Successful seven-year management of recurrent adult pancreatoblastoma with liver metastasis: A case report

Abstract

BACKGROUND

Pancreatoblastoma is a rare malignant epithelial tumor of the pancreas, predominantly affecting children. However, the prognosis is significantly poorer in adults, who typically present with liver metastasis. The management of adult pancreatoblastoma with liver metastases poses a significant challenge, and the median survival remains poor.

CASE SUMMARY

A 49-year-old male was incidentally found to have a pancreatic body/tail mass and liver metastasis during routine health screening. He underwent distal pancreatectomy, splenectomy, and hepatectomy, with pathology confirming pancreatoblastoma. Over a 7-year follow-up, the patient experienced multiple liver recurrences, managed with repeated resections, systemic chemotherapy, targeted therapy with surufatinib, transarterial chemoembolization, and internal radiation therapy following detection of fibroblast growth factor receptor 1-synaptonemal complex protein 1 gene rearrangement. Serial ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography imaging played a crucial role in detecting recurrence and monitoring treatment response. The patient survived 87 months from initial diagnosis, significantly exceeding the reported median survival.

CONCLUSION

This case outlines the positron emission tomography/computed tomography presentation of and therapeutic strategies for pancreatoblastoma with liver metastases.

Key Words: Pancreatoblastoma; Liver metastasis; Positron emission tomography/computed tomography; Fibroblast growth factor receptor 1; Case report

Core Tip: We report the 7-year follow-up of an adult pancreatoblastoma patient with liver metastases, emphasizing the importance of multimodal management, including repeated surgeries and targeted therapy. The case highlights the diagnostic utility of positron emission tomography/computed tomography and identifies a novel fibroblast growth factor receptor 1-synaptonemal complex protein 1 gene rearrangement, suggesting a potential target for future therapeutic strategies.

INTRODUCTION

Pancreatoblastoma is a rare malignant tumor of the pancreas with an estimated annual incidence of 0.004 per 100000 individuals. Pancreatoblastoma may be associated with genetic syndromes such as Beckwith-Wiedemann syndrome or familial adenomatous polyposis[1-3]. Although it predominantly occurs in pediatric patients[4], approximately one-third of reported cases involve adults[5,6]. Adult patients exhibit a poor prognosis, with a median survival of only 17 months post-diagnosis[7]. Approximately 17%-35% of patients present with metastases at diagnosis, most commonly involving the liver[3,8]. The symptoms of pancreatoblastoma are nonspecific, including abdominal pain, abdominal mass, diarrhea, and nausea[4,9]. Some laboratory values may increase, including alpha-fetoprotein, α1-antitrypsin, and lactate dehydrogenase, which are important auxiliary diagnostic clues[9]. However, not all cases show an increase in these values[4]. Clinically, pancreatoblastoma is diagnosed through a combination of patient symptoms, physical signs, laboratory tests, and imaging examinations. Nevertheless, histopathological examination remains the gold standard for diagnosing pancreatoblastoma, characterized by features of epithelial differentiation (acinar, glandular, and trabecular architectures) and the presence of squamous corpuscles[10]. Current treatment options include surgical resection, chemotherapy, radiotherapy, transarterial chemoembolization, and multimodal therapy for patients with liver metastases[11]. However, due to the limited number of reported cases, the optimal treatment for adult pancreatoblastoma remains undefined, resulting in a poor prognosis with a mortality rate exceeding 40%, compounded by key prognostic factors such as metastasis and incomplete surgical resection[6,12]. Owing to long-term close follow-up and a personalized multimodal treatment approach, the patient has achieved an overall survival of 87 months, substantially exceeding the median survival documented in prior literature. This case report aims to detail the long-term follow-up of an adult with pancreatoblastoma and liver metastases to demonstrate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET)/computed tomography (CT) in disease detection and monitoring. Herein, we describe a 49-year-old male with metastatic pancreatoblastoma who achieved 87-month overall survival through repeated surgeries, chemotherapy, and targeted therapy, providing insights into the disease’s management and genetic landscape.

CASE PRESENTATION

Chief complaints

A 49-year-old male was admitted following incidental detection of pancreatic body/tail and liver masses 7 years ago.

