Multiple pilomatricomas in a child with xeroderma pigmentosum: Coincidence or association?

The association of multiple pilomatricomas with xeroderma pigmentosum has not been described. We report a case of a child with multiple pilomatricomas and photosensitivity who was found to have a pathogenic variant in exon 4 of XPA and a likely pathogenic variant in COL6A1.

Pilomatricoma with florid osseous metaplasia: A common tumor with rare histopathological finding.

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a common benign skin adnexal tumor with differentiation toward hair cortex cells, commonly seen in head and neck region of children. It is usually solitary. Herein, we present a rare case of pilomatricoma with extensive osseous metaplasia as a thigh swelling in an adult female, considered clinically to be a sebaceous cyst. Florid osseous metaplasia is extremely rare in cases of pilomatricoma. To date, fewer than 10 cases of pilomatricoma with extensive osseous metaplasia at different sites have been reported in the English literature.

A Novel Phenotype Combining Primary Ovarian Insufficiency Growth Retardation and Pilomatricomas With MCM8 Mutation.

CONTEXT: Primary Ovarian insufficiency (POI) affects 1% of women aged <40 years and leads most often to definitive infertility with adverse health outcomes. Very recently, genes involved in deoxyribonucleic acid (DNA) repair have been shown to cause POI. OBJECTIVE: To identify the cause of a familial POI in a consanguineous Turkish family. DESIGN: Exome sequencing was performed in the proposita and her mother. Chromosomal breaks were studied in lymphoblastoid cell lines treated with mitomycin (MMC). SETTING AND PATIENTS: The proposita presented intrauterine and postnatal growth retardation, multiple pilomatricomas in childhood, and primary amenorrhea. She was treated with growth hormone (GH) from age 14 to 18 years. RESULTS: We identified a novel nonsense variant in exon 9 of the minichromosome maintenance complex component 8 gene (MCM8) NM_001281522.1: c0.925C > T/p.R309* yielding either a truncated protein or nonsense-mediated messenger ribonucleic acid decay.The variant was homozygous in the daughter and heterozygous in the mother. MMC induced DNA breaks and aberrant metaphases in the patient's lymphoblastoid cells. The mother's cells had intermediate but significantly higher chromosomal breaks compared with a control. CONCLUSION: We describe a novel phenotype of syndromic POI related to a novel truncating MCM8 variant. We show for the first time that spontaneous tumors (pilomatricomas) are associated with an MCM8 genetic defect, making the screening of this gene necessary before starting GH therapy in patients with POI with short stature, especially in a familial or consanguineous context. Appropriate familial monitoring in the long term is necessary, and fertility preservation should be considered in heterozygous siblings to avoid rapid follicular atresia.

Mutation analysis of multiple pilomatricomas in a patient with myotonic dystrophy type 1 suggests a DM1-associated hypermutation phenotype.

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease which results from an expansion of repetitive DNA elements within the 3' untranslated region of the DMPK gene. Some patients develop multiple pilomatricomas as well as malignant tumors in other tissues. Mutations of the catenin-ß gene (CTNNB1) could be demonstrated in most non-syndromic pilomatricomas. In order to gain insight into the molecular mechanisms which might be responsible for the occurrence of multiple pilomatricomas and cancers in patients with DM1, we have sequenced the CTNNB1 gene of four pilomatricomas and of one pilomatrical carcinoma which developed in one patient with molecularly proven DM1 within 4 years. We further analyzed the pilomatrical tumors for microsatellite instability as well as by NGS for mutations in 161 cancer-associated genes. Somatic and independent point-mutations were detected at typical hotspot regions of CTNNB1 (S33C, S33F, G34V, T41I) while one mutation within CTNNB1 represented a duplication mutation (G34dup.). Pilomatricoma samples were analyzed for microsatellite instability and expression of mismatch repair proteins but no mutated microsatellites could be detected and expression of mismatch repair proteins MLH1, MSH2, MSH6, PMS2 was not perturbed. NGS analysis only revealed one heterozygous germline mutation c.8494C>T; p.(Arg2832Cys) within the ataxia telangiectasia mutated gene (ATM) which remained heterozygous in the pilomatrical tumors. The detection of different somatic mutations in different pilomatricomas and in the pilomatrical carcinoma as well as the observation that the patient developed multiple pilomatricomas and one pilomatrical carcinoma over a short time period strongly suggest that the patient displays a hypermutation phenotype. This hypermutability seems to be tissue and gene restricted. Simultaneous transcription of the mutated DMPK gene and the CTNNB1 gene in cycling hair follicles might constitute an explanation for the observed tissue and gene specificity of hypermutability observed in DM1 patients. Elucidation of putative mechanisms responsible for hypermutability in DM1 patients requires further research.

