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Characterizing pilomatricomas in children: a single institution experience
Journal of Pediatric Surgery (2013) 48, 1551–1556
www.elsevier.com/locate/jpedsurg
Characterizing pilomatricomas in children: a single institution experience☆ Saif F. Hassan a , Elizabeth Stephens a , Sara C. Fallon a , Deborah Schady b , M. John Hicks b , Monica E. Lopez a , David A. Lazar a , Manuel A. Rodriguez a , Mary L. Brandt a,⁎ a
Division of Pediatric Surgery, Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
b
Received 13 June 2012; revised 10 August 2012; accepted 10 August 2012
Key words: Pilomatricoma; Pediatrics; Benign tumor
Abstract Background/Purpose: Pilomatricomas, or calcifying epitheliomas of Malherbe, are among the most common superficial cutaneous soft tissue lesions in children. Familiarity with the presenting signs and symptoms allows for the diagnosis to be made on physical examination alone in most patients, avoiding expensive and unnecessary diagnostic imaging. Methods: A retrospective IRB-approved review of surgical pathology archives and medical records of all patients undergoing excision of pilomatricomas between 1982 and 2010 was performed to determine the characteristics of the pilomatricoma tumors. Data regarding gender, age, location, size of tumor, and histopathology were collected. Results: There were 916 pilomatricomas resected in 802 patients. Fifty-five percent of the patients were girls (441 patients). The median age at the time of resection was 6 years (range 5 months to 18 years). Multiple lesions were found in 43 patients (5%). The most common location was head and neck (n = 529, 58%), followed by upper limbs (n = 214, 23%), trunk (n = 130, 14%), and lower limbs (n = 43, 5%). Information on size was available for 674 lesions; mean lesion diameter was 14.0 ± 7.4 mm. Twenty-eight patients (3%) had either recurrent (n = 11) or metachronous (n = 17) lesions resected at our institution, with a median interval of 12 months after initial resection (range 5 weeks to 5 years). No cases of pilomatrix carcinoma were observed. Conclusion: The majority of pilomatricomas occur in the head and neck, although they can present in any location. Approximately 5% of children have multiple lesions. Pilomatricomas occur slightly more commonly in girls, and 66% of lesions occur in children b 10 years of age. Complete surgical excision is necessary to prevent recurrence. Recurrences and pilomatrix carcinoma are very rare if complete excision is achieved. © 2013 Elsevier Inc. All rights reserved.
☆
Disclosures: The authors have no affiliations or financial support to disclose with regard to the preparation of this manuscript. ⁎ Corresponding author. Texas Children's Hospital, Houston, TX 77030, USA. Tel.: + 1 832 822 3135; fax: + 1 832 825 3141. E-mail address: [email protected] (M.L. Brandt). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2012.08.007
Pilomatricomas, otherwise known as “calcifying epitheliomas of Malherbe” were first described by Malherbe and Chenantais in 1880 as a skin tumor arising from sebaceous glands [1-3]. Dubreuilh and Cazenave first described the
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histopathologic features of basaloid epithelial cells islands and shadow (ghost) cells, and Turhan and Krainer discovered the origin of the tumor from hair cortex cells [1]. Pilomatricomas are benign skin neoplasms of childhood that present as deep, subcutaneous lesions lying between the dermis and the hypodermis (Fig. 1) [2]. They most commonly occur in the head and neck region, but have been reported in other areas of the body as well [1,4]. On excision these lesions are solid with a gray-tan appearance, and can appear to be in direct continuity with the overlying epidermis (Fig. 2) [5]. Pilomatricomas usually occur as isolated lesions, but have been reported to occur in association with polyposis– colorectal carcinoma predisposition syndromes (Gardner syndrome, Familial adenomatosis polyposis syndrome [FAP, APC gene, MYH (MUTYH) gene], and β-catenin gene mutations) and myotonic muscular dystrophy (Steinert disease) [2,6-12]. Less commonly, these tumors can occur in
Fig. 2 Pilomatrixoma: gross appearance of lesion that was “shelled out,” demonstrating irregular surface architecture (A), a thin membrane encasing the irregularly-shaped mass, and heterogenous nature of the lesional contents on cut surface (B). The irregular surface and lack of complete excision of the mass lead to local recurrence of the lesion in many cases.
Fig. 1 Pilomatrixoma located on posterior neck (A) is wellcircumscribed, present below the epidermis, and has a purple-blue hue with an intact overlying epidermis. Gross examination (B) of the excised pilomatrixoma reveals the close proximity of the tumor to the epidermis and involvement the entire dermis and extending into the subcutis. Note the irregular variegated and granular nature of the tumor's cut surface.
association with sarcoidosis, skull dysostosis, Rubinstein– Taybi syndrome, Churg–Strauss syndrome, Turner syndrome, Soto syndrome, fronto-parietal baldness, gliomatosis cerebri and trisomy 9 [1,6,13-16]. After epidermoid cysts, pilomatricomas are the second most frequently excised pediatric skin mass, accounting for approximately 10% of all superficial masses evaluated by pathologists [5]. They may be misdiagnosed clinically as cysts (dermoid, trichilemmal, or sebaceous), tumors (parotid, giant cell, chondromas, eccrine spiradenomas, hydrocystomas, degenerating fibroxanthomas, osteochondromas, dermatofibroma, trichoepitheliomas, basal cell epitheliomas), and other cutaneous lesions (foreign body reactions, fat necrosis, or lymphadenopathy) [1,2,17]. Due to the broad differential diagnosis, a pre-operative diagnosis of pilomatricoma is correctly made in only 46% of cases [17].
