Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2024;14(2):e2024140 1 Pilomatricoma: Clinical, Dermoscopic Findings and Management in 55 Pediatric Patients and Concise Review of the Literature with Special Emphasis on Dermoscopy Marco Adriano Chessa1,2, Maria Francesca Baracca1,2, Alice Nadia Rossi1,2, Bianca Maria Piraccini1,2, Vittorio De Pietro3, Valentino Marino Picciola4, Alessandra Gelmetti1,2, Iria Neri1 1 Dermatology Unit - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 2 Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy 3 Dermatology Unit – Azienda Ospedaliera-Universitaria di Siena, Siena, Italy 4 University of Bologna, School of Medicine and Surgery, Bologna, Italy Key words: pilomatricoma in children, typical pilomatricoma, atypical pilomatricoma, dermoscopic findings in pilomatricoma, management of pilomatricoma in pediatric patients Citation: Chessa MA, Baracca MF, Rossi AN, et al. Pilomatricoma: Clinical, Dermoscopic Findings and Management in 55 Pediatric Patients and Concise Review of the Literature With Special Emphasis on Dermoscopy. Dermatol Pract Concept. 2024;14(2):e2024140. DOI: https://doi.org/10.5826/dpc.1402a140 Accepted: January 3, 2024; Published: April 2024 Copyright: ©2024 Chessa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Maria Francesca Baracca, via Massarenti 9, 40138 Bologna, Italy. Telephone/fax: +390512144843 E-mail: maria.baracca@studio.unibo.it Introduction: Pilomatricoma is a benign adnexal dermal or subcutaneous tumor derived from imma- ture hair matrix cells. Objectives: The aim of our study is to evaluate clinical and dermoscopic features of pilomatricomas, with a specific focus on pediatric lesions, and to provide a concise review of the existing literature. Methods: A single-center retrospective study was undertaken on 55 patients with a histopathological diagnosis of pilomatricoma referred to the Dermatology Unit, University of Bologna, Bologna, Italy, between 2005 and 2023. Pilomatricomas were retrospectively evaluated relying on clinical and der- moscopic images. A PubMed search was conducted. All the relevant research up to July 31, 2023, was reviewed. We classified the cases as “typical” or “atypical” based on whether they were suspected of being pilomatricomas or not. ABSTRACT 2 Review | Dermatol Pract Concept. 2024;14(2):e2024140 Introduction Pilomatricoma, also called “calcifying epithelioma of Mal- herbe” or “pilomatrixoma”, is a benign adnexal dermal or subcutaneous tumor derived from immature hair ma- trix cells. It was first described in 1880 by Malherbe and Chenantais and, in 1961, Forbis and Helwig coined the term “pilomatrixoma” [1,2]. This tumor typically affects individuals during their first two decades of life. Clinically, it usually manifests as a firm, deep nodule, with a diameter ranging from 3-30 mm, mainly on the upper body. Although the pediatric onset is the most common, der- moscopic features are primarily reported in adult lesions and only a few cases of pediatric patients have been described in the literature (Table 1) [3-13]. Objectives The aim of our study is to evaluate both typical and atypical clinical and dermoscopic features of pilomatricomas, with a specific focus on pediatric lesions, and to provide a concise review of the existing literature. Methods A single-center retrospective study was conducted on 55  patients with a histopathological diagnosis of pilomatri- coma referred to the Pediatric Dermatology Unit, University of Bologna, Bologna, Italy from 2005 to 2023. Pilomatricomas were retrospectively evaluated by four dermatologists with expertise in dermoscopy and pediatric dermatology, relying on clinical and dermoscopic images only, and not allowed to consult histology and ultrasound investigations. A pilomatricoma was considered “atypical” if at least 3 out of 4 dermatologists disagreed on the diagnosis of pilo- matricoma. Two groups were therefore created: lesions that were suspected of being pilomatricomas, and lesions that were not. In the latter cases, other differential diagnoses were