Diagnostic aid to subepidermal calcified nodule with dermoscopy and reflectance confocal microscopy: a case report

Subepidermal calcified nodule (SCN) is a subtype of calcinosis cutis, presenting as a solitary, hard, yellowish-white nodule [1]. Patients with SCN can phenotypically mimic and are often misdiagnosed with pilomatrixoma, molluscum contagiosum, and juvenile xanthogranuloma. Histological confirmation was the only practical option for the diagnosis of SCN when the lesions were equivocal on conventional naked-eye examination. The applications of noninvasive imaging techniques such as dermoscopy and reflectance confocal microscopy (RCM) have expanded following advances in the field of skin cancer [2]. These novel techniques can decrease unnecessary surgical biopsies and broaden treatment options. Here, we report a typical case of eyelid SCN and describe its dermoscopy and RCM findings to provide insight into novel approaches to differential diagnosis and management in the future.

A 14-year-old previously healthy male patient presented to our hospital with a painless yellowish-white papule on the left upper eyelid (Fig. 1A). The papule appeared five years previously and gradually became larger without ulceration or bleeding. Before being referred to our hospital, the patient was diagnosed with a common wart. However, treatment with recombinant human interferon gel was not effective. No history of trauma, local skin lesions, or familial similar skin lesions could be found. Cutaneous examination revealed a solitary yellowish-white papule approximately 5 mm in diameter on the upper left eyelid. Dermoscopy showed closely grouped multiple yellowish-white clods surrounded by linear vessels (Fig. 1B). RCM imaging showed nests of hyperrefractile material at the dermal–epidermal junction level and irregular hyperplasia of the epidermis (Fig. 1C). Surgical excision, the most common treatment option for SCN, was performed. A further histopathological examination revealed small amorphous basophilic deposits scattered throughout the papillary dermis with small numbers of lymphocytes, hyperkeratosis of the epidermis, a thickened stratum spinosum, and a downward-directed basal-layer expansion. Neither ghost cells, a feature of pilomatrixoma, nor a granular layer of keratohyalin granules, characteristic of epidermal cysts, were found (Fig. 1D). The presence of calcium deposits was confirmed by von Kossa staining (Fig. 1E). The levels of calcium, phosphorus and parathyroid hormones in the blood were normal. A diagnosis of eyelid SCN was made based on the above examination. The patient remained recurrence-free for the entire follow-up period (6 months).

Calcinosis cutis can be classified into five major types: dystrophic calcification, metastatic calcification, iatrogenic calcification and traumatic calcinosis cutis, calciphylaxis, and idiopathic calcification [3]. SCN is a rare subtype of idiopathic calcification that usually occurs in healthy individuals and is unrelated to tissue damage, systemic disease, or side effects of treatments. To date, only over a hundred cases of SCN have been reported. The incidence of SCN among men is approximately twice that among women. Seventy-two percent of patients are younger than 18 years old. The lesions present asymptomatic, painless, hard, and freely mobile nodules and can be single (82%) or multiple (18%) [4]. In a few cases, the papule may hemorrhage [5]. Due to the rarity of eyelid SCN, physicians are unfamiliar with this diagnosis, and patients often experience misdiagnosis.

Beyond this, however, its morphological similarities with other skin diseases make SCN challenging to diagnose. It is frequently misdiagnosed as pilomatrixoma, juvenile xanthogranuloma, and molluscum contagiosum. While the naked-eye examination is unreliable in some cases, noninvasive in vivo imaging improves diagnostic accuracy. Dermoscopy is one of the primary imaging modalities used to diagnose cancerous skin lesions, such as melanoma or basal cell carcinoma. Over the last several years, dermoscopy has increasingly been used in the context of general dermatological disorders [6]. RCM is another novel technology that could also provide noninvasive, in vivo imaging of the skin at a near-histological resolution. Here, we showed, for the first time, images of eyelid SCN under dermoscopy and RCM. Dermoscopy showed closely grouped multiple yellowish-white clods surrounded by linear vessels, and RCM showed nests of hyperrefractile material at the dermal–epidermal junction level. These findings may be helpful in the differential diagnosis of SCN and other similar entities (Table 1). Moreover, hematoxylin–eosin (HE) staining showed basophilic materials in a finely granular or lumpy form, and von Kossa staining showed black calcium deposits in the dermis. It has been reported that the histopathological patterns of SCN in children and elderly patients are different [7]. Young patients often show multiple, small calcified bodies within the dermis surrounded by foreign-body giant cells and lymphoplasmacytic chronic inflammation. In contrast, elderly patients present lesions characterized by a single, large, well-demarcated amorphous calcified deposit surrounded by fibrous tissue without chronic inflammation or foreign body reaction. In agreement with this, we found multiple calcium nests in the dermis of this patient. However, it is still being determined why there are two forms of calcified deposits. Further studies are needed.

Dermoscopy and RCM have been proven more accurate and sensitive than naked-eye examination for detecting skin cancers [17]. Although sensitivity and specificity using these methods cannot be calculated for individual cases, dermoscopy and RCM have suggested some distinctive features of SCN. With an increasing number of cases and the prevalence of noninvasive in vivo imaging, the diagnostic value of dermoscopy and RCM in SCN will be enhanced.

The current treatments for SCN include excision, CO₂ laser, conservative care, salicylic acid, and intralesional triamcinolone [4]. The majority of cases are managed using excisional methods. There are two reasons for using excision as a first-line treatment option for SCN. Surgical removal, along with histological examination, is the most effective method of simultaneous treatment and confirmation of diagnosis. Additionally, complete surgical excision can help prevent a recurrence. No recurrence was noted in our patient after surgical excision. Sodium thiosulfate (STS) has been reported as another possible treatment for calcinosis cutis [18], particularly in cases with smaller lesions. However, it is unknown whether it can be used in eyelid SCN. If a diagnosis of SCN can be confirmed with dermoscopy and RCM, topical application of STS may become an option. These methods also allow real-time monitoring of its therapeutic efficacy.

In conclusion, clinicians should consider the possibility of SCN for an adolescent patient with a painless yellowish-white papule. The combination of dermoscopy and reflectance confocal microscopy with conventional histopathology helps improve the diagnostic accuracy of SCN.