RESUMEN
ABSTRACT: A 38-year-old man presented with fever, cough, and jaundice. Four days before, he had started taking amoxicillin/clavulanic acid. He subsequently developed a morbilliform rash, and, according to clinical features and blood analyses, a diagnosis of mononucleosis with Epstein-Barr virus-associated antibiotic-induced exanthema and secondary hemophagocytic lymphohistiocytosis was made. A skin biopsy revealed a superficial perivascular lymphohistiocytic infiltrate with interface dermatitis and many foamy macrophages in the papillary dermis and around the vessels of the superficial dermal plexus. A blood lipid test uncovered marked hypercholesterolemia and hypertriglyceridemia. After treatment with dexamethasone and immunoglobulin, the skin rash, liver function, and lipid profile progressively improved. Xanthomatous cells have been observed in skin biopsies of acute graft-versus-host disease with liver involvement, and these cells have been suggested to represent a clue to the presence of hepatic disease. In our case, underlying cholestatic hepatopathy with hyperlipidemia was present. We believe that the incidental finding of foamy cells in graft-versus-host disease cases and in our case are likely related to the presence of severe liver disease with cholestatic hepatopathy and secondary hyperlipidemia in different background conditions.
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Infecciones por Virus de Epstein-Barr , Exantema , Enfermedad Injerto contra Huésped , Hiperlipidemias , Linfohistiocitosis Hemofagocítica , Masculino , Humanos , Adulto , Linfohistiocitosis Hemofagocítica/patología , Infecciones por Virus de Epstein-Barr/complicaciones , Hiperlipidemias/inducido químicamente , Hiperlipidemias/complicaciones , Herpesvirus Humano 4 , Amoxicilina , Exantema/inducido químicamente , Exantema/complicaciones , Lípidos , Macrófagos/patologíaAsunto(s)
Enfermedades de la Piel , Piel , Humanos , Piel/patología , Enfermedades de la Piel/patologíaAsunto(s)
Dermatosis del Pie/patología , Hemorragia/diagnóstico , Infarto/diagnóstico , Piel/irrigación sanguínea , Trombosis/diagnóstico , Verrugas/patología , Legrado , Diagnóstico Diferencial , Hemorragia/etiología , Hemorragia/patología , Humanos , Infarto/etiología , Infarto/patología , Piel/ultraestructura , Coloración y Etiquetado , Trombosis/etiología , Trombosis/patología , Verrugas/cirugíaRESUMEN
BACKGROUND: Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas. OBJECTIVE: We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior. METHODS: We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed. RESULTS: There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P < .0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P = .01). CONCLUSIONS: IMS diagnosis of ASN better predicted clinical outcome than histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated with aggressive clinical behavior. IMS analysis using a proteomic signature may improve the diagnosis and prediction of outcome/risk stratification for patients with ASN.
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Espectrometría de Masas , Melanoma/diagnóstico por imagen , Melanoma/secundario , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico por imagen , Nevo de Células Epitelioides y Fusiformes/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/química , Persona de Mediana Edad , Recurrencia Local de Neoplasia/química , Nevo de Células Epitelioides y Fusiformes/química , Proteínas/análisis , Estudios Retrospectivos , Medición de Riesgo , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/química , Resultado del Tratamiento , Carga Tumoral , Adulto JovenAsunto(s)
Abdomen , Eritema/etiología , Histiocitosis/diagnóstico , Cadenas kappa de Inmunoglobulina/sangre , Linfoma de Células B de la Zona Marginal/diagnóstico , Paraproteinemias/diagnóstico , Prurito/etiología , Esplenectomía , Biopsia , Cristalización , Dermis/patología , Eritema/patología , Histiocitos/patología , Histiocitosis/patología , Humanos , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana Edad , Paraproteinemias/patología , Prurito/patología , Piel/patologíaRESUMEN
Despite of highly effective new therapeutic strategies, chemotherapy still is an important treatment option in metastatic melanoma. Since predictors of chemotherapy response are rare, drugs and regimens are currently chosen arbitrarily. The present study was aimed at the identification of molecular markers predicting the outcome of chemotherapy in melanoma. Tumor biopsies from metastatic lesions were collected from 203 stage IV melanoma patients prior to chemotherapy onset and used for gene expression profiling (n = 6; marker identification set), quantitative real-time PCR (n = 127; validation set 1), and immunohistochemistry on tissue microarrays (n = 70; validation set 2). The results were correlated to the tumors' in-vitro chemosensitivity and to the patients' in-vivo chemotherapy outcome. SERPINB1 was found to correlate to the in-vitro sensitivity to cisplatin-containing chemotherapy regimens (p = 0.005). High SERPINB1 gene expression was associated with favorable tumor response (p = 0.012) and prolonged survival (p = 0.081) under cisplatin-based chemotherapy. High SERPINB1 protein expression in tumor tissue from cisplatin-treated patients was associated with a favorable survival (p = 0.011), and proved as an independent predictor of survival (p = 0.008) by multivariate analysis. We conclude, that SERPINB1 expression, although not functionally involved, is predictive for the outcome of cisplatin-based chemotherapy in melanoma, and thus may be useful to personalize melanoma chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Serpinas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Cisplatino/administración & dosificación , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Serpinas/metabolismo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Neurothekeoma and nerve sheath myxoma have long been interpreted as related tumors that share nerve sheath linage. Lack of S100 expression in neurothekeoma and similarities of gene expression profiles between neurothekeoma and fibrohistiocytic tumors have created reasonable doubt about this concept. SOX-10 represents a marker for schwannian and melanocytic differentiation, and is expressed in other tumors of nerve sheath linage. Microphthalmia transcription factor (MiTF) expression has been repeatedly reported in cellular neurothekeoma in the recent literature and was proposed as a helpful marker in this entity. METHODS: We investigated 25 cases of cellular neurothekeoma, 8 cases of mixed neurothekeoma and 1 case of nerve sheath myxoma for the expression of SOX-10, MiTF, S100, NKI/C3, Melan-A and smooth muscle actin (SMA) using immunohistochemistry. RESULTS: A lack of SOX-10 expression was demonstrated in 100% of cellular and mixed neurothekeomas, but was present in the case of nerve sheath myxoma. More than two thirds of neurothekeomas showed very focal or no reactivity with MiTF. CONCLUSIONS: Our data suggest that neurothekeoma and nerve sheath myxoma are unrelated, and that cellular and mixed neurothekeoma may not be of nerve sheath lineage. In addition, MiTF should not be regarded as a useful marker in neurothekeoma.
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Biomarcadores de Tumor/análisis , Factor de Transcripción Asociado a Microftalmía/biosíntesis , Neurotecoma/clasificación , Neurotecoma/patología , Factores de Transcripción SOXE/biosíntesis , Adolescente , Adulto , Niño , Femenino , Humanos , Inmunohistoquímica , Masculino , Factor de Transcripción Asociado a Microftalmía/análisis , Persona de Mediana Edad , Neurotecoma/metabolismo , Factores de Transcripción SOXE/análisis , Adulto JovenRESUMEN
BACKGROUND: Extranodal natural killer-/T-cell lymphoma, nasal type (ENKTCL-NT) is a highly aggressive lymphoma and prognosis is usually poor. The genetic background of primary cutaneous cases is poorly understood. OBJECTIVE: We sought to evaluate the clinicopathologic features of cutaneous ENKTCL-NT, and the prognostic significance of genomic copy number alterations. METHODS: Eight cases of cutaneous ENKTCL-NT (5 primary, 2 secondary, 1 no staging performed), including 2 patients with an unusually prolonged course of 5 and 23 years, were investigated using array comparative genomic hybridization. RESULTS: All patients presented with typical clinicopathologic features. Epstein-Barr virus was found in neoplastic cells in all specimens. Copy number alterations were detected in all 8 cases with losses on 6q (37.5% of cases) and 7p (37.5% of cases), and gains on 7q (37.5% of cases) being the most frequent. Complexity of array comparative genomic hybridization profile did not correlate with the course of the disease. However, an increase of copy number alterations was detected in sequential biopsy specimens of 1 long-term survivor. LIMITATIONS: This was a small case series retrospective study. CONCLUSION: Clinicopathologic features of cutaneous ENKTCL-NT are distinctive. Lower number of copy number alterations cannot be used as predictor for prolonged survival in cutaneous ENKTCL-NT.
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Células Asesinas Naturales/patología , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/patología , Neoplasias Nasales/genética , Neoplasias Nasales/patología , Proteínas de Unión a Poli(A)/genética , Adolescente , Adulto , Anciano de 80 o más Años , Biopsia con Aguja , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Inmunohistoquímica , Hibridación in Situ , Linfoma Cutáneo de Células T/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Nasales/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Muestreo , Análisis de Supervivencia , Antígeno Intracelular 1 de las Células TAsunto(s)
Biomarcadores de Tumor/genética , Análisis Mutacional de ADN/métodos , Melanoma/diagnóstico , Melanoma/genética , Técnicas de Diagnóstico Molecular/métodos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Femenino , Pruebas Genéticas/métodos , Humanos , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
There are several recent reports describing hybrid peripheral nerve sheath tumors showing a biphasic component of neoplastic cells. These combinations include a mixture of neurofibroma and schwannoma, schwannoma and perineurioma, neurofibroma and perineurioma, and perineurioma and granular cell tumor. A case of a triphasic combination of neurofibroma, schwannoma, and perineurioma has also been described. We describe the clinicopathologic and immunohistochemical characteristics of 9 cases of a benign cutaneous plexiform nerve sheath tumor located on the lips and exhibiting hybrid features of perineurioma and cellular neurothekeoma. Clinically, lesions were solitary dome-shaped papules located on the lips. Histopathologically, the neoplasms consisted of well-circumscribed but uncapsulated dermal nodules with a plexiform pattern. They were composed of nests or rounded aggregations of neoplastic cells embedded in a slightly myxoid stroma. Within the aggregates, cells were distributed in a storiform and lamellar pattern. Immunohistochemically, most neoplastic cells expressed strong immunoreactivity for S100A6, MiTF, NKI/C3, PGP9.5, EMA, and NSE, whereas variable, focal, and weaker positivity for CD34, claudin-1, and Glut-1 was seen in some cases. On the basis of these findings, we believe that this neoplasm is a distinctive benign cutaneous plexiform nerve sheath tumor with histopathologic and immunohistochemical hybrid features of perineurioma and cellular neurothekeoma.
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Neoplasias de los Labios/patología , Neoplasias Complejas y Mixtas/patología , Neoplasias de la Vaina del Nervio/patología , Neurotecoma/patología , Adulto , Anciano , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Neoplasias de los Labios/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/metabolismo , Neoplasias de la Vaina del Nervio/metabolismo , Neurotecoma/metabolismoRESUMEN
Some cases of specific cutaneous manifestations of acute myelogenous leukemia (AML) may mimic inflammatory dermatoses both clinically and histopathologically, presenting with an inconspicuous maculopapular eruption and with only sparse dermal infiltrates. The authors studied the histopathological and immunohistochemical features of 17 biopsies from 16 patients (11 men and 5 women, age range 15-85 years) presenting with minimal skin infiltrates as the first manifestation of AML or as first sign of recurrence after complete remission of the disease. In all cases, the diagnosis of leukemia has been confirmed by bone marrow examination. Two of these cases had been sent to one of us for second expert consultation. Patients presented with generalized, exanthematic maculopapular eruptions, sometimes with a hemorrhagic note, that were mostly interpreted clinically as drug reactions. Histopathologically, the lesions showed sparse, superficial, and mid-dermal infiltrates with minimal perivascular and periadnexal accentuation. Infiltrating cells consisted mostly of neoplastic monocytoid elements with only few reactive lymphocytes and histiocytes. Immunohistochemical stainings revealed in the majority of cases positivity for CD68 (14 of 16 patients), naphthol chloroacetate esterase (NaSDCl) (7 of 10 patients), and myeloperoxidase (6 of 9 patients). Other markers tested were positive only in a minority of cases. These cases represent a pitfall both in the clinical and in the histopathological diagnosis of cutaneous AML. Accurate morphologic and phenotypic correlation together with a high index of suspicion allows a precise diagnosis in these unconventional cases.
