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Skin nontumor

Dermal collagen and elastic tissue alterations and metabolic disorders

Calcinosis cutis


Daisy Wu, M.D.
Dinesh Pradhan, M.D.

Last author update: 20 February 2025
Last staff update: 21 February 2025

Copyright: 2024-2025, PathologyOutlines.com, Inc.

PubMed Search: Calcinosis cutis

Daisy Wu, M.D.
Dinesh Pradhan, M.D.
Page views in 2024: 1,150
Page views in 2025 to date: 10,361
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Videos | Sample pathology report | Differential diagnosis | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2
Cite this page: Wu D, Pradhan D. Calcinosis cutis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorcalcinosiscutis.html. Accessed August 13th, 2025.
Definition / general
  • Benign deposition of insoluble calcium salts in the skin or subcutaneous tissue due to dystrophic, metastatic, iatrogenic, idiopathic or calciphylaxis etiologies
Essential features
  • Benign calcium deposition in skin or subcutaneous tissue due to pre-existing skin damage, systemic metabolic derangements, idiopathic etiologies or secondary to medical treatment or testing
  • Firm, skin colored to white / yellowish papules, plaques or nodules on the surface of the skin
  • Occasionally solitary but often multiple lesions are common; can ulcerate and extrude a white to yellow chalky substance
  • Histologically, basophilic finely granular to crystalline structures identified within the epidermis or subcutaneous tissue with occasional foreign body multinucleated giant cell reaction
  • Deposits can be confirmed to be calcium by von Kossa (black) or Alizarin Red S stain (red)
Terminology
  • Calcinosis circumscripta
    • Localized skin and subcutaneous calcifications predominantly around joints and extremities
  • Calcinosis universalis
    • Diffuse involvement of skin, subcutaneous tissues, muscles and tendons
ICD coding
  • ICD-10: L94.2 - calcinosis cutis
  • ICD-11
    • EB90.4 - calcification of skin or subcutaneous tissue
    • EB90.40 - dystrophic calcification of the skin of uncertain or unspecified etiology
    • EB90.4Y - other specified calcification of skin or subcutaneous tissue
Epidemiology
  • Dystrophic calcinosis cutis is a frequent manifestation of any systemic disease that causes tissue injury, such as autoimmune rheumatic diseases, including systemic sclerosis, dermatomyositis, mixed connective tissue disease and systemic lupus erythematous (J Rheumatol 2022;49:980)
  • Idiopathic calcinosis cutis of the scrotum occurs in men with an average age ranging from 27 to 47 years (J Med Case Rep 2018;12:366)
  • Subepidermal calcified nodules occur in children with a 2:1 male to female predominance (Dermatol Online J 2023;29:10)
  • Calciphylaxis typically affects patients with end stage renal disease (ESRD) (N Engl J Med 2018;378:1704)
    • Central calciphylaxis occurs more often in women and patients with a high body mass index and it carries a higher risk of death than peripheral lesions
Sites
  • Dystrophic
    • Often associated with autoimmune connective tissue diseases
    • Systemic sclerosis, scleroderma (CREST syndrome), systemic lupus erythematosus (SLE)
      • Hard, skin colored to white papules over bone prominences of the extremities (upper > lower)
    • Childhood / juvenile dermatomyositis
    • Sites of cutaneous tumors or cysts
    • Prior infectious sites, specifically cysts around larvae or worms
  • Metastatic
    • Benign, nodular calcification
      • Deposits occur in otherwise normal skin, especially around joints
  • Idiopathic
    • Subepidermal calcified nodules
      • Head and neck of children
    • Idiopathic calcinosis cutis of the scrotum
      • Scrotum of men
    • Tumoral calcinosis
      • Generally around joints
  • Iatrogenic
    • Previous sites of trauma, including heel sticks in neonates, injection sites and surgical scars
  • Calciphylaxis
    • 2 general locations: central (abdomen or thighs) or peripheral (restricted peripheral sites that have limited adipose tissue, such as digits) (N Engl J Med 2018;378:1704)
Pathophysiology
  • 5 subtypes
    • Dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, calciphylaxis (J Am Acad Dermatol 2011;65:1)
  • Dystrophic
    • Most common cause of calcinosis cutis
    • Tissue damage leads to
      • Phosphate binding proteins from dying cell, which leads to calcification
      • Chronic inflammation and vascular hypoxia
      • High mitochondrial calcium and phosphate levels lead to crystal formation and cell necrosis
      • Cytokines that lead to the formation of calcium salts: tumor necrosis factor, IL6, IL1β
