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BACKGROUND: Activating BRAF gene alterations are central to melanocytic tumor pathogenesis. A small, emerging subset of melanocytic tumors driven by BRAF fusions has distinct therapeutic implications and has been described to have Spitzoid morphology patterns. However, such morphological patterns do not encompass all cases, and little is known about the functional molecular events. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify melanocytic tumors with BRAF fusions. We reviewed clinical, histopathological, and genomic features. We further explored transcriptomic and protein-level findings. RESULTS: Histopathologic patterns varied, with many cases without a distinctive pattern. We identified novel and diverse BRAF gene fusion partners. Differential transcriptomic analysis between low-risk BRAF fusion tumors and reference BRAF V600E tumors showed no differentially expressed genes. However, quantitatively stronger MAPK pathway activation of BRAF fusion tumors over BRAF V600E tumors was demonstrated by statistically significant stronger staining of p-ERK immunohistochemistry. Gene-specific RNA analysis shows comparable BRAF transcript levels between the two groups. DISCUSSION AND CONCLUSION: The quantitatively stronger activation of the MAPK pathway of BRAF fusion tumors, instead of qualitatively different transcriptomes, may account for the morphology difference from conventional BRAF V600E tumors. BRAF fusions likely act through dysregulated protein function rather than RNA upregulation related to the characteristics of the fusion partners.
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BACKGROUND: Granular cell tumor (GCT) is a S100+ neoplasm with atypical and malignant variants. Similar to melanocytic neoplasms, the tumors make nests and can have junctional components raising a differential diagnosis of melanoma. Nevi and melanomas may also have granular cell cytoplasm. MelanA is useful in distinguishing melanocytic from granular cell lineage, but increasingly MelanA/SOX10 negative melanomas have been recognized by correlation with molecular methods. METHODS: We encountered several cases with morphologic overlap between melanoma and atypical GCT necessitating additional molecular workup. We sequenced two cases and searched our archive for similar cases of GCT with overlapping features of melanocytic lineage. RESULTS: In our two index cases, we excluded melanoma driver mutations and identified frameshift or premature stop codons in ATP6AP1/2 pathognomonic of granular cell lineage. Data retrieved from Cosmic identified 24 melanomas with missense single nucleotide variants (SNVs) in ATP6AP1 but no frameshift or premature stop codons. Twenty-one melanomas had missense SNVs in ATP6AP2. One melanoma had a premature stop codon in ATP6AP2, but this lesion also had a melanoma-associated driver mutation NRASQ61K. We found 1 of 23 additional cases of GCT in our archives with a junctional component and no additional cases with maturation. CONCLUSIONS: Atypical and malignant GCT can have histopathologic overlap with melanoma. Frameshift and premature stop codons in ATP6AP1/2 are specific for granular cell lineage, and capable of excluding melanoma, in the absence of known melanoma-associated driver mutations.
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BACKGROUND: Melanocytic tumors driven by MAP2K1 in-frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well-known second molecular "hits." Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with MAP2K1 in-frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single-nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations. RESULTS: Of 27 sequenced tumors, 6 (22%) showed a pathogenic MAP2K1 in-frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque-like or wedge-shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1-2/mm2 ). Five cases (83%) had a small component of nevic-looking melanocytes. Biologically, these tumors likely fall within the spectrum of unusual nevi. Five cases (83%) had a relatively high mutational burden and four (67%) showed an ultraviolet radiation signature. Four cases (67%) showed in-frame deletion involving the p.I103_K104del locus while two cases (33%) showed in-frame deletion involving the p.Q58_E62del locus. SNP array testing showed structural abnormalities ranging from 1 to 5 per case. Five of these cases showed a gain of chromosome 15 spanning the MAP2K1 gene locus. DISCUSSION AND CONCLUSION: Melanocytic tumors with MAP2K1 in-frame deletion could represent another spectrum of melanocytic tumors with close genotypic-phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with BRAF V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.
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Melanoma , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Feminino , Humanos , Masculino , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Raios Ultravioleta , Melanoma/patologia , Neoplasias Cutâneas/patologia , Nevo de Células Epitelioides e Fusiformes/genética , Aberrações Cromossômicas , MAP Quinase Quinase 1/genéticaRESUMO
Mucoepidermoid carcinoma is a malignant neoplasm of exocrine glands that arises predominantly in salivary glands. It is seldom encountered as a primary cutaneous neoplasm, and in those patients, it often involves the external auditory canal. Given their rarity, they can pose a diagnostic challenge and prompt extensive workup. In salivary glands, mucoepidermoid carcinomas commonly harbor CRTC1/3::MAML2 fusions; however, genetic alterations of primary cutaneous neoplasms are less characterized, with previous studies reporting CRTC1 rearrangements in the absence of MAML2 aberrations. Herein, we report a case of a primary cutaneous mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 rearrangement. We also review the clinical, morphologic, and molecular features of this neoplasm and compare them to those reported in the literature and to histopathologic mimics.
