OPBSPathologyMusculoskeletalVigorita chapter 2
Must Know
- Crystal formation needs raised local calcium and phosphate, a nucleator, or removal of inhibitors.
- Matrix vesicles about 100 nm across bud from chondrocytes and osteoblasts and seed hydroxyapatite.
- Phase one is vesicle driven and ALP dependent. Phase two is collagen regulated crystal propagation.
- Pyrophosphate and noncollagenous proteins inhibit calcification. ALP removes pyrophosphate.
- Mitochondria store calcium and phosphate inside cells.
- Metastatic calcification follows high serum calcium or phosphate.
- Dystrophic calcification occurs with normal serum levels in damaged tissue.
- Calcification of almost any type can progress to ossification on histology.
- Deposits look alike in most syndromes, granular nonrefractile aggregates, sometimes with giant cells (granulomatous calcification).
| Type | Serum calcium and phosphate | Examples | Sites |
|---|---|---|---|
| Metastatic | Raised | Hyperparathyroidism, sarcoidosis, vitamin D excess, milk alkali, renal failure, tumoral calcinosis | Kidney, lung, arterial media, stomach, periarticular tissue |
| Dystrophic | Normal | Trauma, dermatomyositis, scleroderma, lupus, calcific tendinitis, infection, tumours | Skin and subcutis, extensor surfaces, fingertips |
More on calcinosis patterns
- Calcinosis circumscripta is localised over extensor surfaces and fingertips.
- Calcinosis universalis is widespread in subcutaneous tissue.
- Primary hyperparathyroidism is the prototype metastatic calcification syndrome.
- Sarcoidosis causes hypercalcaemia in about 15 percent through raised 1,25 vitamin D from granulomas.
- Sarcoid lacy lytic change affects the small bones of the hands and feet.
- Hypophosphatasia shows how ALP deficiency impairs mineralisation.
Tumoral Calcinosis
- Large painless lobulated juxta-articular masses at pressure points, often bilateral.
- Elbows, buttocks and knees are favoured.
- Familial hyperphosphataemic form involves GALNT3, FGF23 or KLOTHO. Normophosphataemic form involves SAMD9.
- Deposits are hydroxyapatite, chalky or milky, ringed by histiocytes and osteoclast-like giant cells.
- Crystals are larger and better formed than bone mineral.
- Radiographs show dense lobulated masses around but not within joints.
- Excision has high recurrence. Phosphate restriction and binders slow new masses but rarely dissolve old ones.
Connective Tissue Disease and Renal Failure
- Dermatomyositis. Calcification along muscle and fascial planes years after onset. Periarticular osteoporosis. Floppy thumb from IP subluxation.
- Scleroderma. Calcification in up to a quarter, mostly hands, with tuft resorption. Part of CREST.
- Renal failure. Raised phosphate, secondary hyperparathyroidism, alkalosis and aluminium all contribute.
- Calciphylaxis. Up to 4 percent of end stage renal failure. Painful necrotic skin from mural arteriolar calcification. Mortality 60 to 80 percent.
Local Calcification Syndromes
| Condition | Crystal or tissue | Pattern |
|---|---|---|
| Calcific tendinitis | Hydroxyapatite after chondroid metaplasia | Supraspinatus insertion, may resolve in 6 to 10 weeks |
| Milwaukee shoulder | Basic calcium phosphate with collagenase | Large cuff tear with glenohumeral destruction |
| Calcific myonecrosis | Dystrophic in necrotic muscle | Lower limb, decades after compartment syndrome |
| Pellegrini-Stieda | Post-traumatic dystrophic | Medial collateral ligament of the knee |
| Tumoral CPPD | Positively birefringent CPPD | Single juxta-articular mass, other joints spared |
| Disc calcification | Unclear | Elderly annulus in lower thoracic spine. Children nucleus in cervical spine, painful |
- Calcification occurs at least microscopically in almost every soft tissue tumour.
- Giant cell tumour of tendon sheath and PVNS are the noted exceptions.
- Cartilaginous tumours calcify most often.
- Fat necrosis can calcify.
Spinal Ligament Ossification
| Disorder | Main ligament | Favoured level |
|---|---|---|
| DISH (Forestier) | Anterior longitudinal | Thoracolumbar |
| OPLL | Posterior longitudinal | Cervical |
| OLF | Ligamentum flavum | Lower thoracic, middle age |
- The three overlap, and OPLL may be a partial form of DISH.
- DISH preserves disc spaces and can cause dysphagia in the neck.
- Isotretinoin can cause DISH-like ligament ossification within a year.
Numbers to Remember
- Matrix vesicle. About 100 nm.
- Sarcoid hypercalcaemia. About 15 percent.
- Scleroderma calcification. Up to 25 percent.
- Calciphylaxis. Up to 4 percent of end stage renal failure, 60 to 80 percent mortality.
- DISH. About 25 percent prevalence in some populations.
Memory Aids
- Metastatic means metabolic. Abnormal serum, normal tissue. Dystrophic means damaged tissue, normal serum.
- Neck, chest, junction. OPLL cervical, OLF lower thoracic, DISH thoracolumbar.
Exam Traps
- Tumoral calcinosis lies around joints and never inside them.
- Lowering serum phosphate does not dissolve existing tumoral calcinosis deposits.
- Calcification in scleroderma and dermatomyositis is dystrophic with normal serum calcium.
- PVNS and giant cell tumour of tendon sheath do not calcify.
Source
Vigorita VJ, Ghelman B, Mintz D. Skeletal and Extraskeletal Calcification and Ossification Syndromes. In. Orthopaedic Pathology. 3rd ed. Philadelphia, Wolters Kluwer, 2016. Chapter 2.
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 17 October 2026.