Characterizing pilomatricomas in children On histopathology, pilomatricomas demonstrate an admixture of islands of enucleated ghost cells surrounded by nucleated basaloid cells [1,2,5]. These ghost cells, sometimes referred to as “shadow cells,” have a distinct border and a central unstained area representing loss of nuclear detail, and are considered to be necessary to establish a definitive diagnosis (Fig. 3) [18]. Tumors typically grow in a regular fashion without atypical cells, and are usually poorly delineated [2]. The conversion of fibroblasts to osteoblasts within the tumor may result in calcification (70%–75%), and in some cases ossification (15%) [1,2].
2. Patients and methods Following approval by the institutional review board (H-19735), we retrospectively reviewed the medical records of all patients with a histopathologically confirmed diagnosis of pilomatricoma, who underwent surgical resection at Texas Children's Hospital from April 1982 to April 2010.
1553 Demographic data, pathologic results, and post-operative information were collected.
3. Results During the study period, 802 children underwent excision of a total of 916 pilomatricomas. Four hundred forty-one patients (55%) were female. The median age at resection was 6 years, with a range of 5 months to 18 years. No patients were diagnosed with an associated disease at the time of excision. Sixty-six percent of lesions occurred in patients younger than 10 years of age. Information about lesion size was available for 674 (74%) lesions, with a mean diameter of 14.0 ± 7.4 mm (range: 1–50 mm). The most commonly affected region was the head and neck region (58%), followed by the upper limbs (23%), the trunk (14%), and the lower limbs (5%) (Table 1). Among the head and neck lesions, 59 lesions (6%) were resected from the periorbital region, 86 lesions (9%) from the midface (maxillary) region,
Fig. 3 Pilomatrixoma: typical histopathologic features (A) consist of a mass comprised of an admixture of basaloid cells (BC), ghost (shadow cells, GC) and foreign body giant cell inflammatory reaction (FBGC) to keratin debris. Epidermal cyst-like structures (B) may be present and these are lined by squamous cells (SC) undergoing keratinization with central keratin debris (KD) and ghost cells (GC). The lesion (C and D) may possess areas of dystrophic fine granular to larger aggregates of basophilic calcifications (DC) and ossification with formation of typical trabecular bone spicules (B). (H&E staining, original magnification 200 ×).
1554 Table 1
S.F. Hassan et al. Distribution of lesions by location and age of patient.
Location Head and neck (a) Periorbital (b) Midface (c) Periauricular (d) Neck (e) Other Trunk Upper extremities Lower extremities Age at surgery 0–5 years 6–10 years 11–15 years N 15 years
No. of lesions 529 (58%) 59 (6%) 86 (9%) 70 (8%) 142 (16%) 172 (19%) 130 (14%) 214 (23%) 43 (5%) No. of patients (%) 384 (42%) 348 (38%) 162 (18%) 22 (2%)
70 lesions (8%) from periauricular region, 142 lesions (16%) from the neck, and 172 lesions (19%) from other locations including scalp, face, lips, and mandible. Forty-three patients (5%) had multiple lesions ranging from two to six lesions per patient. A total of 11 patients (1%) returned to our institution with lesion recurrence at the excision site of excision. Seventeen patients (2%) underwent excision of metachronous lesions a median of 18 months after initial resection (range of 5 weeks to 5 years).
4. Discussion Pilomatricomas are cutaneous neoplasms arising from matrix cells of the hair follicle [1,2,5,19]. Several mechanisms of development have been proposed; however, the most accepted theories involve the inclusion of epidermal elements into abnormal locations. Dubreuilh and Cazenave proposed that pilomatricomas originate from branchial clefts and are of ectodermal origin, while others have described the tumors as epithelial hamartomas [2,20]. Pilomatricomas express human hair keratin basic 1 protein, a marker of normal hair shaft cortical cells, and thus may differentiate into cortical cells during tumor development [21]. The majority of pilomatricomas express abnormal β-catenin, as a result of mutation in CTNNB1, which plays an important role in regulating normal cell growth and function [6,22,23]. Mice expressing a truncated form of β-catenin have abnormal hair follicle morphogenesis and develop tumors similar to human pilomatricomas. Pilomatricoma has a bimodal distribution of age at diagnosis. Most tumors are diagnosed in children, with the majority of lesions occurring before 2 years of age [1,4,5]. In our series, the majority of tumors occurred before 10 years of age. The second peak of increased prevalence is in patients ≥ 60 years of age [1,4,5]. The prevalence of pilomatricoma
is highest among whites and females, with a female-to-male ratio of 1.5–2.0 to 1.0 [24]. In comparison, the current study suggests a lower gender ratio with a female-to-male ratio of 1.2 to 1.0. While a paucity of data have been published regarding the epidemiology of metachronous or recurrent pilomatricoma, multiple tumors are reportedly more common among those of Japanese heritage [25]. Multiple tumors may also be seen in certain polyposis–colorectal cancer predisposition syndromes, such as Gardner's, FAP and MYH-associated polyposis–colorectal carcinoma syndromes [7-10]. The presence of multiple pilomatricomas in a child may be the first indication that the child may have a polyposis–colorectal carcinoma syndrome. This may also lead to identification of cancer predisposition gene mutations in the child's parents and siblings, and allow for early detection, surveillance and treatment of polyposis and colorectal carcinoma. However, in our series, we did not observe any patients with associated disease at the time of surgical excision. Pilomatricomas usually present as slow-growing, markedly firm, subcutaneous masses [1,4]. A delay of 2 months to 3 years in seeking medical attention is typical with the average patient [2]. Tumors may be associated with pain, tenderness, inflammation, abscess formation, ulceration, bullous lesions, and a history of trauma to the region [2,5,26]. These lesions are most commonly found on the face, neck, parotid region, and scalp (58% in the current study); however, these tumors can present anywhere on the body [27]. The overlying skin may appear normal in color, white, or have a bluish tinge, and the lesion slides freely underneath the skin [18]. The “tent sign” may be appreciated as skin stretches over the tumor with multiple facets and angles [5,6,28]. Exophytic, atrophic and perforating pilomatricomas have also been reported [29,30]. The reported tumor size ranges from 5 to 30 mm; however based on our data, the tumor size range may be more broad (1–50 mm) than previously reported [31,32]. Multiple tumors are rare and were seen in our study population at a rate similar to previous reports (5%) [5,32]. Metachronous lesions in our population (2%) were less common than synchronous lesions, and cannot be compared to earlier studies as these rates have not been previously reported. A diagnosis of pilomatricoma can usually be made solely on clinical examination; however, radiographic imaging may be useful in a minority of patients [2,5]. CT scan identifies pilomatricomas as radiopaque subcutaneous lesions with clearly delineated margins and calcifications, and may be particularly useful in the periauricular region in differentiating contrast-enhancing parotid tumors from non-enhancing pilomatricomas. On ultrasound examination, a well-demarcated, round, hyperechogenic mass can be seen with a dense posterior acoustic shadow [2,33-35]. On MRI, the lesions are seen as areas of delayed enhancement and heterogeneous signal intensity on a post-enhanced sequence [5]. While CT scan and magnetic resonance imaging provide additional details about the surrounding structures and depth of the
Characterizing pilomatricomas in children lesion, ultrasound examination is preferred in children because it does not require sedation or exposure to radiation, with an approximately 80% accuracy rate [5,18,25,36]. Fine needle aspiration can obtain a definitive diagnosis via the histopathologic identification of ghost (shadow) cells and/or basaloid cells with or without calcium deposits, but is rarely indicated in children [2,24]. Despite a characteristic appearance, misdiagnosis frequently occurs, and can lead to unnecessary imaging studies [37]. In this study, all patients were taken to the operating room based on clinical exam only, and pre-operative imaging was not used as a part of the pre-operative evaluation. Although malignant pilomatricomas are rare, and almost uniformly confined to adults, metastases to the lung, bone, brain, sinuses, skin, and abdominal organs have been reported [2,38-42]. Pilomatricomas usually have welldefined margins; malignancy should be suspected if margins are ill-defined or the tumor is fixed to surrounding tissue [1,38]. The term “pilomatrix carcinoma” was used for the first time in 1980 by Lopansri and Minm [43] to describe a pilomatricoma with numerous abnormal mitotic figures and an infiltrative border. Pilomatrix carcinomas have been further described as having enlarged epithelial cells, clusters of undifferentiated basaloid cells, invasion of adjacent blood vessels, and infiltration of capsular tissue [2,44]. In comparison with benign lesions, pilomatrix carcinomas most commonly affect middle-aged males, although a case of pilomatrix carcinoma in an 8-year-old girl has been reported [45-47]. This emphasizes the need for submission of these lesions for histopathologic examination and definitive diagnosis. None of our patients had evidence of carcinoma formation on histopathologic evaluation. Surgical excision is the definitive treatment for pilomatricoma, and incomplete resection almost always results in tumor recurrence [2]. Clear margins should be obtained as spontaneous regression has not been reported [1,2,6]. The data in the current study support this management strategy as our recurrence rates were extremely low (1%) and consistent with the 1%–6% recurrence rate previously reported [4,5,28]. In some cases, it may be necessary to remove overlying, adherent skin, but rarely is it necessary to excise tissue beneath the tumor [2,6]. Incision and curettage has been reported, but may leave behind remnant cells, leading to recurrence in most cases [25]. In conclusion, pilomatricomas are common, benign tumors of childhood that predominantly affect the head and neck region, but may affect any cutaneous site. A diagnosis can usually be made on clinical examination alone and not require radiologic examination. Misdiagnosis can occur, and awareness on the part of the practitioner is important so that unnecessary imaging studies and biopsies are not obtained. Complete excision is achieved readily in most cases with minimal trauma to the surrounding tissue. The clinician should be aware that pilomatricomas may be associated with several other entities or syndromes. Multiple pilomatricomas may be the first indication of a polyposis–colorectal cancer
1555 predisposition syndrome in the affected child and his family members. Such affected children, and potentially their families, require clinical and genetic evaluation to determine if a familial cancer predisposition syndrome exists.
