Clinical insights from the management of a giant immature teratoma in an infant—a case report

Introduction

Teratoma growth syndrome, also known as growing teratoma syndrome (GTS), is a rare clinical manifestation that occurs primarily in patients with nonseminomatous germ cell tumors. This syndrome is characterized by the presence of enlarging residual masses that are histologically proven to be mature teratomas, despite the normalization of serum tumor markers during or after chemotherapy (1-5).

The pathogenesis of GTS remains unclear, but it is believed to result from the selective resistance of teratomas to chemotherapy, leading to their growth while other tumor components regress (3,6). Patients with GTS often present with a variety of symptoms depending on the location of the teratoma, which can include abdominal pain, mass effect, or other complications related to the tumor’s size and location (2,7).

Management of GTS typically involves surgical resection of the teratoma, as complete excision has been shown to improve outcomes significantly. In some cases, patients may require additional chemotherapy following surgery, especially if there are concerns about residual disease. The prognosis for patients with GTS is generally favorable when the teratoma is completely resected, but careful monitoring is essential due to the potential for recurrence (3-5).

A previous study has highlighted the importance of recognizing GTS early to avoid unnecessary chemotherapy and to facilitate optimal surgical intervention (8). The association of GTS with other conditions, such as gliomatosis peritonei (GP), has also been documented, indicating a complex interplay between different tumor types in some patients (2,9).

In conclusion, GTS is a rare but significant clinical entity that requires a multidisciplinary approach for diagnosis and management. Awareness of this syndrome among healthcare providers is crucial for improving patient outcomes and minimizing complications associated with delayed diagnosis and treatment. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-249/rc).

Case presentation

The patient was a male born on May 27, 2019, presented at 4 months of age with a palpable mass in the upper abdomen. An ultrasound examination and CT examination at Qilu Children’s Hospital of Shandong University revealed a large abdominal mass. Serum alpha-fetoprotein (AFP) levels were elevated (26,644 ng/mL), indicating the possible presence of a retroperitoneal teratoma or yolk sac tumor. On September 30, 2019, the patient underwent retroperitoneal tumor resection under general anesthesia. Postoperative pathological analysis confirmed the diagnosis of an immature teratoma (IMT), classified as World Health Organization (WHO) grade III, with the immature tissue primarily consisting of primitive neural elements. The Ki-67 proliferation index was observed in 80–90% of the tissue. Ten days after surgery, the child’s AFP level had decreased to 5,152 ng/mL. A follow-up examination showed no significant residual mass, and the patient did not receive adjuvant radiotherapy or chemotherapy.

During the reexamination on January 12, 2020, ultrasound imaging revealed a large cystic solid mass in the patient’s abdominal cavity, with an AFP level of 2,344 ng/mL, suggesting a recurrence of IMT. Despite two cycles of BEP (bleomycin, etoposide, and cisplatin) regimen, abdominal ultrasonography showed progressive tumor growth, although AFP levels gradually decreased. The chemotherapy regimen was thus changed to TIC (paclitaxel, ifosfamide, and carboplatin), leading to a further reduction in AFP levels to 365 ng/mL; however, the tumor continued to increase in diameter.

For further diagnosis and treatment at our hospital, the child’s family consented to an intensive abdominal CT examination, which revealed a substantial mixed-density lesion in the abdominal cavity, with a maximum cross-section of 25.5 cm by 14.3 cm. The lesion was diagnosed as a teratoma involving the liver, retroperitoneum, and pelvic cavity. Given the limited efficacy of BEP chemotherapy in the early stages, and the presence of mixed cystic density along with rapid tumor growth in pediatric cases, we adjusted the chemotherapy regimen to TCAV (nab-paclitaxel, cyclophosphamide, epirubicin, and vincristine). This regimen was selected for its efficacy not only against IMT components but also in treating sarcoma components. After one cycle of TIC therapy, AFP levels dropped to 195 ng/mL; however, the tumor continued to enlarge, leading to increased intra-abdominal pressure. The patient subsequently developed oliguria and abnormal liver and kidney function. At this stage, we suspected the patient might be experiencing teratoma growth syndrome, necessitating immediate surgical intervention due to the critical condition. Despite significant surgical risks, a comprehensive multi-disciplinary consultation was conducted, involving experts from surgery, ultrasound, anesthesiology, and intensive care medicine. The surgical risks and postoperative rehabilitation prospects were thoroughly assessed. After extensive discussions with the family and obtaining informed consent, a retroperitoneal giant tumor resection combined with lymph node dissection under general anesthesia was performed on April 23, 2020. The surgeon carefully protected the surrounding organs while meticulously excising the tumor tissue, removing the omentum, and dissecting the abdominal pelvic lymph nodes despite extensive peritoneal adhesions.

Following the procedure, the child was transferred to the pediatric intensive care unit (PICU) and received specialized nursing, nutritional support, anti-infection measures, blood transfusions, fluid rehydration, and phlegm reduction treatments. Preoperatively, the child’s weight was 8 kg. The combined weight of the intraoperative decompression fluid and excised tumor totaled 4.2 kg, reducing the child’s body weight by more than half. As a result, the child’s vital signs and organ functions were closely monitored postoperatively, and precise fluid rehydration was administered. No complications were observed (Figures 1,2).

