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Morphological subtypes of colorectal low-grade intraepithelial neoplasia: diagnostic reproducibility, frequency and clinical impact
  1. Corinna Lang-Schwarz1,
  2. Maike Büttner-Herold2,
  3. Stephan Burian1,
  4. Ramona Erber3,
  5. Arndt Hartmann3,
  6. Moritz Jesinghaus4,5,
  7. Kateřina Kamarádová6,
  8. Carlos A Rubio7,
  9. Gerhard Seitz8,
  10. William Sterlacci1,
  11. Michael Vieth1,
  12. Simone Bertz3
  1. 1Institute of Pathology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bayreuth, Germany
  2. 2Department of Nephropathology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany
  3. 3Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  4. 4Institute of Pathology, Technical University of Munich, Munich, Germany
  5. 5Institute of Pathology, University Hospital Marburg, Marburg, Germany
  6. 6The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic
  7. 7Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
  8. 8Institute of Pathology, Klinikum Bamberg, Bamberg, Germany
  1. Correspondence to Dr Corinna Lang-Schwarz, Institute of Pathology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bayreuth 95445, Germany; Corinna.Lang-Schwarz{at}


Aims Special histomorphological subtypes of colorectal low-grade intraepithelial neoplasia (LGIN) with variable prognostic impact were recently described in patients with inflammatory bowel disease (IBD) referred to as non-conventional dysplasia. However, they can also be found in patients without IBD. We aimed to analyse the reproducibility, frequency and prognostic impact of non-conventional colorectal LGIN in patients with and without IBD.

Methods Six pathologists evaluated 500 specimens of five different LGIN-cohorts from patients with and without IBD. Non-conventional LGIN included hypermucinous, goblet cell-deficient, Paneth cell-rich and crypt cell dysplasia. A goblet cell-rich type and non-conventional LGIN, not otherwise specified were added. Results were compared with the original expert-consented diagnosis from archived pathology records.

Results Four or more pathologists agreed in 86.0% of all cases. Non-conventional LGIN was seen in 44.4%, more frequently in patients with IBD (52%; non-IBD: 39.3%, p=0.005). In patients with IBD non-conventional LGIN associated with more frequent and earlier LGIN relapse (p=0.006, p=0.025), high-grade intraepithelial neoplasia (p=0.003), larger lesion size (p=0.001), non-polypoid lesions (p=0.019) and additional risk factors (p=0.034). Results were highly comparable with expert-consented diagnoses. In patients without IBD, non-conventional LGIN may indicate a higher risk for concurrent or subsequent colorectal carcinoma (CRC, p=0.056 and p=0.061, respectively). Frequencies and association with high-grade intraepithelial neoplasia or CRC varied between the different LGIN subtypes.

Conclusions Non-conventional histomorphology in colorectal LGIN is frequent and highly reproducible. Our results indicate an increased risk for CRC in patients with non-conventional LGIN, probably independent of IBD. We recommend reporting non-conventional LGIN in routine pathology reports.

  • Histology
  • Intestine, Large
  • Inflammatory Bowel Diseases

Data availability statement

Data are available upon reasonable request. The data sets used and analysed during the current study are available from the corresponding author on reasonable request.

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Data availability statement

Data are available upon reasonable request. The data sets used and analysed during the current study are available from the corresponding author on reasonable request.

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  • Handling editor Runjan Chetty.

  • Contributors CL-S performed study concept, design, development of methodology and writing. MB-H and SBe performed review and revision of the paper. CL-S, MB-H, RE, SBu, SBe, WS, GS, MV and KK were involved in data acquisition. CL-S performed analysis and interpretation of data, and statistical analysis. AH, MJ, WS, MV and CAR performed review of the paper as well as supervision. MV and SBe contributed equally to the work and share last authorship. All authors read and approved the final paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.