JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

A paired sequencing study of goblet cell adenocarcinomas with coincident sessile serrated lesions and low-grade appendiceal mucinous neoplasms

  • 0Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., Boston, MA, 02115, USA.
Virchows Archiv : an International Journal of Pathology +

|

September 19, 2025

|

September 19, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Goblet cell carcinoma (GCA) of the appendix does not appear to arise from precursor lesions like sessile serrated lesions (SSLs) or low-grade appendiceal mucinous neoplasms (LAMNs). Genetic analysis revealed GCAs are clonally unrelated to these coincident appendiceal lesions.

Area Of Science

  • Gastroenterology
  • Oncology
  • Molecular Pathology

Background

  • Goblet cell carcinoma (GCA) is a rare appendiceal tumor lacking a known precursor.
  • Co-occurrence of GCA with sessile serrated lesions (SSLs) and low-grade appendiceal mucinous neoplasms (LAMNs) has been observed.
  • Understanding the clonal relationship between GCA and other appendiceal lesions is crucial for diagnosis and treatment.

Purpose Of The Study

  • To investigate the potential clonal relationship between appendiceal goblet cell carcinoma (GCA) and coincident sessile serrated lesions (SSLs) or low-grade appendiceal mucinous neoplasms (LAMNs).
  • To compare the genetic landscape of GCA with conventional appendiceal adenocarcinomas and their associated precursor lesions.

Main Methods

  • Paired next-generation sequencing was performed on six appendiceal goblet cell carcinomas (GCAs) with coincident SSLs or LAMNs.
  • Three conventional appendiceal adenocarcinomas with goblet cell differentiation and coincident SSLs or LAMNs were also sequenced.
  • Somatic alterations in GCA, SSLs, LAMNs, and conventional adenocarcinomas were analyzed to identify shared mutations.

Main Results

  • All nine sequenced SSLs or LAMNs harbored activating KRAS mutations.
  • No shared somatic alterations were found between the six GCAs and their coincident SSLs or LAMNs.
  • GCAs showed alterations in ARID1A, ERBB2, RHOA, and ARHGAP35, distinct from KRAS mutations in precursor lesions.
  • Conventional adenocarcinomas shared somatic alterations with their coincident SSLs/LAMNs, including in KRAS, SMAD4, and TP53.
  • GCAs were found to be clonally unrelated to coincident KRAS-mutant SSLs and LAMNs.

Conclusions

  • Appendiceal goblet cell carcinomas (GCAs) do not appear to originate from KRAS-mutated precursor lesions like SSLs or LAMNs.
  • The observed co-occurrence of GCA with SSLs/LAMNs may be coincidental, with the underlying reason remaining unclear.
  • Further research is needed to elucidate the pathogenesis of GCA and the association with other appendiceal neoplasms.

Keywords: