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Year : 2013  |  Volume : 58  |  Issue : 5  |  Page : 406
Multiple sub-epidermal calcified nodule mimicking eruptive xanthoma: A case report and review of the literature

1 Clinic of Dermatology, Ankara Etlik Training and Research Hospital, Ankara, Turkey
2 Clinic of Pathology, Ankara Etlik Training and Research Hospital, Ankara, Turkey
3 Clinic of Emergency Medicine, Ankara Etlik Training and Research Hospital, Ankara, Turkey

Date of Web Publication30-Aug-2013

Correspondence Address:
Pinar Ozuguz
Ankara Etlik Training and Research Hospital, Dermatology Clinic, Ankara 06100
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.117327

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Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN.

Keywords: Calcinosis cutis, eruptive xanthoma, sub-epidermal calcified nodule

How to cite this article:
Ozuguz P, Balta I, Bozkurt O, Unverdi H, Dostbil A. Multiple sub-epidermal calcified nodule mimicking eruptive xanthoma: A case report and review of the literature. Indian J Dermatol 2013;58:406

How to cite this URL:
Ozuguz P, Balta I, Bozkurt O, Unverdi H, Dostbil A. Multiple sub-epidermal calcified nodule mimicking eruptive xanthoma: A case report and review of the literature. Indian J Dermatol [serial online] 2013 [cited 2020 Jul 14];58:406. Available from:

What was known?
1. Cutaneous calcification or calcinosis cutis is a result of calcium deposition in skin. It is clinically categorized as dystrophic, iatrogenic, idiopathic, and metastatic. Histologically, aggregates of calcium can be shown with von Kossa stain.
2. SCN is a special type belonging to the idiopathic group, usually presenting as a solitary firm nodule on the head and neck.
3. The pathogenesis of SCN is not understood, yet.

   Introduction Top

Calcinosis cutis is a term used to describe a group of disorders in which calcium deposits form in the skin. Calcium is vital to many biological processes. In the skin, it has a profound effect on keratinocyte proliferation, differentiation, and cell-to-cell adhesion. [1] Cutaneous calcium deposits were describe first in 1877, but it was in 1952 that Winer described congenital nodular calcifications, currently known as SCN. [2] Synonyms include Winer's nodular calcinosis, solitary genital nodular calcification, cutaneous calculi, and solitary congenital calcified nodule. [3]

The etiology of calcinosis cutis may be idiopathic or due to abnormal calcium or phosphorus metabolism of dermal collagen. SCN is a rare form of idiopathic calcinosis (IC) that occurs more commonly in children, particularly in the head-and-neck region. SCN can be present at birth without any previous history of cutaneous and systemic pathology or disturbances in the metabolism of calcium and phosphorus, with a male-to-female ratio of 2/1. [3],[4],[5] Most lesions appeared as solitary, raised, tan, or white nodules on the upper eyelid or medial canthal skin of healthy, young patients. Less commonly multiple lesions may develop. [3],[4],[6] Multiple lesions appear as verrucous papillomas or may mimic juvenile xanthogranulomas.

Pathogenesis of SCN is unclear. All reported patients with SCN had normal serum levels of calcium and phosphates, with no other systemic abnormality or disseminated integumentary deposits. There is typically no history of trauma to the area of the lesions. [2],[3] By contrast, additional calcium deposits beyond the eyelid warrant attention to the patient's health status, as hyper-calcemic states have been reported to associate with eyelid margin, corneal, limbal, and inter-palpebral calcific deposit. [7],[8] The SCN cases, which have been reported in the literature, are usually in the form of case reports in children with placement of the eyelid [Table 1]. [7],[8],[9],[10],[11]
Table 1: To date published the cases

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We report a case of a 22-year-old man with multiple nodules of the bilateral dorsum of hands mimicking eruptive xanthoma with the review of the literature.

