LAUSR

To the Editor: Clear cell change, defined by the presence of clear and/or vacuolated cytoplasm without obvious mucin, occurring in colorectal neoplasms has extremely rarely been reported, although various types of metaplasia or differentiation, including squamous morules and Paneth cell proliferation have been documented in colorectal tumors. One series reported a prevalence of clear cell change in colorectal adenomas of 0.086% (3/3486 cases); only 18 cases have been reported in the English-language literature. In this case report, we describe an additional case with multiple colorectal tubular adenomas showing clear cell change, and also discuss the possible pathogenesis of this phenomenon in colorectal adenomas. A 63-year-old Japanese male with a past history of prostatectomy for prostate cancer (Gleason score 3þ 41⁄47, pT2c) 1 year earlier, underwent a colorectal endoscopic examination to investigate a positive fecal occult blood test. He was found to have 25 polyps (2 in the cecum, 9 in the ascending colon, 5 in the transverse colon, 1 in the descending colon, 5 in the sigmoid colon, and 3 in the rectum). Polypectomy was performed for all the lesions. Microscopic examination of two of the polyps in the ascending colon revealed that approximately 50% of one polyp and 10% of the other polyp showed clear cell change, and the remaining portion of each represented a typical tubular adenoma with high-grade atypia (dysplasia) (Fig. 1a). Clear cell change was characterized histopathologically by the presence of clear cytoplasm in tall columnar neoplastic cells. These neoplastic cells had hyperchromatic elongated nuclei without conspicuous nucleoli. Most of the neoplastic cells had clear cytoplasm in both the apical and subnuclear portions of the cell with apically oriented nuclei (Fig. 1b,c); but in some neoplastic cells, the clear cytoplasm was present only in the apical portion with the nuclei located in the base of the cells. These neoplastic cells had clear multi-vacuolated cytoplasm, and the sizes of the vacuoles varied (Fig. 1b,c). Abrupt transition from typical tubular adenoma cells to the clear cells was observed in both polyps (Fig. 1a–c). No adenocarcinomatous component was noted in either polyp. One polyp in the descending colon and one rectal polyp appeared to be typical tubular adenomas with low-grade atypia (dysplasia) showing clear cell change (approximately 10% of cells). Periodic acid-Schiff (PAS) staining with or without diastase digestion demonstrated that most of the neoplastic clear cells did not have material that was stained by PAS, whereas the typical tubular adenoma cells contained substance that were stained by PAS and digested by diastase. Moreover, none of the clear cells contained material that was stained by alcian blue. The results of the immunohistochemical studies are summarized in Table S1 (the polyp from the descending colon was too small to be evaluated). The clear cells were negative for MUC2 expression, although MUC2 was expressed in the conventional tubular adenoma cells (Fig. 1d). MUC5AC and MUC6 were not expressed in either the clear cells or the conventional adenoma cells. CD10 was expressed in the neoplastic clear cells of all polyps (Fig. 1e). In the conventional tubular adenoma component, CD10 was expressed in one polyp in the ascending colon, but not expressed in the two other polyps. Most of the neoplastic clear cells in the three polyps showed positive immunoreactivity for adipophilin (Fig. 1f), although none of the conventional tubular adenoma cells in the three polyps were positive for adipophilin. Ki-67 labeling index (LI) was 35% and 50% (high-grade dysplasia), and 33% (low-grade dysplasia) in the clear cell components (45%, 62%, and 53% in the conventional adenoma components, respectively). Scattered p53-positive cells were observed in both the neoplastic clear cells and conventional tubular adenoma cells in all polyps. Neither SALL4 nor alpha-fetoprotein was expressed in the clear cells. The remaining 12 polyps were conventional tubular adenomas without clear cell change. Moreover, five polyps (1 in the cecum, 2 in the ascending colon, and 2 in the transverse colon) were sessile serrated adenomas/polyps, and four polyps (2 in the ascending colon, 1 in the transverse colon, and 1 in the sigmoid colon) were hyperplastic polyps. In this report, we described a case with four colorectal tubular adenomas showing clear cell change. Table S1 summarizes the clinicopathological features of the previously reported cases of colorectal adenoma with clear cell change as well as the present one (24 lesions from 20 patients, including the recently reported Japanese case). This extremely rare phenomenon is most commonly observed in the left-side colon (13/20 lesions), and rare in the ascending colon (3 lesions). Most of the patients had a single lesion; only one previously reported case had two lesions. The present case was unique, because clear cell