RESUMO
Syringocystadenocarcinoma papilliferum (SCACP) is a rare and aggressive malignant adnexal tumor originating from apocrine or pluripotent appendageal glands, often associated with a preceding syringocystadenoma papilliferum (SCAP) or nevus sebaceus (NS). This systematic review rigorously examines SCACP through an analysis of 78 cases documented between 1980 and 2024. The study aims to provide a comprehensive review of the clinical manifestations, diagnosis, treatment modalities, and outcomes associated with SCACP, while also reappraising its associations, particularly with NS. SCACP predominantly affects older adults, with an average age of 66.3 years and a slight male predominance, commonly presenting as ulcerated nodules or plaques on the scalp. This review highlights the aggressive nature of SCACP, evidenced by significant rates of metastasis and recurrence. Treatment is primarily surgical, with Mohs micrographic surgery offering potential benefits in terms of margin control and cosmetic outcomes. The association of SCACP with NS is critically evaluated, suggesting a complex etiopathogenesis and underscoring the importance of recognizing this association for timely diagnosis and management. Our review also briefly discusses potential pitfalls faced by clinicians in the diagnosis of SCACP. Our findings emphasize the need for standardized treatment protocols and further research into targeted therapies to improve patient outcomes in SCACP.
Assuntos
Neoplasias das Glândulas Sudoríparas , Humanos , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/cirurgia , Neoplasias das Glândulas Sudoríparas/terapia , Masculino , Feminino , Idoso , Cirurgia de Mohs , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Nevo Sebáceo de Jadassohn/diagnóstico , Nevo Sebáceo de Jadassohn/patologia , Nevo Sebáceo de Jadassohn/cirurgia , Nevo Sebáceo de Jadassohn/terapia , Couro Cabeludo/patologia , Adenomas Tubulares de Glândulas Sudoríparas/diagnóstico , Adenomas Tubulares de Glândulas Sudoríparas/patologia , Adenomas Tubulares de Glândulas Sudoríparas/cirurgia , Pessoa de Meia-IdadeRESUMO
Cerebriform sebaceous naevus (CSN) is a rare morphological sebaceous naevus variant and challenging to diagnose prenatally due to its flat, smooth and waxy appearance and lack of association with extracutaneous manifestations.A multigravida was referred to our tertiary obstetric unit at 24 weeks of gestation for evaluation of fetal auricular lesions. We were able to further characterise the lesions via serial obstetric ultrasound imaging with the aid of three-dimensional (3D) technology. Although the precise diagnosis prenatally was uncertain, the use of 3D technology allowed the reconstruction of the fetal cutaneous lesions for multidisciplinary assessment to facilitate the development of a neonatal management plan. The diagnosis of CSN was made postnatally on biopsy.
Assuntos
Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Adulto , Nevo Sebáceo de Jadassohn/patologia , Nevo Sebáceo de Jadassohn/diagnóstico , Nevo Sebáceo de Jadassohn/diagnóstico por imagem , Recém-Nascido , Nevo/diagnóstico por imagem , Nevo/patologia , Nevo/diagnóstico , Imageamento Tridimensional , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias das Glândulas Sebáceas/diagnóstico por imagemRESUMO
BACKGROUND: Nevus sebaceous (NS) is a rare congenital skin lesion affecting approximately 0.3% of all newborns. Although benign, NS lesions can harbor malignant secondary tumors. The published rate of development of these malignant tumors varies. This meta-analysis aimed to identify the rate of malignant and benign secondary neoplasms occurring in NS. METHODS: A literature search was conducted using PubMed, Embase, and Web of Science from inception to April 2023. Eligible studies reported incidence or risk of secondary neoplasms in patients with NS. Two independent reviewers screened studies, extracted data, and assessed the quality of included studies. The primary outcome was the pooled incidence of secondary neoplasms. Studies with sample sizes greater than 50 patients were eligible for meta-analysis using the random-effects model. RESULTS: Twenty-eight studies were identified, 22 of which were eligible for meta-analysis. The overall rate of secondary neoplasms was 12.8% (95% confidence interval [Cl], 9.2%-17.6%). The rates of development of malignant and benign tumors were 2.4% (95% CI, 1.4%-4.1%) and 10.3% (95% CI, 7.5%-13.9%), respectively. The rate of development of basal cell carcinoma was 1.7% (95% CI, 0.9%-3.2%), whereas the rate of the development of syringocystadenoma papilliferum was 3.6% (95% CI, 2.5%-5.3%) and that if trichoblastoma was 2.6% (95% CI, 1.7%-3.8%). CONCLUSIONS: Although the rate of development of malignant tumors within a primary NS lesion is low, it is not negligible. Prophylactic early excision remains a viable approach to prevent secondary malignant neoplasms, address cosmetic and functional complications, and preempt the need for complex reconstruction in the future. We propose that resection of NS lesions in childhood remains a reasonable first-line option in the appropriate patient keeping in mind that it may leave an undesirable scar.
Assuntos
Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Incidência , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/cirurgia , Nevo Sebáceo de Jadassohn/cirurgia , Nevo Sebáceo de Jadassohn/patologia , Nevo/cirurgia , Nevo/patologiaRESUMO
PURPOSE: To evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of patients with mosaic RASopathy. DESIGN: Single-center retrospective observational study. SUBJECTS: Ten eyes with calcified fundus lesions in 7 patients with mosaic RASopathy. METHODS: The lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT) scan where available. MAIN OUTCOME MEASURES: The imaging characteristics of calcified fundus lesions were assessed. RESULTS: We found 7 patients with mosaic RASopathies, 5 men and 2 women (3 with linear sebaceous nevus syndrome, 3 with oculoectodermal syndrome, and 1 with encephalocraniocutaneous lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but 2 of these lesions involved both the choroid and sclera, with 2 of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography, and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan, and all 4 showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, 1 had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. CONCLUSIONS: We propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Assuntos
Calcinose , Coristoma , Angiofluoresceinografia , Imageamento por Ressonância Magnética , Doenças da Esclera , Humanos , Masculino , Feminino , Estudos Retrospectivos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Angiofluoresceinografia/métodos , Imageamento por Ressonância Magnética/métodos , Doenças da Esclera/diagnóstico , Coristoma/diagnóstico , Adulto , Síndromes Neurocutâneas/diagnóstico , Adolescente , Criança , Fundo de Olho , Tomografia Computadorizada por Raios X , Adulto Jovem , Nevo Sebáceo de Jadassohn/diagnóstico , Doenças da Coroide/diagnóstico , Corioide/patologia , Corioide/diagnóstico por imagem , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodérmica/complicações , Pré-Escolar , Lipomatose/diagnóstico , OftalmopatiasAssuntos
Anticorpos Monoclonais Humanizados , Proteínas Adaptadoras de Sinalização CARD , Guanilato Ciclase , Proteínas de Membrana , Mutação , Nevo Sebáceo de Jadassohn , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Proteínas Adaptadoras de Sinalização CARD/genética , Guanilato Ciclase/genética , Nevo Sebáceo de Jadassohn/genética , Nevo Sebáceo de Jadassohn/patologia , Nevo Sebáceo de Jadassohn/tratamento farmacológico , Proteínas de Membrana/genética , Feminino , MasculinoRESUMO
We present the case of a 20-month-old girl with Schimmelpenning-Feuerstein-Mims (SFM) syndrome with extensive head, neck, and torso skin involvement successfully managed with topical trametinib. Trametinib interferes downstream of KRAS and HRAS in the MAPK signaling pathway, of which KRAS was implicated in our child's pathogenic variant. Although other dermatologic conditions have shown benefit from oral trametinib, its topical use has not been well reported. Our patient showed benefit from the use of twice-daily topical trametinib, applied to the epidermal and sebaceous nevi over a 16-month period, leading to decreased pruritus and thinning of the plaques.
Assuntos
Piridonas , Pirimidinonas , Neoplasias Cutâneas , Humanos , Piridonas/uso terapêutico , Piridonas/administração & dosagem , Feminino , Pirimidinonas/uso terapêutico , Pirimidinonas/administração & dosagem , Lactente , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Nevo/tratamento farmacológico , Insuficiência de Crescimento/tratamento farmacológico , Administração Tópica , Anormalidades Múltiplas/tratamento farmacológico , Nevo Sebáceo de Jadassohn/tratamento farmacológico , Síndromes Neurocutâneas/tratamento farmacológico , Síndromes Neurocutâneas/diagnóstico , Anormalidades da Pele/tratamento farmacológico , Antineoplásicos/uso terapêutico , Anormalidades do Olho/tratamento farmacológico , Doenças da Imunodeficiência Primária/tratamento farmacológicoRESUMO
The fibroblast growth factor receptors comprise a family of related but individually distinct tyrosine kinase receptors. Within this family, FGFR2 is a key regulator in many biological processes, e.g., cell proliferation, tumorigenesis, metastasis, and angiogenesis. Heterozygous activating non-mosaic germline variants in FGFR2 have been linked to numerous autosomal dominantly inherited disorders including several craniosynostoses and skeletal dysplasia syndromes. We report on a girl with cutaneous nevi, ocular malformations, macrocephaly, mild developmental delay, and the initial clinical diagnosis of Schimmelpenning-Feuerstein-Mims syndrome, a very rare mosaic neurocutaneous disorder caused by postzygotic missense variants in HRAS, KRAS, and NRAS. Exome sequencing of blood and affected skin tissue identified the mosaic variant c.1647=/T > G p.(Asn549=/Lys) in FGFR2, upstream of the RAS signaling pathway. The variant is located in the tyrosine kinase domain of FGFR2 in a region that regulates the activity of the receptor and structural mapping and functional characterization revealed that it results in constitutive receptor activation. Overall, our findings indicate FGFR2-associated neurocutaneous syndrome as the accurate clinical-molecular diagnosis for the reported individual, and thereby expand the complex genotypic and phenotypic spectrum of FGFR-associated disorders. We conclude that molecular analysis of FGFR2 should be considered in the genetic workup of individuals with the clinical suspicion of a mosaic neurocutaneous condition, as the knowledge of the molecular cause might have relevant implications for genetic counseling, prognosis, tumor surveillance and potential treatment options.
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Craniossinostoses , Síndromes Neurocutâneas , Nevo Sebáceo de Jadassohn , Feminino , Humanos , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/genética , Genótipo , Mutação de Sentido Incorreto , Nevo Sebáceo de Jadassohn/genética , Nevo Sebáceo de Jadassohn/patologia , Craniossinostoses/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
SIGNIFICANCE: Inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon type of epidermal nevus and is refractory to therapy. We report the effectiveness of photodynamic therapy (PDT) for treating ILVEN with claudication in a young girl. ADDITIONAL CONTRIBUTIONS: We thank the patient for granting permission to publish this information. APPROACH: Aminolaevulinic Acid Hydrochloride (ALA) photodynamic therapy (PDT) was applied six times in 1-month interval. RESULTS: Most lesions and pruritus have subsided markedly, with mild scarring and a marked reduction in claudication. CONCLUSIONS: ALA PDT might be an effective and promising treatment for ILVEN in the future.
Assuntos
Nevo Sebáceo de Jadassohn , Nevo , Fotoquimioterapia , Feminino , Humanos , Nevo Sebáceo de Jadassohn/patologia , Virilha/patologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Nevo/patologiaRESUMO
Schimmelpenning-Feuerstein-Mims syndrome is a rare disorder generally characterised by a craniofacial nevus with multisystemic presentations. Our patient, an infant, was brought to the emergency department in a postictal state following a first seizure episode. A physical examination showed a solitary dark brown, well-demarcated verrucous plaque extending from the patient's left temporal region to the left mandible without crossing the midline. Epibulbar choristomas were present on the ipsilateral side of the craniofacial lesion. Neuroimaging showed benign enlargement of the subarachnoid space. Due to the known risk of seizures associated with this condition, the patient was started on levetiracetam and showed adequate compliance. We present this as the first reported case of Schimmelpenning-Feuerstein-Mims syndrome with benign enlargement of the subarachnoid space in an infant presenting with seizures to emphasise the value of collaboration among multidisciplinary professionals to improve the quality of care for such patients.