References [1] Yencha MW. Head and neck pilomatricoma in the pediatric age group: a retrospective study and literature review. Int J Pediatr Otorhinolaryngol 2001;57:123-8. [2] Duflo S, Nicollas R, Roman S, et al. Pilomatrixoma of the head and neck in children: a study of 38 cases and a review of the literature. Arch Otolaryngol Head Neck Surg 1998;124:1239-42. [3] Lan MY, Lan MC, Ho CY, et al. Pilomatricoma of the head and neck: a retrospective review of 179 cases. Arch Otolaryngol Head Neck Surg 2003;129:1327-30. [4] Pirouzmanesh A, Reinisch JF, Gonzalez-Gomez I, et al. Pilomatrixoma: a review of 346 cases. Plast Reconstr Surg 2003;112:1784-9. [5] Danielson-Cohen A, Lin SJ, Hughes CA, et al. Head and neck pilomatrixoma in children. Arch Otolaryngol Head Neck Surg 2001; 127:1481-3. [6] Cigliano B, Baltogiannis N, De Marco M, et al. Pilomatricoma in childhood: a retrospective study from three European paediatric centres. Eur J Pediatr 2005;164:673-7. [7] Trufant J, Kurz W, Frankel A, et al. Familial multiple pilomatrixomas as a presentation of attenuated adenomatosis polyposis coli. J Cutan Pathol 2012;39:440-3. [8] Pujol RM, Casanova JM, Egido R, et al. Multiple familial pilomatricomas: a cutaneous marker for Gardner syndrome? Pediatr Dermatol 1995;12:331-5. [9] Baglioni S, Melean G, Gensini F, et al. A kindred with MYHassociated polyposis and pilomatricomas. Am J Med Genet A 2005; 134A:212-4. [10] Cetta F, Dhamo A. Inherited multitumoral syndromes including colorectal carcinoma. Surg Oncol 2007;16(Suppl. 1):S17-23. [11] Urabe K, Xia J, Masuda T, et al. Pilomatricoma-like changes in the epidermoid cysts of Gardner syndrome with an APC gene mutation. J Dermatol 2004;31:255-7. [12] Farrell AM, Ross JS, Barton SE, et al. Multiple pilomatricomas and myotonic dystrophy in a patient with AIDS. Clin Exp Dermatol 1995; 20:423-4. [13] Matsuura H, Hatamochi A, Nakamura Y, et al. Multiple pilomatricoma in trisomy 9. Dermatology 2002;204:82-3. [14] Wachter-Giner T, Bieber I, Warmuth-Metz M, et al. Multiple pilomatricomas and gliomatosis cerebri—a new association? Pediatr Dermatol 2009;26:75-8. [15] Gilaberte Y, Ferrer-Lozano M, Olivan MJ, et al. Multiple giant pilomatricoma in familial Sotos syndrome. Pediatr Dermatol 2008;25: 122-5. [16] Bayle P, Bazex J, Lamant L, et al. Multiple perforating and non perforating pilomatricomas in a patient with Churg–Strauss syndrome and Rubinstein–Taybi syndrome. J Eur Acad Dermatol Venereol 2004; 18:607-10. [17] Kumaran N, Azmy A, Carachi R, et al. Pilomatrixoma—accuracy of clinical diagnosis. J Pediatr Surg 2006;41:1755-8. [18] Hughes J, Lam A, Rogers M. Use of ultrasonography in the diagnosis of childhood pilomatrixoma. Pediatr Dermatol 1999;16:341-4. [19] Marrogi AJ, Wick MR, Dehner LP. Pilomatrical neoplasms in children and young adults. Am J Dermatopathol 1992;14:87-94. [20] Lever WF, Griesemer RD. Calcifying epithelioma of Malherbe; report of 15 cases, with comments on its differentiation from calcified epidermal cyst and on its histogenesis. Arch Derm Syphilol 1949;59:506-18. [21] Cribier B, Asch PH, Regnier C, et al. Expression of human hair keratin basic 1 in pilomatrixoma. A study of 128 cases. Br J Dermatol 1999; 140:600-4.
