STEPTRACKERGENERAL PRINCIPLES | PATHOLOGY | HIGH-YIELD REVIEW

Calcification & Pigments

What gets deposited in tissue, why it is there, and the stain that proves it.

FOCUS ON
Dystrophic calcification forms in damaged tissue and serum calcium is normal. Metastatic calcification forms in normal tissue because Ca²⁺ × phosphate is high. Psammoma bodies point to a short list of tumors. Know the colors and stains of hemosiderin, lipofuscin and melanin.
DEPOSIT
WHAT IT IS · MECHANISM
LOOK · STAIN
CLASSIC SETTING
Dystrophic calcification
damaged tissue · normal Ca²⁺
Dying cells release phosphate-rich membrane fragments that nucleate calcium phosphate crystals.
Basophilic (purple) granules on H&E; Alizarin red / von Kossa positive
Atherosclerotic plaque, calcific aortic stenosis, fat necrosis, TB granulomas, old infarcts
Metastatic calcification
normal tissue · ↑ Ca²⁺ or PO₄³⁻
High serum Ca²⁺ × phosphate product drives deposition into healthy interstitium.
Widespread; favors tissues that lose acid and become alkaline
Kidney (nephrocalcinosis), lung, gastric mucosa, vessels — hyperparathyroidism, CKD, vitamin D excess, sarcoidosis, PTHrP tumors
Psammoma bodies
dystrophic, laminated
Single tumor cells die and calcify in concentric rings.
Round, onion-like lamellated purple spheres
Papillary thyroid carcinoma, serous ovarian carcinoma, meningioma, mesothelioma
Lipofuscin
"wear-and-tear" pigment
Oxidized, undigested membrane lipid left inside lysosomes after autophagy.
Yellow-brown, finely granular, perinuclear; not iron (Prussian blue negative)
Heart, liver, neurons of the elderly; brown atrophy
Hemosiderin
stored iron
Aggregated ferritin when iron is in excess, locally or systemically.
Golden-brown, coarse; Prussian blue positive
Bruise, "heart failure cells" in lung, hemochromatosis, transfusion hemosiderosis
Melanin
endogenous, non-iron
Melanocytes convert tyrosine to melanin and pass it to keratinocytes.
Brown-black; Fontana-Masson positive
Nevi, melanoma; diffuse ↑ in Addison disease (ACTH/MSH)
Bilirubin & carbon
yellow · black
Bilirubin: heme breakdown product. Carbon: inhaled coal dust taken up by macrophages.
Yellow tissue (jaundice) · black pigment in lung and hilar nodes
Jaundice, kernicterus · anthracosis in city dwellers and coal miners

Mechanism — two routes to calcium

Tissue injuryNecrosis
→
Phosphate exposedMembrane vesicles
→
DystrophicLocal, serum normal
↑ Ca²⁺ × PO₄³⁻PTH, CKD, vitamin D
→
Normal tissueAlkaline interstitium
→
MetastaticKidney, lung, stomach, vessels

In end-stage kidney disease, vessel calcification can produce calciphylaxis: painful skin necrosis.

Dystrophic vs metastatic

FEATURE
DYSTROPHIC
METASTATIC
Serum Ca²⁺/PO₄³⁻
Normal
High
Tissue
Damaged, necrotic
Normal
Spread
Local
Widespread
Key causes
Necrosis, atheroma, damaged valves
Hyperparathyroidism, CKD, vitamin D toxicity, milk-alkali
Iron
Prussian blue
Calcium
Alizarin red, von Kossa
Melanin
Fontana-Masson

How it's tested

COMMON CONFUSIONA calcified aortic valve in an elderly patient is dystrophic calcification. Serum calcium is normal, so do not call it metastatic.
THE TRAPThe fine-needle aspirate shows "concentric laminated calcifications." That describes psammoma bodies, so the answer is papillary carcinoma (thyroid) or serous carcinoma (ovary).
YOUR APPROACHCheck serum Ca²⁺ and phosphate: if high, the calcification is metastatic. If normal, look for preceding tissue damage (dystrophic). For pigment, ask iron or not, then match the stain.

If you see… think…

Elderly patient, calcified stenotic aortic valve, normal Ca²⁺ → dystrophic calcification
Laminated spheres in a thyroid nodule → papillary thyroid carcinoma
Same spheres in an ovarian mass → serous carcinoma; in a dural mass → meningioma
Dialysis patient with painful necrotic skin plaques → calciphylaxis
Primary hyperparathyroidism with nephrocalcinosis → metastatic calcification
Prussian blue–positive macrophages in lung of HF patient → hemosiderin ("heart failure cells")
Yellow-brown perinuclear granules in an aged heart → lipofuscin
Coal miner with black hilar nodes → anthracosis (carbon)
Hyperpigmentation + hypotension + hyperkalemia → Addison disease (↑ MSH/ACTH)