Primary gastric mixed germ cell tumor in an infant: the pivotal role of dynamic alpha-fetoprotein surveillance in unmasking occult malignancy

Abstract

This paper reports a case of an extremely rare primary mixed germ cell tumor (MGCT) of the stomach in an infant. The patient, an 8-month-old male infant, presented with “black stool for three days.” Abdominal computed tomography (CT) suggested an abdominal space-occupying lesion, and gastroscopy revealed a huge cauliflower-like protrusion on the lesser curvature of the gastric body. The patient first underwent exploratory laparotomy for biopsy and adhesiolysis, followed by open resection of the abdominal mass with gastric wall repair, pyloroplasty, and abdominal drainage. Postoperative pathology suggested an immature teratoma (Grade I). After the initial surgery, although the pathological diagnosis was immature teratoma, serial AFP monitoring revealed persistently elevated levels that further increased significantly (from 465.8 ng/mL to over 1000 ng/mL within one week). Concurrent follow-up CT suggested a space-occupying lesion in the original tumor bed. The second laparotomy was performed for residual lesion in the original tumor bed combined with adhesiolysis and abdominal drainage, with the intent of achieving radical resection. Pathology confirmed MGCT (95% immature teratoma and 5% yolk sac tumor). The patient then received four cycles of alternating Vincristine + Cyclophosphamide + Cisplatin/Isocyclophosphamide + Etoposide + Vincristine (VCP/IEV) chemotherapy, after which AFP normalized. As of the last follow-up (August 2025), the patient has been disease-free for over 48 months and is in good general condition.

Introduction

Germ cell tumors (GCTs) typically arise in the gonads, primarily in the testes of males and the ovaries of females, and rarely occur outside the gonads, such as in the head, mediastinum, and abdomen [1]. Mixed germ cell tumors (MGCTs) are malignant tumors composed of at least two different GCT components. In this case, the tumor consisted of immature teratoma and yolk sac tumor components. Most teratomas are cystic tumors containing mature tissues derived from ectoderm (such as skin, hair follicles, and sebaceous glands), mesoderm (such as muscle and cartilage), and endoderm (such as pulmonary and gastrointestinal tissues). Teratomas most commonly occur in extragonadal regions (such as sacrococcygeal, mediastinal, retroperitoneal, cervical, and intracranial sites) during infancy and early childhood, whereas gonadal locations become more prevalent after childhood. Mature teratomas are also referred to as dermoid cysts, and the cystic contents typically consist of keratin, sebaceous material, and fat. Immature teratomas, also known as malignant teratomas, teratoblastomas, or embryonal teratomas, may be accompanied by somatic differentiation manifesting as sarcoma, carcinoma, or extensive immature neuroectodermal elements [2–4]. Once discovered, such tumors require immediate intervention [5, 6]. This paper reports in detail the diagnosis and treatment process of a case of primary MGCT of the stomach in an infant and reviews the relevant literature, aiming to improve the awareness of clinicians about this rare disease.

Case report

The patient was admitted to the hospital in January 2021 with a 3-day history of black stool. Abdominal computed tomography (CT) showed a large heterogeneous mass shadow in the hepatogastric space of the upper abdomen, with uneven density, multiple scattered high-density spots and patchy low-density areas within it, clear boundaries, a lesion size of approximately 60 mm × 42 mm × 49 mm, a plain CT value of about 23 HU, and the solid part showed progressive heterogeneous enhancement. The CT value in the arterial phase was approximately 43 HU, and in the venous phase, it was about 66 HU. The low-density areas did not show significant enhancement. The pancreas, liver, stomach, and surrounding intestines were compressed. The enhanced scan showed that the lesser-curvature side of the stomach wall appeared to be discontinuous locally, and the mass seemed to protrude into the gastric cavity. The liver had a normal shape and size. A round, significantly enhanced focus was visible in the right posterior lobe of the liver during the arterial phase, with a diameter of about 9 mm, and it appeared isodense in the venous phase, suggesting a possible hemangioma (Fig. 1). Gastroscopy revealed a large amount of old blood in the gastric cavity and a huge cauliflower-like protrusion lesion on the lesser curvature of the gastric body, with surface erosion and ulceration. The pylorus was not involved (Fig. 2). Although gastroscopy visualized the lesion, endoscopic biopsy was not attempted due to the high risk of bleeding from the friable, ulcerated surface and the concern that superficial sampling might miss the deeper malignant components suggested by imaging. Tumor marker tests showed an alpha-fetoprotein (AFP) level of 77.5 ng/mL. On January 26, 2021, the patient underwent laparotomy for biopsy of the abdominal lesion and adhesiolysis of the intestines. The initial pathological diagnosis was teratoma. On February 2, 2021, the patient underwent resection of the abdominal mass, gastric repair, pyloroplasty, and abdominal drainage. Postoperative pathology confirmed the diagnosis of immature cystic and solid teratoma (Grade I) (Fig. 3). Immunohistochemical staining at this time showed negativity for yolk sac tumor markers, including Glypican-3 (-) and SALL-4 (-), supporting a diagnosis of pure immature teratoma.

