Undifferentiated Sarcomatoid Carcinoma of the Pancreas: From Histology and Molecular Pathology to Precision Oncology.

Anastasios Gkountakos,Claudio Luchini,Aldo Scarpa,Elena Bariani,Michele Simbolo

doi:10.3390/ijms23031283

Abstract

Undifferentiated sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of pancreatic cancer. Histologically, SCP is a poorly differentiated tumor characterized by the lack of glandular differentiation and the presence of mesenchymal-like, spindle-shaped tumor cells. Due to its rarity, only sporadic cases have been reported, while its molecular characterization has not been sufficiently described. Surgical resection with curative intent is the gold-standard of SCP management, but this strategy is possible only in a small proportion of cases due to SCP early metastasization. Although SCP is generally associated with a poor prognosis, some clinical cases amenable to surgical resection and followed by adjuvant chemotherapy have demonstrated a remarkably long survival. Preliminary molecular insights on the SCP molecular landscape have demonstrated the recurrent presence of KRAS and TP53 mutations, highlighting genetic similarities with conventional pancreatic ductal adenocarcinoma (PDAC). Although the use of immunotherapy in PDAC remains an unmet challenge, recent insights indicated a potentially significant role of the PD-L1/Notch3 axis in SCP, opening new horizons for immunotherapy in this cancer subtype. In this review, we described the most important clinic-pathologic features of SCP, with a specific focus on their molecular landscape and the potential targets for precision oncology.

Highlights

Academic Editor: Girolamo RanieriPancreatic cancer (PC) is one of the deadliest cancer types, with a constantly increasing incidence [1,2]
Notch3 are co-localized in sarcomatoid cells [40]. All these findings identified a unique biological characterization of sarcomatoid carcinoma of the pancreas (SCP), providing a rationale for future studies evaluating the potential crosstalk between the PD-1/PD-L1 axis and Notch pathways and prompting the development of novel immunotherapy-based strategies
SCP is a rare subtype of pancreatic ductal adenocarcinoma (PDAC) and is generally considered a very-aggressive disease with a dismal prognosis

Summary

Introduction

Pancreatic cancer (PC) is one of the deadliest cancer types, with a constantly increasing incidence [1,2]. Pancreatic ductal adenocarcinoma (PDAC) is the most-common type of PC, accounting for more than 90% of cases and showing a very low survival rate 5-year overall survival) [3] This very poor prognosis is mainly due to the difficulties for early-stage detection of tumors as well as the very-aggressive cancer biology [4]. Immune-checkpoint inhibitors for cancers with microsatellite instability, as well as targeted therapies such as those based on PARP inhibitors for BRCA-mutated tumors, are gradually entering into clinical practice, but these opportunities regard only a small proportion of PDAC patients [6,7,8,9,10]. Sarcomatoid carcinoma of the pancreas (SCP) is an extremely rare but very aggressive subtype with a poor prognosis.

Undifferentiated Sarcomatoid Carcinoma of the Pancreas

Findings

Conclusions