Clinicopathologic features of colorectal carcinoma by histologic subtypes
| Histologic subtype | Reported incidence | Required diagnostic criteria | Unique features | Prognostic implications |
| Serrated adenocarcinoma | 8–10% | No defined criteria, but serrations most specific No required cut-off, but>5% of tumour suggested | Morphology may overlap with mucinous and micropapillary patterns | Unclear |
| Micropapillary adenocarcinoma | 5–19% | Nests of≥5 tumour cells, devoid of fibrovascular cores, with no central lumen Micropapillary architecture comprising≥5% of tumour | Inside-out morphology Mimics: LVI, tumour buds, and poorly differentiated clusters | Possible high rates of LVI and lymph node metastasis Indeterminate survival |
| Medullary carcinoma | Up to 4% | Sheets of malignant cells with prominent nucleoli and abundant eosinophilic cytoplasm No required percentage cut-off | Pushing invasion Brisk inflammation, lymphocytes or neutrophils Frequently dMMR and CDX-2 negative | Likely favourable outcome |
| Neuroendocrine carcinoma | <1% |
Small cell type
: Solid growth pattern, malignant cells with N:C ratio, hyperchromatic nuclei, inconspicuous nucleoli, brisk mitoses and prominent necrosis Large cell type : Solid trabecular nests of malignant cells with abundant cytoplasm, prominent nucleoli, brisk mitoses, and abundant necrosis, with≥1 positive neuroendocrine marker | MiNEN: Mixed tumours with≥30% each of neuroendocrine and non-neuroendocrine components (NOS>SCC) | Worse prognosis than NOS |
| Mucinous adenocarcinoma | 10–20% | Mucinous areas comprising>50% of tumour Large pools of extracellular mucin with floating malignant glands | May have minor components of signet-ring cells and micropapillary features Frequently dMMR | Comparable to NOS HES1 loss associated with worse prognosis |
| Signet-ring cell carcinoma | Up to 1% | Signet-ring cells comprising>50% of tumour | May coexist with mucinous features Frequently dMMR Reporting as features is recommended even when≤50% | Worse outcome than NOS Subset may benefit from ICI-targeted therapy |
| Adenosquamous carcinoma | <0.1% | Presence of distinct or admixed glandular and squamous components No required percentage cutoffs for components | Diagnostic considerations: Endometrioid adenocarcinoma with squamous differentiation, anal SCC with rectal involvement (if pure SCC) | Squamous features linked to poor prognosis |
dMMR, deficient mismatch repair; ICI, immune checkpoint inhibitor; LVI, lymphovascular invasion; MiNEN, mixed neuroendocrine non-neuroendocrine neoplasm; N:C, nuclear to cytoplasmic; NOS, conventional adenocarcinoma not otherwise specified; SCC, squamous cell carcinoma.