A 79-year-old woman underwent total colonoscopy because of a positive fecal occult blood test. Colonoscopy showed a LST-G of approximately 30 mm in diameter in the lower rectum adjacent to the dentate line. Macroscopically, the lesion consisted of not only aggregated small and large nodules typically seen in LST-Gs, but also hardly elevated flat parts (Figure 1a, 1b, 1c). Magnifying chromoendoscopy after 0.4% indigo carmine dye spraying showed a type IIIL pit [6] for small nodules and a type IV pit for the larger ones, whereas dilated round pits were observed in the hardly elevated flat part (Figure 1b, 1c). Magnifying narrow-band imaging (NBI) revealed meshed capillary (MC) vessels (type II capillary pattern according to Sano’s classification [7]) in the nodular areas, whereas no MC vessel (type I capillary pattern according to Sano’s classification) could be seen in the flat areas (Figure 2a, 2b). Based on the above endoscopic findings, this lesion was diagnosed as an adenoma, which is a good candidate for endoscopic local resection.
Approximately 3 months later at the second colonoscopy for endoscopic resection, the nodular parts had increased in height and size, whereas the hardly elevated flat part also increased in height at conventional view. During magnifying chromoendoscopy, the nodules that had increased in height and size showed a type IV pit pattern, and a type IIIL pit was seen in the flat area that had increased in height; however, the dilated round pits decreased in number in the flat area (Figures 1d, 1e, 2c).
The lesion was completely removed en bloc by endoscopic submucosal dissection. Stereomicroscopic examination of the resected specimen showed both nodular parts and flat areas; moreover, multiple smaller nodules were also detected within the flat areas (Figure 3b, 3c). Microscopically, a lower magnified view showed a difference in the density of atypical tubules between the nodular and flat parts (Figure 4a). The nodular part consisted of condensed proliferation of irregular tubules (Figure 4b). In contrast, the flat part consisted of straight tubules that were sparsely distributed compared with nodular part (Figure 4c). Two portions were diagnosed pathologically as tubular adenoma with moderate atypia and tubular adenoma with mild atypia, respectively according to the current pathological criteria.
We performed the sequence analyses on KRAS gene at codons 12, 13, 61, and 146, and BRAF gene at codon 600, and NRAS gene at codons 12, 13, and 61, and PIK3CA gene at codons 542, 545, 546, and 1047 to show the significance of detecting the combined nodular and flat lesions like this case. The DNA of nodular or flat lesions were extracted separately from formalin-fixed and paraffin-embedded tissue and analyzed to examine point mutation. The Luminex method was used for KRAS gene at codons 61 and 146, and BRAF gene at codon 600, and NRAS gene at codons 12, 13, and 61, and PIK3CA gene at codons 542, 545, 546, and 1047, the Scorpion-ARMS method was used for KRAS gene at codons 12 and 13. Interestingly, a mutation of KRAS gene at codon 146 was observed at tubular adenoma with moderate atypia of nodular part, however, there was not any mutation examined in tubular adenoma with mild atypia of flat part.