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Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Neoplasias Cutâneas , Humanos , Proteínas de Ligação a DNA/genética , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Transativadores/genética , Meato Acústico Externo/patologia , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Neoplasias Cutâneas/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias das Glândulas Salivares/genéticaRESUMO
ABSTRACT: Lymphedematous fibroepithelial polyps are rare proliferations involving the glans penis typically associated with chronic condom catheter usage. To the best of our knowledge, less than 20 cases have been reported in the literature with relatively similar clinical presentation. Herein, we report a case of lymphedematous fibroepithelial polyp not associated with condom usage in a 74-year-old man treated with surgical excision. On histopathological examination, the lesion displayed a hypocellular proliferation of spindled and stellate fibroblasts with intermixed Touton-like giant cells embedded within an edematous stroma with thickened vasculature. Immunohistochemical profiling exhibits strong immunoreactivity for smooth muscle actin, weak positivity for factor XIIIa, and no reactivity for CD34 or desmin. We also conducted a review of the reported range of clinical and histopathological features of this entity in addition to the various hypotheses regarding its pathogenesis. We hope to increase awareness and accurate diagnosis of this entity, which could affect clinical management.
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Linfedema , Pólipos , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Preservativos/efeitos adversos , Pólipos/etiologia , Pólipos/cirurgia , Pênis/patologia , Neoplasias Cutâneas/patologia , Catéteres/efeitos adversos , Linfedema/patologiaRESUMO
Kinase fusions play an important role in the pathogenesis of Spitz neoplasms and occasionally non-Spitz neoplasms. We report a case of a 19-year-old woman with a growing nodule on the scalp, morphologically consistent with a diagnosis of melanoma with epithelioid features arising in association with small nevus. This tumor aggressively metastasized and failed to respond to immunotherapy. Next-generation sequencing of a metastatic focus revealed an MYO5A-BRAF kinase fusion with a low mutational burden and fluorescence in situ hybridization (FISH) of the primary melanoma showed similar results. FISH testing of the associated nevus failed because of technical reasons. MYO5A has rarely been reported as the fusion partner with BRAF-rearranged melanocytic tumors. Moreover, this case raises speculations and contributes to the growing literature on the pathogenesis, nomenclature, and tumorigenic pathways in kinase-fusion melanomas. The patient succumbed to disease, which is in concordance with some literature suggesting aggressive behavior of BRAF fusion melanomas with TERT promoter mutations.
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Melanoma , Miosina Tipo V , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Humanos , Hibridização in Situ Fluorescente , Melanoma/patologia , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologiaRESUMO
ABSTRACT: Chondromyxoid metaplasia can rarely lead to the formation of a distinctive tumor-like proliferation in the plantar foot. This is thought to represent a reactive or reparative process, possibly due to chronic trauma. For the unwary dermatopathologist, this could represent a diagnostic challenge. Herein, we review the clinical, histopathological, and molecular presentation of an athletic 17-year-old boy with a soft tissue mass arising in the right plantar foot. Microscopic examination showed a relatively circumscribed proliferation of spindle cells with abundant chondromyxoid stroma, hyalinization, and diffuse ERG reactivity. We also review characteristics of this entity that help differentiate it from clinical and histopathologic mimics and postulate possible links with soft tissue chondromas and immature chondroid choristoma.
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Condroma , Doenças do Pé , Neoplasias de Tecidos Moles , Adolescente , Doenças do Pé/diagnóstico , Humanos , Masculino , MetaplasiaRESUMO
A 60-year-old female presented with a large, left upper eyelid mass that had rapidly expanded in the 3 months prior to presentation. She had a presumed chalazion excised from the same area 1.5 years ago, but no pathology was investigated. On examination, she had a palpebral mass measuring 4.5 cm x 3.5 cm that abutted the globe with extensive conjunctival involvement. Neuroimaging demonstrated lesions concerning for parotid gland metastases. An incisional biopsy demonstrated synaptophysin-positive small blue cells concerning for neuroendocrine carcinoma. The patient underwent orbital exenteration with parotidectomy and radical neck dissection. The excised mass was found to have distinct neuroendocrine carcinoma cells intermingled with sebaceous carcinoma cells, a combination not previously reported.
