Patient presentation A 6-year-old girl presented with a small growth on the left cheek, which she has had for 6 months. The patient’s mother reported that this asymptomatic lesion first appeared as a small deep-seated papule, then continued to grow and became raised, with no surface changes or drainage. On examination of the medial aspect of the left upper cheek, there was a smooth-surfaced, firm-to-hard, whitish-grey papule measuring 8 mm x 8 mm. The rest of the examination was within normal limits.  What is Your Diagnosis?Diagnosis: Pilomatricoma Pilomatricoma was originally reported as an “épitheliome calcifié des glandes sebacées” in 1880 by Malherbe and Chenantais. Interestingly, this first report appeared in two different journals in the same year and by the same authors.1,2 In 1905, the terminology was corrected by Malherbe as it became clear that the origin was not of the sebaceous glands.3 This lesion was later referred to as “L’épithéliome calcifié de Malherbe.”4 The term pilomatrixoma was first used by Forbis in 1961.5 More than a decade later, the exact terminology was corrected to pilomatricoma in 1977 by Arnold in a letter espousing the more accurate terminology.6 Pilomatricomas are benign neoplasms arising from the hair follicle matrix and are misdiagnosed more than 70% of the time.7 A rare malignant variant has also been reported, and suggested to exist in continuum with pilomatricomas.8Epidemiology The cause of pilomatricomas is not known. The mean age of pilomatricoma appearance is 30, with a second peak observed after the fifth decade.9-11 The female:male ratio was reported as 2:1 by Moehlenbeck, and more recently as 1:1 by Lan et al.9,10 The incidence rate has been calculated as one in every 824 dermatopathological specimens in one study.9 Pilomatricomas also exhibit anatomic regional preferences with the most common sites of occurrence being the head (47%) (mostly periorbital), the neck (9%) and upper limbs (35%). Less common sites include the lower extremities and thorax, with only 2% appearing in multiple sites.12 Finally, a letter by Aquilana et al. reported a case of this lesion arising at the site of a previous BCG vaccination.13Clinical Features and DiagnosisPilomatricomas usually present as firm, non-tender, subcutaneous skin-colored to faintly blue/transparent palpable papules or nodules adherent to the skin but not to underlying tissue.14 Pilomatricoma growth is usually slow and may occur over a period of months to years. Pilomatricomas may become inflamed and erythematous. The overlying skin can have color alterations — keratinization mimicking squamous cell carcinoma, or be telangiectatic mimicking basal cell carcinoma.15Diagnosis of pilomatricoma is suspected on palpation of a superficial hard nodule or papule. Ultimately, diagnosis is confirmed with histology. The differential diagnosis should include epidermoid and dermoid cysts. Epidermoid cysts are firm, round, mobile and have normal overlying skin. Dermoid cysts are similar, but firmly attached to the underlying tissue. Other considerations include basal cell carcinoma, ossifying hematoma, brachial arch remnants, adenopathy, giant cell tumor, foreign body reaction and osteoma cutis.Pilomatricomas may be associated with a variety of internal disease states or genetic syndromes. For example, multiple or recurring pilomatricomas have been associated with myotonic dystrophy, spina bifida, Gardner syndrome, Turner syndrome, Churg Strauss syndrome, and Rubinstein-Taybi syndrome.16-21 Thus, when multiple lesions are noted in a patient, further workup should be undertaken to rule out associated diseases or syndromes.PathogenesisPilomatricomas are considered to be of ectodermic origin. More specifically, pilomatricomas are thought to arise from germinal matrix cells of the hair follicle. Supporting this theory, pilomatricomas retain morphological signs of cortical differentiation with preserved differential hair keratin pattern.22 Recent pathogenesis studies have focused on beta-catenin, a signal transduction protein in differentiation and proliferation of hair follicles. Beta-catenin mutation is believed to contribute to pilomatricoma formation.23 As beta-catenin is found to be mutated in both pilomatricoma and pilomatrix carcinoma, this mutation has been used to reinforce the theory that a continuum exists