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Histological progression of small intrapulmonary metastatic tumor from primary lung adenocarcinoma


  • This work was supported in part by the Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare, the Grant for Scientific Research Expenses for Health Labor and Welfare Programs, the Foundation for the Promotion of Cancer Research, 3rd-Term Comprehensive 10-year Strategy for Cancer Control, and Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.

Genichiro Ishii, MD, PhD or Atsushi Ochiai, MD, PhD, Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-city, Chiba-prefecture, 277-8577, Japan. Email: (G. Ishii), (A. Ochiai)


The histopathology of small metastases is thought to reflect the early metastatic process. To clarify the morphological features of early metastatic tumor progression, we analyzed the histological heterogeneity of many small intrapulmonary metastases. Histological typing based on the World Health Organization classification (bronchioloalveolar carcinoma, acinar, papillary, and solid subtype) was used to evaluate 234 metastases from the primary lung adenocarcinomas of 139 patients. The predominant subtype of metastasis 3 mm or less in diameter was bronchioloalveolar carcinoma when the primary lesion was diagnosed as predominant bronchioloalveolar carcinoma, acinar, and papillary subtype. When the histology of the primary tumor was predominantly a solid subtype, the predominant subtype of metastatic tumor was also a solid subtype. However, analysis of metastases that were more than 3 mm showed that the predominant subtype of the metastasis reflected the predominant subtype of the primary tumor. Furthermore, we evaluated the number of subtypes in primary and metastatic tumors. As the metastasis grew larger, the number of subtypes in the metastatic lesion increased and came close to the number composed in the primary lesion. These findings suggest that implanted cancer cells display lepidic growth in the early metastatic phase and recapitulate the morphological heterogeneity of the original tumor as the metastasis enlarges.