A gyulladásos bélbetegséggel (IBD) élő betegekben a colorectalis carcinoma kialakulásának esélye az átlagpopulációban észleltek kétszerese. Az invazív daganatokat megelőzően ezekben a betegekben nagyobb a rizikó dysplasia kialakulására is. Az utóbbi években számos, IBD-hez társult, ún. non-conventionalis dysplasia altípust azonosítottak, melyekről a jelenleg is zajló kutatásoknak köszönhetően egyre több információval rendelkezünk. Egy 62 éves, 14 éve relabáló colitis ulcerosával diagnosztizált és kezelt nőbeteg subtotalis colectomiás preparátumában colitis ulcerosa mellett a sigmabélben invazív adenocarcinomát azonosítottunk mucinosus területekkel. A daganat közvetlen környezetében kehelysejtszegény, valamint hypermucinosus IBD-hez társult, non-conventionalis dysplasiát észleltünk, az utóbbinak intestinalis és foveolaris altípusa is elkülöníthető volt. A felhalmozódó ismeretek tükrében az IBD-hez társult, non-conventionalis dysplasiák ismerete több szempontból is fontos lehet a diagnosztikában és a klinikai ellátásban, ugyanis ezek a laesiók makroszkóposan laposak vagy láthatatlanok lehetnek, megnehezítve a dysplasia endoszkópos szűrését. Ismeretük a patológus számára kiemelten fontos, hiszen a reaktív és reparatív folyamatoktól való elkülönítésük sokszor nagy kihívást jelent. Továbbá, a hagyományos típusoknál gyakrabban társultak ’high-grade’ dysplasiával, valamint colorectalis carcinomával. Molekuláris hátterüket tekintve, sokkal gyakrabban észlelhető bennük aneuploidia. Mindezen ismeretek a hagyományos neoplasiákhoz képest rosszabb prognózis rizikót vetítenek elő, és az esetlegesen nehezen azonosítható endoszkópos képüket is figyelembe véve felismerésük után az IBD-s betegek szorosabb utánkövetése és esetleges véletlenszerű biopsziás mintavétel mérlegelendő. Orv Hetil. 2023; 164(51): 2039–2044.

OBJECTIVE: Patients with Crohn\'s disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs.
RESULTS: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313).
CONCLUSIONS: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs.

Compared to the general population, patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) or Crohn\'s disease (CD), are at increased risk of developing some cancers, particularly colorectal cancers (CRC). CRCs, the vast majority of which are adenocarcinomas, develop from a precancerous lesion called dysplasia (or intraepithelial neoplasia) via an inflammation-dysplasia-adenocarcinoma sequence. The advancements of new endoscopic techniques, including visualisation and resection techniques, has led to a reclassification of dysplasia lesions into visible and invisible lesions and their therapeutic management, with a more conservative approach to the colorectal setting. In addition, besides conventional dysplasia, of intestinal phenotype, classically described in IBD, non-conventional dysplasias (as opposed to conventional dysplasia of intestinal phenotype) are now described, including at least seven subtypes. Recognition of these unconventional subtypes, which are still poorly known from pathologists, is becoming crucial, as some of these subtypes appear to be at high risk of developing advanced neoplasia (i.e. high-grade dysplasia or CRC). This review briefly describes the macroscopic features of dysplastic lesions in IBD, as well as their therapeutic management, followed by the clinicopathological features of these dysplastic lesions, with particular emphasis on the new subtypes of unconventional dysplasia, both from a morphological and molecular point of view.

Most Crohn\'s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.