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BACKGROUND: PRAME (PReferentially expressed Antigen in Melanoma) immunohistochemistry has demonstrated high specificity for unequivocal melanomas; however, its utility in ambiguous melanocytic neoplasms has yet to be fully elucidated. METHODS: Cases of challenging melanocytic neoplasms were subclassified into one of three categories: challenging, favor benign (FB), challenging, cannot be subclassified (CCS), or challenging, favor malignant (FM). Using a previously published system, whereby cases with diffuse staining (>75%) were considered positive, scoring of PRAME was performed. Additionally, tumors with hotspot staining were also considered positive. RESULTS: Sixteen out of 85 tumors showed positive staining representing 5% of FB tumors, 24% of CCS tumors, and 47% of FM. In FB and CCS tumors, positive staining was mainly encountered in atypical intraepidermal melanocytic proliferations and spitzoid neoplasms. The specificity of positive PRAME staining was 95% and its concordance with the final diagnostic interpretation was 75%. CONCLUSIONS: PRAME positivity is more common in neoplasms favored to be malignant by histopathologic evaluation. Its clinical utility may include early diagnosis of incipient melanoma in situ. Rarely, benign melanocytic neoplasms could show diffuse expression of PRAME, and additional studies are needed to determine optimal utilization. Lastly, hotspot staining may increase its sensitivity without much compromise in specificity.
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Antígenos de Neoplasias/metabolismo , Imuno-Histoquímica/métodos , Melanócitos/patologia , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Melanoma/classificação , Melanoma/diagnóstico , Melanoma/ultraestrutura , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sensibilidade e Especificidade , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/ultraestrutura , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
BACKGROUND: The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by imaging mass spectrometry (IMS). METHODS: Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine classification model. RESULTS: We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, 2 misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations. CONCLUSION: This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists.
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Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Humanos , Sensibilidade e EspecificidadeRESUMO
Extranodal NK/T-cell lymphoma (NKTCL) is a rarely occurring non-Hodgkin lymphoma with predilection for the nasal cavity. Cutaneous involvement, rarely occurring and often aggressive in behavior, may present as nodular mass-forming lesions with or without ulceration. Histologically, lesions are characterized by an atypical dermal lymphoid infiltrate with angioinvasion and associated necrosis. Fortuitously, Epstein-Barr virus (EBV) infection, implicated in the pathogenesis of this entity, serves as a useful diagnostic marker (i.e. EBER in situ hybridization). We present a 54-year-old-man who initially presented with two ulcerations on the right lower leg which progressed despite antibiotic therapy. Histologic examination demonstrated dense lymphoid infiltrates exhibiting epidermotropism, angiocentricity and angioinvasion extending into the deep dermis. Immunohistochemical staining demonstrated expression of CD2, CD3, CD8, TIA-1, perforin, and granzyme-B, consistent with a cytotoxic T-cell phenotype. Additionally, CD56 was positive, confirming the presence of a coexistent NK cell phenotype. Testing also demonstrated significant CD30 expression, and molecular analysis was positive for TCR gene rearrangement. These findings, in conjunction with EBER in situ hybridization positivity, confirmed a diagnosis of extranodal NKTCL. We aim to increase awareness of this rarely occurring lymphoma with cutaneous involvement. CD30 expression in NKTCL raises the possibility of targeted treatment with brentuximab.
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Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Neoplasias Cutâneas , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Humanos , Antígeno Ki-1 , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/patologia , Neoplasias Cutâneas/patologiaRESUMO
Increasingly, molecular methods are being utilized in the workup of melanocytic neoplasms. To this end, we sought to correlate data from a single nucleotide polymorphism (SNP) array platform based on molecular inversion probes with clinical data. Copy number variation (CNV) data were obtained on 95 melanocytic tumors (6 ordinary nevi, 15 atypical nevi, 34 ambiguous neoplasms, and 40 melanomas) from 92 patients. The average number of significant CNVs was 0 for nevi, 0.6 for atypical nevi (range 0-3), 2.8 for ambiguous neoplasms (range 0-17), and 18.1 for melanomas (range 0-69). Clinical follow-up data were available in 57 of 95 lesions (56 of 92 patients). Tumors from patients with adverse events demonstrated an average number of CNVs of 24.5 (range 6-69) as compared with 7.9 (range 0-35) among tumors without an associated adverse event (p ≤ 0.001). No adverse events were observed in nevi including atypical nevi. Adverse events were found in 2 of 19 ambiguous neoplasms and 10 of 32 melanomas with follow up. In these two latter groups of neoplasms, the correlation between adverse events and the average number of CNVs remained statistically significant even when controlled for Breslow depth (21.5 versus 8.7, p value = 0.036). No neoplasm with adverse events had ≤3 CNVs. These results provide further evidence that SNP array testing for CNVs may be helpful in the classification and prognostication of ambiguous neoplasms. Based on these results, an algorithmic approach to challenging melanocytic neoplasms using CNV data is suggested, using as cutoff of >3 CNVs with some caveats, as the threshold for a positive result. Future clinical validation, using a larger cohort of relevant tumors, will be necessary.
