Pancreatoblastoma (PB) is a rare malignant neoplasm that originates from pancreatic epithelial cells (1). With an incidence of approximately 0.004 per 100,000 cases every year, PB is one of the most common pancreatic tumors (2, 3). Pancreatoblastoma mostly occurs in children, often under 10 years old, with an average age of 4 years old, and it is rare in adults (4, 5).

Pancreatoblastoma often presents with nonspecific clinical symptoms and is often incidentally discovered as a solitary nodule in the abdomen, which can spread extensively. The pathological histological features include acinar cell differentiation and the presence of squamous corpuscles/squamous epithelial islands, along with varying degrees of endocrine and ductal differentiation. In the second-generation sequencing of adult pancreatoblastoma, APC mutations were found to be the most common mutations, indicating that APC mutation is the primary driver of this tumor (6). The APC/β-catenin signaling pathway has also been identified in 67% of pancreatoblastomas, with biallelic inactivation of the APC gene and activating mutations of the CTNNB1 (β-catenin) gene (7).

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of numerous adenomatous polyps in the colon and rectum and is associated with a near 100% lifetime risk of colorectal cancer (CRC) (8). FAP is caused by germline mutations in the adenomatous polyposis coli (APC) gene, which is located on the long arm of chromosome 5 (5q21-22) (9). The global prevalence of FAP is ~1/10,000 in individuals, with men and women being affected equally (10). In addition to the gastrointestinal manifestations, FAP patients may exhibit extraintestinal manifestations, including gastric fundic gland polyps, fibromas, osteomas, epidermoid cysts, and pituitary adenoma (11, 12).

Both pancreatoblastoma and FAP are associated with APC mutations, suggesting that pancreatoblastoma may be a tumor related to FAP. However, it remains uncertain whether FAP independently increases the risk of developing pancreatoblastoma. To date, cases of pancreatoblastoma combined with FAP are rarely reported. In this study, we present a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis.

This study presents a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis in a 28-year-old male patient.

Familial adenomatous polyposis(FAP) is an autosomal dominant syndrome characterized by the presence of numerous adenomatous polyps throughout the colon and rectum, which have a tendency to progress to adenocarcinoma (13). In this case, dozens of polyps were found throughout the colon and rectum, which were confirmed by pathology as tubular adenomas or tubular-villous adenomas. Some areas of these polyps also showed progression to high-grade intraepithelial neoplasia, including in situ carcinoma. It is important to note that some FAP patients may develop extraintestinal manifestations, such as thyroid and pancreatic cancer, hepatoblastomas, CNS tumors (especially medulloblastomas), and various benign tumors like adrenal adenomas, osteomas, desmoid tumors, and dental abnormalities (14, 15). In this case, two years and three months after being diagnosed with FAP, a pituitary adenoma was also diagnosed, which could potentially be a new extraintestinal manifestation of FAP.

Familial adenomatous polyposis (FAP) is a rare autosomal dominant disease characterized by germline mutations in the Adenomatous Polyposis Coli (APC) gene (16). APC mutations are also found to be the most frequent mutation in an adult pancreatoblastoma, indicating that APC mutation is a driver mutation of the tumor (6). The APC/β-catenin signalling pathway has also been identified to be associated with 67% of pancreatoblastomas, and abnormalities can include biallelic inactivation of the APC gene and activating mutations of CTNNB1 (β-catenin) gene (7). The above studies suggest that pancreatoblastoma might be associated with FAP by the linkage of APC mutation. A report also shows that there is a non-random association between adult pancreatoblastoma and FAP (17). However, APC mutation was not detected in this case. Therefore, we have no direct proof to confirm the association of pancreatoblastoma and FAP in this only one case.

Pancreatoblastoma often has no obvious clinical symptoms or only presents as abdominal pain, so it is easy to misdiagnose. This patient came to the hospital 1 year and 3 months after being diagnosed with FAP due to abdominal pain induced by incomplete intestinal obstruction caused by FAP, and a pancreatic nodule was incidentally found on abdominal CT, which was first diagnosed as pancreatic neuroendocrine carcinoma with high-differentiation that needed to be differentiated from pancreatoblastoma. Regrettably, this case was not discussed at a multidisciplinary tumor board, as it had not been established in the First Affiliated Hospital of Kunming Medical University until 2020. Therefore, the first diagnosis was not clear and the doctors tended to think of it as pancreatic neuroendocrine carcinoma with high differentiation, according to the Eighth Edition of the AJCC TNM Staging System of Pancreatic Neuroendocrine Tumors, the pathological stage was T2N0M0. The patient was not given chemotherapy after the first pancreatectomy. However, the early recurrence was found seven months after the first pancreatectomy, then the patient underwent the second pancreatic tail resection, and the final diagnosis was pancreatoblastoma. This is a rare case of adult pancreatoblastoma combined with FAP.As the first diagnosis was not accurate, pancreatoblastoma is more malignant than neuroendocrine carcinoma, and some tiny cancerous lesions can’t be identified by the naked eye and imaging examination,the early recurrence was likely due to inadequate resection.

