Pathologic Calcification

Pathologic calcification is the abnormal tissue deposition of calcium salts, together with smaller amounts of iron,magnesium, and other mineral salts. There are two forms of pathologic calcification.When the deposition occurs locally in dying tissues it is known as dystrophic calcification; it occurs despite normal serum levels of calcium and in the absence of derangements in calcium metabolism. In contrast, the deposition of calcium salts in otherwise normal tissues is known as metastatic calcification, and it almost always results from hypercalcemia secondary to some disturbance in calcium metabolism

Dystrophic Calcification

Dystrophic calcification is encountered in areas of necrosis, whether they are of coagulative, caseous, or liquefactive type, and in foci of enzymatic necrosis of fat. Calcification is almost always present in the atheromas of advanced atherosclerosis. It also commonly develops in aging or damaged heart valves, further hampering their function.Whatever the site of deposition, the calcium salts appear macroscopically as fine, white granules or clumps, often felt as gritty deposits. Sometimes a tuberculous lymph node is virtually converted to stone. 

This is dystrophic calcification in the wall of the stomach. At the far left is an artery with calcification in its wall. There are also irregular bluish-purple deposits of calcium in the submucosa. Calcium is more likely to be deposited in tissues that are damaged.

MORPHOLOGY

Histologically, with the usual hematoxylin and eosin stain, calcium salts have a basophilic, amorphous granular, sometimes clumped appearance. They can be intracellular, extracellular,or in both locations. In the course of time, heterotopic bone may be formed in the focus of calcification. On occasion single necrotic cells may constitute seed crystals that become encrusted by the mineral deposits. The progressive acquisition of outer layers may create lamellated configurations, called psammoma bodies because of their resemblance to grains of sand. Some types of papillary cancers (e.g., thyroid) are apt to develop psammoma bodies. In asbestosis, calcium and iron salts gather about long slender spicules of asbestos in the lung, creating exotic, beaded dumbbell forms. 

Metastatic Calcification

Metastatic calcification may occur in normal tissues whenever there is hypercalcemia. Hypercalcemia also accentuates dystrophic calcification. There are four principal causes of hypercalcemia: 

1. Increased secretion of parathyroid hormone (PTH) with subsequent bone resorption, as in hyperparathyroidism due to parathyroid tumors, and ectopic secretion of PTH-related protein by malignant tumors  
2. Resorption of bone tissue, secondary to primary tumors of bone marrow (e.g., multiple myeloma,leukemia) or diffuse skeletal metastasis (e.g., breast cancer), accelerated bone turnover (e.g., Paget disease), or immobilization;
3. Vitamin D–related disorders, including vitamin D intoxication, sarcoidosis (in which macrophages activate a vitamin D precursor), and idiopathic hypercalcemia of infancy (Williams syndrome), characterized by abnormal sensitivity to vitamin D; and 
4. Renal failure, which causes retention of phosphate, leading to secondary hyperparathyroidism.

Here is so-called "metastatic calcification" in the lung of a patient with a very high serum calcium level (hypercalcemia).

Less common causes include aluminum intoxication, which occurs in patients on chronic renal dialysis, and milk-alkali syndrome, which is due to excessive ingestion of calcium and absorbable antacids such as milk or calcium carbonate. 

Metastatic calcification may occur widely throughout the body but principally affects the interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, and pulmonary veins. Although quite different in location, all of these tissues excrete acid and therefore have an internal alkaline compartment that predisposes them to metastatic calcification. In all these sites, the calcium salts morphologically resemble those described in dystrophic calcification. Thus, they may occur as noncrystalline amorphous deposits or, at other times, as hydroxyapatite crystals.Usually the mineral salts cause no clinical dysfunction, but on occasion massive involvement of the lungs produces remarkable x-ray images and respiratory compromise.Massive deposits in the kidney (nephrocalcinosis) may in time cause renal damage .

Important MCQs

• Calcification starts in mitochondria or microsomal vesicles , except for kidney, starts in basement membrane
• Lungs is the most common site for metastatic calcification
• Causes of Psammoma Body
• @MOST for PG
• Meningoma, Mesothelima of pleura and peritoneum
• Papillary carcinoma of Ovary
• Papillary carcinoma of Salivary gland
• Papillary carcionoma of Thyroid
• Prolactinoma,
• Glucoganoma

Reference:

• Robbins and Cotran Pathological Basis of Disease 9/E
• The Internet Pathology Laboratory for Medical Education