Esophageal carcinoma with SMARCA4 mutation: Unique diagnostic challenges

Area of Science:

• Oncology
• Pathology
• Molecular Biology

Background:

• Esophageal carcinoma with SMARCA4 deficiency or dysfunction is a recently identified condition.
• SMARCA4 mutations, including deep deletions and missense mutations, are implicated in this rare entity.

Purpose of the Study:

• To describe the clinicopathologic features of esophageal carcinoma associated with SMARCA4 mutations.
• To highlight diagnostic challenges and necessary molecular tools for accurate classification.

Main Methods:

• Clinicopathologic analysis of four cases with SMARCA4 mutations.
• Histological examination, including assessment of mitotic activity, nuclear features, glandular, and rhabdoid morphology.
• Immunohistochemistry for BRG1 and next-generation sequencing for SMARCA4 and TP53 mutations.

Main Results:

• Four cases (3 males, 1 female; age 45-68) exhibited variable morphology, including frequent mitoses, large nuclei, and occasional glandular or rhabdoid features.
• SMARCA4 deep deletion or mutation was confirmed by next-generation sequencing.
• TP53 mutations were present in all three cases with SMARCA4 deep deletion.
• Two patients died within 78 days; others showed poor treatment response.

Conclusions:

• Esophageal carcinoma with SMARCA4 mutation poses diagnostic difficulties for pathologists due to variable morphology and immunoprofile.
• Accurate diagnosis necessitates recognizing the morphological spectrum and employing BRG1 immunostaining and next-generation sequencing.