   Case Report Top

A 22-year-old healthy White man presented with asymptomatic, multiple nodules on the bilateral dorsum of hands since he was 10 years old. There was no history of pain, ulceration, or discoloration. Clinical examination was remarkable for 13 lesions (range in diameter 0.2-1 cm), white to yellowish, hard, non-sensitive nodules on the bilateral dorsum of hands [Figure 1]. The case was misdiagnosed as verruca vulgaris and was treated with cryotherapy at different centers. There was no history of preceding lesion or trauma. One of the patient's lesions was excised. Our clinical impression was xanthoma and calcinosis cutis. Histopathology showed homogeneous basophilic masses and granules in the upper dermis, which were surrounded by foreign body reaction and epidermal hyperplasia, an appearance consistent with cutaneous calcinosis [Figure 2].
Figure 1: The lesions on the dorsum of righthand

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Figure 2: The histopathological image

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Routine laboratory tests and metabolic evaluations (calcium, phosphate, and parathyroid hormone), hematological parameters, and blood sedimentation rate were within normal limits. Anti-nuclear antibody was negative. X-ray of the affected hands showed small radio-opaque focuses, but the bony structure did not show any pathology.

   Discussion Top

Calcinosis cutis or cutaneous calcification is used to describe calcium accumulation in the skin. The cause and histogenesis of these deposits have not been fully established, but several theories have been proposed. The most favored theory has been proposed by Steigleder who believed that the calcium was deposited on a pre-existing lesion such as a hamartoma or nevus. [3] Cutaneous calcification may be divided into four major categories such as metastatic, dystrophic, idiopathic, and iatrogenic. [12],[13]

Metastatic calcinosis (MC) occurs in the presence of primary disorders of calcium/phosphate metabolism as well as from secondary causes such as hyper-parathyroidism, hyper-vitaminosis D, sarcoidosis, neoplastic involvement of bone, renal insufficiency, and milky alkali syndrome. [5],[6],[14] Clinically it is usually seen in the form of fluctuant nodules around large joints. Metastatic calcification can occur in the media layer of the blood vessels and this may result in vascular occlusion.

Dystrophic calcification (DC) is the most common type of calcinosis cutis and occurs in the presence of normal serum levels of calcium and phosphates but in previously diseased skin. The DC that occurs in conjunction with the above entities does not likely involve a bacterial etiology. The cause of these entities remains unknown. [15] DC is common in childhood in the presence of such diseases as dermatomyositis, systemic scleroderma, CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome, morphea, subcutaneous fat necrosis of the newborn, and cutaneous neoplasms. Neri et al. investigated cytodiagnosis for SCN. [5],[12],[15]

Iatrogenic calcinosis is a result of extravasation of some intravenous liquids such as calcium gluconate, calcium chloride solutions, during intravenous application, forming nodules in the skin.

IC appears without an underlying cutaneous disease; the clinical picture resembles the one seen in DC. Serum Ca levels are within normal range. [5] Lesions are usually seen in young and middle-aged men, presenting as asymptomatic round yellow multiple papules, ranging from a few millimeters to centimeters. IC occurs in the absence of evident tissue or metabolic abnormalities, and is further subdivided into three distinctive disorders of childhood: Calcinosis circumscripta, IC of the scrotum, and SCN. [16] Idiopathic scrotal calcification is seen more often than the other two. [14],[15],[17] A vulvar counterpart is also reported. [14],[15] There is also a "milia-like" form that occurs on the hands, and face, of some patients with Down syndrome. The milia-like calcinosis cutis lesions are mostly multiple especially seen on hands, feet, knees, and elbows to be more widely distributed. [18] Evans et al. reported 21 cases of SCN showing a male predominance with a male-to-female ratio of 2:1. Patients were 1-17 years old (mean 8.4 years). [3] Alper et al. [19] presented a case where the lesion was localized on the knees of a 23-year-old female patient. The oral cavity is very rarely affected by calcinosis cutis of any type [Table 1]. [20],[21]

Histopathologically, SCN is characterized by an intensely basophilic sub-epithelial calcium deposit beneath the acanthotic and papillomatous epidermis on hematoxylin and eosin-stained preparations. The deposits stain with von Kossa's stain for calcium and are surrounded by foreign body reactions, and trans-epidermal eliminations of calcium granules can be observed. [3],[4],[6]

The clinical diagnosis of SCN is not easy and it is most often mistaken for verruca, molluscum contagiosum, pilomatricoma, epidermal cyst, milium, syringoma, congenital inclusion cyst, sebaceous cyst, or xanthoma. [3],[16],[22],[23],[24] In our case, the diagnosis was made by histopathology, rather than the clinic.

