Copyright © 2016 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited. Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2016 1 Purpose: Subepidermal calcified nodule of the eyelid is considered as one of the types of calcinosis cutis. It generally occurs in children, and is not known to be associated with systemic disease. The authors report histopathological and clinical findings in 14 cases of subepidermal calcified nodule of the eyelid, including 3 older patients with unique microscopic features. Methods: Clinical records and pathological materials were critically reviewed in each case, including von kossa, CD3, CD20, and CD68 stains. Results: The 14 cases presented clinically as nodular eyelid lesions. All were treated with surgical excision. The authors found 2 distinct histopathological patterns which correlated with the patients’ age. In young patients, the authors observed multiple, small calcified bodies within the dermis surrounded by chronic inflammation and granulomatous foreign body reaction. On the other hand, in elderly patients, lesions were characterized by a single, large, well-demarcated amorphous calcified deposit surrounded by fibrous tissue, without chronic inflammation or foreign body reaction. One of these patients, a 70-year-old man, also suffered from gout. The presence of subepidermal calcified nodule was not documented as a preoperative diagnostic possibility in any of the cases. Conclusions: Subepidermal calcified nodule of the eyelid is a rare condition, but should be considered in any patient presenting with a painless white to yellowish colored nodule of the ocular adnexa, particularly during the teenage years. Clinicians and pathologists should be aware that this entity has a distinct appearance and could be associated with systemic conditions in elderly patients. (Ophthal Plast Reconstr Surg 2016;XX:00–00) C alcinosis cutis is a condition characterized by abnormal deposition of calcium within the epidermis. It is gener- ally subdivided into 5 types: dystrophic, metastatic, iatro- genic, idiopathic, and subepidermal calcified nodule (SCN). 1,2 Subepidermal calcified nodule is an uncommon manifestation of calcinosis cutis that typically presents as a solitary white or yellow nodule on the head or neck. It is predominantly seen in young children and early adolescence, although there are isolated instances of SCN pre- senting in patients of much greater age. 3,4 Due to its rarity and nonspecific appearance, SCN of the eyelid presents a diagnos- tic challenge and is frequently mischaracterized clinically as a dermal cyst, xanthelasma, molluscum contagiosum, or other entities. 2,4,5 Localized SCN of the eyelid has not been found to be associated with metabolic disturbances (such as calcium or phosphate dysregulation), metastasis, or other systemic dis- ease. 5 However, 1 patient with hyperphosphatemia and tumoral calcinosis at multiple sites, including the eyelid, has been reported. 6 To the best of our knowledge, no study has compared the histologic appearance of calcified nodules in children with those in older patients. Therefore, the authors reviewed a series of 14 patients with SCN of the eyelid, including several older patients, in an attempt to elucidate the clinical features and his- topathological differences in between patients according to age, as well as any associations with systemic disease. METHODS The authors retrospectively searched the patient database in the Department of Ophthalmic Pathology at Johns Hopkins Hospital and King Khaled Eye Specialist Hospital from the year 1984 to 2013. These studies were approved by the Johns Hopkins institutional review board and were HIPPA compliant. There were 14 patients identified who had been diagnosed with SCN of the eyelid within that period. A chart re- view was conducted on all patients to identify any salient past medical history, trauma, or concurrent systemic disease. Patients up to 19 years of age were considered children. Histopathological analysis was per- formed for each case using hematoxylin eosin stains. In selected cases, a Von Kossa stain was used to confirm calcium salt (phosphate or carbon- ate) deposition, CD3 and CD20 immunostains used to identify T and B lymphocytes, and CD68 immunostain to highlight macrophages. RESULTS The 14 SCN cases in the ophthalmic pathology archives includ- ed 9 males and 5 females, with a mean age of 25 years (range 12–88 years). Clinical information is summarized in the Table, and shows that 11 of the patients were in their teenage years, while 3 were quite elderly (70–88 years old). Two of these patients also had known, possibly rel- evant systemic diseases, including hypertension and gout. The latter pa- tient was a 70-year-old male with a history of chronic tophaceous gout and obesity, as well as severe obstructive sleep apnea. He previously had an excision of a right distal thumb palmar nodule that histopathologi- cally was described as tumoral calcinosis. The patient also developed DOI: 10.1097/IOP.0000000000000778 Accepted for publication June 30, 2016. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Charles Eberhart, M.D., Ph.D., Department of Ophthalmic Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. E-mail: ceberha@jhmi.edu or Saeed AlWadani, M.D., Department of Ophthalmology, King Saud University College of Medicine, Riyadh, Saudi Arabia. E-mail: alwsaeed@KSU.EDU.SA Subepidermal Calcified Nodules of the Eyelid Differ in Children and Adults Saeed AlWadani, M.D.*§, Maria J. Suarez, M.D.†, Jonathan J. Kass, M.D.†, Emily MacQuaid, M.D.‡, Deepak P. Edward, M.D.†§, Hind Alkatan, M.D.*§, and Charles Eberhart, M.D., ph.d.† *Department of Ophthalmology, King Saud University College of Medicine, Riyadh, Saudi Arabia; †Department of Ophthalmic Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.; ‡Katzen Eye Group, Mercy Medical Center, Baltimore, Maryland, U.S.A.; and §King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia ORIGINAL INVESTIGATION