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Nevo Sebáceo de Jadassohn , Nevo , Neoplasias Cutâneas , Humanos , Lactente , Convulsões/etiologia , Convulsões/complicações , Neoplasias Cutâneas/complicações , Espaço Subaracnóideo/diagnóstico por imagemRESUMO
Schimmelpenning-Feuerstein-Mims syndrome (SFMS), an epidermal nevus disease, features skin lesions including craniofacial nevus sebaceous and extracutaneous anomalies (e.g. brain, eye, and bone). Recent genetic studies implicate HRAS, KRAS, and NRAS genes in somatic mutations. Our case, a 48-year-old man, presented with nevus sebaceous on the scalp; pigmented skin lesions on the right side of his neck, back, and chest along the Blaschko lines; a history of epilepsy; and mild intellectual disability. Accordingly, SFMS was suspected. DNA analysis of nevus sebaceous skin and peripheral blood leukocytes showed a pathogenic HRAS variant NM_005343.4:c.34G > A p.(Gly12Ser) in biopsy specimens from different skin layers but not blood, indicating somatic mosaic mutation. Until now, the HRAS p.(Gly12Ser) mutation has been reported in somatic RASopathies but not SFMS. The authors report this mutation in a case of SFMS, review another 15 cases of SFMS, and discuss HRAS c.34G > A p.(Gly12Ser) somatic mutations. RAS mutations of somatic RASopathies share activating hotspot mutations found in cancers, and produce different phenotypes depending on the developmental stage at which the somatic mutations occur.
Assuntos
Nevo Pigmentado , Nevo Sebáceo de Jadassohn , Nevo , Neoplasias Cutâneas , Humanos , Nevo Sebáceo de Jadassohn/genética , Nevo Sebáceo de Jadassohn/patologia , Nevo/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
In a rare case of concurrent verrucous epidermal naevi (VEN) with psoriasis, previous treatments with oral methotrexate and acitretin showed minimal improvement. However, treatment with oral apremilast resulted in complete resolution of psoriasis and significant improvement in VEN lesions after 1 month. This is the first documented case of successful VEN treatment with apremilast, highlighting its potential efficacy in treating verrucous epidermal naevus. Further studies are needed to validate its effectiveness.
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Nevo Sebáceo de Jadassohn , Psoríase , Neoplasias Cutâneas , Humanos , Psoríase/complicações , Psoríase/tratamento farmacológico , Acitretina/uso terapêutico , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento , Anti-Inflamatórios não Esteroides/uso terapêutico , Índice de Gravidade de DoençaAssuntos
Nevo Sebáceo de Jadassohn , Nevo , Neoplasias Cutâneas , Masculino , Humanos , Nevo Sebáceo de Jadassohn/diagnóstico , Pelve , PênisRESUMO
Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous disorder caused by somatic gain-of-function mutations in KRAS or HRAS. LNSS brains have neurodevelopmental defects, including cerebral defects and epilepsy; however, its pathological mechanism and potentials for treatment are largely unclear. We show that introduction of KRASG12V in the developing mouse cortex results in subcortical nodular heterotopia and enhanced excitability, recapitulating major pathological manifestations of LNSS. Moreover, we show that decreased firing frequency of inhibitory neurons without KRASG12V expression leads to disrupted excitation and inhibition balance. Transcriptional profiling after destabilization domain-mediated clearance of KRASG12V in human neural progenitors and differentiating neurons identifies reversible functional networks underlying LNSS. Neurons expressing KRASG12V show molecular changes associated with delayed neuronal maturation, most of which are restored by KRASG12V clearance. These findings provide insights into the molecular networks underlying the reversibility of some of the neuropathologies observed in LNSS caused by dysregulation of the RAS pathway.