RESUMO
AIMS: There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series. METHODS AND RESULTS: Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea. CONCLUSION: Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.
Assuntos
Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Micose Fungoide/genética , Masculino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Feminino , Pessoa de Meia-Idade , Adulto , Esclerodermia Localizada/patologia , Esclerodermia Localizada/diagnóstico , Diagnóstico Diferencial , IdosoRESUMO
ABSTRACT: PCR-based fragment analysis of the T-cell receptor (TCR) gene is used extensively in diagnostic labs to assess clonality in T-cell populations in multiple tissue sites. Of the numerous TCR assays that have been reported, studies assessing use on biopsies suspicious for mycosis fungoides specifically are lacking. We compared clonality findings from a previously run 2-tube/2-fluorochrome dye assay to a redesigned 1-tube/1-fluorochrome dye assay on formalin-fixed skin biopsies. Overall, the accuracy of the 2-tube assay was marginally better (75.7% vs. 71.4%), when using clinical history combined with histologic diagnosis as the gold standard. The 2-tube assay had better sensitivity (73.7% vs. 65.8%), while the 1-tube assay had superior specificity (93.8% vs. 87.5%). Clonality results were easier to interpret with the 1-tube assay. In nearly 19% of cases, a change of assays on the same biopsy resulted in a change of clonality interpretation. For laboratories that change TCR-γ clonality assays, follow-up biopsies for mycosis fungoides assessment may result in a change of diagnosis.
Assuntos
Micose Fungoide , Neoplasias Cutâneas , Micose Fungoide/genética , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Micose Fungoide/imunologia , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia , Biópsia , Reação em Cadeia da Polimerase , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Células ClonaisRESUMO
OBJECTIVES: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma; it arises from tissue-resident memory T-cells (TRM). In the present study, we investigated potential functional genetic variations that may predispose MF development. METHODS: A case-control study was conducted using whole-exome sequencing, with a focus on genes that are essential to TRM function. RESULTS: We included 21 patients and 19 healthy subjects in the study. Single nucleotide polymorphisms in the following genes were significantly more common in patients than in healthy subjects: GZMB, HLA-DRB1, CD103, and NOTCH1. Moreover, the number of patients carrying single nucleotide polymorphisms in LAG3, NR4A2, and CD26L was significantly greater in the patient group than in the control group. CONCLUSIONS: The presence of genetic variations in one or more TRM functional gene may predispose patients to develop MF. Further studies involving a larger patient population and a comparative analysis of protein expression will be necessary to validate these findings.
Assuntos
Micose Fungoide , Neoplasias Cutâneas , Humanos , Estudos de Casos e Controles , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Células T de Memória , Micose Fungoide/genética , Micose Fungoide/patologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
ABSTRACT: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.
Assuntos
Progressão da Doença , Micose Fungoide , Humanos , Micose Fungoide/genética , Micose Fungoide/mortalidade , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Masculino , Feminino , Genômica/métodos , Pessoa de Meia-Idade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Mutação , Prognóstico , Adulto , Sequenciamento do Exoma , Idoso , Fatores de RiscoRESUMO
The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). PIM2 is a well-known oncogene and is regulated by cell signaling pathways like the JAK/STAT- and NF-kB-pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin-fixed paraffin-embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced-stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced-stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID.
Assuntos
Micose Fungoide , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas , Humanos , Micose Fungoide/genética , Micose Fungoide/patologia , Micose Fungoide/metabolismo , Masculino , Feminino , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Pessoa de Meia-Idade , Adulto , Idoso , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Imuno-Histoquímica , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Biópsia , Pele/patologia , Pele/metabolismo , Adulto JovemAssuntos
Progressão da Doença , Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/genética , Micose Fungoide/patologia , Micose Fungoide/imunologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/imunologia , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino , Pele/patologia , Pele/imunologia , Pessoa de Meia-Idade , Linfócitos T/imunologiaRESUMO
Abstract: The growth factor receptor c-kit (CD117) is expressed in immature T-cells and in some advanced forms of mycosis fungoides. c-kit gene mutation results in unrestricted neoplastic proliferation. We aimed to detect by PCR the most frequent exon mutations in seventeen plaque-stage MF patients, in their perilesional skin and in healthy skin donors. We secondarily evaluated CD117 expression by immunohistochemistry in plaque-stage and tumor-stage MF. We detected no mutation in c-kit gene and low CD117 expression was confirmed on atypical cells in one patient. Complete c-kit exon and intron sequences should be assessed and more sensitive sequencing method could be also applied.
