Pathologic Calcification

1. Dystrophic Calcification

Definition

Key Features

Where It Occurs

• Areas of necrosis - coagulative, caseous, or liquefactive necrosis; enzymatic fat necrosis
• Atherosclerotic plaques - almost always present in advanced atheromas
• Aging or damaged heart valves - especially calcific aortic stenosis
• Tuberculous lymph nodes - may become virtually converted to stone
• Tumors - papillary cancers (thyroid) form psammoma bodies
• Parasitic infections - calcified cysts around Taenia solium, Onchocerca volvulus
• Scars, burns, keloids - any site of local tissue injury

Mechanism

1. Dying cells lose membrane integrity, allowing intracellular calcium influx
2. The acidity associated with cell damage may disrupt normal calcium handling
3. Necrotic cells or their debris serve as seed crystals (nidi)
4. Progressive mineral encrustation around the nidus

Morphology

• Macroscopic: fine white granules or clumps; gritty texture on cut section
• Microscopic (H&E): basophilic, amorphous granular to clumped deposits; can be intracellular or extracellular
• Special forms:
  • Psammoma bodies - lamellated (concentric ring) calcifications; seen in papillary thyroid carcinoma, meningioma, serous ovarian tumors
  • Asbestos bodies - calcium and iron deposited around asbestos spicules creating beaded dumbbell shapes
  • Heterotopic bone - may eventually form within old calcified foci

Clinical Significance

• May be an incidental marker of past cell injury (e.g., old TB)
• Can cause significant organ dysfunction: calcific aortic stenosis, acceleration of atherosclerosis

Robbins - The thickened, fibrotic semilunar cusps of the aortic valve with irregular masses of piled-up calcification behind each cusp.

2. Metastatic Calcification

Definition

Key Features

Causes of Hypercalcemia

1. Increased PTH secretion - primary hyperparathyroidism (parathyroid adenoma); ectopic PTH-related protein (PTHrP) from malignant tumors
2. Bone resorption - multiple myeloma, diffuse skeletal metastases (breast cancer), Paget disease, immobilization
3. Vitamin D-related disorders - vitamin D intoxication; sarcoidosis (macrophage-activated vitamin D precursor); Williams syndrome (idiopathic hypercalcemia of infancy)
4. Renal failure - phosphate retention triggers secondary hyperparathyroidism
5. Other - milk-alkali syndrome (excess calcium + absorbable antacids); aluminum intoxication (in dialysis patients)

In renal disease, metastatic calcification occurs when the calcium-phosphate product [Ca²⁺ (mg/dL) × PO₄ (mg/dL)] exceeds 70-80. - Tintinalli's Emergency Medicine

Preferred Sites

• Lungs (alveolar septa, bronchiolar and vessel walls - especially elastic fibers)
• Kidneys (nephrocalcinosis)
• Gastric mucosa
• Systemic arteries and pulmonary veins

Morphology

• Calcium salts appear identical to those in dystrophic calcification: basophilic, amorphous, granular deposits on H&E
• May be non-crystalline amorphous deposits or hydroxyapatite crystals
• In the lung: selective early deposition on elastic fibers (ultrastructurally)

Fishman's Pulmonary Diseases - Calcium forming a dark red precipitate within the alveolar septa (Alizarin red ×280).

Clinical Significance

• Usually clinically silent
• Massive pulmonary involvement can cause radiographic opacities mimicking pneumonia and respiratory compromise
• Massive renal deposits (nephrocalcinosis) can lead to renal failure
• Chest CT is more sensitive than plain film for detection; bone scan agents (⁹⁹ᵐTc-MDP, ¹⁸F-NaF) show increased uptake

Side-by-Side Comparison

Mixed Calcification