Fertility-sparing approach in concurrent gliomatosis peritonei and growing teratoma syndrome in a young woman

Abstract

Gliomatosis peritonei (GP) and Growing Teratoma Syndrome (GTS) are rare and clinically significant conditions often associated with ovarian teratomas. GP involves the development of benign glial implants on the peritoneal surface, while GTS is characterised by the growth of benign, yet enlarging peritoneal implants following chemotherapy for malignant germ cell tumours. These implants are typically histologically mature teratomas devoid of malignancy. Our report documents a unique case where both GP and GTS manifested in a patient undergoing treatment for an immature ovarian teratoma. This dual occurrence is scarcely reported in the existing literature. The patient, a nulliparous woman in her 20s, developed a tumour indicative of GTS immediately after completing three cycles of bleomycin, etoposide and cisplatin therapy. This chemotherapy regimen followed fertility-sparing surgery for a stage IIIb ovarian immature teratoma. Given that total tumour resection is pivotal in positively influencing the prognosis of GTS, early minimally invasive surgical intervention before significant tumour growth is essential. This approach is particularly crucial considering that ovarian germ cell tumours are commonly present in younger patients, necessitating a focus on fertility preservation in most cases.

Background

Gliomatosis peritonei (GP), a very rare condition linked to ovarian teratomas of any grade, features benign glial implants on the peritoneal surface. It is predominantly associated with immature ovarian teratomas and is more frequently diagnosed during relaparotomy than initial surgery. Approximately 100 cases of GP have been documented.¹ Due to its rarity, GP’s prognostic implications and clinical characteristics are not fully understood. However, some studies suggest that patients with GP may experience quicker and more frequent relapses.¹ Growing Teratoma Syndrome (GTS) is associated with ovarian and testicular teratomas, first described in 1970 and named in 1982 by Logothethis et al.² Diagnosis hinges on three criteria: normalised tumour markers, enlargement of tumour masses or new appearances in various locations postchemotherapy and the exclusive presence of mature teratoma cells in the removed mass.^{3 4} Continuing chemotherapy has no impact on reducing the tumour mass. To date, over 100 cases of GTS in the context of ovarian immature teratomas have been reported in the English-language literature, with GP concurrent occurrence rarely noted.⁵

Case presentation

In 2021, a previously healthy, nulliparous woman in her early 20s visited the emergency department at our centre, with a 3-day history of generalised abdominal pain accompanied by abdominal distension. She described the pain as cramping, located in the suprapubic region and radiating to her back. A transabdominal ultrasound revealed a large solid cystic ovarian mass, measuring 18 × 10 cm and free fluid extending up to Morrison’s pouch.

Given the suspicion of a ruptured ovarian tumour, CT of the abdomen and pelvis was deemed unnecessary, and she was promptly taken for emergency laparotomy. During the procedure, a ruptured right ovarian tumour, approximately 15 × 12 × 7 cm in size, was discovered with its solid portion about 10 × 5 cm protruding into the peritoneum. Additionally, a left ovarian cyst was found, measuring 6 × 4 × 3 cm, likely a dermoid cyst, characterised by its content of hair and sebum and an intact capsule. A right salpingo-oophorectomy, left cystectomy and omentectomy were performed. No other significant intraperitoneal findings were noted. The patient recovered well postoperatively and was discharged 3 days later.

Investigations

Histopathological analysis from the initial surgery identified a Grade 3 WHO immature cystic teratoma in the right ovary (figure 1) and a mature cystic teratoma in the left ovary, with no malignancy detected in the omentum. Eight weeks postsurgery, contrast-enhanced CT scans of the thorax, abdomen and pelvis showed no signs of local recurrence or distant metastasis.

Figure 1.

This photo showed a section taken from the right ovarian tumour exhibiting a mixture of immature and mature elements. The mature elements are composed of cartilage tissue (star), epithelial lining (yellow arrow) and brain-like tissue (red arrow). High-power view of the immature elements is shown in the inset. The immature component is composed of immature neuroepithelial tissue forming rosettes and tubules (ie, seen more than three in low-power fields).

