

Contrast-enhanced CT scan of abdomen and pelvis (A, C, E: prechemotherapy, B, D, F, G: postchemotherapy). Right-sided subdiaphragmatic mass increased from 3×3 cm to 10×8 cm (shown with red circle in A and B). Left-sided subdiaphragmatic mass increased from 4×2.6 cm to 13×10x 17 cm (shown with yellow circle in C and D). Infrahepatic mass increased from 6×6 cm to 9×10 cm (shown with yellow StAR in E and F). Adnexal mass size increased from 9×6×7 cm to15×10×9 cm) (shown with red arrow in E and G).

Figure 2.

Histopathology of pelvic mass. (A’): H&E×10—prechemotherapy tissue biopsy histopathology; and (A”): H&E×20—prechemotherapy tissue histopathology suggestive of immature teratoma, (neural tissue shown with yellow StAR). (A–E): histopathology of pelvic mass biopsy and liver biopsy (postchemotherapy): mature teratoma. (A, B, D)—(H&E×40, ×200 and ×200) stained sections shows multiple cystic spaces lined by hyperplastic stratified squamous epithelium with lumen containing keratin Perl (red StAR) along with mature skeletal muscle (green arrow) bone (blue arrow) and cartilage tissue formation (red arrow). (C, E)—(H&E×100) small intestine (yellow StAR) serosal aspect and spleen parenchyma (green StAR) shows a well-defined lesion comprises of mature tissue fragments from epithelial, bone, muscle and cartilage. No immature neuro epithelium or rosettes are seen.

Investigations

On the evaluation, her tumour markers AFP 26.6 ng/mL and LDH 174 U/L were markedly decreased and Cancer antigen (CA 19.9) 1970 IU/mL was increased. Repeat CECT abdomen and pelvis (figure 1) showed progressive disease. A note was made of a heterogeneous lesion in the pelvis involving bilateral adnexa measuring 15×10×9 cm having indistinct fat planes with bladder, rectum and sigmoid colon along with multiple peritoneal deposits. Bilateral subdiaphragmatic deposits showed an increase in size (left 13.5×17 cm and right 10.3×8 cm). Few large deposits (8.7×9.5 cm, 11×7 cm) were seen in infrahepatic location with infiltration into segments VI, IV, V, II and III of the liver. Multiple deposits were also seen around the spleen, pancreas, stomach and bowel loops. Histopathology report of pelvic mass and liver deposit biopsy showed features of mature teratoma (figure 2).

Differential diagnosis

An important differential diagnosis, in this case, was progressive malignancy on chemotherapy. This was ruled out by histopathology of pelvic and liver masses, which showed a mature teratoma, further confirming the diagnosis of GTS.

Treatment

She underwent extensive cytoreductive surgery (duration: 6 hours with 5 L blood loss) with R0 resection, which involved the removal of pelvic, abdominal and peritoneal masses, splenectomy, ultralow anterior resection with end-to-end colorectal anastomosis, ileocecal resection, double-barrelled ileostomy and omentectomy (figure 3). She had a prolonged intensive care unit (ICU) stay of 28 days and received multiple blood products. After 3 months of surgery, she had intermittent watery discharge per vaginum. On local examination, no vesicovaginal fistula was demonstrable. However, there was a 3×3 cm rectovaginal fistula in the posterior vaginal wall, 5 cm from the anal verge. Colonoscopy revealed an anastomotic site stricture 12 cm from the anal verge and the rectovaginal fistula was noted at the same distance. Biopsy was taken from the erythematous nodular mucosa at the anastomotic site which showed no evidence of malignancy. Her tumour markers were within normal limits. After 10 months, a second look laparotomy with rectovaginal fistula repair and fascia lata graft interposition was done (figure 3). Her postoperative period was uneventful and she was discharged on postoperative day 9 in stable condition.

Figure 3.

