Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma

The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

“…Four studies had overlapping cohorts [21][22][23][24], leaving twenty-eight independent studies with a total of 11423 patients [9,. Two studies did not find a significant survival difference for any H&E-based method [9,37], whereas the other twenty-six studies found significantly prolonged survival for patients with higher local inflammatory infiltrate with a total number of 10887 patients [25][26][27][28][29][30][31][32][33][34][35][36][38][39][40][41][42][43][44][45][46][47][48][49][50][51].…”

“…Fourteen studies reported CLR or plasma cell counts although three of these had overlapping cohorts [21,22,24], leaving eleven independent studies comprising a total of 6595 patients, all of which found a significantly better survival for high CLR [23,26,28,36,41,43,45,46,[48][49][50]. Seven independent studies (3803 patients) used the Graham-Appelman (G-A) method of assessment: four of these (2337 patients) used a cut-off of greater that one (grouping absent and mild together) [28,46,48,54], of which only one found that CLR was not associated with survival and this was in a cohort of solely MSI tumours [54]; while the other three (1466 patients) used a cut-off of greater than zero (grouping mild and intense together) [22,26,36], of which one found that CLR was not associated with survival [22].…”

In reply to ‘Hynes et al. Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population‐based study’

“…Hynes et al . employed semiquantitative assessment of the CLR as described by Graham and Appelman; however, it has recently been reported that more objective assessment of lymphoid follicle density or size increases not only reproducibility, but also prognostic value . Similarly, although not associated with survival, it is of interest that the ‘focal’ assessment of TSP reflects a refinement of the previously described ‘global’ assessment, and again has previously been internationally validated in the context of retrospective analysis of clinical trial data …”

Towards tumor immunodiagnostics

“…These structures are usually located at the periphery and beyond the confines of tumors, such as colorectal, breast or lung carcinomas. In the colon, they are usually noted around the muscularis propria or in the pericolic adipose tissue and because they are reminiscent of Crohn's disease they are called Crohn's-like reaction (CLR) (24,25). They are considered as tertiary lymphoid organs developing as part of the adaptive immune response to the tumor (25), are associated with prominent tumor infiltration by effectormemory CD8+ T cells and are considered important in educating CD8+ TILs in situ in order to control tumor growth (23,26,27).…”