Syndromes associated with multiple pilomatricomas: When should clinicians be concerned?

BACKGROUND: Multiple pilomatricomas have been linked to various syndromes. However, these associations are poorly defined, leaving practitioners conflicted on management of these patients. OBJECTIVE: To perform a comprehensive review to clarify the strength of these relationships and identify which patients may benefit from additional screening and/or genetic screening. METHODS: A literature search was performed using the PubMed, Ovid, and Cochrane databases. Syndromic, familial, and sporadic cases of multiple pilomatricomas were stratified based on number of pilomatricomas. This information was graphed for visual comparison. RESULTS: Sixty-six syndromic cases from 52 publications were identified, with the majority (54) of cases representing myotonic dystrophy, familial adenomatous polyposis-related syndromes (including Gardner syndrome), Turner syndrome, or Rubinstein-Taybi syndrome. Twenty-five of the 54 cases (46.3%) had six or more pilomatricomas. Of sporadic cases, 128 out of 134 (95.5%) had five or less pilomatricomas. LIMITATIONS: Most articles were case reports and series, which are vulnerable to publication bias. Specific details were not explicitly noted in some original articles, and incomplete data could not always be included in analysis. Syndromes may have been missed in sporadic cases. CONCLUSION: The presence of six or more pilomatricomas is highly suggestive of an underlying syndrome (>95% specificity). These patients should undergo additional screening. Patients with less than six pilomatricomas and family history of myotonic dystrophy, first-degree relative with colon cancer or FAP-related syndrome, or family history of pilomatricomas should also undergo further screening.

Neurosis and true dermatosis: a case of ossified pilomatricoma developing within a self-inflicted ulcer.

Clinicians have a tendency to dismiss patients with psychiatric illness like skin picking disorder without assessing completely for organic disease. Patients with psychocutaneous disease have the potential to develop true dermatopathology and should always be examined thoroughly. We describe a case of skin picking disorder with underlying pilomatricoma. The patient met criteria for skin picking disorder and had been prescribed numerous topical treatments without efficacy by countless physicians over 18 years. In addition, a pilomatricoma was discovered within a self-inflicted ulcer. Pilomatricomas can rarely result from trauma and develop ossification, both of which were true of this lesion. The prevalence of skin picking disorder proves more pervasive than previously realized and it has only recently been recognized by the DSM-5 as an independent diagnosis. Therefore, it is necessary to clarify the diagnosis as well as remind clinicians not to discount underlying dermatologic disease. In addition to the risk of bleeding and infection, these patients are at risk for masking neoplasms, which should be removed. Our case emphasizes the need for thorough examination of patients with psychocutaneous disease and further work-up when necessary to prevent permanent disfigurement.

Childhood pilomatricomas: Associated anomalies.

