Large-duct pattern invasive adenocarcinoma of the pancreas–a variant mimicking pancreatic cystic neoplasms: A minireview

Pancreatic cancer currently has no subtypes that inform clinical decisions;hence,there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics.Nonetheless,accumulating studies to date have revealed the large-duct type variant,a unique subtype of pancreatic ductal adenocarcinoma(PDA)with cystic features.This subtype often radiographically mimics intraductal papillary mucinous neoplasms(IPMNs)and involves multiple small cysts occasionally associated with solid masses.The“bunch-of-grapes”sign,an imaging characteristic of IPMNs,is absent in large-duct PDA.Large-duct PDA defines the mucin profile,and genetic alterations are useful in distinguishing large-duct PDA from IPMNs.Histologically,neoplastic ducts measure over 0.5 mm,forming large ductal elements.Similar to classic PDAs,this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions,and KRAS mutations in codon 12 are nearly ubiquitous.Despite such morphological similarities with IPMNs,the prognosis of large-duct PDA is equivalent to that of classic PDA.Differential diagnosis is therefore essential.

Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas

Adenosquamous carcinoma of the pancreas(ASCP)is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate.However,little is known about its genomic landscape and prognostic biomarkers.A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma(PDAC)tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers.The homozygous deletion of the 9p21.3 region(including CDKN2A,CDKN2B,and MTAP)(9p21 loss)occurred in both ASCP and PDAC,and a higher frequency of 9p21 loss was observed in ASCP(12.5%vs 2.0%,P=0.022).Notably,9p21 loss was significantly associated with poor disease-free survival(DFS)in ASCP patients(mDFS(Median DFS)=4.17 vs 7.33 months,HR(Hazard Ratio)=3.70,P=0.009).The most common gene alterations in patients with ASCP were KRAS(96%),TP53(81%),CDKN2A(42%),SMAD4(21%),CDKN2B(13%),and FAT3(13%).The mutation rates of ACVR2A(6.25%vs 0%),FANCA(6.25%vs 0%),RBM10(6.25%vs 0%),and SPTA1(8.33%vs 1.02%)were significantly higher in ASCP than in PDAC.In conclusion,we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP,which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.