    • Normal calcium and phosphorus levels
    • Associated with systemic diseases
      • Systemic sclerosis, dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjögren syndrome, porphyria cutanea tarda, mixed connective tissue disease
  • Metastatic
    • Deposition of calcium salts in the presence of abnormal serum calcium and phosphorus levels (calcium phosphate level above 70 mg2/dL2)
    • Most common cause is chronic kidney failure
  • Idiopathic
    • Scrotal calcinosis
      • Dystrophic calcification of cyst contents suspected
    • Subepidermal calcified nodule
      • Hypotheses of pathogenesis include generation and calcification of stroma, degranulation of mast cells and dystrophic calcification following dermal damage from unknown cause
  • Iatrogenic
    • Patients that are receiving calcium or phosphate containing substances
  • Calciphylaxis
    • Small vessel calcification that mainly affects blood vessels of the dermis or subcutaneous fat
    • Predominantly occurs in patients with end stage renal disease
    • Pathogenesis is uncertain but it is suspected that narrowed vessels lead to chronic, low grade ischemia, thrombosis and endothelial injury (N Engl J Med 2018;378:1704)
Etiology
  • Dystrophic
  • Metastatic
    • Deposition of calcium from elevated serum calcium and phosphorus levels (calcium phosphate level above 70 mg2/dL2)
  • Idiopathic
    • Deposition of calcium salts without underlying tissue damage or abnormal calcium or phosphate levels; cause uncertain
  • Iatrogenic
    • Administration of calcium or phosphate containing agents that induce precipitation of calcium salts
    • Trauma
  • Calciphylaxis
Clinical features
  • Dystrophic calcinosis cutis
    • Often associated with autoimmune connective tissue diseases
    • Systemic sclerosis, scleroderma (CREST syndrome), systemic lupus erythematosus (SLE)
      • Hard, skin colored to white papules over bone prominences of the extremities (upper > lower)
    • Childhood / juvenile dermatomyositis
    • Sites of cutaneous tumors or cysts
    • Associated with pseudoxanthoma elasticum, Werner syndrome, Ehlers-Danlos, pilomatrixoma, cysticercosis, histoplasmosis, cryptococcosis, trauma and burns (StatPearls: Calcinosis Cutis [Accessed 16 December 2024])
  • Metastatic calcinosis cutis
    • Benign nodular calcification
      • Deposits occur in otherwise normal skin, especially around joints
    • Associated with chronic kidney failure, hypervitaminosis D, hyperparathyroidism, sarcoidosis, milk alkali syndrome, malignant neoplasms (StatPearls: Calcinosis Cutis [Accessed 16 December 2024])
  • Idiopathic calcinosis cutis
    • Subepidermal calcified nodules
      • Head and neck of children
    • Idiopathic calcinosis cutis of the scrotum
      • Scrotum of men
    • Tumoral calcinosis
  • Iatrogenic calcinosis cutis
    • IV calcium gluconate, calcium chloride, para-aminosalicylic acid (J Vasc Access 2024;25:1860)
    • Seen after administration of electrodes with pastes containing calcium chloride for electroencephalography
    • Tumor lysis syndrome and calcinosis cutis after organ transplant (J Am Acad Dermatol 2011;65:1)
  • Calciphylaxis
    • Calciphylaxis causes painful skin lesions and may include induration, plaques, nodules, livedo or purpura
    • > 70% of patients require hospitalization for severe ulcers and can have ongoing pain, anorexia, insomnia and depression throughout life
    • Risk factors
      • End stage renal disease, female sex, obesity diabetes mellitus, hypercalcemia, hyperphosphatemia, hyperphosphatemia, hyperparathyroidism (both primary and secondary), overexpressed parathyroid hormone (PTH) with adynamic bone disease (low bone turnover), elevated alkaline phosphatase, vitamin K deficiency, hepatobiliary disease, thrombophilia, autoimmune disorder, hypoalbuminemia, metastatic cancers, POEMS syndrome, genetic polymorphisms, skin trauma, recurrent hypotension, rapid weight loss, exposure to ultraviolet light, exposure to aluminum, medication (N Engl J Med 2018;378:1704)
Diagnosis
  • May be suspected clinically in patients with risk factors
  • Thorough physical exam would include firm papules or nodules, especially if the papules or nodules extrude chalky white-yellow material (J Surg Case Rep 2024;2024:rjae068)
  • Skin biopsy of involved area confirms diagnosis and would demonstrate calcium deposits in the dermis or the subcutis (J Am Acad Dermatol 2011;65:1)
  • Xrays show hyperdense deposits in the cutaneous and subcutaneous tissues (J Surg Case Rep 2024;2024:rjae068)
Laboratory
Radiology description
Radiology images