suggested. We identified all the studies indexed in PubMed until 31 July 2023. All papers reported in the present study were based on clinical studies involving humans, including case reports, case series and reviews. The search parameters included the terms ‘‘pilomatricoma in children”, “dermo- scopic findings in pilomatricoma”, “typical dermoscopy of pilomatricoma”, “atypical dermoscopy of pilomatricoma” and “pilomatricoma dermoscopy”. A subsequent review of the respective bibliographies aimed to identify any un- detected reports. Apart from two articles in German and French, only papers written in English were considered in the review. Results We observed and studied 55 children with pilomatricomas. Results are summarized in Table 2. Females were involved in 60% of cases. Mean age was 7 years. Two patients presented with 2 pilomatricomas with- out extracutaneous manifestations, leading to the identifica- tion of 58 pilomatricomas in our retrospective analysis. Thirty-eight of 58 (65%) pilomatricomas were located on the head-neck region, 14 (24%) on the upper limbs and a few cases on the lower limbs, back and abdomen. Clinically, pilomatricomas typically present as pigmented nodules. Forty-six pilomatricomas in our case series (79%) exhibited single or multiple colors ranging from blue to red or yellow (Figure 1, A, C and E). The nodules were exophytic, ulcerated, or subcutaneous in 17.2% of cases (Figure 1G). The mean diameter of the lesions was 7 mm. Furthermore, rare clinical types of pilomatricomas char- acterized by anetodermic or keloid-like appearance were de- scribed (3% of cases). An ultrasound scan was prescribed for 24 children (44%) and the report included the following features: dimensions, Results: A total of 55 children with pilomatricomas were observed and studied. Two patients pre- sented with 2 pilomatricomas, leading to the identification of 58 pilomatricomas. ‘Typical’ piloma- tricomas were observed in 79% of cases as nodular and pigmented lesions with one or more colors, ranging from blue-gray to red to yellow/white, evident on clinical examination and even better on dermoscopy. In 21% of cases, pilomatricomas presented in an ‘atypical’ form, which did not allow for a well-founded suspicion, placing them in differential diagnosis with other lesions and therefore requiring histological examination. Conclusions: According to our case series and systematic review of the literature, clinical appearance and dermoscopy may be sufficient to diagnose or suspect pilomatricoma in around 80% of cases, while histological examination is necessary to confirm the diagnosis in the remaining 20% of cases. Review | Dermatol Pract Concept. 2024;14(2):e2024140 3 Table 1. Overview of the Literature Review. Patients Study and Year of Publication Type of Study N. of Patients Involved With Dermoscopy Aviable Case N. Age and Sex Cutaneous Area Involved Typical at Dermoscopy Atypical at Dermoscopy Pedro Zaballos et al, 2008 [3] Clinical study 10 1 75, F Arm Tricolor pathognomonic appearance 2 40, M Arm 3 45, M Arm 4 12, F Face Tricolor pathognomonic appearance 5 36, F Neck 6 52, F Face Tricolor pathognomonic appearance 7 16, M Face 8 18, F Arm 9 14, F Face 10 60, F Face Hernández- Núnez et al 2014 [4] Retrospective Study of Pilomatricoma 1 1 Children Face Tricolor pathognomonic appearance Martinez- Moran et al, 2014 [5] Case report 1 61, F Right frontoparietal region Tricolor pathognomonic appearance Ivette Alarcon et al, 2014 [6] Case report 1 12, M Left cheek Tricolor pathognomonic appearance Erhan Ayhan et al, 2014 [7] Case report 3 1 67, F Right cheek Molluscum- like appearance 2 48, M Left eyebrow Nodular bicolor appearance 3 58, M Left side of the nose Nodular bicolor appearance Wolff et al, 2014 [8] Case report 1 4, M Left cheek Nodular pilomatricoma with blue- red color mimicking vascular lesion Chen et al, 2020 [9] Case report 1 14, M Left arm Nodular bicolor appearance Neema et al. 2022 [10] Case report 2 1 34, F Left cheek Tricolor pathognomonic appearance 2 42, F Right pinna Tricolor pathognomonic appearance Table1 continues 4 Review | Dermatol Pract Concept. 2024;14(2):e2024140 Patients Study and Year of Publication Type of Study N. of Patients Involved With Dermoscopy Aviable Case N. Age and Sex Cutaneous Area Involved Typical at Dermoscopy Atypical at Dermoscopy Anubha Dev et al, 2022 [11] Case report 3 1 40, M Right shoulder Anetodermic pilomatricoma 2 42, M Left mammary area Anetodermic pilomatricoma 3 70, F Left forehead region Anetodermic pilomatricoma Fink et al, 2017 [12] Case report 1 1 3, M Right zygomatic arch Molluscum- like appearance Huet et al, 2018 [13] Case report 1 1 10, M Left temporal region Tricolor pathognomonic appearance Table 1. Overview of the Literature Review. (continued) margins, depth, both hypoechogenicity and hyperechoge- nicity, hypoechoic rim, shadow cone, calcifications, non- homogeneous ecostructure. In 5 cases (21%) lesions had regular margins. The shadow cone was documented in 9 cases (37%) and in 10 cases (42%) there was calcification. Among the lesions presenting calcification, 8 (80%) were coarse formations, while 2 (20%) had a dotted appearance. Concerning ultrasound examination, in 15 patients (62%), it was able to confirm the diagnosis of pilomatri- coma. In 8 (33%) it did not contradict the clinical hypothesis of pilomatricoma, while in 2 (8%) it was inconclusive. In 36 of the 58 examined cases (62%), pilomatricomas presented as pigmented exophytic nodules, ulcerated or not, red and/or blue-gray in color, with or without visible ves- sels on the surface, classifiable as pigmented nodular type (Figure 1, A and B). In 24 cases (41%), mainly located on head-neck region, pilomatricomas were characterized by blue-yellow-reddish homogeneous areas, representing a pathognomonic tricolor nodular type (Figure 1, C-F). If only 2 colors were present, lesions were still suspected to be pilo- matricomas (bicolor type lesions). In 10 cases (17%), pilo- matricomas were classified as deep because of the presence of a pseudonetwork and a slight white-yellowish perifollic- ular discoloration associated with the underlying calcifica- tions (Figure 1, G and H). In such cases, a hard nodule on palpation may also suggest a calcified cyst as a differential diagnosis. Diagnosis of pilomatricoma was suspected in 79% of cases based on clinical and dermoscopic evaluation. The clinical and dermoscopic presentation was atypical or not suggestive in 12 of 58 cases (21%). Among them, 4 pilomatricomas (33%) presented as small nodules with a central white-yellowish component, surrounded either by an erythematous (red) halo or by crown vessels. In these cases, a dermoscopic diagnosis of molluscum contagiosum was proposed (Figure 2, A and B). In 4 cases (33%), pilomatricomas presented as subcutaneous nodules with a red or blue background and arborizing-like or reticular pattern linear-irregular flat vessels, mimicking calcified vascular lesions (Figure 2, C and D). Two piloma- tricomas (17%) resembled melanocytic lesions showing a brown pseudonetwork or homogeneous blue pattern at der- moscopy (Figure 2, E and F). In 2 cases (17%) the clinical presentation was keloid-like. Furthermore, biopsy of a lesion was performed to exclude a possible malignancy such as der- matofibrosarcoma protuberans (Figure 2, G and H). Histological examination revealed a relatively well- circumscribed, dermal or dermal-subcutaneous, multilob- ulated tumor, surrounded by a variable connective tissue stroma. The tumor consisted of islands of cells in a circular distribution with anucleated shadow cells in the center and basophilic cells in the periphery. In addition, certain distinctive histological characteristics may be associated with the particular clinical-dermoscopic variant. Tricolor pilomatricomas, for example, showed cal- cifications or melanin pigment in the lobules (Figure 3A). Dilated blood vessels overlying the tumor were observed in the vascular type (Figure 3B). Keloid-like pilomatricomas, on the other hand, featured a loss of collagen and elastic fibers in the superficial dermis overlying the lesion. Dermoscopic- histopathological correlation showed that bluish areas were associated with the presence of melanin pigment, white areas Review | Dermatol Pract Concept. 