Adult pancreatoblastoma is an exceptionally rare malignant tumor of the pancreas that mimics other solid cellular neoplasms of the pancreas, which may pose diagnostic difficulties. It is important to distinguish pancreatoblastoma from morphological mimics such as pancreatic acinar cell carcinomas, neuroendocrine neoplasms, and solid pseudopapillary neoplasms (5). Pancreatic acinar cell carcinomas are glandular and have amphophilic/eosinophilic cytoplasm, presenting acinar, solid, and trabecular structures (18). Acinar cell carcinomas have a relatively single-cell component, and all tumor cells show the characteristics and immunophenotypes of acinar cells, without squamous corpuscles/squamous epithelial islands. Neuroendocrine neoplasms of the pancreas have different clinical manifestations and laboratory abnormalities depending on the hormones secreted by the tumor, with rich blood sinusoids in the stroma and no squamous corpuscles/squamous corpuscles/squamous epithelial islands (19). Solid pseudopapillary neoplasms in the pancreas often occur in young women and are extremely rare in men. The tumor cells are arranged in the form of solid sheets, micro cysts and pseudopapillary areas that show characteristic pseudopapillae with the fibrovascular axis of the branch-shaped area surrounded by several layers of polygonal epithelioid cells, and there are numerous thin-walled blood vessels or sinuses in the stroma, without squamous corpuscles/squamous epithelial islands. Regional cystic degeneration, haemorrhage, necrosis, aggregates of foamy histiocytes, and cholesterol clefts are common (20, 21).

In this case, the tumor cells in the pancreatic nodule were abundant and separated by fibrous septa into well-defined epithelial cell islands, arranged in large nests. There was acinar cell differentiation and atypical squamous corpuscles/squamous epithelial cell islands, and some cells showed neuroendocrine differentiation. Therefore, according to the characteristic acinar-like cells and squamous corpuscles/squamous epithelial cell islands, this case should be diagnosed as adult pancreatoblastoma. After the second pancreatectomy, five renowned pathological experts from highly regarded tertiary hospitals in China confirmed the final diagnosis as adult pancreatoblastoma.

Adult pancreatoblastomas are aggressive tumours with frequent invasion, recurrence, and distant metastasis (22). Due to the low incidence of pancreatoblastoma, there is a lack of standardized treatment strategies internationally. Surgical resection is the major treatment for pancreatoblastoma. Chemotherapy and radiotherapy may have a role in the treatment of recurrent, residual, unresectable, and metastatic tumors. However, the use of chemotherapy and its efficacy in adult pancreatoblastoma remains unclear, and the prognosis documented in existing literature for adults is worse when compared to paediatric presentations (23).

In this case, the patient received surgical resection of pancreatoblastoma, and pancreatoblastoma recurred in the patient 7 months after the first resection, and the patient received a second resection of the pancreatoblastoma. Abdominal metastases appeared 3 months after the second resection, which is consistent with the clinical characteristics of pancreatoblastoma. Then the patient received 3 cycles of chemotherapy including Vincristine 2mg on Day 1 + Cyclophosphamide 1.0g on Day 2 + Etoposide 0.1g on Day 1 to Day 3 + Cisplatin on Day 3, Day 4, and Day 5. However, this patient was not sensitive to the chosen chemotherapy regimen.

The malignant behaviors of pancreatoblastomas often lead to a poor prognosis. In general, despite aggressive treatment, pancreatoblastoma in adults is associated with poorer outcomes than in children, with a median survival time of 18.5 months (24). In a report of 11 cases of adult pancreatoblastoma, 5(45%) patients died of pancreatoblastoma during the follow-up period(0.8–348 months) (25). In this case, due to poor response to the chosen chemotherapy regimen and intolerance of adverse reactions, the patient discontinued chemotherapy and was discharged. Subsequently, the patient received regular phone follow-ups. Remarkably, the patient has survived for 4 years and 11 months since the diagnosis of pancreatoblastoma till January 2024(last follow-up). However, the treatment details of this patient after discharge were unknown and the imaging data were not obtained.

We also reviewed the data of 18 cases of adult pancreatoblastomas in 6 previous reports (3, 6, 22, 25–27). Age: The average age at diagnosis was 50.4 ± 14.2 years old, with the minimum age being 32 years old and the maximum age being 76 years old. Gender: The male to female ratio is 1:1, suggesting that pancreatoblastomas have no gender predilection. Size: The tumor diameter at diagnosis in all cases was ≥2.5 cm, of which 9 cases (50%) were > 7 cm, and the maximum was 18.7 cm. This suggests that pancreatoblastomas are generally discovered late, which may be caused by asymptomatic or atypical symptoms of PB. Location: Pancreatoblastomas occurred in the pancreatic head in 8 cases, in the pancreatic tail in 8 cases, in the pancreatic body and tail in 1 case and in the pancreatic body in 1 case, suggesting that pancreatoblastomas can occur in any part of the pancreas, but they are more likely to occur in the head and tail of the pancreas. First diagnosis: Among the 18 cases, only 4 cases were initially diagnosed as PB, and 6 cases were initially diagnosed as neuroendocrine neoplasm/carcinoma/tumor. This indicates that the diagnosis of PB is difficult, especially especially when using a small number of biopsy specimens. Neuroendocrine tumors are most similar to PB in morphology and require differential diagnosis from PB. Combined with FAP: There were only 1 cases with FAP and 2 cases with FAP-related syndromes- Gardner syndromes. However, APC mutations were not available in the 3 cases (25). This suggests PB combined with FAP is rare. APC mutations: Only 4 cases were tested for APC mutations, including 2 negative cases and 2 positive cases, but FAP was not found in the 2 positive cases (6, 26). Recurrence:There were only 2 cases of recurrence, indicating that PB is not easy to relapse, and the recurrence of 2 cases might be related to surgical residue. Metastasis:Lymph node or distant metastasis was present in 12 cases(66.7%), and only 6 cases(33.3%) had metastasis, indicating that PB has a high degree of malignancy. Survival period:The longest survival period was >348 months and the shortest survival period was 0.8 months after diadnosis of PB (25). And 13 cases survived for more than 12 months, including 7 cases with a survival period exceeding 60 months. The 1-year survival rate was 72.2%, and the 5-year survival rate was 38.9%, suggesting that some patients with PB have a good prognosis.

Adult pancreatoblastoma can display genetic heterogeneity, diverse histological appearance, and overlapping IHC findings, so the differential diagnosis with other adult pancreatic tumors may be challenging. Although molecular findings might provide useful information, the integration of clinical, radiological, and histopathological findings is essential in pancreatoblastoma diagnosis (26). Here we reported a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis. In this case, we integrated the clinical, radiological, and histopathological findings to make a final diagnosis of pancreatoblastoma. This case report mainly highlights the challenges associated with diagnosing and managing adult pancreatoblastoma.

This patient was diagnosed with pancreatoblastoma 1 year and 3 months after being diagnosed with FAP. This suggests pancreatoblastoma may occur in patients with familial adenomatous polyposis or a family history of the condition, indicating a possible association between the two tumors. Therefore, pancreatoblastoma should be included in a differential diagnosis for FAP patients with a pancreatic mass. The final diagnosis of pancreatoblastoma depends on the pathological diagnosis. Acinar-like cells and squamous corpuscles/squamous epithelial cell islands under light microscopy are the key diagnostic points. This case report also can improve the awareness of clinicians, radiologists, and pathologists on the presence of rare tumor-adult pancreatoblastoma in patients with familial adenomatous polyposis.

Strengths and limitations of this study Pancreatoblastoma (PB) is a rare malignant epithelial neoplasm of the pancreas that demonstrates multiple patterns of differentiation. In this study, an extremely rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis was reported and the clinical, radiological, and morphological features, immunophenotypes, and prognosis of adult pancreatoblastoma combined with familial adenomatous polyposis were summarized. However, APC mutation was not tested in this patient. And this report is only 1 case, our results may need to be verified in more cases.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

The studies involving humans were approved by The Ethical Review Board of the First Affiliated Hospital of Kunming Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.

Y-XW: Data curation, Formal analysis, Investigation, Methodology, Writing – original draft. S-SF: Data curation, Formal analysis, Writing – original draft. X-RP: Data curation, Formal analysis, Writing – original draft. Y-SZ: Data curation, Formal analysis, Writing – original draft. XZ: Conceptualization, Funding acquisition, Supervision, Validation, Writing – review & editing.