An Asymptomatic Whitish Nodule on the Cheek of An Adult Male: What is Your Diagnosis?

A 28-year-old previously healthy male presented with a slowly progressive, mildly tender nodule over the right cheek since 6 months. There was no history of trauma prior to the onset of the lesion [Figure 1]. There was no history suggestive of connective tissue disorder. He was not on any medication and had not undergone any surgery. A dermatologist at his native place had diagnosed it as acne pustulosa. Our differential diagnoses were verruca, xanthoma, epidermoid cyst and giant molluscum contagiosum. The laboratory investigations revealed low-normal serum calcium and normal phosphorus levels. All other hematological and biochemical parameters were normal. The histopathology with the hematoxylin and eosin staining showed basophilic deposits in the dermis Figures 2–4.

Figure 1

Whitish asymptomatic nodule on the right cheek

Figure 2

Granular basophilic deposits in the dermis with acanthosis of the overlying epidermis (H and E, ×4 view)

Figure 4

Lamellar appearance within the basophilic deposit (H and E, ×400 view)

Basophilic deposits in the dermis under higher magnification (H and E, ×100 view)

Question

What is your diagnosis?

Answer

Idiopathic calcinosis cutis

Discussion

Calcinosis cutis is a term used to describe a group of disorders characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue. It is classified into five subtypes: Dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification and calciphylaxis.[1]

The term idiopathic calcinosis is used for cases in which there is no identifiable underlying cause, or the cause is obscure. It occurs in the absence of any metabolic condition, inherited disease or tissue disorder. The calcification is most commonly localized to one area, but a case of unusually widespread calcinosis cutis has been reported.[2]

Differential diagnosis of calcinosis cutis is made with molluscum contagiosum, colloid milium, warts, xanthomas, osteoma cutis, gout, perforating granuloma annulare and epidermoid cyst.

Histopathology of molluscum contagiosum shows characteristic intracytoplasmic bodies that compress the keratinocyte nucleus in the upper layers of the epidermis. Nodular masses of homogeneous, eosinophilic material expanding the papillary dermis and extending into the mid- dermis are seen in colloid milium. Colloid material may be stained positively with crystal violet and congo red and fluorescence with thioflavin. Tophi in gout can be seen to consist of variously sized, sharply demarcated aggregates of needle-shaped urate crystals lying closely packed in the form of bundles. In xanthoma, nodules containing foamy cells with numerous Touton giant cells are seen in the dermis.

Scanning power of osteoma cutis reveals the presence of dense eosinophilic deposits in the dermis or subcutaneous tissue Bone is identified by osteocytes held within small lacunae and the hydroxyapatite eosinophilic support material. In larger deposits, Haversian systems can be seen as concentric osteocytes around a central blood vessel.

Verrucae vulgaris show acanthosis, papillomatosis, and hyperkeratosis. The characteristic koilocytes are located in the upper stratum malpighii and in the granular layer. Epidermal cysts have a wall composed of true epidermis. The cyst is filled with horny material arranged in laminated layers. Histologically, granuloma annulare shows an infiltrate of histiocytes and a perivascular infiltrate of lymphocytes that is usually sparse. The histiocytes may be present in an interstitial pattern without apparent organization, or in palisades, surrounding areas with prominent mucin. Stains such as colloidal iron and alcian blue can be used to highlight mucin.

The histopathology with the hematoxylin and eosin staining in our patient showed amorphous basophilic deposits in the dermis. There was no epithelial lining or any cystic structure. Corroborating the clinical and histopathological findings, a diagnosis of idiopathic calcinosis cutis was made.

In our case, dystrophic, metastatic and iatrogenic calcinosis cutis were ruled out, by the lack of history of trauma, no preceding pathologic lesions at the sites of the nodular lesion, normal serum calcium and phosphorus levels and absence of history of parenteral therapy.

Idiopathic calcinosis cutis (ICC) is subclassified into (a) tumoral calcinosis, characterized by masses around major joints mainly appearing in otherwise healthy adolescents; (b) subepidermal calcified nodules occurring on the head and extremities, the disorder being usually seen in children and (c) scrotal calcinosis.[3]

Tumoral calcinosis is a disorder characterized by the deposition of calcific masses around major joints, such as hips, shoulders, elbows, and knees. It usually occurs in otherwise healthy adolescents. The masses are intramuscular or subcutaneous and they may enlarge to a size causing significant impairment of joint function. Familial occurrences among siblings and associated hyperphosphatemia in some are well documented.[4] The calcium deposits cause a swelling around joints and have propensity to enlarge progressively and ulcerate the overlying skin and extrude.

Subepidermal calcified nodule (SCN) is an uncommon, but specific subtype of idiopathic calcinosis. It presents as an asymptomatic, solitary, yellow-white or erythematous filiform tumor. Although most cases of SCN are solitary, multicentric cases have also been reported. It mainly occurs on the face and neck of children, and some cases exist from birth.[5]

Idiopathic scrotal calcinosis presents as painless firm papules and nodules on the scrotal skin. Lesions begin to appear in childhood or adolescence and gradually increase in size, ranging from pinhead size to 3 cm in diameter. They also increase in number, ranging from a few papules to multiple lesions. Lesions may, however, be solitary and pedunculated.[67]

The pathogenic mechanism of ICC is unknown. Some advocate an active role of the increased sweat duct calcium levels in the development of these lesions. Therefore, the high concentration of sweat glands in the groin and pubic areas may play a role in the development of calcium deposits at these sites.[7]

Few workers suggested that it is due to the dystrophic calcification of pre-existing structures. Intensely basophilic subepithelial calcific deposits beneath the acanthotic, papillomatous epidermis are pathognomonic of ICC on histopathology. The deposits stain with von Kossa stain for calcium. The foreign body giant cell reaction and transepidermal elimination of calcium granules can be observed.[8]

Because calcinosis cutis is rare, there is a notable lack of controlled clinical trials on its treatment. The efficacy of treatment has only been reported in single cases or small case series. No treatment has been generally accepted as standard therapy although various treatments have been reported to be beneficial. Curettage or surgical excision is the first-line therapy for ICC. Indications for surgical treatment include painful masses, recurrent infection, ulcerations, functional impairment and cosmetic concerns.[39]

Disseminated, extended calcinosis often requires systemic treatment. No pharmacological treatment is generally accepted as standard treatment to prevent or reduce calcinoisis. Warfarin, colchicine, probenecid, aluminum hydroxide, bisphosphonates and diltiazem have been tried. Newer advances in treatment include intralesional steroids, anti-tumor necrosis factor agents, intravenous immunoglobulins and extracorporeal shockwave lithotripsy.[39]

Idiopathic calcinosis cutis is a rare entity. To the best of our knowledge, very few cases of idiopathic calcinosis cutis on the face of an otherwise healthy adult have been reported.[37101112] The case under discussion is remarkable due to the atypical location of a rare entity.