between the two lesions.24HistologyInitial histopathologic examination of pilomatricoma shows sharply demarcated dermal nodules surrounded by a capsule of compressed fibrous tissue, located in the dermis and the subcutaneous fat. Closer examination reveals a tumor with lobules of strongly basophilic cells that differentiate into shadow cells, the characteristic hallmark of pilomatricomas.22 Because differentiation is believed to be from hair follicles, it has been suggested that S-100 protein in shadow cells may be used as a biomarker when diagnosis is unclear.25In slightly more detail, it is interesting to note that the histology of pilomatricomas varies by age of the lesion. Overall, pilomatricomas are composed of two major cell types, basophilic cells and eosinophilic shadow cells. However, early lesions tend to have a cyst-like structure with a predominance of basophilic cells grouped in islands and forming the walls of the tumor. A transition period then exists wherein eosinophilic shadow cells form, with loss of their nuclei, leaving pale-staining areas with abundant cytoplasm. These shadow cells form the central portion of established lesions. Ossification and deposition of hemosiderin and melanin occur commonly, whereas amyloid deposition is rare.26When fully developed, pilomatricomas no longer show cystic structure and instead become a solid collection of basaloid matrical cells and shadow cells. The matrical cells elicit inflammation and are highly proliferative, with many mitotic figures mimicking malignant invasion. Foreign body giant cell reaction, which represents a granulomatous response to the shadow cells, can also be identified in regions where keratinized debris is abundant.10 When found in older adults, clinical and microscopic appearance is more likely to mimic that of basal cell carcinoma with matrical differentiation.27Variants of pilomatricomas have also been reported. These include perforating pilomatricoma,28 anetodermic changes with atrophic skin over the pilomatricoma,29 and melanocytic matricoma.30 On The HorizonA variety of advanced non-invasive techniques are in development to diagnose and assess pilomatricomas. Recent reports have been made with alternate techniques to dermoscopy such as Raman spectroscopy, which has been used to differentiate and grade skin lesions.31 The advantages of this method include the fact that no pretreatment or staining is necessary and samples are not destroyed. In addition, although not tried in this study, Raman spectroscopy could theoretically be applied in vivo. Other interesting approaches include the use of ultrasound, where pilomatricoma is noted, as a well-defined nodule with inner echogenic foci and a peripheral hypoechoic rim, or a completely echogenic nodule with acoustic shadowing.32 The benefits of this technique include the ability to diagnose and differentiate without a biopsy. Management and TreatmentThe treatment of choice for pilomatricomas is surgical excision.33 This allows both complete samples for biopsy and confirmation of clinical diagnosis. Less aggressive techniques commonly lead to misdiagnosis.33 Pilomatricomas are benign and easily treated with rare recurrence. In cases of recurrence, malignancy must be suspected and complete excision must be preformed.Our patient’s pilomatricoma was surgically excised without complication and with good cosmetic results. No recurrence was noted on a 3-month follow-up visit.Pilomatricoma At A GlancePilomatricoma is a common, painless, firm, slow-growing, benign skin neoplasm that derives from hair follicle matrix cells. It is typically found in the head region presenting as a small nodule or papule. The characteristic histopathologic appearance consists of basaloid cells and the classic shadow cells. Recurrence after complete surgical excision is rare. Misdiagnosis is common and careful histology should be performed. Because multiple pilomatricomas have been associated with more serious pathologies, when clinically suspected, consider further work up to rule out such diseases and syndromes.  If you have a case you’d like to see published, send a write-up (1,200 to 1,500 words) and an image of the patient’s condition to:Dr. Amor KhachemouneSUNY Downstate Medical CenterDepartment of Dermatology Box 46450 Clarkson AvenueBrooklyn, NY 11203Or, e-mail them to amorkh@pol.net.