Intraoperative images. (A): pelvic masses (blue arrow), peritoneal masses (yellow arrow), (B): pelvic masses (blue StAR), bladder (yellow StAR), (C): peritoneal mass with spleen (green arrow), (D): surgical specimen (whole excised tumour deposits), (E): Gloved finger tips depicting vaginal wall defect and rectal wall defect (yellow arrow), (F): repaired rectovaginal fistula, (G): fascia lata harvested and interposed over anastomotic site (yellow arrow).

Outcome and follow-up

The patient is under regular follow-up and is recurrence-free after 1 year of surgical resection.

Discussion

GTS is described as multiple tumour masses in the retroperitoneum or abdomino pelvic cavity, chest, liver or bone during or after chemotherapy for non-seminomatous germ cell tumour (GCT) of ovary/testis. These are generally resistant to chemotherapy and radiation; surgery is the only curative modality of treatment and it may require extensive multivisceral resections like the present case.

Logothetis described three criteria for GTS: the presence of enlarging masses during or after chemotherapy, normalisation of serum tumour markers (AFP, β HCG) and mature teratoma only in resected specimens.²

The developmental hypothesis for GTS was described by Hiester et al.³ According to them, during chemotherapy, embryonal carcinoma cells might develop/differentiate into transit-amplifying cells (TAC), which is known as ‘chemotherapeutic retroconversion’. These TACs self-renew or differentiate further into cells resembling tissues of all three germ layers.

Approximately 100 cases of GTS postovarian GCT have been reported to date, most of them published as case series, the largest of 38 cases by Bentivegna et al.⁴ Another case series of 35 cases of GTS diagnosed after a follow-up of 175 cases of immature ovarian teratoma between 1980 and 2018 was published by Wang et al. Eighteen (51.4%) patients underwent complete resection of GTS and 20 patients required a multidisciplinary team for surgery. The second GTS relapse occurred in 11/35 (31.4%) cases. The presence of residual disease at initial surgery (OR 11) and gliomatosis peritonei (OR 2.9) are independent risk factors for the development of GTS.⁵

Many cases of GTS require multivisceral resection similar to the present case. Oyama et al reported a case of GTS, which developed in a 12-year-old girl of grade 1 immature teratoma left ovary while on chemotherapy (second cycle), similar to our case.⁶ Resection of pelvic and peritoneal tumours, omentectomy, segmental ileal resection, rectosigmoid resection and anastomosis was done and the girl was recurrence-free till 5 years of follow-up.

Saso et al also reported a case of GTS following unilateral salpingo-oophorectomy in a 33-year-old woman with a mixed germ cell tumour of the ovary, where disease progression was noticed during BEP chemotherapy.¹ CECT scan showed a massive tumour in the abdomen, pelvis and lung requiring hemihepatectomy, cholecystectomy, resection of right hemidiaphragm and left lung lobectomy in the first setting. Three months later, completion debulking surgery was performed involving the removal of the uterus, right tube and ovary, omentum and spleen.

Incomplete resection leads to an increased chance of recurrence (50%–83%), while complete resection leads to a recurrence of 0%–4% only.⁷ Malignant transformation into sarcoma, squamous cell carcinoma, adenocarcinoma or carcinoids has been reported in 3%–5% of cases.⁸ The prognosis of completely resected GTS is good as R0 resection is often curative with a 5-year survival rate of 89%–90%.^{1 5}

Patient’s perspective.

I had progressive abdominal distension and pain abdomen with significant weight loss and loss of appetite for 8 months. I underwent two abdominal surgeries at a local hospital but with minimal relief. I again had similar symptoms, for which I was referred to a tertiary cancer centre, where I underwent thorough evaluation and treatment with a team of doctors of varied specialties. I am now completely asymptomatic and cancer-free for the last 1 year and on regular follow-up.

Learning points.

• Diagnosis of growing teratoma syndrome (GTS) is confirmed by the exclusive presence of a mature teratomatous element with normalisation of tumour markers.

• Extensive surgery with multivisceral resections may be needed to achieve complete cytoreduction in GTS.

• Gynaecological oncologists must be aware of the surgical complexity and morbidity involved in dealing with such cases.

• A multidisciplinary team might be needed for complete cytoreduction.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).