2024;14(2):e2024140 5 localized on the head-neck region [14]. Multiple pilomatri- comas may be associated with myotonic dystrophy, famil- ial adenomatous polyposis-related syndromes (including Gardner syndrome), Turner syndrome, or Rubinstein- Taybi syndrome [15,16]. Ciriacks Ket al found that the presence of six or more pilomatricomas is highly sugges- tive for an underlying syndrome (>95% specificity), so these patients should undergo additional screening [15]. In our retrospective analysis, two children presented with multiple pilomatricomas but further investigations were negative. Pilomatricomas may present with a varied morphology, therefore, making preoperative diagnosis challenging. The literature highlights an exophytic pigmented lesion as the with calcification, red areas with dilated blood vessels and white streaks corresponded to fibrosis on histopathology. Conclusions According to our study and the review of the literature, pilomatricoma is more common in females and it is mainly Table 2. Epidemiological Data, Anatomical Site, Clinical and Dermoscopic Findings of Pilomatricomas. General Data Number of patients 55 Number of pilomatricomas 58 of which are atypical 12 (21%) Epidemiological Findings Mean age at diagnosis (years) 7.2 Male gender, N (%) 22 (40%) Female gender, N (%) 33 (60%) Anatomical Site N (%) Face 35 (60.3%) Upper extremities 14 (24%) Lower limbs 2 (3.4%) Back 3 (5.2%) Neck 3 (5.2%) Abdomen 1 (1.7%) Patients With Multiple Lesions 2 (3.6%) Dermoscopic Features Yellow-white structureless areas 29 (50%) Perilesional Yellow area 2 (3.5%) Central yellow area 2 (3.5%) Reddish homogeneous areas 42 (72.4%) Linear irregular unfocused vessels 36 (62%) Dotted vessels 4 (6.9%) Structureless blue-gray areas 27 (46.5%) Ulceration 7 (12%) Clinical-dermoscopic Findings of Typical or Suspected Pilomatricomas 46/58 (79%) Pigmented bicolor nodular type 12 (20.7%) Pigmented tricolor nodular type 24 (41.4%) Deep pilomatricomas with pseudonetwork and follicular openings 10 (17.1%) Clinical-Dermoscopic Findings of Atypical Pilomatricomas 12/58 (13.8%) Molluscum-like pilomatricomas 4 (6.9%) Vascular-like pilomatricomas 4 (6.9%) Melanocytic-like pilomatricomas 2 (3.5%) Keloid-like pilomatricomas 2 (3.5%) Figure 1. (A) Ulcerated nodule with erythematous halo on the face of a 10-year-old child. (B) Bicolor yellow-white structures with un- focused linear-irregular vessels around the lesion. (C-F) Exophytic red, blue-gray, whitish nodule localized on the head and neck respec- tively; dermoscopy shows a pathognomonic 3 colors appearance characterized by blue-yellow-reddish homogeneous areas plus linear irregular vessels. (G,H) Deep variant of pilomatricoma: subcutane- ous nodule surrounding by normal skin with mild skin changes at clinic and dermoscopy. 6 Review | Dermatol Pract Concept. 2024;14(2):e2024140 Dermoscopy may be a useful tool in order to improve the detection of pilomatricomas. In the largest case series described by Zaballos et al, the use of dermoscopy in- creased the diagnostic sensitivity for pilomatricoma from 50% to 90% [3]. On the other hand, in our retrospective analysis, clinical and dermoscopic features were suspicious or suggestive of pilomatricoma in only 79% of children, while in 21% of cases, they were insufficient to make the diagnosis and histology was required. Zaballos et al re- ported the presence of multiple irregular whitish structures and streaks on dermoscopy in 90% of cases [3]. In con- trast, in our retrospective study, yellow/whitish areas were found only in 50% of pilomatricomas. These differences in sensitivity and dermoscopic findings may be related to the larger and different sample size (55 pediatric patients included in our analysis versus only 3 children described by Zaballos et al). The systematic review of the literature highlighted that both cases of typical and atypical