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Biomarcadores Tumorais/genética , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
OPINION STATEMENT: Liquid biopsies are still far from widely implanted in the clinical arena. Issues related to the added sensitivity of this test beyond conventional methods have not been fully resolved. Additionally, issues related to the specificity of these results especially as many cancers may share common mutation need further investigations. One way to resolve this may include the development and testing of large gene panels to add higher specificity. On the other hand, further studies are needed to support the idea that ctDNA or circulating tumor cells may constitute a better representation of the tumor subpopulation that is capable of metastasizing, which will strongly support its clinical value. Finally, survival studies showing a positive impact of this technology will also justify its widespread implementation in clinical practice.
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Biomarcadores Tumorais , Biópsia Líquida , Melanoma/diagnóstico , Melanoma/genética , Mutação , DNA Tumoral Circulante , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Biópsia Líquida/métodos , Células Neoplásicas CirculantesRESUMO
Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare delayed drug reaction that often occurs 2-6 weeks after initiation of therapy and may develop into a life-threatening systemic reaction. Besides immediate discontinuation of the suspected inciting drug, initiation of high dose systemic corticosteroids has long been the mainstay of treatment for severe cases. Nevertheless, significant drawbacks associated with systemic corticosteroid therapy, such as the requirement of a long tapering period post resolution and extensive adverse side effects profile, have motivated clinicians to seek alternative treatment options. Over the past decade, an undisputed increasing number of favorable case reports has highlighted cyclosporine as an emerging, safe, and effective alternative despite inconsistent dosing regimens reported. Herein, we report a severe case of vancomycin-induced DRESS syndrome in which the patient failed initial intervention with cyclosporine and needed rescue with methylprednisolone. To the best of our knowledge, this constitutes the first unsuccessful report of cyclosporine treatment for DRESS syndrome.
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Ciclosporina/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Vancomicina/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/patologia , Resistência a Medicamentos , Eosinofilia/induzido quimicamente , Eosinofilia/patologia , Exantema/induzido quimicamente , Feminino , Antebraço/patologia , HumanosRESUMO
Dedifferentiated metastatic melanoma can pose a significant diagnostic challenge, especially if the history of primary melanoma is not known or is remote. BRAF and NRAS mutations are common melanoma driver mutations that are usually sequenced to evaluate for treatment targets. We evaluated whether BRAF and NRAS mutational testing could contribute to the diagnosis of dedifferentiated metastatic melanoma when immunostains are negative. Seven patients with melanoma who had an additional diagnosis of poorly differentiated sarcoma with negative melanocytic immunostains were tested for BRAF and NRAS mutations. Three patients showed identical BRAF mutations in the melanoma and the poorly differentiated sarcoma and hence were re-classified as metastatic dedifferentiated melanoma. In these three patients, there was an average delay of 7 months before appropriate testing, workup and treatment for metastatic melanoma was initiated. Two of these patients currently have stable metastatic disease and show sustained therapeutic response to melanoma-specific treatment including BRAF inhibitors. BRAF mutational analysis should therefore be considered in cases of poorly differentiated sarcoma, especially if there is a known history of melanoma or with unusual localization of disease. The administration of melanoma-specific treatments in such dedifferentiated cases can show therapeutic response, highlighting the importance of rendering accurate diagnoses on such cases.
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Erros de Diagnóstico , Melanoma/diagnóstico , Metástase Neoplásica/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Sarcoma , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/genética , Melanoma/terapia , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica/genética , Metástase Neoplásica/terapia , Sarcoma/diagnóstico , Sarcoma/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapiaRESUMO
Germline mutations in BRCA1-associated protein 1 (BAP1) are associated with several neoplasms, including BAP1-inactivated melanocytic tumors (BIMTs). BIMTs are classically described as biphenotypic melanocytic proliferations with BAP1-deficient large epithelioid and rhabdoid melanocytes showing various degrees of cytologic atypia. This morphology has been traditionally classified as "spitzoid" despite the various differences between these lesions and the more classic Spitz nevi. Herein, we report a case of an otherwise healthy 11-year-old female patient with a family history of several malignancies who presented with multiple pink to brown papules. Histologic and immunohistochemical evaluation identified three lesions with loss of nuclear BAP1 staining. The histologic spectrum of these lesions included junctional spitzoid cells within a triphenotypic proliferation and a separate lesion composed entirely of dermal small to medium-sized epithelioid melanocytes with maturation. BAP1 gene sequencing revealed a germline frameshift pathogenic BAP1 mutation, denoted c.1717delC. This case provides further evidence that not all BIMTs conform to classic morphological criteria and that the morphologic spectrum includes lesions resembling conventional nevi. As BIMTs can serve as an early marker of the BAP1 hereditary tumor predisposition syndrome, we believe a need exists for a more comprehensive combined clinical and pathological approach for BIMT identification.
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Mutação em Linhagem Germinativa , Melanócitos , Síndromes Neoplásicas Hereditárias , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase , Criança , Feminino , Humanos , Melanócitos/metabolismo , Melanócitos/patologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/metabolismo , Síndromes Neoplásicas Hereditárias/patologia , Nevo de Células Epitelioides e Fusiformes/genética , Nevo de Células Epitelioides e Fusiformes/metabolismo , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismoRESUMO
BACKGROUND: Pediatric Drug reaction with eosinophilia and systemic symptoms (DRESS) is an uncommon disease that can be difficult to diagnose. This case series and literature review highlights the clinical features of pediatric DRESS and underscores the differential diagnoses, culprit medications, and need for clinical follow-up to detect associated autoimmune sequelae. OBJECTIVE: To describe the clinical and laboratory features of pediatric DRESS, identify associated culprit medications, and discuss the natural history of disease. METHODS: Ten cases of pediatric DRESS were identified in the electronic medical record by searching the inpatient dermatology consultation list at Indiana University between 2013 and 2018. Clinical and laboratory data were collected including demographics, differential diagnoses, culprit medications, resolution of disease, and autoimmune sequelae. RESULTS: Pediatric patients with DRESS presented at a mean age of 11.5 years and demonstrated a mean time from drug initiation to onset of symptoms of 4 weeks. The most common inciting drugs included antibiotics (62.5%) followed by antiepileptics (37.5%). Rash and transaminitis resolved by 3 weeks, and 20% of patients, all female, developed autoimmune sequelae including Hashimoto's thyroiditis and an undifferentiated connective tissue disorder and occurred at an average of 14.5 weeks after diagnosis. LIMITATIONS: This was a small retrospective study of an uncommon clinical diagnosis at a single institution. CONCLUSIONS: Pediatric DRESS was most commonly caused by antibiotics which are being increasingly recognized in the literature as the predominant culprit medications. The development of autoimmune sequelae is a notable consequence that can present weeks after illness and may preferentially affect female patients.
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Antibacterianos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Cutaneous syncytial myoepithelioma is a recently described rare tumor of the dermis. It is derived and composed purely of myoepithelial cells and shows a characteristic syncytial growth pattern of neoplastic cells with little intervening stroma and no recognizable ductal structures. It represents a diagnostic challenge to dermatopathologists given its rarity and unusual immunophenotype. Molecular testing for rearrangement of the EWSR1 gene plays a significant role in confirming the diagnosis in most cases. Herein, we present 2 cases with mundane clinical presentations and challenging histopathological findings. In both cases, the lesion was composed of relatively well-circumscribed proliferation of epithelioid and spindle cells in the superficial dermis growing in a syncytial fashion and showing focal adipocytic metaplasia. The 2 cases had slightly different immunohistochemical profiles, but shared focal positivity for S100, EMA and pan-keratin or p63. Break-apart FISH demonstrated the presence of an EWSR1 gene rearrangement confirming the diagnosis in both cases. We discuss the most important differential diagnoses, particularly melanocytic lesions and epithelioid sarcoma and the original diagnostic considerations that the cases were referred to us with. We also review the molecular features and spectrum of immunohistochemical findings in these lesions and their role in excluding entities in the differential diagnosis.