Case of the Month: February 2024

The answer to February’s Case of the Month is poorly differentiated adenocarcinoma.

Most cancers are graded based on how similar they look to the tissue the cancer originated from. Adenocarcinomas are epithelial cell cancers that are derived from glandular-type cells (adeno=gland, carcinoma=cancer). Adenocarcinomas of the lung derive from the epithelial cells lining the alveolar spaces. They can have a variety of different patterns depending on how differentiated the cancer is: lepidic (well-differentiated), acinar and papillary (moderately differentiated), micropapillary and solid (poorly differentiated). When cancers are poorly differentiated (e.g. form solid nests without any hint of differentiation), then immunohistochemistry is necessary to determine the cell of origin because poorly differentiated cancers can all look similar on routine H&E stains. Specific stains for lung adenocarcinoma are TTF-1 and napsin-A. Squamous cell carcinomas stain for p40/p63. Neuroendocrine carcinomas stain for CD56, synaptophysin, and/or chromogranin.

Once the type of cancer is determined by immunohistochemistry, additional ancillary testing can be performed to look for specific mutations common to that cancer type. This is called prognostic and predictive biomarker testing and helps oncologists provide personalized treatment plans to patients. Many mutations can be detected via a technique called next-generation sequencing. Important genes to evaluate in lung adenocarcinomas are EGFR, ROS1, and ALK. Other genes tested include BRAF, MET, RET, FGFR1, HER2, KRAS, PIK3CA, NTRKs, and TP53. Many of these gene mutations are commonly seen in other cancers as well.

PD-L1 is another important biomarker, which is tested using immunohistochemistry.  PD-L1 is short for programmed death-ligand 1, which binds PD-1 receptors on T-cells and tells the T-cells not to kill the cell expressing PD-L1. Cancer cells can evolve to upregulate PD-L1 to trick the immune system into not killing them, but therapies now exist (immunotherapy) to unmask the tumour cells and let the immune system do its job to destroy the cancer.