Subepidermal Calcinosis

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 by Krista Stewart, MD on September 28, 2022.


Subepidermal calcified nodule (SCN) of the ocular adnexa is a rare, benign subtype of calcinosis cutis. It typically arises as a painless lesion in young African American or Hispanic males. The nodules are classically described as yellow-white, mobile and firm.[1][2] Complete surgical excision with histopathologic examination is diagnostic as well as curative.[2][3][4]


Calcinosis cutis describes the abnormal deposition of calcium in the skin.[5] It may divided into 5 subtypes: dystrophic, metastatic, iatrogenic, SCN and calciphylaxis.[5] [6] SCN was first described by Winer in 1952, and several cases have since been reported on the ocular adnexa.[7]


The pathogenesis of SCN remains unclear, as it typically arises in the setting of normal serum calcium levels and in the absence of systemic disease.[2][3][6] The condition is notably distinct from CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia).[2]Proposed mechanisms include preexisting lesions, mast cell degranulation, calcification of sweat gland ducts and prior trauma or infection.[2]Patient historical data are largely inconsistent with trauma, making dystrophic calcification unlikely.[2] Similarly, correlation with milia and syringomas have been reported, but a causal link has not been proven.[2][8][9] The theory of mast cell degranulation leading to secondary calcium deposition is supported by multiple histopathologic studies, however further research is necessary.[2][6][10]


Reported cases of SCN demonstrate a 2:1 male predominance, with a racial predilection for African Americans and Hispanics.[2][11]A review of 43 cases of SCN found that 63% occurred in “non-Caucasians”.[2] Although SCN has been reported in every age group, the majority (>90%) of cases occur in patients younger than 21 years of age.[1][2]


A thorough history should be performed to assess for underlying malignancy, rheumatological conditions, and disorders of calcium homeostasis. Clinicians should be aware that SCN is commonly overlooked or misdiagnosed.[2]One review found that 76% of patients sought medical care >6 months after discovering the lesion.[2] The high rate of clinical misdiagnosis makes histopathologic examination necessary.[1][2]

Clinical diagnosis

SCN rarely involves the ocular adnexa. In a review of the 146 previously reported cases of SCN, only 53 (36%) were found to have eyelid involvement.[2] Most nodules measured <5mm, with the majority arising on the upper eyelid or medial canthus.[2] SCN typically presents as an asymptomatic, unilateral lesion, although cases of multiple and bilateral nodules have been described.[3] The nodules appear yellow-white with raised, wart-like features.[4][11] On manipulation, the nodules are firm and mobile.[2]


Hematoxylin and eosin staining reveals an acanthotic or hyperkeratotic epidermis overlying basophilic calcium deposition in the upper dermis.[2][3] "> Large amorphic deposits and small calcified globules have both been described.[12] The Von Kossa staining protocol is commonly used to confirm the presence of calcium deposition (positive, black staining).[2][13] Mast cells surrounding the calcification and chronic inflammatory giant cell reaction may also be identified, particularly in younger patients.[1][2][6]

Differential diagnosis

Warty papilloma.[1][2][3]

  • Sebaceous cyst.[1]
  • Seborrheic keratosis.[2]
  • Keratocanthoma.[3]
  • Cutaneous horn.[2][3]
  • Mulluscum contagiosum.[2][3]
  • Milia.[2][3]
  • Other subtypes of calcinosis cutis (metastatic, dystrophic).[14]


Definitive treatment of SCN is by surgical excision.[2][9][13] Intralesional corticosteroid injection, topical steroid use, and saucerization with electrodessication have all been proposed, but their use is limited and evidence is lacking.[2][13] Incomplete excision has demonstrated recurrence, so long-term follow up is encouraged.[2][14]


  1. 1.0 1.1 1.2 1.3 1.4 1.5 Shields CL, Marous MR, Casey MG, et al. Subepidermal Calcified Nodule in the Periocular Region: A Report of 6 Cases. Ophthalmology. 2016;123(3):671-673.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 Khine KT, Shi DS, Bernhisel A, et al. Subepidermal Calcinosis in the Ocular Adnexa: A Systematic Review. Ophthalmic Plast Reconstr Surg. 2018;34(2):101-105.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Koylu MT, Uysal Y, Kucukevcilioglu M, Ceylan OM, Deveci MS. Bilateral Symmetrical Subepidermal Calcified Nodules of the Eyelids. Orbit. 2014;33(4):295-297.
  4. 4.0 4.1 Cursiefen C, Jünemann A. Subepidermal Calcified Nodule. Arch Ophthalmol Chic Ill 1960. 1998;116(9):1254-1255.
  5. 5.0 5.1 Reiter N, El-Shabrawi L, Leinweber B, Berghold A, Aberer E. Calcinosis Cutis: Part I. Diagnostic Pathway. J Am Acad Dermatol. 2011;65(1):1-12.
  6. 6.0 6.1 6.2 6.3 AlWadani S, Suarez MJ, Kass JJ, et al. Subepidermal Calcified Nodules of the Eyelid Differ in Children and Adults. Ophthalmic Plast Reconstr Surg. 2017;33(4):304-306.
  7. Winer LH. Solitary Congenital Nodular Calcification of the Skin. AMA Arch Dermatol Syphilol. 1952;66(2):204-211.
  8. Shin BS, Choi H, Choi KC, Kim MS. Recurrent Milia-Like Idiopathic Calcinosis Cutis on the Upper Eyelid. Ann Dermatol. 2013;25(4):520-522.
  9. 9.0 9.1 Zeglaoui F, Khaled A, Fazaa B, Riahi O, Zermani R, Kamoun MR. Multiple Subepidermal Calcified Nodules on the Eyelids with Eruptive Syringomas: A Possible Ethiopathogenic Relationship. J Eur Acad Dermatol Venereol JEADV. 2009;23(3):337-339.
  10. Tezuka T. Cutaneous Calculus - its Pathogenesis. Dermatologica. 1980;161(3):191-199.
  11. 11.0 11.1 Carvounis PE, Santi M, Stern JB, Miller M. Subepidermal Calcified Nodules. Ophthalmol J Int Ophtalmol Int J Ophthalmol Z Augenheilkd. 2005;219(2):112-114.
  12. Juzych LA, Nordby CA. Subepidermal Calcified Nodule. Pediatr Dermatol. 2001;18(3):238-240.
  13. 13.0 13.1 13.2 Nguyen J, Jakobiec FA, Hanna E, Fay A. Subepidermal Calcified Nodule of the Eyelid. Ophthal Plast Reconstr Surg. 2008;24(6):494-495.
  14. 14.0 14.1 Kim HJ, Johnson PB, Kropinak M, et al. Subepidermal Calcified Nodules of the Eyelid. Ophthal Plast Reconstr Surg. 2009;25(6):489–490.
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