1556 [22] Lazar AJ, Calonje E, Grayson W, et al. Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding beta-catenin. J Cutan Pathol 2005;32:148-57. [23] Moreno-Bueno G, Gamallo C, Perez-Gallego L, et al. Beta-catenin expression in pilomatrixomas. Relationship with beta-catenin gene mutations and comparison with beta-catenin expression in normal hair follicles. Br J Dermatol 2001;145:576-81. [24] Wang J, Cobb CJ, Martin SE, et al. Pilomatrixoma: clinicopathologic study of 51 cases with emphasis on cytologic features. Diagn Cytopathol 2002;27:167-72. [25] Avci G, Akan M, Akoz T. Simultaneous multiple pilomatrixomas. Pediatr Dermatol 2006;23:157-62. [26] Gustin AF, Lee EY. Pilomatricoma in a pediatric patient. Pediatr Radiol 2006;36:1113. [27] Diomedi Camassei F, Francalanci P, Boldrini R, et al. Paratesticular pilomatricoma: a new location. Pediatr Surg Int 2001;17:652-3. [28] Price HN, Zaenglein AL. Diagnosis and management of benign lumps and bumps in childhood. Curr Opin Pediatr 2007;19:420-4. [29] Tay YK. Exophytic pilomatricoma. Pediatr Dermatol 2003;20:373. [30] Holme SA, Varma S, Holt PJ. The first case of exophytic pilomatricoma in an Asian male. Pediatr Dermatol 2001;18:498-500. [31] Solano JG, Acosta-Ortega J, Perez-Guillermo M. Pilomatrixoma: never lower your guard. Diagn Cytopathol 2007;35:457-8. [32] Migirov L, Fridman E, Talmi YP. Pilomatrixoma of the retroauricular area and arm. J Pediatr Surg 2002;37:E20. [33] Choo HJ, Lee SJ, Lee YH, et al. Pilomatricomas: the diagnostic value of ultrasound. Skeletal Radiol 2010;39:243-50. [34] Mendes Neto JA, Raposo RM, Segalla DK, et al. Pilomatrixoma in the head and neck. Braz J Otorhinolaryngol 2009;75:618. [35] Som PM, Shugar JM, Silvers AR. CT of pilomatrixoma in the cheek. AJNR Am J Neuroradiol 1998;19:1219-20.
S.F. Hassan et al. [36] Lim HW, Im SA, Lim GY, et al. Pilomatricomas in children: imaging characteristics with pathologic correlation. Pediatr Radiol 2007;37:549-55. [37] Roche NA, Monstrey SJ, Matton GE. Pilomatricoma in children: common but often misdiagnosed. Acta Chir Belg 2010;110:250-4. [38] Dutta R, Boadle R, Ng T. Pilomatrix carcinoma: case report and review of literature. Pathology 2001;33:248-51. [39] Mikhaeel NG, Spittle MF. Malignant pilomatrixoma with multiple local recurrences and distant metastases: a case report and review of the literature. Clin Oncol 2001;13:386-9. [40] Autelitano L, Biglioli F, Migliori G, et al. Pilomatrix carcinoma with visceral metastases: case report and review of the literature. J Plast Reconstr Aesthet Surg 2009;62:e574-7. [41] Bremnes RM, Kvamme JM, Stalsberg H, et al. Pilomatrix carcinoma with multiple metastases: report of a case and review of the literature. Eur J Cancer 1999;35:433-7. [42] Yadia S, Randazzo CG, Malik S, et al. Pilomatrix carcinoma of the thoracic spine: case report and review of the literature. J Spinal Cord Med 2010;33:272-7. [43] Lopansri S, Mihm Jr MC. Pilomatrix carcinoma or calcifying epitheliocarcinoma of Malherbe: a case report and review of literature. Cancer 1980;45:2368-73. [44] Liegl B, Leibl S, Okcu M, et al. Malignant transformation within benign adnexal skin tumours. Histopathology 2004;45:162-70. [45] Geh JL, Wilson GR. Unusual multiple pilomatrixomata: case report and review of the literature. Br J Plast Surg 1999;52:320-1. [46] Hardisson D, Linares MD, Cuevas-Santos J, et al. Pilomatrix carcinoma: a clinicopathologic study of six cases and review of the literature. Am J Dermatopathol 2001;23:394-401. [47] Zachariades N, Mezitis M, Rallis G, et al. Malignant pilomatricoma in a child with a previous vascular malformation. Br J Oral Maxillofac Surg 2008;46:152-3.
