A Case of Adult Pancreatoblastoma With Novel APC Mutation and Genetic Heterogeneity

Abstract

BackgroundPancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas that mainly occurs in children and involves abnormalities in the WNT/β-catenin pathway, such as CTNNB1 mutation. However, the molecular abnormalities in adult pancreatoblastoma are not well known.Case PresentationAn elderly man, who underwent elective distal pancreatectomy and splenectomy, was referred to our hospital with a mass in the tail of the pancreas. Histologically, the lesion revealed proliferation of clear, basophilic, and cartilaginous tumor cells with lymphatic metastasis. Each of the morphologically distinct tumor components showed different immunohistochemical patterns, indicating heterogeneous differentiation, including epithelial (both acinar and ductal), mesenchymal, and neuroendocrine differentiation. All tumor components showed nuclear expression of β-catenin and cyclin D1. Per next-generation sequencing (NGS), the clear and basophilic tumor cells shared mutations in APC, GRM8, LAMP1, and AKA9. Among the mutations, APC, c.1816_1817insA showed the highest frequency in both cell types, indicating that APC mutation was a driver mutation of the tumor. A diagnosis of PB was rendered.SummaryIn conclusion, the clear and basophilic cells of the tumor were supposedly derived from the same clone and subsequently acquired additional mutations. This is the first report of clonal evolution in pancreatoblastoma.

Adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis: a rare case report

“…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 ).…”

“…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.…”

“…We also reviewed the data of 18 cases of adult pancreatoblastomas in 6 previous reports (3,6,22,(25)(26)(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.…”

“…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 ).…”

MCL1 as putative target in pancreatoblastoma

“…Third, other contributing factors may include sensitivity differences, clonal heterogeneity, sampling bias, and different tumoral ploidy. Intratumoral heterogeneity has been demonstrated in PB as well, and genetic heterogeneity seemed to be associated with morphologic differentiation lineages in a reported case of a PB patient [ 36 ]. We observed MCL1 amplification in cellular areas with more basophilic appearance.…”