A POLE P286R-Mutated Hepatoid Adenocarcinoma of the Lung Showing Substantial Response to Immune Checkpoint Inhibition
A POLE P286R-Mutated Hepatoid Adenocarcinoma of the Lung Showing Substantial Response to Immune Checkpoint Inhibition

A POLE P286R-Mutated Hepatoid Adenocarcinoma of the Lung Showing Substantial Response to Immune Checkpoint Inhibition

Cancer Rep (Hoboken). 2026 Sep;9(9):e70661. doi: 10.1002/cnr2.70661.

ABSTRACT

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is a rare form of lung cancer with histological and morphological properties of hepatocellular carcinoma, characterized by an aggressive course of the disease and unfavorable prognosis. Given the rarity of the pathology and the lack of unambiguous therapeutic protocols, descriptions of clinical cases of HAL deserve attention.

CASE: We describe a case of metastatic HAL in a 61-year-old patient, harboring a mismatch repair deficiency associated with the loss of PMS2 protein expression. Molecular-genetic study identified several oncogenic variants including PMS2 p.Arg421Ter, PMS2 p.Arg107Trp, and POLE p.Pro286Arg and confirmed their somatic status. The laboratory findings clinically justified the use of immunotherapy with pembrolizumab, which afforded stabilization of the disease according to computed tomography data and complete tumor response according to morphological examination data.

CONCLUSION: The presented case highlights the room for immunotherapy in the highly aggressive HAL. The POLE p.Pro286Arg missense mutation has been attributed as a predictor for immune checkpoint inhibition efficacy.

PMID:42707040 | DOI:10.1002/cnr2.70661