Undifferentiated Pancreatic Carcinomas, Clinical Features and Therapeutic Options: What We Know

Abstract

Undifferentiated pancreatic carcinomas are rare malignant tumors of the pancreas that are very aggressive and challenging to diagnose. The WHO categorizes them into undifferentiated osteoclast-like giant cell, sarcomatoid, and rhabdoid pancreatic carcinomas. Patients present with nonspecific symptoms such as jaundice, vague abdominal or back pain and itchy skin. Their histological characteristics include positive pan-cytokeratin mononuclear pleomorphic cells, osteoclast-like giant cells and CD68. Patients may have KRAS, TP53 and SMAD4 alterations, homozygous deletions of CDKN2A and CDKN2B, as well as INI1 deficiency. Surgical resection is the only curative treatment. Patients may benefit from postoperative adjuvant therapy. There are no widely accepted guidelines specific to this type of tumor; however, some chemotherapy regimens may be promising. The patient prognosis is mostly poor, especially in patients with unresectable tumors. However, several studies have shown patients achieving long-term survival with adjuvant therapy. In conclusion, although undifferentiated pancreatic carcinoma is rare and very aggressive, there is still potential for improved patient survival with proper diagnosis and treatment.

High-grade Solid Pseudopapillary Neoplasms of the Pancreas

“…Undifferentiated carcinoma often shows partial glandular/ tubular formation, whereas HG-SPN lacks it. Mutations in KRAS, CDKN2A, and/or SMAD4 (DPC4) are frequently observed in undifferentiated carcinomas [21][22][23] but not in HG-SPNs. Poorly differentiated acinar cell carcinoma shows acinar differentiation confirmed by immunohistochemical expression of bcl-10 and/or trypsin, contrary to HG-SPN.…”

Expression of Selected miRNAs in Undifferentiated Carcinoma with Osteoclast-like Giant Cells (UCOGC) of the Pancreas: Comparison with Poorly Differentiated Pancreatic Ductal Adenocarcinoma

“…The tumor comprises three main cell types: (1) neoplastic cytokeratin-positive mononuclear cells exhibiting cytonuclear atypia, (2) non-neoplastic mononuclear macrophages, and (3) non-neoplastic osteoclast-like multinucleated giant cells, which vary in quantity and are often accompanied by hemorrhage and necrosis. Despite their morphological differences, the DNA mutational profiles of UCOGCs surprisingly mirror those of conventional PDAC, frequently featuring KRAS activation and the inactivation of SMAD4, TP53, and CDKN2A [5][6][7][8]. Many neoplastic pathways in pancreatic cancer are regulated by microR-NAs.…”

Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases

“…In the case of characteristic morphology, UCOGC diagnosis is based on histopathological examination [ 5 ]. However, despite their different morphology, the DNA mutational profiles in UCOGCs show surprising similarities with those of conventional PDAC [ 6 ], including the frequent activation of KRAS and deactivation of SMAD4 , TP53 , and CDKN2A [ 7 , 8 , 9 ]. The carcinogenesis of PDAC encompasses a cascade of molecular events, including telomere shortening, activating mutations in KRAS , inactivating mutations or the epigenetic silencing of p16/ CDKN2A , and inactivating mutations in TP53 and SMAD4 .…”