pilomatricomas have been reported. The tricolor appearance could be considered as a der- moscopic clue to make the diagnosis. In this regard, several authors reported typical pilomatricomas characterized by a bi- or tricolor nodular aspect at dermoscopy [3-6,9,10,13]. In contrast, dermoscopy of atypical pilomatricoma has rarely been reported in the literature [7,8,11,13-15]. Several authors have described nodules characterized by yellowish lobules on an erythematous background, surrounded by crown-like branching vessels features that can also be found in molluscum contagiosum, which must be considered as a differential diagnosis [7,13]. Wolff et al reported a 4-year-old boy with a red-blue nodule, 0.5 cm in diameter, characterized by a homogeneous blue-red color and linear white structures on non-polarized dermoscopy. Histology was required to exclude a calcified hemangioma. In addition, Dev et al reported three cases of anetodermic pilomatricoma, which is extremely rare and presents clinically with a scar-like appearance [11,15]. Dermoscopy is inconclusive in these cases and dermoscopic- histopathological correlation is essential to differentiate between dermatofibroma and dermofibrosarcoma protuber- ans [15]. Clinical and dermoscopic findings of pilomatricoma in pediatric age are poorly reported in the literature. Our large case series and systematic review of the literature indicate that in approximately 80% of cases der- moscopy may be sufficient to diagnose or suspect pilomatri- coma, whereas in the remaining 20% of cases histological examination is necessary to confirm the diagnosis and exclude malignancy of the lesion. Figure 2. (A,B) Shiny papulo-nodular lesion localized on the face of a 9-year-old child showing homogeneous yellow-white central area with crown vessels at dermoscopy. (C,D) Subcutaneous red nodule on the malar region of a 12-year-old child characterized by large linear- irregular vessels on yellow-whitish background at der- moscopy. (E,F) Flat blue lesion localized on the neck of a 11-year- old child, dermoscopy shows light blue homogeneous areas. (G,H) Plaque irregular in shape 1.5cm diameter nodule, localized on the back of a 8-year-old child, dermoscopy shows an unspecific red ho- mogeneous pattern with unfocused vessels. typical and suggestive presentation of pilomatricoma in the pediatric population. Such lesions can be ulcerated or non-ulcerated and may exhibit variable pigmentation with combinations of blue-gray, red, and white/yellow colors [4,6-8,10,12-14]. Additionally, atypical pilomatricomas with an anetodermic appearance have also been reported [5,9,11]. In the literature, ultrasound was used to con- firm, support or exclude the diagnosis of pilomatricoma [18,19]. Once the diagnosis has been confirmed, surgical excision may be considered for aesthetic and functional reasons. Review | Dermatol Pract Concept. 2024;14(2):e2024140 7 A Case Report. Acta Derm Venereol. 2020;100(6):adv00088. 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Hu JL, Yoo H, Kwon ST, et al. Clinical analysis and review of literature on pilomatrixoma in pediatric patients. Arch Cranio- fac Surg. 2020;21(5):288-293. DOI: 10.7181/acfs.2020.00528. PMID: 33143396. PMCID: PMC7644346. 15. Ciriacks K, Knabel D, Waite MB. Syndromes associated with multiple pilomatricomas: When should clinicians be concerned? Pediatr Dermatol. 2020;37(1):9-17. DOI: 10.1111/pde.13947. PMID: 31618803. 16. Mesa-Álvarez L, Batalla A, Iglesias-Puzas Á, Álvarez C, Flórez Á. Multiple Pilomatricomas: A Retrospective Study and Literature References 1. Malherbe A, Chenantais J. Note sur l’ epitheliome calcifiédes glandes sebacées. Prog Med. 1880;8:826-828. 2. FORBIS R Jr, HELWIG EB. Pilomatrixoma (calcifying epitheli- oma). Arch Dermatol. 1961;83:606-618. DOI: 10.1001/archderm .1961.01580100070009. PMID: 13700704. 3. Zaballos P, Llambrich A, Puig S, Malvehy J. Dermoscopic find- ings of pilomatricomas. Dermatology. 2008;217(3):225-230. DOI: 10.1159/000148248. PMID: 18663304. 4. 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