A 55-year-old miner with 20 years of coal dust exposure has bilateral upper lobe nodules with progressive massive fibrosis (PMF) on CT. Histology shows black pigment deposits with stellate fibrotic nodules. The pathophysiology involves activation of which key cellular pathway?

• A Type II pneumocyte hyperplasia directly secreting excess collagen
• B Mast cell degranulation releasing histamine causing chronic bronchoconstriction
• C NK cell-mediated killing of dust-laden macrophages releasing fibrogenic cytokines
• D Alveolar macrophage activation releasing NLRP3 inflammasome-driven IL-1β and TGF-β, stimulating fibroblast proliferation ✓

Explanation

In coal worker's pneumoconiosis and silicosis, inhaled dust particles are phagocytosed by alveolar macrophages, activating the NLRP3 inflammasome (by crystalline silica or carbon nanoparticles) and releasing IL-1β, TNF-α, and TGF-β. These cytokines stimulate fibroblast proliferation and collagen deposition, leading to nodular fibrosis progressing to progressive massive fibrosis. The fibrosis is not directly from pneumocytes or mast cells; NK cells play a minor role in this process.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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