Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

Area of Science:

• Gastroenterology
• Surgical Pathology
• Molecular Pathology

Background:

• Colorectal medullary carcinoma is recognized as a distinct histologic subtype by the World Health Organization.
• It is often considered to have a unique molecular pathogenesis and improved prognosis.
• A key question is the diagnostic reproducibility of this entity.

Purpose of the Study:

• To assess the diagnostic reproducibility of colorectal medullary carcinoma using World Health Organization criteria.
• To investigate the clinicopathologic features and prognostic implications of colorectal medullary carcinoma.
• To determine if colorectal medullary carcinoma is a distinct entity with prognostic relevance.

Main Methods:

• Analysis of 80 colorectal adenocarcinomas with a dominant solid growth pattern.
• Detailed morphological description of the spectrum from classic medullary histology to nonmedullary poorly differentiated histologies.
• Interobserver agreement assessment among 5 gastrointestinal pathologists using 2010 World Health Organization criteria.
• Classification into "classic medullary," "indeterminate medullary," and nonmedullary poorly differentiated tumors.
• Evaluation of mismatch repair protein deficiency and survival in relation to tumor groups.

Main Results:

• Significant morphological overlap was observed between medullary carcinoma and its mimics.
• Interobserver agreement for diagnosing medullary carcinoma was poor (κ=0.157).
• Medullary and indeterminate medullary tumors were more likely to exhibit mismatch repair protein deficiency compared to nonmedullary tumors (P<.001).
• No significant survival benefit was detected for medullary or indeterminate medullary tumors compared to nonmedullary tumors.

Conclusions:

• The diagnosis of colorectal medullary carcinoma, as currently applied, may primarily indicate an increased likelihood of mismatch repair deficiency.
• Further evidence and a more objective classification system are required to establish medullary carcinoma as a distinct entity with prognostic relevance.
• Caution is advised when diagnosing medullary carcinoma and comparing study results until further evidence is available.