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Dermatitis/patología , Leucemia Mieloide Aguda/patología , Infiltración Leucémica , Piel/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Examen de la Médula Ósea , Diagnóstico Diferencial , Erupciones por Medicamentos/patología , Femenino , Humanos , Inmunohistoquímica , Leucemia Mieloide Aguda/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Piel/química , Adulto JovenRESUMEN
In this study, we describe the clinicopathologic features of pseudolymphomatous infiltrates found within lesions of acrodermatitis chronica atrophicans (ACA). We studied 11 patients (10 females, 1 male, age range 60-88 years). The diagnosis of ACA in all cases was confirmed by clinicopathologic correlation and positive serology for Borrelia. Histopathologic examination revealed prominent, pseudolymphomatous inflammatory cell infiltrates in all cases, with 2 distinct patterns. Eight of 11 cases showed a band-like lymphocytic infiltrate, exocytosis of lymphocytes and a fibrotic papillary dermis, similar to features seen in mycosis fungoides. The other 3 cases showed dense, nodular-diffuse dermal infiltrates with many plasma cells and without germinal centers. The plasma cells expressed both kappa and lambda immunoglobulin light chains with a polyclonal pattern in all 3 cases. In conclusion, ACA may present with pseudolymphomatous infiltrates showing both a T-cell and, less frequently, a B-cell pattern. These lesions need to be distinguished from a cutaneous lymphoma. In the context of the knowledge of Borrelia-associated cutaneous lymphomas, follow-up seems advisable in these cases.
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Acrodermatitis/patología , Infecciones por Borrelia/patología , Linfocitos/patología , Células Plasmáticas/patología , Seudolinfoma/patología , Piel/patología , Acrodermatitis/genética , Acrodermatitis/inmunología , Acrodermatitis/microbiología , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biopsia , Borrelia/genética , Borrelia/inmunología , Infecciones por Borrelia/genética , Infecciones por Borrelia/inmunología , Infecciones por Borrelia/microbiología , ADN Bacteriano/análisis , Diagnóstico Diferencial , Femenino , Reordenamiento Génico de Linfocito T , Humanos , Cadenas kappa de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/análisis , Inmunohistoquímica , Linfocitos/inmunología , Linfocitos/microbiología , Masculino , Persona de Mediana Edad , Células Plasmáticas/inmunología , Células Plasmáticas/microbiología , Valor Predictivo de las Pruebas , Seudolinfoma/genética , Seudolinfoma/inmunología , Seudolinfoma/microbiología , Piel/inmunología , Piel/microbiologíaAsunto(s)
Mutación de Línea Germinal , Melanoma/genética , Mesotelioma/genética , Neoplasias Peritoneales/genética , Neoplasias Pleurales/genética , Neoplasias Cutáneas/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Adulto , Femenino , Heterocigoto , Humanos , Masculino , Melanoma/patología , Mesotelioma/patología , Persona de Mediana Edad , Linaje , Neoplasias Peritoneales/patología , Neoplasias Pleurales/patología , Factores de Riesgo , Neoplasias Cutáneas/patología , Población Blanca/genéticaAsunto(s)
ADN (Citosina-5-)-Metiltransferasas/genética , Eliminación de Gen , Leucemia Monocítica Aguda/genética , Mutación/genética , Proteínas de Unión a Fosfatidiletanolamina/genética , Western Blotting , Estudios de Cohortes , ADN Metiltransferasa 3A , Cartilla de ADN/química , Cartilla de ADN/genética , Humanos , Proteínas de Unión a Fosfatidiletanolamina/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis.
