Pilomatrixoma (Pilomatricoma)

Background

Pilomatrixoma (pilomatricoma), also referred to as calcifying epithelioma of Malherbe, is a benign appendageal tumor with differentiation toward hair follicle matrix cells. It usually manifests as a solitary, asymptomatic, firm nodule. Long considered a relatively rare tumor, pilomatrixoma may be less rare than was previously realized. It is more common in children, but occurrence in adults is increasingly being recognized. The recommended treatment is surgical excision.^[1]

Multiple pilomatrixomas have been observed, mainly in association with myotonic dystrophy^[2] but also in association with other syndromes, including Rubenstein-Taybi syndrome^[3] and constitutional mismatch repair deficiency (CMMRD) syndrome.^[4]  Pilomatrix carcinoma (PMC) is a rare development.^{[5, 6, 7, 8]}  Appropriate surgical interventions for PMC include Mohs micrographic surgery (MMS) to prevent any recurrences or metastases.^[9]

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Pathophysiology

In a study of 10 pilomatrixoma lesions, all immunostaining results were strongly positive for BCL2,^[10] which is a proto-oncogene that helps suppress apoptosis in benign and malignant tumors. These data suggest that faulty suppression of apoptosis contributes to the pathogenesis of these tumors.

Subsequently, investigators demonstrated that the proliferating cells of human pilomatrixomas show prominent staining with antibodies against LEF-1 (a marker for hair matrix cells). Evidence has also indicated that S100 proteins can be used as biochemical markers in characterizing pilomatrixomas.^[11] These data provide biochemical support of morphologic evidence that these tumors are derived from hair matrix cells. Studies have also shown that at least 75% of persons with pilomatrixomas who have examined have mutations in the gene CTNNB1; these data directly implicate beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans.^{[12, 13, 14]}

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Epidemiology

United States and international statistics

Pilomatrixomas have long been considered uncommon cutaneous tumors; however, they may be more common than has generally been realized, especially in children and young adults. In one American dermatopathology laboratory, pilomatrical neoplasms were considered the most common solid cutaneous tumors in patients aged 20 years or younger.^[15]

In one dermatopathology laboratory in the United Kingdom, pilomatrixomas accounted for 1 in 500 histologic specimens. A retrospective study by Kinoshita et al reported 1559 patients with pilomatrixomas at a single hospital in Japan between 2016 and 2020.^[16]  A multicenter study from Mexico reported 52 pediatric patients (< 18 y) with pilomatrixoma (74 lesions) in two tertiary hospitals between 2017 and 2023.^[17]  

Age-, sex-, and race-related demographics

Most reported cases have occurred in children. Lesions are often discovered in the first 2 years of life; however, in a retrospective study of 209 cases, investigators found that the age of presentation showed a bimodal pattern, with the first peak being 5-15 years and the second being 50-65 years.^[18]  In a study of 171 pediatric patients (mean age, 5.7 y) with pilomatrixomas, age peaks were found at less than 1 year and between 5 and 11 years.^[19] In a comprehensive review of 150 pilomatrixoma articles, the mean age at excision was 16 years and 7 months (range, 5 mo to 97 y).^[1]

Most studies have reported a slight predominance in females. In a comprehensive review by Jones et al, the female-to-male ratio was 1.15:1.^[1]  A single-center study from Japan cited to female-to-male ratio of 1.6:1.^[16]

Most reported cases have occurred in Whites. Whether this represents publication bias or a true racial predisposition is unclear.

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Prognosis

Pilomatrixomas are not associated with mortality. Very large tumors (≤ 18 cm) can cause considerable discomfort but are uncommon. Pilomatrix carcinomas are also uncommon, but they are locally invasive and can cause visceral metastases and death.

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History

Patients usually present with a solitary, firm, nontender subcutaneous nodule that has been slowly growing over a period of several months or years. Although patients are usually asymptomatic, some report pain during episodes of inflammation or ulceration. Rapid growth is rare, but reports have described one lesion reaching 35 mm in 8 months and another reaching 1 cm in 2 weeks. Occurrence in more than one member of the same family is rare and is usually observed in association with myotonic dystrophy.

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Physical Examination

Approximately 50% of pilomatrixoma (pilomatricoma) lesions occur on the head and neck, especially the cheek, preauricular area, eyelids, forehead, scalp, and lateral and posterior neck. They are among the most common head and neck tumors in pediatric patients and typically occur as isolated firm, nontender, slow-growing lesions.^[20]  Eyelid lesions may mimic chalazion.^[21] Lesions can also occur on the upper and lower extremities and trunk.^[22]  Lesions have been observed in the middle ear and the ovary.^{[23, 24]}

In a review of 137 pediatric patients, tumors occurred predominantly on the face or neck (70%) and upper extremities (22%).^[25]  In a review of 14 studies where the pilomatrixoma lesions were located in the head and neck region, 229 lesions (75%) were located on the head and 76 (25%) on the neck.^[15]

Most pilomatrixoma lesions are between 0.5 and 3 cm in diameter (average, 1.2 cm).^[20]  In rare instances, giant lesions as large as 15 cm are reported. Patients usually have a single firm, stony, hard nodule. Lesions are typically the color of the normal skin, but reddish-purple lesions have been observed (probably resulting from hemorrhage). Stretching of the overlying skin can give the lesion a multifaceted, angulated appearance known as the "tent sign," which is probably due to calcification in the lesion.