Images hosted on other servers:
Amorphous and multilobulated calcification

Amorphous and multilobulated calcification

Calcium layering (CT)

Calcium layering (CT)

Inhomogeneous high signal intensity (T2 MRI)

Inhomogeneous
high signal
intensity
(T2 MRI)

Prognostic factors
  • Dystrophic calcinosis cutis (StatPearls: Calcinosis Cutis [Accessed 16 December 2024])
    • Manageable with the treatment of underlying autoimmune connective tissue disease
    • Sodium thiosulfate and calcium channel blockers (diltiazem) may be effective in some patients
  • Metastatic calcinosis cutis
    • Management of serum calcium levels
    • If symptomatic and feasible, surgical excision
  • Idiopathic calcinosis cutis
    • If symptomatic and feasible, surgical excision with resolution
  • Iatrogenic calcinosis cutis
    • If symptomatic and feasible, surgical excision with resolution
  • Calciphylaxis
    • Patients without end stage renal disease have a better prognosis (1 year mortality, 25 - 45%) than those who have end stage renal disease (1 year mortality, 45 - 85%)
    • Patients with central distribution of lesions (abdomen or thighs) have a higher risk of death than those with peripheral lesions (N Engl J Med 2018;378:1704)
Case reports
Treatment
  • Dystrophic calcinosis cutis (StatPearls: Calcinosis Cutis [Accessed 16 December 2024])
    • Treatment of underlying autoimmune connective tissue disease
    • Excision of localized deposits
    • Sodium thiosulfate and calcium channel blockers (diltiazem) may be effective in some patients
  • Metastatic calcinosis cutis
    • Management of serum calcium levels
    • If symptomatic and feasible, surgical excision
  • Idiopathic calcinosis cutis
    • If symptomatic and feasible, surgical excision
  • Iatrogenic calcinosis cutis
    • If symptomatic and feasible, surgical excision
  • Calciphylaxis (N Engl J Med 2018;378:1704)
    • Pain management: opioids, gabapentin, ketamine or application of spinal anesthetic agents used in refractory cases
    • Remove exudate and necrotic tissue to prevent infection
    • Sodium thiosulfate
      • Antioxidant and vasodilatory properties also inhibit adipocyte calcification and block the ability of adipocytes to induce calcification of vascular smooth muscle cells
    • Bisphosphonates
      • Pyrophosphate analogue used to treat patients with a genetic ENPP1 deficiency
    • Vitamin K1 supplementation
      • Slowed progression of preexisting coronary artery calcification by 6% at 3 year follow up
Gross description
  • White, chalky and nodular material within the epidermis or subcutaneous tissue
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Dinesh Pradhan, M.D.
Calcium deposit in subcutaneous tissue

Calcium deposits in subcutaneous tissue

Dark purple, amorphous crystals

Dark purple, amorphous crystals

Well circumscribed<br>crystalline deposit

Well circumscribed
crystalline deposit


Fine, powdery to chunky,<br>thick crystals

Fine, powdery to chunky,
thick crystals

Foreign body giant cells

Foreign body giant cells

Crystalline deposit in subcutaneous

Crystalline deposit in subcutaneous

Videos

Example of scrotal calcinosis
by Dr. Gardner

Sample pathology report
  • Skin, right posterior thigh, punch biopsy:
    • Calcinosis cutis
Differential diagnosis
  • Clinical differential
    • Osteoma cutis:
      • Hard nodules / papules from ossification due to tissue damage or tumor
    • Gouty tophi:
      • White, chalky nodules around joints, particularly in the large great toe
      • Elevated uric acid levels and pain support gout
    • Mycetoma:
      • Large, coalescing, painful nodules with sinus tracts
      • Fungal culture or biopsy can lead to diagnosis
    • Xanthoma:
      • Yellow to pink papules located on upper eyelids, fingers and knees; generally painless
      • Associated with hyperlipidemia
      • Histology reveals xanthoma cells
  • Histological differential
    • Gout:
      • White spaces representing ghosts of the needle shaped crystals should be identified within the pale, amorphous deposition
      • Polarization of the sample should reveal negatively birefringent, needle shaped crystals
      • Often surrounded by histiocytes and multinucleated giant cells
    • Oxalosis:
      • Polarizable, chunky white to lightly eosinophilic crystals, generally seen in kidney biopsies
      • Can be seen in the skin but are polarizable pink, yellow, green and blue
    • Eruptive xanthoma:
      • Foamy macrophages containing lipids can be identified throughout the lesion
    • Calcium pyrophosphate deposition disease (CPPD) / pseudogout:
      • Also consists of aggregates of basophilic material within tissue with possible surrounding chronic inflammation and foreign body giant cell reaction
      • CPPD is polarizable with positive birefringence
Practice question #1
What is the most common etiology of calcinosis cutis?

  1. Calciphylaxis
  2. Dystrophic calcinosis cutis
  3. Iatrogenic calcinosis cutis
  4. Idiopathic calcinosis cutis
  5. Metastatic calcinosis cutis
Practice answer #1
B. Dystrophic calcinosis cutis is the most common etiology of calcinosis cutis; it is caused by tissue damage in systemic diseases. Answers A, C, D and E are incorrect because metastatic, idiopathic, iatrogenic and calciphylaxis are rarer causes of calcinosis cutis.

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Reference: Calcinosis cutis
Practice question #2


The deposits in the image shown above suggest what diagnosis?

  1. Calcinosis cutis
  2. Eruptive xanthoma
  3. Gout
  4. Oxalosis
Practice answer #2
A. Calcinosis cutis. The deposits are dark purple and crystalloid, consistent with calcifications within the skin. Answer C is incorrect because on an H&E stain for gout, one would see amorphous, needle-like crystals surrounded by giant cell reaction. Answer D is incorrect because oxalosis crystals are clear to light brown with a clover-like architecture and are polarizable. Answer B is incorrect because eruptive xanthoma would have sheets of foamy macrophages and occasionally, cholesterol clefts.

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Reference: Calcinosis cutis
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