Postoperatively, the patient underwent three cycles of chemotherapy (bleomycin, etoposide and cisplatin) at the National Cancer Institute. However, severe side effects, including excessive vomiting leading to significant hypokalaemia and hyponatraemia, led her to decline the final chemotherapy cycle. Six months postsurgery, tumour markers AFP (Alpha fetoprotein), CA125, Beta HCG and Ca 19–9 normalised.

During a 6-month surveillance period, a transabdominal ultrasound incidentally detected a pelvic mass, despite normal tumour marker levels. Subsequent, CT scans of the abdomen and pelvis revealed a large tumour mass in the lesser pelvis, with one anterior to the bladder and another in the left ovary, raising suspicions of recurrence (figure 2).

Figure 2.

Axial CT scan of the abdomen and pelvis revealed tumour mass anterior to the bladder (yellow arrow) and tumour mass on the left ovary (red arrow).

An ultrasound-guided biopsy of the bladder-adjacent mass revealed mature neural tissue. However, due to the potential for non-representative sampling, the presence of immature or malignant components could not be conclusively ruled out. Consequently, an urgent positron emission tomography scan was performed indicating possible tumour recurrence and GTS (figure 3).

Figure 3.

Sagittal (A) and axial (B) view of fluorodeoxyglucose (FDG) positron emission tomography images showed FDG avid lesion at the anterior to the urinary bladder. The absence of FDG uptake in other regions suggests a lack of distant metastasis.

In preparation for further intervention, a multidisciplinary team meeting involving gynaecology, radiology and pathology specialists was convened. The meeting concluded with a consensus on the potential diagnosis of GP, supported by two consistent findings of mature neural cells and normal tumour markers since the completion of chemotherapy.

Treatment

The patient opted for a second fertility-sparing surgery to remove the tumour, which was conducted at our centre. The procedure included laparoscopic removal of the left peritoneal tumour, biopsies of the anterior abdominal wall, right cornual end and epiploica of the rectum, as well as cystoscopy. Intraoperatively, small peritoneal seedlings, each less than 0.5 cm in size, were identified on the anterior wall of the rectum, and on the left and right pelvic sidewalls (figure 4). Minimal tumour deposits were noted on the uterus’s surface and at the right cornual end (figure 4). Additionally, a 4 × 4 cm tumour with a rubbery consistency was located at the left broad ligament (figure 5). A small amount of straw-coloured fluid was present in the peritoneal cavity. All tumour tissues and peritoneal fluids were excised and sent for histopathological analysis.

Figure 4.

Laparoscopic image of multiple peritoneal seedlings on the rectal anterior wall, pelvic wall, right cornual end and surface of uterus.

Figure 5.

Laparoscopic image of left peritoneal tumour at the left broad ligament measuring 4 × 3 cm.

Outcome and follow-up

The histopathological analysis of the excised tissues confirmed the presence of mature neural tissue without malignancy (figures 6 and 7). Consequently, combining these findings with the intraoperative observations, the diagnosis of GTS and GP was established. Following the surgery, the patient has been under regular surveillance and remains disease-free to date.

Figure 6.

Section of tumour deposit at the abdominal wall (postchemotherapy) showed only mature neuroglial tissue. No immature components are seen. Inset: high-power view of the tissue shows benign spindle cells with eosinophilic fibrillary cytoplasm within a background of neural-like stroma.

Figure 7.

Recurrent pelvic mass (postchemotherapy) located on the broad ligament displaying mature teratoma which is composed of stratified squamous epithelial lining, smooth muscle bundles and brain-like tissue. No immature components were noted.

Additionally, the fertility-sparing approach proved successful as the patient conceived and underwent a healthy pregnancy, culminating in the term delivery of a healthy baby.

Discussion

GTS involves the transformation of immature teratomas into mature forms during or after chemotherapy, a process known as chemotherapy retroconversion. This phenomenon suggests either a direct conversion of malignant cells into benign ones or selective destruction of malignant tissue by chemotherapy, leaving mature components to proliferate.⁴ GP, on the other hand, is defined as the implantation of mature glial cells in the peritoneum from ovarian teratomas and is considered benign.¹

The coexistence of GTS and GP, as seen in our case, is exceptionally rare. Similar cases where GTS led to GP have been reported in a few literatures as presented in table 1.^{3 6–8} The standard treatment for these conditions is surgical intervention, which aims to prevent malignant transformation and confirm the diagnosis.⁷ Despite the benign nature of GTS, it often resists chemoradiotherapy, and incomplete surgical clearance can lead to rapid tumour growth and potential inoperability.⁹

Table 1.

