Pilomatrixoma

Introduction

Background

A pilomatrixoma is a benign appendageal tumor with differentiation toward hair cells. It usually manifests as a solitary, asymptomatic, firm nodule. It has long been considered a rare tumor, but it may be more common than previously realized. It is more common in children, but occurrence in adults is increasingly being recognized. Recommended treatment is surgical excision. Multiple pilomatrixomas have been observed, mainly in association with myotonic dystrophy. Pilomatrix carcinoma is a rare condition.

Pathophysiology

In one study of 10 pilomatrixoma lesions, all immunostaining results were strongly positive for BCL2.³⁸ This 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.

More recently, investigators have demonstrated that the proliferating cells of human pilomatrixomas show prominent staining with antibodies directed against LEF-1 (a marker for hair matrix cells). Evidence also indicates that S100 proteins can be used as biochemical markers in characterization of pilomatrixomas.³⁹ These data provide biochemical support of morphological evidence that these tumors are derived from hair matrix cells. Furthermore, investigators have 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.^40,41,42

Frequency

United States

Pilomatrixomas have long been considered uncommon cutaneous tumors; however, they may be more common than is 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.

International

In one dermatopathology laboratory in the United Kingdom, pilomatrixomas accounted for 1 in 500 histologic specimens. Investigators found 37 cases published in Japanese dental journals between 1977 and 1994.⁴³ In Turkey, 15 patients were seen in a pediatric surgery clinic from 1984-1994.³ In France, a retrospective study of records in one surgery clinic revealed 33 patients who had undergone surgery for pilomatrixomas between 1989 and 1997.⁴

Mortality/Morbidity

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.

Race

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

Sex

Most studies report a slight preponderance in females. In one retrospective study of 209 cases, the female-to-male ratio was 1.5:1.

Age

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 published in 1998, investigators found the age of presentation showed a bimodal pattern, with the first peak being 5-15 years and the second being 50-65 years.⁴⁴

Clinical

History

• Patients usually present with a solitary nodule that has been slowly growing over several months or years.
• Patients are usually asymptomatic, but some report pain during episodes of inflammation or ulceration.
• Rapid growth is rare, but reports indicate 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.

Physical

• Approximately 50% of the lesions occur on the head and neck, especially the cheek, preauricular area, eyelids, forehead, scalp, and lateral and posterior neck.^45,46,47
  • Lesions can also occur on the upper and lower extremities and trunk.⁴⁸
  • One lesion was observed in the middle ear and another in the ovary.^49,50
• Most lesions measure 0.5-3 cm, but, rarely, giant lesions up to 15 cm are reported.
• Patients usually have a single, firm, stony, hard nodule.
• Lesions are usually 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," likely due to calcification in the lesion.
• One lesion showed the "dimple sign," which is often associated with dermatofibromas.
• Unusual morphological variants include perforating, cystic, bullous, lymphangiectatic, hornlike, keratoacanthomalike, pigmented, and lesions that show anetodermalike changes on the surface.^{51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67}

Causes

Investigators in one study showed that at least 75% of the lesions studied had mutations in the gene CTNNB1; these data directly implicate beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans.