Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance

Background and study aims: Laterally spreading tumors (LST) are classified into two subtypes, with the nongranular type harboring a higher risk of (pre)malignant changes than the granular type. Further subdifferentiation into two subgroups each has been suggested, but the clinical significance of such a subdifferentiation has not previously been studied in detail in larger numbers.

Patients and methods: Out of 6499 patients diagnosed with colorectal adenomas between January 2006 and November 2008, 153 patients (2.35 %) had 158 LSTs, 96 with a granular and 62 with a nongranular pattern. The former group was subdivided into homogeneous and nodular mixed, the latter group into flat elevated and pseudodepressed. Clinical and histopathological parameters were compared among the four subtypes.

Results: Parameters were variably distributed between the four groups, with nodular mixed tumors being larger than the other three types (P < 0.0001). As in other studies, malignant transformation and premalignant lesion (HGIN/CIS) were more frequent in nodular mixed than in homogeneous tumors (45.0 % vs. 5.6 %, P < 0.001), and also more common in pseudodepressed than in flat elevated tumors (41.7 % vs. 13.2 %, P = 0.011). Submucosal invasive cancer was present in 8.3 % of nodular mixed tumors, 7.9 % of flat elevated, and 12.5 % of pseudodepressed, while it was absent in homogeneous tumors. Serrated adenoma was identified in 10.8 % of all LSTs, and sessile serrated adenoma tended to be more common in flat elevated tumors.

Conclusions: Further subdifferentiation of the LST lesions to identify lesions at risk of malignant transformation makes most sense in the granular type. Among nongranular LSTs, both subtypes carry a significant risk.

References

• 1 Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer.  Endoscopy. 1993;  25 455-461
• 2 Kudo S E, Takemura O, Ohtsuka K. Flat and depressed types of early colorectal cancers: from East to West.  Gastrointest Endosc Clin N Am. 2008;  18 581-593, xi
• 3 Kudo S, Lambert R, Allen J I et al. Nonpolypoid neoplastic lesions of the colorectal mucosa.  Gastrointest Endosc. 2008;  68 S3-S47
• 4 Hiraoka S, Kato J, Tatsukawa M et al. Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations.  Gastroenterology. 2006;  131 379-389
• 5 Uraoka T, Saito Y, Matsuda T et al. Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum.  Gut. 2006;  55 1592-1597
• 6 Huang Y, Liu S, Gong W et al. Clinicopathologic features and endoscopic mucosal resection of laterally spreading tumors: experience from China.  Int J Colorectal Dis. 2009;  24 1441-1450
• 7 Li S C, Burgart L. Histopathology of serrated adenoma, its variants, and differentiation from conventional adenomatous and hyperplastic polyps.  Arch Pathol Lab Med. 2007;  131 440-445
• 8 Ohno Y, Terai T, Ogihara T et al. Laterally spreading tumor: clinicopathological study in comparison with the depressed type of colorectal tumor.  J Gastroenterol Hepatol. 2001;  16 770-776
• 9 Tanaka S, Haruma K, Oka S et al. Clinicopathologic features and endoscopic treatment of superficially spreading colorectal neoplasms larger than 20 mm.  Gastrointest Endosc. 2001;  54 62-66
• 10 Saito Y, Fujii T, Kondo H et al. Endoscopic treatment for laterally spreading tumors in the colon.  Endoscopy. 2001;  33 682-686
• 11 Kusaka T, Fukui H, Sano Y et al. Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal nodule-aggregating tumors.  J Gastroenterol Hepatol. 2000;  15 1151-1157
• 12 Han K S, Sohn D K, Choi D H et al. Prolongation of the period between biopsy and EMR can influence the nonlifting sign in endoscopically resectable colorectal cancers.  Gastrointest Endosc. 2008;  67 97-102
• 13 Uno Y, Munakata A. The non-lifting sign of invasive colon cancer.  Gastrointest Endosc. 1994;  40 485-489
• 14 Ishiguro A, Uno Y, Ishiguro Y et al. Correlation of lifting versus non-lifting and microscopic depth of invasion in early colorectal cancer.  Gastrointest Endosc. 1999;  50 329-333
• 15 Sohn D K, Chang H J, Park J W et al. Histopathological risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma of pedunculated or semipedunculated type.  J Clin Pathol. 2007;  60 912-915
• 16 Choi P W, Yu C S, Jang S J et al. Risk factors for lymph node metastasis in submucosal invasive colorectal cancer.  World J Surg. 2008;  32 2089-2094
• 17 Kitajima K, Fujimori T, Fujii S et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.  J Gastroenterol. 2004;  39 534-543
• 18 Hamilton S R, Aaltonen L A. Pathology and genetics of tumours of the digestive system.. Lyon: IARC Press; Oxford: Oxford University Press; 2000: 314
• 19 Greene F L. AJCC cancer staging manual. 6th ed.. New York: Springer; 2002: xiv, 421
• 20 Dixon M F. Gastrointestinal epithelial neoplasia: Vienna revisited.  Gut. 2002;  51 130-131
• 21 The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002.  Gastrointest Endosc. 2003;  58 3-43
• 22 Lee S K, Chang H J, Kim T I et al. Clinicopathologic findings of colorectal traditional and sessile serrated adenomas in Korea: a multicenter study.  Digestion. 2008;  77 178-183
• 23 Tantau A I, Tantau M V, Serban A et al. Prevalence, histology, endoscopic treatment and long-term follow-up of large colonic polyps and laterally spreading tumors. The Romanian experience.  J Gastrointest Liver Dis. 2008;  17 419-425
• 24 Hurlstone D P, Sanders D S, Cross S S et al. Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection.  Gut. 2004;  53 1334-1339
• 25 Chiu H M, Lin J T, Chen C C et al. Prevalence and characteristics of nonpolypoid colorectal neoplasm in an asymptomatic and average-risk Chinese population.  Clin Gastroenterol Hepatol. 2009;  7 463-470
• 26 Snover D C, Jass J R, Fenoglio-Preiser C, Batts K P. Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept.  Am J Clin Pathol. 2005;  124 380-391
• 27 Saito Y, Uraoka T, Matsuda T et al. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video).  Gastrointest Endosc. 2007;  66 966-973
• 28 Tanaka S, Oka S, Kaneko I et al. Endoscopic submucosal dissection for colorectal neoplasia: possibility of standardization.  Gastrointest Endosc. 2007;  66 100-107
• 29 Mukawa K, Fujii S, Takeda J et al. Analysis of K-ras mutations and expression of cyclooxygenase-2 and gastrin protein in laterally spreading tumors.  J Gastroenterol Hepatol. 2005;  20 1584-1590
• 30 Takahashi T, Nosho K, Yamamoto H et al. Flat-type colorectal advanced adenomas (laterally spreading tumors) have different genetic and epigenetic alterations from protruded-type advanced adenomas.  Mod Pathol. 2007;  20 139-147
• 31 Noro A, Sugai T, Habano W, Nakamura S. Analysis of Ki-ras and p53 gene mutations in laterally spreading tumors of the colorectum.  Pathol Int. 2003;  53 828-836
• 32 Nosho K, Yamamoto H, Takahashi T et al. Correlation of laterally spreading type and JC virus with methylator phenotype status in colorectal adenoma.  Hum Pathol. 2008;  39 767-775