www.elsevier.com/locate/jpedsurg
Characterizing pilomatricomas in children: a single institution experience☆ Saif F. Hassan a , Elizabeth Stephens a , Sara C. Fallon a , Deborah Schady b , M. John Hicks b , Monica E. Lopez a , David A. Lazar a , Manuel A. Rodriguez a , Mary L. Brandt a,⁎ a
Division of Pediatric Surgery, Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
b
Received 13 June 2012; revised 10 August 2012; accepted 10 August 2012
Key words: Pilomatricoma; Pediatrics; Benign tumor
Abstract Background/Purpose: Pilomatricomas, or calcifying epitheliomas of Malherbe, are among the most common superficial cutaneous soft tissue lesions in children. Familiarity with the presenting signs and symptoms allows for the diagnosis to be made on physical examination alone in most patients, avoiding expensive and unnecessary diagnostic imaging. Methods: A retrospective IRB-approved review of surgical pathology archives and medical records of all patients undergoing excision of pilomatricomas between 1982 and 2010 was performed to determine the characteristics of the pilomatricoma tumors. Data regarding gender, age, location, size of tumor, and histopathology were collected. Results: There were 916 pilomatricomas resected in 802 patients. Fifty-five percent of the patients were girls (441 patients). The median age at the time of resection was 6 years (range 5 months to 18 years). Multiple lesions were found in 43 patients (5%). The most common location was head and neck (n = 529, 58%), followed by upper limbs (n = 214, 23%), trunk (n = 130, 14%), and lower limbs (n = 43, 5%). Information on size was available for 674 lesions; mean lesion diameter was 14.0 ± 7.4 mm. Twenty-eight patients (3%) had either recurrent (n = 11) or metachronous (n = 17) lesions resected at our institution, with a median interval of 12 months after initial resection (range 5 weeks to 5 years). No cases of pilomatrix carcinoma were observed. Conclusion: The majority of pilomatricomas occur in the head and neck, although they can present in any location. Approximately 5% of children have multiple lesions. Pilomatricomas occur slightly more commonly in girls, and 66% of lesions occur in children b 10 years of age. Complete surgical excision is necessary to prevent recurrence. Recurrences and pilomatrix carcinoma are very rare if complete excision is achieved. © 2013 Elsevier Inc. All rights reserved.
☆
Disclosures: The authors have no affiliations or financial support to disclose with regard to the preparation of this manuscript. ⁎ Corresponding author. Texas Children's Hospital, Houston, TX 77030, USA. Tel.: + 1 832 822 3135; fax: + 1 832 825 3141. E-mail address: [email protected] (M.L. Brandt). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2012.08.007
Pilomatricomas, otherwise known as “calcifying epitheliomas of Malherbe” were first described by Malherbe and Chenantais in 1880 as a skin tumor arising from sebaceous glands [1-3]. Dubreuilh and Cazenave first described the
1552
S.F. Hassan et al.
histopathologic features of basaloid epithelial cells islands and shadow (ghost) cells, and Turhan and Krainer discovered the origin of the tumor from hair cortex cells [1]. Pilomatricomas are benign skin neoplasms of childhood that present as deep, subcutaneous lesions lying between the dermis and the hypodermis (Fig. 1) [2]. They most commonly occur in the head and neck region, but have been reported in other areas of the body as well [1,4]. On excision these lesions are solid with a gray-tan appearance, and can appear to be in direct continuity with the overlying epidermis (Fig. 2) [5]. Pilomatricomas usually occur as isolated lesions, but have been reported to occur in association with polyposis– colorectal carcinoma predisposition syndromes (Gardner syndrome, Familial adenomatosis polyposis syndrome [FAP, APC gene, MYH (MUTYH) gene], and β-catenin gene mutations) and myotonic muscular dystrophy (Steinert disease) [2,6-12]. Less commonly, these tumors can occur in
Fig. 2 Pilomatrixoma: gross appearance of lesion that was “shelled out,” demonstrating irregular surface architecture (A), a thin membrane encasing the irregularly-shaped mass, and heterogenous nature of the lesional contents on cut surface (B). The irregular surface and lack of complete excision of the mass lead to local recurrence of the lesion in many cases.
Fig. 1 Pilomatrixoma located on posterior neck (A) is wellcircumscribed, present below the epidermis, and has a purple-blue hue with an intact overlying epidermis. Gross examination (B) of the excised pilomatrixoma reveals the close proximity of the tumor to the epidermis and involvement the entire dermis and extending into the subcutis. Note the irregular variegated and granular nature of the tumor's cut surface.
association with sarcoidosis, skull dysostosis, Rubinstein– Taybi syndrome, Churg–Strauss syndrome, Turner syndrome, Soto syndrome, fronto-parietal baldness, gliomatosis cerebri and trisomy 9 [1,6,13-16]. After epidermoid cysts, pilomatricomas are the second most frequently excised pediatric skin mass, accounting for approximately 10% of all superficial masses evaluated by pathologists [5]. They may be misdiagnosed clinically as cysts (dermoid, trichilemmal, or sebaceous), tumors (parotid, giant cell, chondromas, eccrine spiradenomas, hydrocystomas, degenerating fibroxanthomas, osteochondromas, dermatofibroma, trichoepitheliomas, basal cell epitheliomas), and other cutaneous lesions (foreign body reactions, fat necrosis, or lymphadenopathy) [1,2,17]. Due to the broad differential diagnosis, a pre-operative diagnosis of pilomatricoma is correctly made in only 46% of cases [17].
