Appendiceal mucinous neoplasms: Optimizing treatment strategies based on clinical, histological, and molecular features

Table 1 Comparison of pathological features of low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, and invasive mucinous adenocarcinomas

Criteria	LAMN	HAMN	Invasive mucinous adenocarcinoma
WHO criteria	Mucinous epithelial tumor with low atypia; mild cellular atypia without invasive growth; loss or thinning of the lamina muscularis; submucosal fibrosis; flattening or pushing growth of the tumor epithelium	Severe cellular atypia; loss of nuclear polarity, multilayered nuclei throughout all layers, enlarged and hyperchromatic nuclei, and an active mitotic profile are observed; patterns of non-invasive growth; the tumor demonstrates a ‘pushing-type’ growth pattern and lacks a clear invasive profile; similar to LAMN, the mucosa-specific layer and mucosal muscle plate disappear, accompanied by fibrosis of the submucosal layer; resembles LAMN, except for distinct foci of high-grade dysplasia	More than 50% of the tumor tissue consists of mucus, with glandular duct structures and epithelial cells suspended within it; mucinous adenocarcinoma exhibiting moderate to severe atypia
PSOGI criteria	Mucinous neoplasm exhibiting low-grade cytologic atypia; loss of the muscularis mucosae; submucosal fibrosis; pushing invasion (characterized by expansile or diverticulum-like growth); dissection of acellular mucin within the wall; undulating or flattened growth of the epithelium; appendiceal rupture; mucin and/or cells beyond the appendix	Mucinous neoplasm exhibiting the architectural features of LAMN, lacking infiltrative invasion, but demonstrating high-grade cytologic atypia	Mucinous neoplasm with infiltrative growth; features of infiltrative invasion include tumor budding (discohesive single cells or small clusters of up to five cells) and/or small, irregular glands typically embedded in a desmoplastic stroma with a proteoglycan-rich extracellular matrix and activated fibroblasts/myofibroblasts exhibiting vesicular nuclei

HAMN: High-grade appendiceal mucinous neoplasm; LAMN: Low-grade appendiceal mucinous neoplasm; PSOGI: Peritoneal Surface Oncology Group International; WHO: World Health Organization.