A 55-year-old postmenopausal woman has a 2.5 cm breast lump. Core biopsy shows infiltrating lobular carcinoma (ILC). Which molecular alteration is the hallmark of ILC and explains its characteristic 'Indian file' growth pattern and diffuse infiltration without forming a mass?

• A Loss of E-cadherin (CDH1 mutation/deletion) causing failure of cell-cell adhesion, resulting in single-file infiltration ✓
• B HER2 amplification with loss of cell-cell contact mediated by E-cadherin loss
• C BRCA1 mutation causing a triple-negative phenotype with solid growth pattern
• D PIK3CA mutation with AKT hyperactivation causing spindle cell metaplasia

Explanation

Invasive lobular carcinoma is defined by loss of E-cadherin (CDH1 gene), which encodes a transmembrane glycoprotein mediating Ca2+-dependent homotypic cell-cell adhesion. CDH1 loss (mutation, LOH, promoter methylation) causes cells to lose cohesion, enabling single-cell infiltration in 'Indian file' or 'targetoid' patterns around existing structures without forming a distinct mass or eliciting desmoplastic reaction. This also makes ILC radiologically occult on mammography. ILC is typically ER+/PR+/HER2-negative. Molecularly, ILC also frequently has CDH1 and FOXA1 mutations (TCGA data), distinct from IDC.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.