Growing teratoma syndrome

Overview

Growing teratoma syndrome (GTS) is a rare clinical condition that occurs in patients treated for non-seminomatous germ cell tumors (NSGCTs), most often testicular or ovarian cancers. GTS is characterized by the paradoxical growth of metastatic masses during or after chemotherapy, despite normalization of tumor markers. The enlarging masses consist of mature teratoma tissue, which is benign but can grow aggressively and compress surrounding organs. GTS is most commonly seen in young adults and requires surgical intervention due to its resistance to chemotherapy and radiation.

Causes

The exact mechanism behind growing teratoma syndrome is not fully understood, but there are two main hypotheses:

• Chemotherapy-induced maturation: Chemotherapy may eliminate malignant germ cell components, allowing the benign mature teratoma cells to proliferate unchecked.

• Selective survival of mature elements: Chemotherapy may be ineffective against mature teratomatous elements from the beginning, which then continue to grow while malignant cells are destroyed.

GTS occurs in the setting of previously diagnosed NSGCTs, typically following partial treatment response where tumor markers such as AFP (alpha-fetoprotein) and hCG (human chorionic gonadotropin) return to normal, yet masses continue to enlarge.

Symptoms

Symptoms of growing teratoma syndrome are related to the enlarging tumor masses and depend on their location. Common symptoms include:

• Abdominal or pelvic pain or fullness

• Palpable mass

• Obstruction: Gastrointestinal or urinary symptoms if masses compress organs

• Respiratory symptoms: If thoracic metastases grow and press on lungs or airways

• Weight loss or fatigue (in rare cases due to mass effect or nutritional compromise)

Many patients may be asymptomatic and only detected during routine imaging follow-up.

Diagnosis

Diagnosing GTS involves a combination of clinical history, tumor markers, and imaging studies:

• Patient history: Prior treatment for NSGCTs, especially with normalizing tumor markers

• Serum tumor markers: AFP and hCG levels are normal or decreasing, distinguishing GTS from recurrence of malignant disease

• Imaging studies: CT or MRI shows growing masses despite appropriate chemotherapy

• Histological confirmation: Surgical biopsy or resection reveals mature teratoma tissue without malignant components

GTS must be differentiated from malignant recurrence, which would typically show elevated tumor markers and histologically malignant tissue.

Treatment

The mainstay of treatment for growing teratoma syndrome is complete surgical excision of all tumor masses. Key treatment principles include:

• Radical surgery: Complete resection of the mature teratoma is essential to prevent local complications and recurrence

• Multidisciplinary surgical teams: May be required due to mass size or involvement of multiple anatomical structures

• Surveillance post-surgery: Regular imaging to monitor for regrowth or new lesions

Neither chemotherapy nor radiation therapy is effective for GTS, making surgery the only curative option.

Prognosis

The prognosis for growing teratoma syndrome is generally favorable when complete surgical resection is achieved. Most patients have excellent long-term outcomes and survival rates. However, recurrence can occur if resection is incomplete, and large or unresectable tumors may cause significant morbidity due to compression of surrounding organs. Regular follow-up is essential to detect any recurrence early. In rare cases, malignant transformation of the mature teratoma tissue has been reported, further emphasizing the importance of timely and complete surgical management.