One size does not fit all for pancreatic cancers: A review on rare histologies and therapeutic approaches

Abstract

Exocrine pancreatic neoplasms represent up to 95% of pancreatic cancers (PCs) and are widely recognized among the most lethal solid cancers, with a very poor 5-year survival rate of 5%-10%. The remaining < 5% of PCs are neuroendocrine tumors that are usually characterized by a better prognosis, with a median overall survival of 3.6 years. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for roughly 85% of all exocrine PCs. However up to 10% of exocrine PCs have rare histotypes, which are still poorly understood. These subtypes can be distinguished from PDAC in terms of pathology, imaging, clinical presentation and prognosis. Additionally, due to their rarity, any knowledge regarding these specific histotypes is mostly based on case reports and a small series of retrospective analyses. Therefore, treatment strategies are generally deduced from those used for PDAC, even if these patients are often excluded or not clearly represented in clinical trials for PDAC. For these reasons, it is essential to collect as much information as possible on the management of PC, as assimilating it with PDAC may lead to the potential mistreatment of these patients. Here, we report the most significant literature regarding the epidemiology, typical presentation, possible treatment strategies, and prognosis of the most relevant histotypes among rare PCs.

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

“…UDC, also called anaplastic carcinoma, is a rare pancreatic cancer variant (1–7% of frequency of ductal adenocarcinoma), principally localized in the head of the pancreas and often associated with worse prognosis. UDC is characterized by the lack of a defined differentiation as demonstrated by the presence of pleomorphic mononuclear cells interspersed with rhabdoid or spindle cells, and several morphological variants (i.e., anaplastic, sarcomatoid) ( Figure 1 ) [ 24 , 91 ].…”

The Match between Molecular Subtypes, Histology and Microenvironment of Pancreatic Cancer and Its Relevance for Chemoresistance

“…Squamous and adenosquamous tumors represent 1–4% of all PCs, are often generated in the head of the pancreas [ 62 ], and present the worst survival ratios even detected at early stages [ 63 ]. These tumors frequently carry TP53 mutations and present 3p loss compared to adenocarcinomas ( Figure 1 and Table 1 ).…”

“…ADEX presents upregulation in transcription factors involved in healing and regeneration after pancreatitis events such as RBPJL, NR5A2, MIST1 and their associated downstream cascade factors ( Figure 3 and Table 1 ) [ 100 , 101 ]. This molecular subtype exhibits an expression profile associated with extremely rare acinar histopathology ( Figure 3 and Table 1 ) [ 59 , 63 ]. Macroscopically, this histology shows large tumors, frequently presented in encapsulated form and well circumscribed.…”

Impact of COVID-19 on pancreatic cancer surgery: A high-volume Polish center experience

“…These tumors differ slightly in biology, prognosis and treatment management from the most common pancreatic adenocarcinoma. 7 The diagnosis of pancreatic cancer, despite the recent progress in diagnostic methods, is still challenging and causes a delay of the final diagnosis by about 4-9 months, which has probably increased during the COVID-19 pandemic, yet it is difficult to make an exact estimation.…”