Fig. 1.

A and B, Coronal arterial and venous phase images, respectively. The green arrows indicate a large, heterogeneous mass shadow in the upper abdomen between the liver and stomach. The mass exhibits uneven density, with multiple scattered hyperdense spots and patchy areas of hypodensity, suggesting calcification and fatty tissue. The border is relatively well-defined. The red arrow points to a roundish enhancing focus that appears isodense in the venous phase. C and D, Axial arterial and venous phase images, respectively. The green arrows indicate a large space-occupying lesion in the abdominal cavity. E and F, Sagittal arterial and venous phase images, respectively. The green arrows indicate a large space-occupying lesion in the abdominal cavity

Fig. 2.

An arrow indicates a huge cauliflower-like protrusion on the lesser curvature of the gastric body, with surface erosion, ulceration, and old blood, and no signs of pyloric involvement

Fig. 3.

Histological examination revealed fibrous connective tissue, intestinal-type glands, focal cartilage, and cavities lined by either stratified squamous or columnar epithelium. Teratomatous neural elements show immature neuroectodermal components. Immunohistochemically, the lesion exhibited the following profile: CK highlighted the epithelial component; Vimentin labeled the stromal cells; NSE and GFAP were positive in the neuroglial areas; Desmin stained smooth muscle. The tumor was negative for Glypican-3, SALL-4, Myo-D1, and Myogenin. The Ki-67 proliferation index was approximately 20% in the most cellular areas

During postoperative outpatient follow-up, the patient’s AFP level continued to rise significantly (2021-03-22: 465.8 ng/mL; 2021-03-29: 1035.0 ng/mL). Contrast-enhanced CT of the whole abdomen showed a slightly low-density mass in the hepatogastric space of the upper abdomen, protruding into the gastric cavity, with clear boundaries, irregular shape, a lesion size of about 21.7 mm × 33.2 mm × 19.5 mm, had relatively uniform density and a plain CT value of about 24 HU, and the solid part showed progressive heterogeneous enhancement. The CT value in the arterial phase was about 60 HU, and in the venous phase, it was about 79 HU. Blood vessels were visible at the edge of the mass. The contrast-enhanced scan showed that the lesser-curvature side of the gastric wall was locally discontinuous, and the mass protruded into the gastric cavity. The liver had a normal shape and size. A round, significantly enhancing focus was visible in the right posterior lobe of the liver during the arterial phase, with a diameter of about 9 mm, and it appeared isodense in the venous phase (similar to the previous findings). The thorax was symmetrical, with symmetric lung field transparency and increased lung markings. A small nodular shadow was seen at the level of the right middle lobe fissure, with a diameter of about 4 mm (similar to the previous findings) (Fig. 4).

Fig. 4.