Characterizing pilomatricomas in children On histopathology, pilomatricomas demonstrate an admixture of islands of enucleated ghost cells surrounded by nucleated basaloid cells [1,2,5]. These ghost cells, sometimes referred to as “shadow cells,” have a distinct border and a central unstained area representing loss of nuclear detail, and are considered to be necessary to establish a definitive diagnosis (Fig. 3) [18]. Tumors typically grow in a regular fashion without atypical cells, and are usually poorly delineated [2]. The conversion of fibroblasts to osteoblasts within the tumor may result in calcification (70%–75%), and in some cases ossification (15%) [1,2].
2. Patients and methods Following approval by the institutional review board (H-19735), we retrospectively reviewed the medical records of all patients with a histopathologically confirmed diagnosis of pilomatricoma, who underwent surgical resection at Texas Children's Hospital from April 1982 to April 2010.
1553 Demographic data, pathologic results, and post-operative information were collected.
3. Results During the study period, 802 children underwent excision of a total of 916 pilomatricomas. Four hundred forty-one patients (55%) were female. The median age at resection was 6 years, with a range of 5 months to 18 years. No patients were diagnosed with an associated disease at the time of excision. Sixty-six percent of lesions occurred in patients younger than 10 years of age. Information about lesion size was available for 674 (74%) lesions, with a mean diameter of 14.0 ± 7.4 mm (range: 1–50 mm). The most commonly affected region was the head and neck region (58%), followed by the upper limbs (23%), the trunk (14%), and the lower limbs (5%) (Table 1). Among the head and neck lesions, 59 lesions (6%) were resected from the periorbital region, 86 lesions (9%) from the midface (maxillary) region,
Fig. 3 Pilomatrixoma: typical histopathologic features (A) consist of a mass comprised of an admixture of basaloid cells (BC), ghost (shadow cells, GC) and foreign body giant cell inflammatory reaction (FBGC) to keratin debris. Epidermal cyst-like structures (B) may be present and these are lined by squamous cells (SC) undergoing keratinization with central keratin debris (KD) and ghost cells (GC). The lesion (C and D) may possess areas of dystrophic fine granular to larger aggregates of basophilic calcifications (DC) and ossification with formation of typical trabecular bone spicules (B). (H&E staining, original magnification 200 ×).
1554 Table 1
S.F. Hassan et al. Distribution of lesions by location and age of patient.
Location Head and neck (a) Periorbital (b) Midface (c) Periauricular (d) Neck (e) Other Trunk Upper extremities Lower extremities Age at surgery 0–5 years 6–10 years 11–15 years N 15 years
No. of lesions 529 (58%) 59 (6%) 86 (9%) 70 (8%) 142 (16%) 172 (19%) 130 (14%) 214 (23%) 43 (5%) No. of patients (%) 384 (42%) 348 (38%) 162 (18%) 22 (2%)
70 lesions (8%) from periauricular region, 142 lesions (16%) from the neck, and 172 lesions (19%) from other locations including scalp, face, lips, and mandible. Forty-three patients (5%) had multiple lesions ranging from two to six lesions per patient. A total of 11 patients (1%) returned to our institution with lesion recurrence at the excision site of excision. Seventeen patients (2%) underwent excision of metachronous lesions a median of 18 months after initial resection (range of 5 weeks to 5 years).
4. Discussion Pilomatricomas are cutaneous neoplasms arising from matrix cells of the hair follicle [1,2,5,19]. Several mechanisms of development have been proposed; however, the most accepted theories involve the inclusion of epidermal elements into abnormal locations. Dubreuilh and Cazenave proposed that pilomatricomas originate from branchial clefts and are of ectodermal origin, while others have described the tumors as epithelial hamartomas [2,20]. Pilomatricomas express human hair keratin basic 1 protein, a marker of normal hair shaft cortical cells, and thus may differentiate into cortical cells during tumor development [21]. The majority of pilomatricomas express abnormal β-catenin, as a result of mutation in CTNNB1, which plays an important role in regulating normal cell growth and function [6,22,23]. Mice expressing a truncated form of β-catenin have abnormal hair follicle morphogenesis and develop tumors similar to human pilomatricomas. Pilomatricoma has a bimodal distribution of age at diagnosis. Most tumors are diagnosed in children, with the majority of lesions occurring before 2 years of age [1,4,5]. In our series, the majority of tumors occurred before 10 years of age. The second peak of increased prevalence is in patients ≥ 60 years of age [1,4,5]. The prevalence of pilomatricoma
is highest among whites and females, with a female-to-male ratio of 1.5–2.0 to 1.0 [24]. In comparison, the current study suggests a lower gender ratio with a female-to-male ratio of 1.2 to 1.0. While a paucity of data have been published regarding the epidemiology of metachronous or recurrent pilomatricoma, multiple tumors are reportedly more common among those of Japanese heritage [25]. Multiple tumors may also be seen in certain polyposis–colorectal cancer predisposition syndromes, such as Gardner's, FAP and MYH-associated polyposis–colorectal carcinoma syndromes [7-10]. The presence of multiple pilomatricomas in a child may be the first indication that the child may have a polyposis–colorectal carcinoma syndrome. This may also lead to identification of cancer predisposition gene mutations in the child's parents and siblings, and allow for early detection, surveillance and treatment of polyposis and colorectal carcinoma. However, in