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Biomarcadores de Tumor/genética , Aberraciones Cromosómicas , Melanocitos/patología , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Austria , Biopsia , Hibridación Genómica Comparativa , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Masculino , Melanoma/clasificación , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Neoplasias Cutáneas/clasificaciónRESUMEN
We recently reported that germline mutations in BAP1 cause a familial tumor syndrome characterized by high penetrance for melanocytic tumors with distinct clinical and histologic features. Melanocytic neoplasms in affected individuals harbored BRAF mutations, showed loss of BAP1 expression, and histologically resembled so-called "atypical Spitz tumors" (ASTs). ASTs are an ill-defined and probably heterogenous group of melanocytic tumors that display histologic features seen in both Spitz nevi and melanomas. Their biological behavior cannot be reliably predicted. In view of the histologic similarities of the familial tumors and ASTs, we hypothesized that a subset of ASTs might harbor genetic alterations seen in the familial tumors. To address this hypothesis, we analyzed 32 sporadic ASTs for BRAF mutations and for BAP1 expression. Nine (28%) sporadic ASTs showed loss of BAP1 expression, of which 8 (89%) had concomitant BRAF mutations. Only 1 of the BAP1-positive ASTs (4%) had a BRAF mutation (P<0.0001). BRAF-mutated, BAP1-negative tumors were primarily located in the dermis and were composed entirely or predominantly of epithelioid melanocytes with abundant amphophilic cytoplasm and well-defined cytoplasmic borders. Nuclei were commonly vesicular and exhibited substantial pleomorphism and conspicuous nucleoli. The combination of BRAF mutation and loss of nuclear BAP1 expression thus characterizes a subset of ASTs with distinct histologic features. The typical morphology of these tumors and BAP1 immunohistochemistry provide pathologic clues that will enable accurate identification of this subset. Future studies are necessary to determine whether this subset has a predictable clinical behavior.
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Mutación , Nevo de Células Epitelioides y Fusiformes/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Adolescente , Adulto , Biomarcadores de Tumor/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/patología , Niño , Preescolar , Citoplasma/metabolismo , Citoplasma/patología , Células Epitelioides/metabolismo , Células Epitelioides/patología , Salud de la Familia , Femenino , Humanos , Masculino , Melanocitos/metabolismo , Melanocitos/patología , Persona de Mediana Edad , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , Neoplasias Cutáneas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Adulto JovenRESUMEN
The recent identification of DNMT3A mutations in de novo acute myeloid leukemia prompted us to determine their frequency, patterns and clinical impact in a cohort of 98 patients with either therapy-related or secondary acute myeloid leukemia developing from an antecedent hematologic disorder. We identified 24 somatic mutations in 23 patients with a significantly higher frequency in secondary acute myeloid leukemia (35.1%) as compared to therapy-related acute myeloid leukemia (16.4%, P=0.0486). DNMT3A mutations were associated with a normal karyotype and IDH1/2 mutations, but did not affect survival. In contrast to de novo acute myeloid leukemia, most mutations did not affect arginine on position 882, but were predominantly found in the methyltransferase domain. All DNMT3A mutations identified in secondary acute myeloid leukemia were already present in the antecedent disorders indicating an early event. Reduction to homozygosity by uniparental disomy was observed in 2 patients with secondary acute myeloid leukemia during disease progression.
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Biomarcadores de Tumor/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Leucemia Mieloide Aguda/genética , Mutación/genética , Neoplasias Primarias Secundarias/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , ADN Metiltransferasa 3A , Femenino , Humanos , Leucemia Mieloide Aguda/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/epidemiologíaRESUMEN
A recent report has suggested that the numbers of regulatory T cells correlate with stage of disease and prognosis in mycosis fungoides (MF). To evaluate the role of FOXP3+ Tregs in different stages of MF, we investigated sequential biopsies in 14 patients with patch/plaque and subsequent tumor stage using FOXP3 antibody. Our data neither show a significant difference in the percentage of FOXP3+ cells between patch/plaque and tumor stage biopsies of MF nor demonstrate a predictable shift of Tregs in the course of disease progression. Additionally, we could observe FOXP3-expressing neoplastic cells in 4 patch/plaque stage biopsies, where they represented almost 100% of the epidermotropic infiltrate. Only in one of these patients, FOXP3+ cells could also be detected in the tumor stage biopsy, indicating that FOXP3 expression can be acquired or lost during the course of the disease, comparable to other phenotypic markers.
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Factores de Transcripción Forkhead/metabolismo , Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Biomarcadores de Tumor/metabolismo , Recuento de Células , Progresión de la Enfermedad , Humanos , Micosis Fungoide/inmunología , Micosis Fungoide/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patologíaRESUMEN
Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.