Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> 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>Kirs...
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MDPI AG
2025-04-01
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| author | Mitsuhiro Tachibana Yutaro Ito Ryo Fujikawa Kei Tsukamoto Masahiro Uehara Jun Kobayashi Takuo Hayashi |
| author_facet | Mitsuhiro Tachibana Yutaro Ito Ryo Fujikawa Kei Tsukamoto Masahiro Uehara Jun Kobayashi Takuo Hayashi |
| author_sort | Mitsuhiro Tachibana |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| issn | 2075-4418 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-66b7f0b5cd8d4a579f6007d4e2359dfc2025-08-20T03:06:29ZengMDPI AGDiagnostics2075-44182025-04-0115789410.3390/diagnostics15070894Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> MutationMitsuhiro Tachibana0Yutaro Ito1Ryo Fujikawa2Kei Tsukamoto3Masahiro Uehara4Jun Kobayashi5Takuo Hayashi6Department of Diagnostic Pathology, Shimada General Medical Center, Shimada 427-8502, JapanDepartment of Respiratory Medicine, Shimada General Medical Center, Shimada 427-8502, JapanDepartment of Respiratory Surgery, Shimada General Medical Center, Shimada 427-8502, JapanDepartment of Diagnostic Radiology, Shimada General Medical Center, Shimada 427-8502, JapanDepartment of Respiratory Medicine, Shimada General Medical Center, Shimada 427-8502, JapanDepartment of Respiratory Surgery, Shimada General Medical Center, Shimada 427-8502, JapanDepartment of Human Pathology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8431, JapanSince 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.https://www.mdpi.com/2075-4418/15/7/894<i>KRAS</i><i>MET</i> exon 14 skippingthanatosomeshyaline globuleslung adenocarcinomaTTF-1 |
| spellingShingle | Mitsuhiro Tachibana Yutaro Ito Ryo Fujikawa Kei Tsukamoto Masahiro Uehara Jun Kobayashi Takuo Hayashi Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> Mutation Diagnostics <i>KRAS</i> <i>MET</i> exon 14 skipping thanatosomes hyaline globules lung adenocarcinoma TTF-1 |
| title | Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> Mutation |
| title_full | Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> Mutation |
| title_fullStr | Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> Mutation |
| title_full_unstemmed | Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> Mutation |
| title_short | Lung Adenocarcinoma Exhibiting Thanatosomes (Hyaline Bodies), Cytoplasmic Clearing, and Nuclear Pleomorphism, with a <i>KRAS</i> Mutation |
| title_sort | lung adenocarcinoma exhibiting thanatosomes hyaline bodies cytoplasmic clearing and nuclear pleomorphism with a i kras i mutation |
| topic | <i>KRAS</i> <i>MET</i> exon 14 skipping thanatosomes hyaline globules lung adenocarcinoma TTF-1 |
| url | https://www.mdpi.com/2075-4418/15/7/894 |
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