Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Globules), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a KRAS Mutation

Since epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were introduced in 2004, various driver gene mutations have been identified in non-small cell lung cancer, particularly adenocarcinoma, where mutations are typically mutually exclusive. <i>EGFR</i> and <i>Kirsten rat sarcoma viral oncogene (KRAS)</i> mutations are most prevalent in Japan, with routine testing now standard. However, hematoxylin and eosin staining often fails to detect mutations, except in cases such as <i>ALK</i> fusion lung cancer. We report a 76-year-old non-smoking Japanese woman diagnosed with adenocarcinoma confirmed as <i>KRAS</i> G12D/S-positive. Histological features, including thanatosomes (hyaline globules), nuclear pleomorphism, and cytoplasmic clearing, may aid in identifying mutations. Numerous thanatosomes were identified, some containing nuclear dust. Thanatosomes revealed periodic acid-Schiff reactivity with diastase resistance, fuchsinophilia with Masson's trichrome stain, and dark blue-black color with Mallory's PTAH stain. This is the first report linking thanatosomes in <i>KRAS</i>-mutant pulmonary adenocarcinoma to apoptosis via cleaved caspase-3 staining.