Assuntos
Humanos , Masculino , Feminino , Idoso , Éxons/genética , Micose Fungoide/genética , Proteínas Proto-Oncogênicas c-kit/genética , Mutação/genética , Imuno-Histoquímica , Estudos de Casos e Controles , Expressão Gênica , Reação em Cadeia da Polimerase , Estudos ProspectivosRESUMO
Las regiones organizadoras del nucleolo (NORs) se encuentran ubicadas, en humanos, a nivel de las constricciones secundarias de los cromosomas acrocéntricos y corresponden a la localización de los genes de ARNr. Existen evidencias de modificaciones de la expresión de ADNr en diferentes tumores. En este trabajo se estudió la expresión de NORs en células de médula ósea (MO) de pacientes con neoplasias linfoides: mieloma múltiple (MM), micosis fungoides (MF) y leucemia linfoblástica aguda (LLA) y de 10 individuos sanos. Se efectuó cultivo de MO de corto plazo (24 hs) a 37º en medio F-10 suplementado con suero fetal bovino, empleándose la técnica de Howell y Black (1980) para medir la actividad NOR. El análisis estadístico mostró incrementos significativos en el número de cromosomas Ag-NORs para las tres patologías (p < 0,001) y en la proporción de células marcadas con plata en MF (p < 0,005) y en LLA (p < 0,00025), respecto de los controles, encontrándose correlación entre este parámetro y la edad de los individuos sanos (rK = 0,59, p < 0,02). No se observaron diferencias en la frecuencia de Asociaciones de Satélites. Estos estudios mostraron la relación entre la actividad NOR y las características proliferativas y de diferenciación /maduración de las patologías estudiadas.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Cromossomos , DNA Ribossômico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Mieloma Múltiplo/genética , Micose Fungoide/genética , Região Organizadora do Nucléolo , Fatores Etários , Senescência CelularRESUMO
Fundamentos- Na doença de Jorge Lobo, devido ao não cultivo do P.loboi, utiliza-se material obtido de biopsias de pacientes, sendo a determinação da viabiliadade imprescindivel para os estudo experimentais da doença. Objetivos- Determinar a viabilidade do P. loboi, por meio de diferentes metodos de coloração, e investigar a influencia da temperatura e de diferentes soluções na viabilidade do fungo. Casuistica e Metodos- Biopsias de 15 pacientes foram processadas em solução salina 0,85%(SS), solução salina de Hank´s(SSH) e solução salina glicerinada a 30% com vitamina B(SSG). A viabilidade foi determinada no momento da coleta da biopsia (tempo 0), empregando-se os corantes diacetato de fluoresceina-brometo de etideo (DF-BE), lactofenol azul-algodão, azul-tripan e verde-janus. As suspensões foram mantidas a 4°C, 23°C e 37°C, e a viabilidade foi determinada a cada tres dias, utilizando-se a coloração DF-BE. Resultados - A viabilidade do P. loboi no tempo 0 variou de 21 a 46%, utilizando-se a coloração de DF-BE. A viabilidade com os demais corantes não foi satisfatoria, devido a dificuldades em separar os fungos viaveis dos não viaveis. A temperatura de 4°C foi mais eficaz em manter a viabilidade do fungo (ate 15 dias). Por outro lado, nenhuma das soluções empregadas conseguiu manter a viabilidade do fungo ou favorecer sua multiplicação. Conclusões - A determinação da viabilidade do P. loboi com DFG-BE podera auxiliar nas tentativas de cultura do fungo, nas inoculações em animais e no controle terapeutico da doença. Alem disso, a temperatura parece ser fator importante no crescimento do P. loboi.