Eiji Harada

Correlation between colorectal lesions and BLF methylation

Although tuberculosis is a major underlying cause of pulmonary mycetoma due to Scedosporium apiospermum, little is known about coinfection with nontuberculous mycobacteria (NTM) and S. apiospermum. A 67‐year‐old man with NTM presented with recurrent haemoptysis. Computed tomography of the chest revealed pulmonary mycetoma in the left upper lobe of the lung, and culture of bronchial washing fluid yielded S. apiospermum. Oral voriconazole therapy ameliorated both haemoptysis and mycetoma findings. As far as we are aware, this is the first reported case of S. apiospermum lung disease in a patient with NTM but without tuberculosis. The possibility of S. apiospermum infection should thus be considered in the differential diagnosis of pulmonary mycetoma. Although S. apiospermum mycetoma resembles aspergilloma, antifungal strategies for these two conditions differ, with the collection of culture specimens such as by bronchoscopy being compulsory for accurate diagnosis and appropriate management of S. apiospermum infection.

Background Recent studies revealed that colorectal tumors are composed of genetically diverse subclones. We aimed to clarify whether the surface microstructures of colorectal tumors are associated with genetic intratumoral heterogeneity (ITH). Methods The surface microstructures (pit patterns) of colorectal tumors were observed using magnifying endoscopy, and biopsy specimens were obtained from respective areas when tumors exhibited multiple pit patterns. A total of 711 specimens from 477 colorectal tumors were analyzed for BRAF, KRAS and TP53 mutations using pyrosequencing and direct sequencing. A panel of cancer-related genes was analyzed through targeted sequencing in 7 tumors. Results Colorectal tumors with multiple pit patterns exhibited more advanced pit patterns and higher frequencies of KRAS and/or TP53 mutations than tumors with a single pit pattern. In tumors with multiple pit patterns, mutations were observed as public (common to all areas) or private (specific to certain areas), and private KRAS and/or TP53 mutations were often variable and unrelated to the pit pattern grade. Notably, invasive CRCs frequently exhibited public TP53 mutations, even in adenomatous areas, which is indicative of their early malignant potential. Targeted sequencing revealed additional public and private mutations in tumors with multiple pit patterns, indicating their single clonal origin. Conclusions Our results suggest intratumoral pit pattern variation does not simply reflect the process of colorectal tumor evolution, but instead represents genetically diverse subclones, and this diversity may be associated with malignant potential.