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

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1283
• Main Authors: Gkountakos, Anastasios, Simbolo, Michele, Bariani, Elena, Scarpa, Aldo, Luchini, Claudio
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Cancer; Chemotherapy; Chemotherapy, Adjuvant - methods; EMT; Histology; Humans; Immunotherapy; Immunotherapy - methods; Immunotherapy - trends; Medical Oncology - methods; Medical prognosis; mesenchymal; Mesenchyme; Metastasis; Mutation; Oncology; p53 Protein; Pancreas; Pancreas - pathology; Pancreatic cancer; Pancreatic carcinoma; pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - pathology; Patients; PD-L1 protein; PDAC; Precision medicine; Precision Medicine - methods; Proto-Oncogene Proteins p21(ras) - genetics; Radiation therapy; Review; Sarcoma - physiopathology; sarcomatoid; Senescence; Surgery; Tumor cells; Tumor Suppressor Protein p53 - genetics; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031283

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 and 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.