The "dimple sign," often associated with dermatofibromas, has been observed. Unusual morphologic variants include perforating, cystic, bullous, lymphangiectatic, hornlike, keratoacanthomalike, and pigmented forms, as well as lesions that show anetodermalike changes on the surface.^{[26, 27, 28, 29]}

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Approach Considerations

Pilomatrixoma (pilomatricoma) may be associated with Turner syndrome, constitutional mismatch repair deficiency (CMMRD), Kabuki syndrome, Steiner myotonic dystrophy, and Gardner syndrome. In the case of Gardner syndrome, pilomatrical change may be noted within epidermoid cysts.^[31]

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Imaging Studies

Radiography

Plain radiography often shows nonspecific calcification of the lesion.

Ultrasonography

Pilomatrixomas can give rise to varying findings on ultrasonography (US).^[32] A study by Zhu et al found that although pilomatrixomas shared some similarities with epidermoid cysts and dermatofibrosarcoma protuberans on US, differentiation of these conditions could be facilitated by the addition of information on vascularity from color Doppler US.^[33] The major features of pilomatrixomas on US were found to include hyperechoic or isoechoic solid composition, scattered punctate foci, posterior acoustic shadowing or no evident change, and the presence of vascularity.

US also shows calcification. For lesions overlying the parotid gland, US helps delineate the relationship between the lesion and the parotid gland.

Magnetic resonance imaging

Pilomatrixomas may show as homogenous, well-defined intermediate signal intensity on T1-weighted magnetic resonance imaging (MRI) and heterogenous-to-high intensity on T2-weighted images.^[1] MRI may be diagnostic if further reports can confirm the correlation between the high-signal bands in T2-weighted images and the bands formed by basaloid cells evident upon histologic examination.^[34]

Computed tomography

In a study (N = 33; 38 lesions) by Duflo et al involving children with pilomatrixomas of the head and neck, computed tomography (CT) of the parotid region was performed and showed a well-delineated subcutaneous tumor exhibiting microcalcifications and metabolic activity; however, in four of the cases, the diagnosis proposed by the radiologist was adenopathy.^[35]

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Other Tests

Fine-needle aspiration (FNA) has been studied as a diagnostic tool for pilomatrixoma^{[36, 37]} ; however, misinterpretation of the lesion as carcinoma, basal cell carcinoma, or pleomorphic adenoma with squamous metaplasia has been reported. The presence of ghost cells, basaloid cells, and calcium deposits in the appropriate clinical setting permits diagnosis by aspiration.

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Procedures

Dermoscopy (dermatoscopy) may be useful in the workup. In a study by Chessa et al (N = 55), dermoscopy in conjunction with clinical examination sufficed to define proven or suspected pilomatrixoma in approximately 80% of cases, with only about 20% requiring histologic examination for diagnosis.^[38]

A biopsy specimen may be obtained to look for characteristic changes that establish the diagnosis and to rule out other conditions that can clinically resemble pilomatrixoma.

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Histologic Findings

The pilomatrixoma lesion is usually found in the lower dermis and subcutaneous fat. It is sharply demarcated and is usually surrounded by a connective tissue capsule. Irregularly shaped islands of epithelial cells are seen; they can be recognized as either basophilic cells or shadow cells. Basophilic cells are usually arranged either on one side or along the periphery of the tumor islands. The shadow cells have a central unstained area, corresponding to the lost nucleus. As the lesion ages, the number of basophilic cells decreases.^[39] Calcium deposits are seen in 75% of lesions with von Kossa staining. (See the images below.)

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Pilomatricoma with prominent basaloid cells.

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Ghost cells (shadow cells) and basaloid cells, associated with granulomatous reaction. Shadow cells are also seen in this high-power micrograph.

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Medical Care

Medical treatment of pilomatrixoma (pilomatricoma) has yet to be successful.^[1]  Surgical excision with complete excision is the best and most effective means of ensuring the removal of the tumor. Appropriate complete excision with clear margins is important for reducing the chance of recurrence.

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Surgical Care

Spontaneous regression of pilomatrixoma has never been observed. The treatment of choice is surgical excision.^[1]  Lesions are mostly poorly delineated, but encapsulated forms have been observed; these are less likely to recur because complete resection is easier. Incomplete resections have been followed by local recurrence; wide resection margins (1-2 cm) have been recommended to minimize the risk of recurrence. Recurrence rates are relatively low (1.4%).^[1]  Minimally invasive curettage may be considered in some pediatric cases with the aim of minimizing scarring.^[40]

Secondary lesions after surgery are rare; this risk decreases progressively with age. In addition, Mohs micrographic surgery has been used in an effort to ensure better margin control.^[7] For patients with numerous pilomatrixomas, all lesions should be excised, and the presence of associated or familial conditions should be considered.^[1]

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Long-Term Monitoring

Patients should be monitored to watch for recurrence of lesions after surgical excision. Although recurrence of pilomatrixoma is rare, it may develop after incomplete excision. Accordingly, patients should be advised to monitor any new growth in previously excised areas.

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