Figure 1 Preoperative images of our patient at presentation and gross tumor appearance following surgery. This image is published with the consent of the patient’s parent.

Figure 2 Comparison of preoperative and postoperative abdominal contrast-enhanced CT. CT, computed tomography.

Postoperative pathology confirmed an IMT, grade I (Figure 3). After postoperative rehabilitation, the patient received an additional four cycles of alternating TCAV and TIC chemotherapy. During this period, the patient’s condition remained stable, and AFP levels returned to the normal range (Figure 4). The treatment regimen was completed on August 14, 2020. Subsequent follow-up examinations over the next 4 years showed no abnormalities in AFP levels or imaging results. Currently, at the age of 6 years, the child’s growth, development, and cognitive abilities are comparable to those of his peers (Figure 5).

Figure 3 Postoperative immunopathological images. (A) and (B) are H&E staining and Ki-67 staining (80–90%) performed following the first surgery, and (C) is the H&E staining conducted after the second surgery (EnVision ×100). H&E, hematoxylin and eosin.

Figure 4 Fluctuation in alpha-fetoprotein level of our patient during treatment.

Figure 5 Recent picture of the patient. This image is published with the consent of the patient’s parent.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from patient’s legal guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

IMT is an exceptionally rare tumor arising from the abnormal development of embryonic cells within the primary germ layer. This neoplasm is characterized by the presence of immature tissues that exhibit varying degrees of differentiation, which may be either partial or complete. Notably, the insidious onset and lack of specific clinical symptoms in the early stages make diagnosis challenging. Typically, affected children present with palpable masses, abdominal pain, and abdominal distension as the primary clinical manifestations. The gonads are the most common sites of tumor occurrence, followed by the retroperitoneal and sacrococcygeal regions. Histopathologically, teratomas are categorized into mature, immature, and malignant types (10). IMTs can be graded based on the differentiation and maturation of nerve-derived tissues (8). There is no consensus on whether children with resected IMTs require chemotherapy. However, surgical removal is generally recommended upon diagnosis. For grade I pathology, complete surgical resection is typically sufficient, whereas treatment for grade III should follow protocols used for malignant teratomas. The need for postoperative chemotherapy in grade II cases generally depends on a thorough evaluation of factors such as AFP levels (11), the completeness of tumor resection, tumor rupture, and other relevant considerations. Consequently, the AFP levels in this infant were elevated both pre- and post-operatively, with pathological analysis revealing a Grade III teratoma. It is imperative that the local hospital provide the infant’s family with appropriate chemotherapy guidance. This oversight in treatment warrants careful consideration and reflection. Moreover, some scholars have emphasized the importance of monitoring the Ki-67 expression rate in tumor tissue for pediatric patients (12).

GTS is characterized by the enlargement of peritoneal implants during or after chemotherapy for malignant germ cell tumors, while histologically presenting as mature teratomas without malignant elements. In cases where serum AFP levels normalize following systemic chemotherapy, but the tumor continues to grow, GTS should be considered (13-15). When mature glial tissue extensively implants on the peritoneum, the condition is referred to as GP. GP is characterized by the presence of mature neural tissues on the surfaces of internal organs or the peritoneal wall. This condition can occur in patients with both mature teratoma and IMT, provided that the implanted elements are mature glial tissues. If any immature components are present in the implants, the diagnosis of GP should be reconsidered, and the possibility of metastasis from an IMT should be evaluated (16). One study also suggests that the relationship between peritoneal gliomatosis, as a distinct manifestation of GTS, and the risk of recurrence warrants further investigation (17).

Conclusions

Therefore, for pediatric patients showing insensitivity to specific chemotherapeutic agents, particularly when AFP levels decrease but tumor volume continues to increase, it is crucial to remain vigilant for the potential occurrence of GTS. Prompt adjustment of the therapeutic strategy or treatment sequence is essential to improve the chances of achieving a cure. Herein, the patient’s AFP levels remain elevated beyond the normal range, suggesting that, in addition to the mature teratoma component, the tumor may also contain elements of IMT or other malignant germ cell components. At this point, it is difficult to definitively diagnose the condition as GTS, IMT recurrence, or GP. Determining the optimal timing for surgical intervention is crucial, while remaining alert to the possibility of cisplatin resistance in germinoma. Furthermore, promptly adjusting the medication regimen to address the risk of peritoneal gliomatosis or malignant transformation of the germinoma is essential to ensure the patient receives the most effective treatment.

The child’s family members expressed high levels of satisfaction with our treatment and demonstrated active cooperation both pre- and post-operatively. They expressed profound regret for not having pursued chemotherapy following the initial surgical procedure. His mother said, “Thank you for giving the child a second life.”

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-249/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-249/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-249/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from patient’s legal guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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