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Rectal Neuroendocrine and L-cell Tumors: Diagnostic Dilemma and Therapeutic Strategy

Lee, Suk Hee MD, PhD*; Kim, Byung Chang MD; Chang, Hee Jin MD, PhD; Sohn, Dae Kyung MD; Han, Kyung Su MD*; Hong, Chang Won MD; Lee, Eun-Jung MD; Lee, Jae-Bum MD; Lee, Doo-Seok MD, PhD; Lee, In Taek MD; Youk, Eui-Gon MD, PhD

The American Journal of Surgical Pathology: July 2013 - Volume 37 - Issue 7 - p 1044–1052
doi: 10.1097/PAS.0b013e3182819f0f
Original Articles

Rectal neuroendocrine tumors (NETs) are currently divided into L-cell and non–L-cell types. In the World Health Organization 2010 classification, L-cell tumors are defined as borderline, whereas non–L-cell tumors are considered to represent malignancies. To establish differential diagnostic criteria and therapeutic strategy, we investigated the pathologic features of rectal NETs associated with lymph node metastasis and the clinicopathologic significance of the L-cell phenotype. We analyzed 284 patients with rectal NETs. Factors, including T stage, mitosis, histologic pattern, lymphatic invasion, tumor border, and lymph node metastasis, were retrospectively evaluated. We also evaluated tumor immunoreactivity for L-cell markers, including glucagon-like peptide 1, pancreatic peptide, and peptide YY, in 240 cases. L-cell immunoreactivity was detected in 189 of 240 NETs (79%). Of the factors evaluated, only age and the frequency of lymphatic invasion were significantly different between patients with L-cell and non–L-cell tumors. Of the 284 patients, 18 (6.3%) had lymph node metastases. Lymphatic invasion and T stage were independent risk factors for lymph node metastasis. Subgroup analysis based on tumor size showed lymph node metastasis in 0%, 4%, 24%, and 100% of patients with NETs with a size of <5, 5 to 9, 10 to 14, and ≥15 mm, respectively. Depth of tumor invasion, lymphatic invasion, and mitosis were correlated with tumor size (P<0.0001). In conclusion, L-cell phenotype alone does not guarantee favorable biological characteristics. The clinical management of rectal NETs should depend on tumor size. Careful pathologic examination of lymphatic invasion is necessary.

Departments of *Pathology

Surgery, Daehang Hospital, Seoul

Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea

S.H.L. and B.C.K. contributed equally.

Conflicts of Interest and Source of Funding: Supported by the Converging Research Center Program funded by the Ministry of Education, Science, and Technology (Project No. 1131150). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Hee Jin Chang, MD, PhD, Department of Pathology and Center for Colorectal Cancer, National Cancer Center, 111 Jungbalsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea (e-mail:

© 2013 by Lippincott Williams & Wilkins.