An arrow indicates a slightly low-density mass shadow in the hepatogastric space of the upper abdomen, protruding into the gastric cavity, with clear boundaries, irregular shape, a lesion size of approximately 21.7 mm × 33.2 mm × 19.5 mm, relatively uniform density, and the solid part shows progressive heterogeneous enhancement. A: Venous phase axial view B: Venous phase coronal view C: Arterial phase axial view D: Arterial phase coronal view

On April 6, 2021, the patient underwent a second surgery (resection of the hepatogastric mass + abdominal drainage + intestinal adhesiolysis, etc.). The postoperative pathological diagnosis was: MGCT (95% immature cystic and solid teratoma, 5% yolk sac tumor) (ICD-O code 9085/3) (Fig. 5). In contrast to the initial pathology, immunohistochemistry on the second specimen now revealed positivity for yolk sac tumor markers, including SALL4 (partial +), OCT-4 (focal +), and Glypican-3 (focal +), confirming the presence of a yolk sac tumor component that was not identified in the first resection. The postoperative stage was II, and the patient was classified into the intermediate-risk group. From April 20, 2021, to August 5, 2021, the patient completed four cycles of alternating VCP/IEV chemotherapy according to the extracranial malignant GCT protocol. After the completion of chemotherapy, the patient was regularly followed up. As of August 2025, the patient remained in good general condition, with no tumor recurrence detected by imaging examinations, and the AFP level remained within the normal range.

Fig. 5.

The tumor tissue contains numerous cystic cavities lined with intestinal-like epithelium, columnar epithelium, and cuboidal epithelium. The surrounding stroma is loose and reticular or rich in spindle cells with hemorrhage. Immature neural components are seen in some areas, including primitive neural tubes (>2 low-power fields, Red boxes indicate the areas shown in Fig. 5A and B) and small foci of yolk sac tumor components(green box indicates the area shown in Fig. 5B.)The tumor tissue involves the perigastric omentum and the entire gastric wall, with ulceration of the luminal surface. The tumor is closely adjacent to the resection margin. Tumor emboli are seen in the blood vessels (Fig. 5C). Immunohistochemical results: In slide No. 6, GFAP (-), CK (epithelial +), EMA (epithelial +), LCA (-), SALL4 (partially +), AFP (-), Ki-67 (about 60% + in dense areas), NSE (neural tissue +), CD56 (neural tissue), OCT-4 (focal +), Glypican-3 (focal +). In slide No. 8, GFAP (-), EMA (epithelial +), Ki-67 (about 60% + in dense areas), NSE (neural tissue +), CD56 (neural tissue +)

Furthermore, regarding the entire clinical course, we have integrated the Clinical Management Pathway (Fig. 7) and the AFP Time-Series Trend Graph (Fig. 6) to reconstruct the management logic and biological behavior of this case from multiple dimensions. Figure 7 outlines the key phases along a timeline, from initial diagnosis and recurrence exploration to secondary surgery confirming MGCT, followed by standardized chemotherapy and long-term surveillance. Embedded within this pathway as its core driving signal is the dynamic change in serum AFP, visually illustrated in Fig. 6. Specifically, the continuously rising trend of AFP demonstrated in Fig. 6 following the first surgery—with values increasing sharply from 77.5 ng/mL preoperatively to 465.8 ng/mL at first follow-up and further to 1035 ng/mL within one week—served as the direct laboratory evidence triggering the critical decision for a second tumor resection. The subsequent sustained normalization of AFP post-intervention, also shown in Fig. 6, confirmed therapeutic efficacy and long-term disease remission. Ultimately, together they reveal a complete evidence chain: the aberrant trend captured through serial AFP monitoring (Fig. 6) guided critical clinical interventions (Fig. 7), and the favorable post-treatment AFP trajectory validated the success of this approach. This systematically demonstrates that, in managing pediatric malignant germ cell tumors, the close integration of dynamic biomarker monitoring (AFP) with a structured clinical pathway (treatment stages) is indispensable for early warning, precise intervention, and successful follow-up.

Fig. 7.

The Complete Clinical Management Pathway of Gastric MGCT: From Initial Diagnosis Through regrowth of residual disease, Definitive Diagnosis, Treatment, and Postoperative Follow-up

Fig. 6.

Dynamic changes in serum AFP levels during treatment and follow-up

Serum AFP levels (ng/mL) are shown over time on a linear y-axis. The red and orange dashed lines mark the dates of the first and second surgeries, respectively, and the gray shaded area indicates the chemotherapy course. AFP rose to > 1000 ng/mL before re-operation, decreased substantially after the second surgery, and normalized during chemotherapy.