our series, we did not observe any patients with associated disease at the time of surgical excision. Pilomatricomas usually present as slow-growing, markedly firm, subcutaneous masses [1,4]. A delay of 2 months to 3 years in seeking medical attention is typical with the average patient [2]. Tumors may be associated with pain, tenderness, inflammation, abscess formation, ulceration, bullous lesions, and a history of trauma to the region [2,5,26]. These lesions are most commonly found on the face, neck, parotid region, and scalp (58% in the current study); however, these tumors can present anywhere on the body [27]. The overlying skin may appear normal in color, white, or have a bluish tinge, and the lesion slides freely underneath the skin [18]. The “tent sign” may be appreciated as skin stretches over the tumor with multiple facets and angles [5,6,28]. Exophytic, atrophic and perforating pilomatricomas have also been reported [29,30]. The reported tumor size ranges from 5 to 30 mm; however based on our data, the tumor size range may be more broad (1–50 mm) than previously reported [31,32]. Multiple tumors are rare and were seen in our study population at a rate similar to previous reports (5%) [5,32]. Metachronous lesions in our population (2%) were less common than synchronous lesions, and cannot be compared to earlier studies as these rates have not been previously reported. A diagnosis of pilomatricoma can usually be made solely on clinical examination; however, radiographic imaging may be useful in a minority of patients [2,5]. CT scan identifies pilomatricomas as radiopaque subcutaneous lesions with clearly delineated margins and calcifications, and may be particularly useful in the periauricular region in differentiating contrast-enhancing parotid tumors from non-enhancing pilomatricomas. On ultrasound examination, a well-demarcated, round, hyperechogenic mass can be seen with a dense posterior acoustic shadow [2,33-35]. On MRI, the lesions are seen as areas of delayed enhancement and heterogeneous signal intensity on a post-enhanced sequence [5]. While CT scan and magnetic resonance imaging provide additional details about the surrounding structures and depth of the
Characterizing pilomatricomas in children lesion, ultrasound examination is preferred in children because it does not require sedation or exposure to radiation, with an approximately 80% accuracy rate [5,18,25,36]. Fine needle aspiration can obtain a definitive diagnosis via the histopathologic identification of ghost (shadow) cells and/or basaloid cells with or without calcium deposits, but is rarely indicated in children [2,24]. Despite a characteristic appearance, misdiagnosis frequently occurs, and can lead to unnecessary imaging studies [37]. In this study, all patients were taken to the operating room based on clinical exam only, and pre-operative imaging was not used as a part of the pre-operative evaluation. Although malignant pilomatricomas are rare, and almost uniformly confined to adults, metastases to the lung, bone, brain, sinuses, skin, and abdominal organs have been reported [2,38-42]. Pilomatricomas usually have welldefined margins; malignancy should be suspected if margins are ill-defined or the tumor is fixed to surrounding tissue [1,38]. The term “pilomatrix carcinoma” was used for the first time in 1980 by Lopansri and Minm [43] to describe a pilomatricoma with numerous abnormal mitotic figures and an infiltrative border. Pilomatrix carcinomas have been further described as having enlarged epithelial cells, clusters of undifferentiated basaloid cells, invasion of adjacent blood vessels, and infiltration of capsular tissue [2,44]. In comparison with benign lesions, pilomatrix carcinomas most commonly affect middle-aged males, although a case of pilomatrix carcinoma in an 8-year-old girl has been reported [45-47]. This emphasizes the need for submission of these lesions for histopathologic examination and definitive diagnosis. None of our patients had evidence of carcinoma formation on histopathologic evaluation. Surgical excision is the definitive treatment for pilomatricoma, and incomplete resection almost always results in tumor recurrence [2]. Clear margins should be obtained as spontaneous regression has not been reported [1,2,6]. The data in the current study support this management strategy as our recurrence rates were extremely low (1%) and consistent with the 1%–6% recurrence rate previously reported [4,5,28]. In some cases, it may be necessary to remove overlying, adherent skin, but rarely is it necessary to excise tissue beneath the tumor [2,6]. Incision and curettage has been reported, but may leave behind remnant cells, leading to recurrence in most cases [25]. In conclusion, pilomatricomas are common, benign tumors of childhood that predominantly affect the head and neck region, but may affect any cutaneous site. A diagnosis can usually be made on clinical examination alone and not require radiologic examination. Misdiagnosis can occur, and awareness on the part of the practitioner is important so that unnecessary imaging studies and biopsies are not obtained. Complete excision is achieved readily in most cases with minimal trauma to the surrounding tissue. The clinician should be aware that pilomatricomas may be associated with several other entities or syndromes. Multiple pilomatricomas may be the first indication of a polyposis–colorectal cancer
1555 predisposition syndrome in the affected child and his family members. Such affected children, and potentially their families, require clinical and genetic evaluation to determine if a familial cancer predisposition syndrome exists.
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