Calcifying Epithelioma of Malherbe

Article Author:
Cuong Le
Article Editor:
Paul Bedocs
Updated:
9/5/2019 4:01:36 PM
PubMed Link:
Calcifying Epithelioma of Malherbe

Introduction

Pilomatrixoma, or calcifying epithelioma of Malherbe, are benign tumors of the hair follicle matrix. In 1880, Malherbe and Chenantais originally called the calcifying lesion "epithelioma" because they thought the cell of origin was sebaceous. Forbis and Helwing proposed the term pilomatrixoma in 1961 because further studies have elucidated that the origin is the hair follicle matrix. Some authors are now suggesting a pan-follicular differentiation. These tumor cells can differentiate into hair matrix, hair cortex, follicular infundibulum, outer root sheath, and hair bulge. It commonly occurs in the pediatric patient on the hair-bearing areas of the head and neck but can also involve the extremities and trunk. On the head, the preauricular region is most commonly involved. The tumors only occur in hair-bearing areas. Case studies report the tumor occurring in other areas of the body including periocular and on the scrotum and vulva.[1][2][3]

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 the 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 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 contain 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 in 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 changes 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 are 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 are 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.

Enhancing Healthcare Team Outcomes

Pilomatrixoma, or calcifying epithelioma of Malherbe, are benign tumors of the hair follicle matrix. Most healthcare professionals usually will not encounter this lesion but they need to know when to refer the patient to the dermatologist. These tumor cells can differentiate into hair matrix, hair cortex, follicular infundibulum, outer root sheath, and hair bulge. It commonly occurs in the pediatric patient on the hair-bearing areas of the head and neck but can also involve the extremities and trunk. On the head, the preauricular region is most commonly involved. The tumors only occur in hair-bearing areas. Case studies report the tumor occurring in other areas of the body including periocular and on the scrotum and vulva. Unless the lesion is symptomatic, no treatment is required. All malignant lesions require excision.


References

[1] Kim YS,Na YC,Huh WH,Kim JM, Malignant pilomatricoma of the cheek in an infant. Archives of craniofacial surgery. 2018 Dec;     [PubMed PMID: 30613091]
[2] Ciucă EM,Sălan AI,Camen A,Matei M,Şarlă CG,Mărgăritescu C, A patient with pilomatricoma in the parotid region: case report and review of the literature. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2018;     [PubMed PMID: 30534834]
[3] Arora A,Nanda A,Lamba S, Cyto-Histopathological Correlation of Skin Adnexal Tumors: A Short Series. Journal of cytology. 2018 Oct-Dec;     [PubMed PMID: 30498290]
[4] Lloyd M,Eagle RC,Wasserman BN, Pilomatrixoma Masquerading as Giant Chalazion. Ophthalmology. 2018 Dec;     [PubMed PMID: 30454715]
[5] Pinheiro TN,Fayad FT,Arantes P,Benetti F,Guimarães G,Cintra LTA, A new case of the pilomatrixoma rare in the preauricular region and review of series of cases. Oral and maxillofacial surgery. 2018 Dec;     [PubMed PMID: 30284072]
[6] Caprio MG,Di Serafino M,Pontillo G,Vezzali N,Rossi E,Esposito F,Zeccolini M,Vallone G, Paediatric neck ultrasonography: a pictorial essay. Journal of ultrasound. 2018 Sep 5;     [PubMed PMID: 30187386]
[7] Yi KM,Chen K,Wang L,Deng XJ,Zeng Y,Wang Y, Pilomatricoma (calcifying epithelioma): MDCT and MR imaging findings in 31 patients with radiological-pathological correlation. European journal of radiology. 2018 Sep;     [PubMed PMID: 30150057]
[8] Jones CD,Ho W,Robertson BF,Gunn E,Morley S, Pilomatrixoma: A Comprehensive Review of the Literature. The American Journal of dermatopathology. 2018 Sep;     [PubMed PMID: 30119102]
[9] Bax D,Bax M,Pokharel S,Bogner PN, Pilomatricoma of the scalp mimicking poorly differentiated cutaneous carcinoma on positron emission tomography/computed tomography (PET/CT) scan and fine-needle aspiration (FNA) cytology. JAAD case reports. 2018 Jun;     [PubMed PMID: 29984278]