History of present illness

The patient was incidentally found to have a pancreatic mass during routine health screening and was asymptomatic, with no reports of abdominal pain, nausea, vomiting, or jaundice. Magnetic resonance imaging (MRI) demonstrated a mass in the pancreatic body and tail, and a metastatic liver mass in the left lobe.

Physical examination upon admission

Physical examination revealed no abnormalities.

Laboratory examinations

Tumor markers and liver function parameters were within normal ranges, as follows: (1) Carcinoembryonic antigen: 0.86 ng/mL (0.00-5.00 ng/mL); (2) Alpha-fetoprotein: 1.91 ng/mL (0.00-9.00 ng/mL); (3) Carbohydrate antigen 125: 7.85 U/mL (0.00-35.00 U/mL); (4) Carbohydrate antigen 199: 7.82 U/mL (0.00-27.00 U/mL); (5) Total bilirubin: 17.5 μmol/L (7.0-19.0 μmol/L); (6) Albumin: 42.5 g/L (40.0-55.0 g/L); (7) Aspartate aminotransferase: 17 U/L (15-40 U/L); and (8) Alanine aminotransferase: 14 U/L (9-50 U/L).

Imaging examinations

Preoperative ¹⁸F-FDG PET/CT maximum intensity projection images revealed intense uptake of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in the pancreatic body and tail (Figure 1A) and liver segment 4 (Figure 1B). The positron emission tomography (PET), CT, and fused PET/CT images showed a contrast-enhanced round mass of 4.4 cm × 3.4 cm in the pancreatic body and tail, encircling the splenic artery and vein (Figure 1C-E). Additionally, the PET, CT, and fused PET/CT images revealed a liver metastasis of 4.7 cm × 4.2 cm in segment 4 (Figure 1F-H).

Figure 1 Preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography imaging characteristics of the patient. A: Preoperative ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (CT) maximum intensity projection images revealed intense uptake of ¹⁸F-FDG in the pancreatic body and tail (standardized uptake value maximum of 4.7); B: Preoperative ¹⁸F-FDG positron emission tomography/CT maximum intensity projection images revealed intense uptake of ¹⁸F-FDG in liver segment 4 (S4) (standardized uptake value maximum of 7.3); C: Positron emission tomography (PET) image showed a contrast-enhanced round mass of 4.4 cm × 3.4 cm in the pancreatic body and tail, encircling the splenic artery and vein; D: CT image showed a contrast-enhanced round mass of 4.4 cm × 3.4 cm in the pancreatic body and tail, encircling the splenic artery and vein; E: Fused PET/CT image showed a contrast-enhanced round mass of 4.4 cm × 3.4 cm in the pancreatic body and tail, encircling the splenic artery and vein; F: PET image revealed a liver metastasis of 4.7 cm × 4.2 cm in S4; G: CT image revealed a liver metastasis of 4.7 cm × 4.2 cm in S4; H: Fused PET/CT image revealed a liver metastasis of 4.7 cm × 4.2 cm in S4.

FINAL DIAGNOSIS

The initial diagnosis was pancreatic cancer with liver metastasis. Postoperative pathology (Figure 2A and B) initially indicated a highly proliferative neuroendocrine tumor of the pancreas with liver metastasis. Intriguingly, immunohistochemistry confirmed the diagnosis as pancreatoblastoma with liver metastasis. Immunophenotype and special staining results were as follows: (1) Liver tumor: Trypsin, partially positive (++); chymotrypsin, partially positive (++); synaptophysin, mostly positive (+++); Ki67, approximately 30% positive; CD56, a small subset of cells were positive (++); CK7, only a minority of cells were positive (+); β-catenin, nuclear positivity; and (2) Pancreatic tumor: Trypsin, partially positive (++); chymotrypsin, partially positive (++).

Figure 2 Postoperative pathology revealing atypia, moderately abundant pale cytoplasm, prominent nucleoli, and identifiable mitotic figures with trabecular cords or forming pseudo-glandular structures in tumor cells. A: Postoperative pathology for the first surgery, low-power field; B: Postoperative pathology for the first surgery, high-power field; C: Postoperative pathology for the second surgery, low-power field; D: Postoperative pathology for the second surgery, high-power field; E: Postoperative pathology for the third surgery, low-power field; F: Postoperative pathology for the third surgery, high-power field.

