English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

We present two rare cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon. A literature search revealed only three published cases with similar histology but none of these reports provided profound molecular and mutational analyses. Our two cases exhibited a distinct, colon‐like immunophenotype with strong nuclear CDX2 and  β ‐catenin expression in more than 90% of the tumour cells of both components. We analysed the two carcinomas regarding microsatellite stability,  RAS ,  BRAF  and  PD‐L1  status. In addition, next‐generation panel sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 was performed. This approach revealed mutations in  FBXW7 ,  CTNNB1  and  PIK3CA  in the first case and  FBXW7  and  RB1  mutations in the second case. We looked for similar mutational patterns in three publicly available colorectal adenocarcinoma data sets, as well as in collections of colorectal mixed neuroendocrine‐non‐neuroendocrine neoplasms (MiNENs) and colorectal neuroendocrine carcinomas. This approach indicated that the  FBXW7  point mutation, without being accompanied by classical adenoma–carcinoma sequence mutations, such as  APC ,  KRAS  and  TP53 , likely occurs at a relatively high frequency in mixed neuroendocrine and squamous cell carcinoma and therefore may be characteristic for this rare tumour type.  FBXW7  codifies the substrate recognition element of an ubiquitin ligase, and inactivating  FBXW7  mutations lead to an exceptional accumulation of its target  β ‐catenin which results in overactivation of the Wnt‐signalling pathway. In line with previously described hypotheses of de‐differentiation of colon cells by enhanced Wnt‐signalling, our data indicate a crucial role for mutant  FBXW7  in the unusual morphological switch that determines these rare neoplasms. Therefore, mixed large cell neuroendocrine and a squamous cell carcinoma can be considered as a distinct carcinoma entity in the colon, defined by morphology, immunophenotype and distinct molecular genetic alteration(s).

the journal of pathology: clinical research

Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity