Using studies that correlate NET prognosis, the Ki-67 proliferation index, and the mitotic count, the NET classifications of the World Health Organization (WHO) were updated in 2010.
11 Although the natural course of rectal NETs is not fully understood, recent studies suggest that the WHO classification system correlates well with the metastatic potential and prognosis of rectal NETs.
9,12 Moreover, recent Korean studies suggest that the endoscopic treatment of small (i.e., <10 mm) rectal NETs without evidence of regional or distant metastasis can achieve highly favorable long-term outcomes.
13,14 Another recent Korean study suggested that the risk of recurrence is markedly increased in rectal NET patients with metastatic lymph nodes, even after radical surgery (hazard ratio, 12.8; 90% CI, 4-41 on univariate analysis), although this study did not investigate the histological grade of NETs.
15 Therefore, before deciding on therapy for a small rectal NET, the presence of metastatic lesions should be investigated by using various imaging modalities, such as CT, MRI, or endoscopic ultrasonography. However, all these imaging modalities have demonstrated limited diagnostic accuracy for assessing perirectal metastatic lymph nodes.
16 Although indium-111 pentetreotide scintigraphy remains the gold standard for the diagnosis and localization of most NETs, its utility in colorectal NETs has not been validated owing to the sparse data available, and it may be more difficult to detect lesions of these types because of the greater background activity in the colon and rectum.
17 Fludeoxyglucose (FDG) used in PET accumulates only in high-grade NETs,
18 and therefore, FDG-PET has not been considered for imaging in low-grade NETs. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for perirectal lesions could be another option to confirm perirectal lymph node metastasis, but it was not a well-established diagnostic procedure for perirectal lesions less than 10 mm in size in 2005, when the patient described in the current report was treated.
19 In our case, a small NET was noted in the distal rectum and a 7-mm-sized perirectal lymph node was also identified. As mentioned above, it was highly difficult to assess the histological nature of the lymph node without performing surgery at that time. Meanwhile, radical surgery for distal rectal lesions carries the potential risks of bladder or bowel dysfunction and stoma formation.
20 Therefore, after discussion with the patient, we decided to first perform endoscopic resection of the rectal NET. After removal of that lesion, we discussed the favorable histology of the resected specimen, as well as the question of the unresected small perirectal lymph node with uncertain histology, and the patient finally elected a course of follow-up without invasive surgery.
Because the size of the initially noted lymph node remained unchanged for up to 7 years of follow-up examinations, our initial belief was that this lymph node was benign. However, 7 years and 1 month after the initial local excision, the lymph node was found to have slightly enlarged, and it was finally diagnosed as a metastatic, grade 1 NET. If the initial perirectal lymph node was a metastasis from the rectal NET, this case suggests that metastatic lesions from grade 1 rectal NET might demonstrate an extremely slow growth rate. Therefore, any patients with small, grade-1, rectal NETs that are locally excised should receive long-term follow-up examinations when lesions are suspected to be metastatic but are too small for the performance of EUS-FNA for histological confirmation. Highly aggressive approaches such as surgical lymph node dissection can also be considered. However, considering the operation-related complications, the extremely slow growth rate, and the very low incidence of lymph node metastasis from small rectal NETs, surgical excision might be substituted by EUS-FNA or by regular follow-up with imaging modalities if EUS-FNA is impossible or does not help in the diagnosis. However, little is known about the adequate follow-up interval in these kinds of situations. On the other hand, if the locally excised primary lesions demonstrate grade 2 histology and any lesions suspected of metastasis are present, either EUS-FNA or surgical excision should be considered to rule out the possibility of metastasis. FDG-PET may also be useful for the staging of grade 2 or 3 NETs compared with grade 1 NETs.
18
Generalization of the information presented in this extremely rare case should be avoided. Nonetheless, to the best of our knowledge, the natural course of untreated perirectal lymph node metastasis from a grade 1 rectal NET has never been previously described. Thus, this case discussed here can help clinicians understand the nature of metastatic lesions from small, grade 1 rectal NETs.