Summary of four cases with concurrent GP and GTS

Author	Age at diagnosis	Surgical procedure	Histology	Timing of GP/GTS diagnosis	Treatment	Outcome
Amsalem et al 3	12	Unilateral adnexectomy, partial omentectomy and peritoneal lavage	Immature neuroectodermal tissues, mesenchymal tissues and squamous epithelium grades I and II	7 months after the first surgery (with completion of 3 cycles of cisplatin, VP-16 and bleomycin chemotherapy)	Second laparotomy and debulking surgery	Symptom-free for 2 years follow-up after the second surgery
Umekawa et al 6	34	Unilateral oophorectomy and peritoneal lavage	Immature neuroectodermal tissues, mesenchymal tissues and squamous epithelium, grade 3	6 months after completion of 5 cycles of cisplatin, etoposide and bleomycin chemotherapy	Second-look laparotomy and resection of peritoneal implants	Symptom-free for 2 years after the first surgery
Małgorzata et al 7	15	Unilateral salpingo-oophorectomy	Immature teratoma with epithelial elements	8 months after the first surgery	2 cycles of etoposide-ifosfamide-cisplatin (VIP) regime followed by debulking surgery and another 2 cycles of VIP regime	Not mentioned
Tangjitgamol et al 8	5	Unilateral salpingo-oophorectomy	Ovarian immature teratoma, grade 3	5 months after the first surgery	2 cycles of bleomycin-etoposide-cisplatin regime followed by 2 cycles of vincristine-actinomycin-cyclophosphamide regime then debulking surgery	Recurrent abdominal mass with normal AFP 2 years after the second surgery

GP, Gliomatosis peritonei; GTS, Growing Teratoma Syndrome.

Long-term surveillance is crucial as recurrences have been reported even after a decade.¹⁰ Our patient’s case was challenging due to her young, nulliparous status and the appearance of a recurrent pelvis mass postchemotherapy, raising concerns for immature teratoma recurrence. Second-look surgery despite initial biopsy reports of mature tissue was critical to ensure comprehensive diagnosis and treatment.

In summary, while the co-occurrence of GTS and GP is infrequent, it necessitates careful long-term surveillance and a strategic approach to preserve fertility while ensuring complete tumour removal. This case adds to the growing body of evidence on the complex nature of these rare entities.

Patient’s perspective.

When I first experienced generalised abdominal pain and distension, I had no idea it would lead to a diagnosis of stage 1 ovarian immature teratoma. After undergoing an emergency laparotomy at HSAAS UPM Serdang, the diagnosis came as a shock to me. Following the surgery, I was referred to the National Cancer Institute for chemotherapy. I was scheduled for four cycles, but the severe side effects were too much for me to handle, and I could only complete three. Over the next 7 months, my condition was closely monitored through blood tests. The situation took another turn when I was diagnosed with a left ovarian cyst at a private centre. The doctor there suggested removing my left ovary and uterus. As a young woman who was unmarried at the time, this recommendation was daunting. Fearing the loss of my fertility, I sought a second opinion at HSAAS. There, I underwent keyhole surgery instead of the more invasive procedure initially suggested. Thankfully, the histopathology report from this surgery showed no malignancy. Looking back, I am so grateful for seeking that second opinion. It not only saved my fertility but also allowed me to conceive naturally. Seven months after getting married, I successfully conceived, which was a joyous milestone in my life. This journey taught me the importance of advocating for myself and the value of exploring all medical options before making such a life-changing decision.

Learning points.

• In patients with a history of immature teratoma, the presence of an abdominopelvic mass, even after chemotherapy completion and normalisation of tumour markers, should prompt consideration of gliomatosis peritonei.

• For young, nulliparous women facing second-look surgery, fertility-sparing options should be prioritised until histopathological analysis definitively confirms malignancy.

• Even when ultrasound-guided biopsy suggests benign histopathology, cytoreductive surgery remains a crucial step, ensuring comprehensive treatment and addressing the potential for unrecognised malignancy.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).