Surgical removal is the treatment of choice for SCN. [3] The lesion may recur following excision. [3],[25],[26] Intra-lesional steroid injection [16] and CO 2 laser [25] have also have been used as alternative treatment modalities. [3]

Eruptive xanthoma is in clusters throughout the body in the yellow-orange-colored papular lesions that are often surrounded by an erythematous halo. They appear in crops on the buttocks, extensor surfaces of the extremities, and flexural creases. In our case, yellow-white colored papules on the bilateral dorsum of the hands composed of a large number of settlers is similar to eruptive xanthoma. We considered cutaneous eruptive xanthomas in the differential diagnosis, which are characteristic lesions of hyper-lipidemia and chylomicronemia. Rarely, eruptive xanthomas have been reported with hypo-thyroidism, nephrotic syndrome, and von Gierke's glycogen storage disease. Rarely, these lesions may present with prominent leukocytoclasis as seen in papular neutrophilic xanthomas, which have been described in HIV-positive and immunocompromised patients. Aldabagh and Bergfeld [27] described a patient with eruptive neutrophilic xanthomas with neither hyper-lipidemia nor immunocompromise. [27] Lesions usually resolve spontaneously over weeks and may result in hypertrophic scars. Histologically, foamy macrophages are present in the dermis with an inflammatory infiltrate of lymphocytes and neutrophils. [28]

Tendon xanthomatosis often accompanies familial hyper-cholesterolemia, but it can also occur in other pathological states. Achilles tendons are the most common sites of tendon xanthomas. Low-density lipoprotein derived from the circulation accumulates into tendons. [29] Lesions of our case were not his tendons and our patient's lipid profile was normal.

Our patient did not have any history of trauma or any previous lesion. Our patient's serum calcium and phosphorus levels were normal and there was no history of parenteral treatment. DC, metastatic calcification, and iatrogenic calcification were excluded in order. Patient's current physical examination, laboratory, and histopathological findings led us to the diagnosis of IC of the subcutaneous calcified nodule. For treatment of multiple lesions, the patient is advised to have follow-up examinations.

   Conclusions Top

SCN, settled in the form of yellow-white-colored lesions, may be multiple and at atypical localization. SCN may rarely be misdiagnosed as xanthoma. Clinicians should be aware that calcinosis cutis may involve the bilateral dorsum of hands and elicits appropriate history to exclude metastatic cutaneous calcification. Dermatologists should include this entity in the differential diagnosis of multiple papular lesions on bilateral hand dorsums.

   References Top

1.Lanka P, Lanka LR, Ethirajan N, Krishnaswamy B, Manohar U. Idiopathic calcinosis cutis. Indian J Dermatol 2009;54:388-9.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.Winer LH. Solitary congenital nodular calcification of the skin. AMA Arch Derm Syphilol 1952;66:204-11.  Back to cited text no. 2
3.Evans MJ, Blessing K, Gray ES. Subepidermal calcified nodule in children: A clinicopathologic study of 21 cases. Pediatr Dermatol 1995;12:307-10.  Back to cited text no. 3
4.Nico MM, Bergonse FN. Subepidermal calcified nodule: Report of two cases review of the literature. Pediatr Dermatol 2001;18:227-9.  Back to cited text no. 4
5.Orlow SC, Watsky KL, Bolognia JL. Cutaneous deposition diseases: Skin and bone, part 2. J Am Acad Dermatol 1991;25:455-62.  Back to cited text no. 5
6.Juzych LA, Nordby CA. Subepidermal calcified nodule. Pediatr Dermatol 2001;18:238-40.  Back to cited text no. 6
7.Butt KI, Tsuboi R, Takimoto R, Suga Y, Ogawa H. Multiple subepidermal calcified nodules on the eyelids. Br J Dermatol 1995;133:664-5.  Back to cited text no. 7
8.Carvounis PE, Santi M, Stem JB, Miller M. Subepidermal calcified nodule. Ophthalmologica 2005;219:112-4.  Back to cited text no. 8
9.Evans LA, Evans CM, Cobb MW. An asymptomatic papule on the face. Pediatr Dermatol 1996;13:253-4.  Back to cited text no. 9
10.Nguyen J, Jakobiec FA, Hanna E, Fay A. Subepidermal calcified nodule of the eyelid. Ophthal Plast Reconstr Surg 2008;24:494-5.  Back to cited text no. 10
11.Kim HJ, Johnson PB, Kropinak M, Brazzo B, Sims L, Lauer S, et al. Subepidermal calcified nodules of the eyelid. Ophthal Plast Reconstr Surg 2009;25:489-90.  Back to cited text no. 11
12.Neri I, Patrizi A, Bianchi F, Piraccini BM. Medical pearl: Cytodiagnosis for subepidermal calcified nodule. J Am Acad Dermatol 2003;49:900-1.  Back to cited text no. 12
13.Qader MA, Almalmi M. Diffuse cutaneous calculi (subepidermal calcified nodules): Case study. Dermatol Ther 2010;23:312-5.  Back to cited text no. 13
14.Fartasch M, Haneke E, Hornstein OP. Mineralization of collagen and elastic fibers in superficial dystrophic cutaneous calcification: An ultrastructural study. Dermatologica 1990;181:187-92.  Back to cited text no. 14
15.Morgan MB. Nanobacteria and calcinosis cutis. J Cutan Pathol 2002;29:173-5.  Back to cited text no. 15
16.Lee SS, Felsenstein J, Tanzer FR. Calcinosis cutis circumscripta: Treatment with an intralesional corticosteroid. Arch Dermatol 1978;114:1080-1.  Back to cited text no. 16
17.Mehta V, Balachandran C. Idiopathic vulvar calcinosis. The counterpart of idiopathic scrotal calcinosis. Indian J Dermatol 2008;53:159-60.  Back to cited text no. 17
[PUBMED]  Medknow Journal  
18.Becuwe C, Roth B, Villedieu MH, Chouvet B, Kanitakis J, Claudy A. Milia-like idiopathic calcinosis cutis. Pediatr Dermatol 2004;21:483-5.  Back to cited text no. 18
19.Alper M, Parlak AH, Kandemir Belenli O. Subepidermal calcified nodule. West Indian Med J 2003;52:255-6.  Back to cited text no. 19
20.El Mofty SK, Santa Cruz D, Mo SL. Oral calcified nodule. Med Oral Pathol 1992;73:472-5.  Back to cited text no. 20
21.Afzal MN, Dancea S, de Nanassy J. Mucosal calcified nodule of the hard palate in an infant: Case report and review of the literature. Pediatr Pathol Lab Med 1997;17:611-5.  Back to cited text no. 21
22.Kim HS, Kim MJ, Lee JY, Kim HO, Park YM. Multiple subepidermal calcified nodules on the thigh mimicking molluscum contagiosum. Pediatr Dermatol 2011;28:191-2.  Back to cited text no. 22
23.Lee YW, Kim BC, Park EJ, Kwon IH, Cho HJ, Kim KH, et al. Four cases of subepidermal calcified nodule on a child's sole. Int J Dermatol 2012;51:316-20.  Back to cited text no. 23
24.Juzych LA, Norby CA. Subepidermal calcified nodule. Pediatr Dermatol 2001;18:238-40.  Back to cited text no. 24
25.Joo YH, Kwon IH, Huh CH, Park KC, Youn SW. A case of persistent subepidermal calcified nodule in an adult treated with CO 2 laser. J Dermatol 2004;31:480-3.  Back to cited text no. 25
26.Plott T, Wiss K, Raimer SS, Solomon AR. Recurrent subepidermal calcified nodule of the nose. Pediatr Dermatol 1988;5:107-11.  Back to cited text no. 26
27.Aldabagh B, Bergfeld W. Eruptive neutrophilic xanthomas. Dermatol Online J 2010;16:6.  Back to cited text no. 27
28.Naik NS. Eruptive xanthomas. Dermatol Online J 2001;7:11.  Back to cited text no. 28
29.Tsouli SG, Kiortsis DN, Argyropoulou MI, Mikhailidis DP, Elisaf MS. Pathogenesis, detection and treatment of Achilles tendon xanthomas. Eur J Clin Invest 2005;35:236-44.  Back to cited text no. 29

What is new?
1. Sub.epidermal calcified nodules (SCNs) can rarely present with multiple nodules resembling xanthoma.
2. Although the head.and.neck region is the common location, unusual presentations on the dorsum of hands can occur.


  [Figure 1], [Figure 2]

  [Table 1]


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