TREATMENT

The patient underwent distal pancreatectomy, splenectomy, cholecystectomy, and hepatectomy. Given the propensity for recurrence, the patient received four cycles of chemotherapy (S-1 + oxaliplatin), initiated 2 months postoperatively.

OUTCOME AND FOLLOW-UP

During follow-up, the patient experienced multiple recurrences and remains under active surveillance. Ten months postoperatively, abdominal MRI revealed suspected tumor recurrence in liver segment 2/3, segment 5, and segment 8, with diameters of 4.3 cm, 1.2 cm, and 1.2 cm, respectively (Figure 3). Consequently, the patient underwent segment 2 hepatectomy and local resection for segment 5 and segment 8 tumors, which were pathologically confirmed as liver metastases from pancreatoblastoma (Figure 2C and D). Considering the rapid recurrence, the multidisciplinary team recommended four cycles of albumin-bound paclitaxel and gemcitabine, administered every 3 weeks. However, a second tumor recurrence was detected 73 months after the operation. Abdominal CT revealed a 6.9 cm × 7.2 cm liver mass in segment 7/8 (S7/8). Subsequent ¹⁸F-FDG PET/CT for staging showed uptake of ¹⁸F-FDG with standardized uptake value maximum of 8.4 in the liver, with no discernible avid lesions elsewhere (Figure 4A). The PET, CT, and fused PET/CT images confirmed a 6.9 cm × 7.8 cm round mass in liver S7/8, suspected to be liver metastasis (Figure 4B-D). Contrast-enhanced ultrasound of the liver revealed a slightly hyperechoic mass in the right lobe, demonstrating heterogeneous hyperenhancement in the arterial phase with washout commencing in the portal phase, progressing to mild washout in the delayed phase and marked washout in the Kupffer phase (Figure 5). Local tumor resection confirmed liver metastasis from pancreatoblastoma with microvascular invasion (Figure 2E and F). Next-generation sequencing of the recurrent liver metastatic lesion revealed FGFR1 and SYCP1 gene rearrangement (80%). The patient then received surufatinib, a tyrosine kinase inhibitor targeting VEGFR1-3 and FGFR1. At 87 months after the initial operation, routine abdominal CT revealed two liver masses in S7/8, measuring 1.8 cm × 1.4 cm and 1.9 cm × 1.4 cm, suggesting a third recurrence. The maximum intensity projection (Figure 6A-C) showed uptake of ¹⁸F-FDG in the liver, rib, and ilium. Fused PET/CT (Figure 6D-F) images demonstrated multiple hepatic metastases and metastases in the right ninth rib, both lungs, and the right ilium. After deliberation by the multidisciplinary team, hepatic and bone metastases were treated by transarterial chemoembolization and internal radiation therapy, respectively. The patient is currently undergoing regular hospitalizations for internal radiation therapy. The treatment flowchart for the whole follow-up period is presented in Figure 7.

Figure 3 Abdominal magnetic resonance imaging findings at 10 months postoperatively. A: Abdominal magnetic resonance imaging (MRI) revealed suspected tumor recurrence in liver segment 2/3 (S2/3) and segment 5 (S5), with diameters of 4.3 and 1.2 cm on coronal images, respectively; B: Abdominal MRI revealed suspected tumor recurrence in liver S5 with a diameter of 1.2 cm; C: Abdominal MRI revealed suspected tumor recurrence in liver S2/3 and S5, with diameters of 4.3 and 1.2 cm on axial images, respectively; D: Abdominal MRI revealed suspected tumor recurrence in liver segment 8, with a diameter of 1.2 cm; E: Abdominal MRI revealed suspected tumor recurrence in liver S2/3, with a diameter of 4.3 cm; F: Abdominal MRI revealed suspected tumor recurrence in liver segment 8, with a diameter of 1.2 cm. The orange arrows point to the liver lesions.

Figure 4 The ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography imaging characteristics of the patient at 73 months postoperatively. A: ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) for staging showed uptake of ¹⁸F-fluorodeoxyglucose, with standardized uptake value maximum of 8.4 in the liver and no discernible avid lesions elsewhere; B: Positron emission tomography image confirmed a 6.9 cm × 7.8 cm round mass in liver segment 7/8 (S7/8); C: CT image confirmed a 6.9 cm × 7.8 cm round mass in liver S7/8; D: Fused positron emission tomography/CT image confirmed a 6.9 cm × 7.8 cm round mass in liver S7/8.

Figure 5 Contrast-enhanced ultrasound of the second liver recurrence. A: Slightly hyperechoic mass in the right hepatic lobe demonstrated heterogeneous hyperenhancement in the arterial phase; B: Washout began in the portal phase.

Figure 6 The ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography imaging characteristics of the patient at 87 months after operation. A: Maximum intensity projection (MIP) showed uptake of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in the liver; B: MIP showed uptake of ¹⁸F-FDG in the rib; C: MIP showed uptake of ¹⁸F-FDG in the ilium; D: Fused positron emission tomography (PET)/computed tomography (CT) image demonstrated hepatic metastasis; E: Fused PET/CT image demonstrated metastasis in the right ilium; F: Fused PET/CT image demonstrated metastasis in the right ninth rib.

Figure 7 Treatment flowchart for the whole follow-up period. CT: Computed tomography; FGFR1-SYCP1: Fibroblast growth factor receptor 1-synaptonemal complex protein 1; MRI: Magnetic resonance imaging; NGS: Next-generation sequencing; PET: Positron emission tomography; SOX: S-1 and oxaliplatin; S2: Segment 2; S4: Segment 4; S5: Segment 5; S7/8: Segment 7/8; S8: Segment 8; TACE: Transarterial chemoembolization.

DISCUSSION

Pancreatoblastoma, though more common in children, carries a particularly poor prognosis in adults, with 45% succumbing to the disease due to its high metastatic potential[5,13]. Notably, the patient in this case has survived 87 months since diagnosis, significantly exceeding the reported mean survival of 17 months[7]. This prolonged survival may be attributed to early detection through ¹⁸F-FDG PET/CT, and consistent adherence to a multimodal therapeutic strategy including surgery, chemotherapy, and radiotherapy. Previous studies suggested that most patients who were alive at their last follow-up had experienced recurrence or metastatic disease[13]. The multiple recurrences and distant metastases observed at the last follow-up in this case align with these findings, highlighting the critical importance of early diagnosis and comprehensive treatment in improving patient outcomes.

Contrary to Zhang et al[2], who reported that pancreatoblastoma typically exhibited minimal uptake on ¹⁸F-FDG PET/CT, our case demonstrated intense ¹⁸F-FDG uptake in suspicious tumor lesions throughout follow-up. This discrepancy may be attributed to tumor heterogeneity, underscoring the variable metabolic behavior of pancreatoblastoma. Furthermore, compared with conventional imaging modalities such as CT and MRI, PET/CT offers superior sensitivity in detecting metastases, making it valuable for monitoring disease progression in pancreatoblastoma. Nevertheless, the high cost of PET/CT remains a significant barrier to its widespread clinical implementation.

Radical resection remains the optimal therapeutic approach for pancreatoblastoma, with resection of metastases considered in selected cases[14]. For metastatic pancreatoblastoma, chemotherapy regimens such as cisplatin and doxorubicin, as well as FOLFOX/FOLFIRINOX (folinic acid, fluorouracil, oxaliplatin with or without irinotecan), were the primary treatment options[8]. Advances in next-generation sequencing have opened new avenues for identifying genetic biomarkers, potentially paving the way for novel targeted therapies. Previous studies highlighted key genetic alterations in pancreatoblastoma, including loss of heterozygosity on chromosome 11p, CTNNB1 or APC gene mutations, and FGFR alterations[11,14]. Interestingly, our case demonstrated an FGFR1-SYCP1 gene rearrangement, a finding not previously reported in the literature. This discovery suggests that tyrosine kinase inhibitors, such as surufatinib, may warrant consideration for treating pancreatoblastoma patients with similar genetic profiles. Further research is needed to elucidate the underlying mechanisms of these genetic rearrangements, their impact on prognosis, and their potential therapeutic implications.

CONCLUSION

This rare case of recurrent adult pancreatoblastoma with liver metastasis supports a multimodal treatment strategy incorporating surgery, chemotherapy, and targeted therapy. It demonstrates the diagnostic and monitoring value of ¹⁸F-FDG PET/CT and highlights the importance of investigating the prognostic and therapeutic implications of recurrent genetic alterations, particularly in the FGFR pathway, for developing novel targeted therapies.