Pilomatricoma is a common benign tumor in children. We present a review of the literature with the aim of helping clinicians manage these patients. A detailed review of the literature was performed in the PubMed database using an exhaustive list of Medical Subject Heading words. One thousand four hundred fifty-eight children were described in retrospective series and case reports. An associated disease was found in 32 children (2.2%), most of whom had several pilomatricomas (n = 23); 9 had a single lesion. Based on this literature review, we recommend reassuring the family and then conducting a detailed interview regarding past medical and family history and a thorough clinical examination for signs of Turner syndrome, constitutional mismatch repair deficiency, Kabuki syndrome, Steiner's myotonic dystrophy, or Gardner syndrome. Regular long-term clinical follow-up is recommended. Specific paraclinical examinations should be performed only in cases of other clinical anomalies or a positive family history. Pilomatricoma requires management because it may be associated with other potentially serious diseases, especially when multiple lesions are present.

Familial papular epidermal nevus with "skyline" basal cell layer and multiple pilomatricomas: A new association?

Papular epidermal nevus with "skyline" basal cell layer is a newly described keratinocytic nevus. Recently, papular epidermal nevus with "skyline" basal cell layer has been reported in association with extracutaneous involvement, and the term papular epidermal nevus with "skyline" basal cell layer syndrome is used to indicate a neurocutaneous syndrome characterized by the presence of papular epidermal nevus with "skyline" basal cell layer and different neurologic symptoms that seem to improve during infancy and adolescence. Multiple pilomatricomas have been reported in association with various syndromes. We report herein papular epidermal nevus with "skyline" basal cell layer associated with multiple pilomatricomas in two members of a family with the aim of drawing attention to this peculiar epidermal nevus to improve our knowledge of the syndrome.

Pilomatricoma Associated with Kabuki Syndrome.

We report three cases of pilomatricomas associated with Kabuki syndrome (KS), supporting the hypothesis proposed of an association between pilomatricomas and KS and suggesting a noncoincidental association, because the Wnt pathway mutations involved could affect both morphogenesis and tumorigenesis in these patients.

Pilomatrixoma of the breast in a patient with type 1 myotonic dystrophy: successful surgical approach.

Malherbe’s calcifying epithelioma is an uncommon cutaneous tumour that originates from the matrix cells of hair follicle. It was initially described by Malherbe as a benign calcifying epithelioma. Several ultra-structural and electron-microscopic studies later demonstrated its origin from matrix cells and the term pilomatrixoma was introduced. The treatment of this tumour remains mainly surgical. Malignant cases with post-surgical recurrences have been described in literature and recurrences have been related to an incomplete surgical treatment or tumour aggressiveness. We present the case of 31-year-old female patient with pilomatrixoma of the breast, which was very similar to fibroadenoma, in terms of size and other clinical features. We successfully treated this patient surgically, and the aesthetic results were good, despite the proximity of the tumour to the areola-nipple complex. Fifteen months later, the patient is doing well, free of any clinical local recurrence.

Metastatic pilomatrix carcinoma: Not so rare after all? A case report and review of the literature.

Pilomatrixoma is a slowly growing benign tumor of the dermal hair cells. Metastatic disease is exceptionally rare. Pilomatrixoma can occur at any age, but most patients are older than 40 years at presentation. Approximately 60% of these lesions occur in the head and neck region. Their size is usually about 4 cm at the time of presentation. Surgical excision with adequate margins is still the preferred treatment. We report a case of an aggressive malignant metastatic pilomatrixoma in a 43-year-old woman who underwent multiple extensive local resections. However, she died within 4 months of presentation.

Multiple pilomatricomas in the setting of myotonic dystrophy.

The association between multiple pilomatricomasand the autosomal dominant neurodegenerativedisorder myotonic dystrophy has been described inthe literature. Although the mechanism is unknown,it is hypothesized that the dystrophia myotonicaprotein kinase mutation in myotonic dystrophyaffects intracellular calcium levels, which alterproliferation and terminal differentiation that leads tocells that are observed in pilomatricomas. We presenta patient with multiple, symptomatic pilomatricomasand myotonic dystrophy, with a strong family historyof both of these rare disorders.