Discussion

GCTs, originating from primordial germ cells, are highly heterogeneous tumors that occur predominantly in the gonads [7]. However, in this case, the tumor originated in the gastric body, which is extremely rare site. The presenting symptoms of gastric teratomas are generally related to the tumor’s size, location, ulceration, and bleeding. Common clinical manifestations therefore include an abdominal mass, abdominal distension, vomiting, hematemesis (frequently associated with the endogastric variety), and respiratory distress (often seen in the exogastric variety). Gastric teratomas most commonly originate from the greater curvature and posterior wall of the stomach, while the lesser curvature is a less frequent site [8, 9].

In terms of pathogenesis, the occurrence of GCTs at the rare site of the stomach can be reasonably explained by the “abnormal migration of primordial germ cells” theory. During early embryonic development, primordial germ cells migrate from the yolk sac to the hindgut and ultimately colonize the genital ridge [10]. Any disruption of the c-KIT signaling pathway or the SDF-1/CXCR4 chemotactic axis may cause primordial germ cells (PGCs) to abnormally linger along the midline migration path [11, 12]. If these germ cells that linger in the gastric wall subsequently experience abnormal activation of the MAPK pathway or epigenetic dysregulation, they can escape apoptosis and may proliferate and differentiate into MGCTs with various components [11]. The presentation of this gastric MGCT in an infant, occurring along the midline migration path of primordial germ cells, provides anatomical and clinical consistency with this embryological theory of origin.

Extragonadal germ cell tumors (EGCTs) usually lack specific clinical manifestations, which mainly depend on the location of the tumor and its invasion of adjacent organs. Mediastinal EGCTs often present with symptoms such as dyspnea, cough, or superior vena cava syndrome due to compression of the trachea and large blood vessels by the tumor [13]. Intracranial EGCTs are mostly located in the pineal region and the sellar region, which can cause symptoms of increased intracranial pressure or neuroendocrine dysfunction [14]. Retroperitoneal EGCTs, due to their concealed location, are usually detected when the tumor has grown large. Most cases present with abdominal masses or bloating at the initial diagnosis, and may be accompanied by abdominal pain, back discomfort, or compressive symptoms [15]. In this case, the patient with primary MGCT of the stomach presented with “black stool” and upper gastrointestinal bleeding as the initial symptoms. Endoscopy revealed a huge cauliflower-like protrusion on the lesser curvature of the gastric body, which is consistent with the clinical features reported in previous cases of primary yolk sac tumors of the stomach [16]. Throughout the diagnostic and treatment period, a liver hemangioma was identified but caused no symptoms. It subsequently resolved on its own by the final imaging study, confirming it had no clinical bearing on the patient’s condition.

The diagnosis process of this case highlights the complexity of the pathological composition of GCTs and the challenges they pose to diagnosis. The WHO classification divides GCTs into seminomas and non-seminomas, the latter of which includes teratomas, yolk sac tumors, embryonal carcinoma, and other components [7]. The pathological diagnosis of grade I immature teratoma and the subsequent diagnosis of MGCT with a minor yolk sac tumor component raise the question of sampling limitation versus biological evolution versus a metachronous lesion. In our view, the most plausible explanation is that an occult AFP-producing yolk sac component was already present at the time of the first surgery but was under-sampled, and that microscopic residual disease was responsible for this early progression. This interpretation is supported by the lack of postoperative AFP decline and the rapid AFP rise, together with the very small yolk sac fraction (~ 5%) identified at the second resection, which is inherently vulnerable to sampling error. While biological evolution or a metachronous tumor cannot be completely excluded, the short interval and the biochemical behavior favor early progression of residual disease. A limitation is the lack of molecular clonality testing between the two resections; in future cases, paired specimens could be compared using microdissection-based STR profiling or targeted NGS to better clarify clonal relatedness.

More extensive sampling would have been ideal given the AFP level. However, this case emphasizes that in pediatric mixed germ cell tumors, serum AFP is a more sensitive marker for occult yolk sac tumor than routine histopathological sampling, approximately 90% of patients with yolk sac tumors exhibit significantly elevated AFP levels [17].A significant AFP elevation should be considered definitive evidence of a secreting component, mandating adjuvant therapy, even if only focal elements are identified on pathology(for example, Glypican-3 +). Dynamic monitoring of AFP is a key tool to compensate for sampling errors in pathology and to warn of potential malignant components [18]. It should be noted that, in addition to AFP, serum beta-human chorionic gonadotropin(β-HCG)and lactate dehydrogenase(LDH) are also effective serological markers for monitoring tumor ([19, 20]. Therefore, in the future management of similar cases, it is recommended to combine these three markers in surveillance to comprehensively exclude all potential secreting components and optimize post-treatment surveillance.

In terms of treatment, notably the marked postoperative elevation in AFP and the early progression of residual disease, underscored critical lessons regarding tumor biology and clinical management. Specifically, it highlights that elevated or rising AFP should prompt extensive pathological sampling of the specimen and, in cases of incomplete margins, warrants consideration of additional excision. Complete surgical resection is the cornerstone for curing localized GCTs [21]. However, for tumors containing malignant components such as yolk sac tumor, even with gross total resection, the presence of minimal residual disease carries the risk of early progression, necessitating adjuvant systemic chemotherapy [22]. After resection of the progressive residual lesion, the patient received alternating Adriamycin + Vincristine + Cyclophosphamide + Cisplatin/Isocyclophosphamide + Etoposide + Vincristine (AVCP/IEV) chemotherapy according to the intermediate-risk treatment protocol for pediatric malignant GCT. This regimen is an optimized choice for infants and young children based on cisplatin-containing standard chemotherapy, aiming to reduce the risk of long-term side effects such as bleomycin-related pulmonary toxicity while ensuring core efficacy [22, 23]. The patient responded well to this regimen, with AFP levels rapidly returning to normal and maintaining long-term disease-free survival, fully demonstrating the correctness of this treatment strategy.

A review of the literature shows that the prognosis of extragonadal GCTs in children is closely related to clinical stage, histological components, and the rate of decline of AFP after treatment [24]. Although mixed tumors containing yolk sac tumor components usually indicate higher aggressiveness, many children can still achieve long-term survival through thorough radical surgery and standardized cisplatin-based chemotherapy. With over 48 months of disease-free survival, this case demonstrates a favorable long-term prognosis, further emphasized AFP served both as an early warning marker and as a key indicator guiding escalation to malignant GCT-directed systemic treatment. It is important to note, however, that although the majority of recurrences are observed within the initial 7 months, the potential for late recurrence extends to at least 3 years, which defines the necessary window for rigorous postoperative surveillance.

Conclusion

The present case of a primary gastric MGCT in an infant delineates key tenets in management: the superiority of serial AFP monitoring over static histology in signaling occult malignant components and early progression of residual disease; the necessity of combining radical surgery with cisplatin-based chemotherapy for curative intent; and the imperative of long-term, imaging- and biomarker-based surveillance given the tumor’s aggressiveness. These observations consolidate the paradigm that an effective strategy for pediatric extragonadal GCTs must integrate dynamic biomarker assessment, multidisciplinary treatment, and committed long-term follow-up into a unified framework.

Abbreviations

MGCT

Mixed germ cell tumor

CT

Computed tomography

AFP

Alpha-fetoprotein

VCP

Vincristine + Cyclophosphamide + Cisplatin

IEV

Isocyclophosphamide + Etoposide + Vincristine

Authors’ contributions

Qiyang Shen, Shiyuan Wang, and Chenyang Wang contributed equally to this work and share first authorship. Qiyang Shen, Shiyuan Wang, and Chenyang Wang contributed to the conception, data collection, and drafting of the manuscript. Haiyan Wu and Chunlei Zhou contributed to the pathological analysis and interpretation of the data. Tao Li and Xingyu Liu contributed to the clinical management and follow-up of the patient. Jianfeng Zhou and Hanjun Yin contributed to the study design, supervision, and critical revision of the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by Suqian Sci&Tech Program, Grant No. K202407.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Ethical Approval: This study was reviewed and approved by the Institutional Review Board (IRB) of Children’s Hospital of Nanjing Medical University, under approval number 202402005-1. Informed consent was obtained from all parents or legal guardians of the children participating in this study. This study was conducted in accordance with the Declaration of Helsinki.

Consent for publication

Written informed consent was obtained from the parents/legal guardians of the pediatric patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare no competing interests.