Calcifying Epithelioma of Malherbe

Etiology

The cause of pilomatrixoma is uncertain. A familial component is seen in some cases as there is a genetic component to these lesions. A small percentage (3.9%) of cases are caused by an external insult such as trauma, insect bites, or surgery.[4][5][6]

Epidemiology

Pilomatrixomas are most common in the pediatric population and occur on the head and neck. It is unusual in infants. The mean age of onset is 4.5 years, and 90% of patients are younger than ten years old. There is a bimodal distribution, with a peak incidence between 0 and 20 years old and a second peak incidence between 50 and 65 years old. There is a slight female predilection, and it occurs more commonly in whites. The incidence of pilomatrixoma is reported to be between 0.001% and 0.0031% of all dermatopathology specimens and 20% of all pilar lesions. Another report listed the incidence at 0.18%.

Pathophysiology

The exact cause of pilomatrixoma is not known, but some studies link it to a mutation in exon 3 of the B-catenin gene (CTNNB1). B-catenin is a component of the cadherin protein, and it plays a role in hair follicle differentiation. High expression of B-catenin leads to activation of the Wnt signaling pathway, and this is seen in the matrix cells that are proliferating. B-catenin, during development, controls the adhesion between epithelial cells. Overexpression of BCL2 proto-oncogene also has been seen in immunohistochemical studies.

Histopathology

Histopathology of pilomatrixoma shows a well-demarcated tumor with a surrounding capsule. Dermal cells extend into the subcutaneous tissue. There are islands of epithelial cells that contain basaloid matrical cells, shadow, ghost, or anucleated cells with eosinophilic cytoplasm, foreign body giant cells, and calcifications.

Pilomatrix carcinoma shows basaloid cells, atypia, and a high mitotic rate on histology. Ghost cells are present. Not many calcifications are seen. The histological features between pilomatrixoma and pilomatrix carcinoma are similar and can be difficult to differentiate.

History and Physical

Patients present with a slow-growing subcutaneous tumor that is hard and freely mobile and surrounded by a fibrous capsule. Over 70% of the tumors arise from the head and neck. There are reported cases of rapidly growing tumors. Pilomatrixomas are usually solitary but can occur in multiples. There can be a blue or red color to the overlying skin, which can occasionally ulcerate. Patients are usually asymptomatic but can report some pain or itching. The tent sign, a flattening of a part of the lesion with angulation resembling a tent, may be seen when the skin is stretched. Pigmented pilomatrixoma contains melanin or melanocytes, and it is thought to be rare. Two case series reported the incidence to be around 10% or less, but a Japanese case series in 2013 reported the incidence to be 24.6% in 53 Japanese patients. There are two reported cases of pilomatrixoma associated with alopecia, with one presenting with an area of hair loss surrounding a scalp lesion. The pilomatrixoma was on the left forehead of a 5-year-old Japanese girl in the second case. She had hair loss involving her left eyebrow, and hair regrowth was observed after the tumor was removed.

Evaluation

Diagnosis is clinical or histological. The correct diagnosis was seen in only 12.5% to 55.5% of cases. There is low diagnostic accuracy because providers are unaware of the tumor and because pilomatrixoma mimics other lesions. Imaging is generally not performed. If imaging is necessary, x-ray, computed tomography, or ultrasound can be done to rule out vascular or lymphatic malignancies. Ultrasound can be used to distinguish heterogeneous echotexture, calcifications, hypoechoic rim, and posterior shadowing. Ultrasound can help correctly diagnose lesions preoperatively in 76% of cases compared to 33% when the diagnosis was made clinically.[7][8][9]

Treatment / Management

Pilomatrixomas are benign tumors that can be observed without further need for treatment unless characteristics of the tumor change such as an increase in size or pain. Surgical excision is the treatment of choice when indicated. There is a 2% to 6% chance of recurrence, and that could be due to incomplete excision. There are no current guidelines on appropriate margins.

Malignant pilomatrixoma can arise from benign pilomatrixoma through transformation, but de novo tumors can occur. There are 125 reported cases of these rare, malignant pilomatrixoma, which are termed "pilomatrix carcinomas." Pilomatrixomas that are likely to undergo malignant transformation have a higher degree of cellular pleomorphism, high mitotic rate and atypia, central necrosis, and more extensive infiltration into the skin, soft tissue, and blood and lymphatic vessels. It occurs more commonly in men in the fifth to the seventh decade of life. There is only one known case of the carcinoma occurring in a child. It presents similar to pilomatrixoma and is firm non-tender nodules on the head or neck. The tumor is locally aggressive and can metastasize in 10% of cases. A predictor of metastasis is a local recurrence. The most common site of metastasis is the lungs. Treatment is excision with wide margins (5 to 30 mm), but the recurrence rate is high (50% to 60%). Adjuvant radiation therapy or chemotherapy is used for recurrent disease or metastatic disease.

Pilomatrixomas usually occur as solitary lesions, but multiple lesions can occur, often seen in syndromes such as myotonic dystrophy, Familial adenomatous polyposis, Gardner syndrome, Turner syndrome, xeroderma pigmentosum, Rubinstein-Taybi syndrome, Sotos syndrome, and basal cell nevus syndrome.

Differential Diagnosis

The differential diagnosis includes sebaceous and epidermoid cysts, epitheliomas, neurofibromas, foreign body reactions, calcified cysts or hematomas, chondromas, fibroxanthomas, osteoma cutis, and giant cell tumor.