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1.
Eur J Cancer ; 197: 113479, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128263

RESUMO

INTRODUCTION: Follicular helper T-cell lymphomas (TFHL) have an aggressive course with a poor outcome. European and US guidelines recommend anthracycline-based chemotherapy as a first-line treatment, but the 5-year overall survival rate is still approximately 30%. We describe here the features of a cohort of TFHL patients who experienced prolonged survival despite the absence of specific treatment or the initiation of steroid-based therapy. PATIENTS AND METHODS: In our study, we describe 15 adult patients who suffered from TFHL and had not received intensive chemotherapy at diagnosis for any reason. Biopsies of these cases were centrally reviewed, and the mutational pattern was determined using next-generation sequencing. RESULTS: These 15 patients had the classic clinical, biological and pathological features of TFHL, angioimmunoblastic-type. TET2 mutations were found in 83% of patients; RHOA G17V, IDH2 R172 and DNMT3A mutations were found in 67%, 42% and 33% of the patients, respectively. Among the 15 patients, 8 did not receive any treatment, and 7 received steroid-based treatment. Ten patients had progression (5 in each group). Four patients died (3 of them from the progression of their lymphoma). The median follow-up in our cohort was 53 months. The 5-year OS was 66%, 100% for untreated patients and 29% for the others. In those 2 groups, the median time to treatment initiation was 22 months from diagnosis. CONCLUSION: We described a series of 15 well-characterized TFHL patients with an indolent outcome, suggesting that a watch-and-wait approach can be proposed in selected patients. Identifying factors predicting such evolution is warranted.


Assuntos
Linfoma de Células T , Linfoma , Adulto , Humanos , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/patologia , Mutação , Esteroides , Células T Auxiliares Foliculares/patologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-34020934

RESUMO

OBJECTIVE: Peritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process. DESIGN: We performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes. RESULTS: Abdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease. CONCLUSION: Diagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.


Assuntos
Histiocitose , Neoplasias , Diagnóstico Tardio , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos
3.
J Neuropathol Exp Neurol ; 77(9): 769-781, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30011033

RESUMO

Infiltration of the peripheral nervous system (PNS) by lymphoma, called neurolymphomatosis, is a rare condition among the spectrum of lymphoma-associated neuropathies; its diagnosis is challenging. Cerebrospinal fluid (CSF) analysis is of great value, but nerve biopsy (NB) may be necessary to prove invasion by malignant cells. Clonality polymerase chain reaction (PCR)-based analysis is a validated method in the diagnosis of hematological malignancies, but there are very little data on its diagnostic yield on NB samples. We explored the contribution of NB with clonality analysis to the diagnosis of neurolymphomatosis in 15 patients with negative CSF analysis. Moreover, we assessed the performance of clonality testing in a case-control manner, using patients with inflammatory infiltrates on NB as controls. Neurolymphomatosis was the first manifestation of lymphoma in 60% and could be diagnosed on routine histology alone in 40%. Clonality testing showed monoclonal rearrangement in 86.7% and was unsuccessful in 8.1%. Performance of clonality testing was as follows: 92.9% positive predictive value, 90% negative predictive value, 86.7% sensitivity, 94.7% specificity. This study confirms the diagnostic challenge of neurolymphomatosis, the usefulness of NB in patients with negative CSF analysis, and highlights the high yield of PCR-based clonality testing to assess the malignant nature of PNS lymphoid infiltrates.


Assuntos
Biópsia/métodos , Neurolinfomatose/genética , Neurolinfomatose/patologia , Nervos Periféricos/patologia , Reação em Cadeia da Polimerase , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Feminino , Fluordesoxiglucose F18 , Humanos , Imunomodulação , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Neurolinfomatose/líquido cefalorraquidiano , Neurolinfomatose/terapia , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
4.
Br J Cancer ; 113(6): 934-44, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26284337

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a fatal malignancy that needs to identify new targets for additional therapeutic options. This study aimed to clarify the clinical and biological significance of endogenous neurotrophin (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) in DLBCL biopsy samples and cell lines. METHODS: We analysed expression of NGF, BDNF, and their receptors (Trk, p75(NTR)) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting. To investigate the biological role of BDNF/TrkB/p75(NTR) axis, effects of neurotrophin signalling inhibition were determined on tumour cell survival and vascular endothelial growth factor (VEGF) secretion. The pharmacological pan-Trk inhibitor K252a was used for in vitro and in vivo studies. RESULTS: A BDNF/TrkB axis was expressed in all biopsies, which was independent of the germinal centre B-cell (GCB)/non-GCB profile. p75(NTR), TrkB, and BDNF tumour scores were significantly correlated and high NGF expression was significantly associated with MUM1/IRF4, and the non-GCB subtype. Diffuse large B-cell lymphoma cell lines co-expressed neurotrophins and their receptors. The full-length TrkB receptor was found in all cell lines, which was also phosphorylated at Tyr-817. p75(NTR) was associated to Trk and not to its cell death co-receptor sortilin. In vitro, inhibition of neurotrophin signalling induced cell apoptosis. K252a caused cell apoptosis, decreased VEGF secretion, and potentiated rituximab effect, notably in less rituximab-sensitive cells. In vivo, K252a significantly reduced tumour growth and potentiated the effects of rituximab in a GCB-DLBCL xenograft model. CONCLUSIONS: This work argues for a pro-survival role of endogenous neurotrophins in DLBCLs and inhibition of Trk signalling might be a potential treatment strategy for rituximab resistant subgroups.


Assuntos
Apoptose , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carbazóis/farmacologia , Alcaloides Indólicos/farmacologia , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptor trkB/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Biópsia , Linhagem Celular Tumoral , Sobrevivência Celular , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Receptor trkB/antagonistas & inibidores , Rituximab/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Leuk Lymphoma ; 56(2): 332-41, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24766492

RESUMO

Finding new prognostic factors to identify patients with Hodgkin lymphoma (HL) at risk of treatment resistance or relapse remains challenging in daily practice. We evaluated the relationship between CD68 expression, interim positron emission tomography (iPET) results and outcome in 158 patients with HL diagnosed from February 1995 to July 2011. Immunohistochemistry (anti-CD68) gave two groups: low with ≤25% positive cells (121 patients) and high with >25% (37 patients). Five-year overall survival was higher in the low group (88.4% vs. 63.2%, p=0.0151), as was progression-free survival (74.5% vs. 40.7%, p=0.0003). In 68 patients evaluable, iPET correlated with CD68: 13/52 patients (25%) in the low group had positive iPET as compared to 11/16 patients (68%) in the high group (p=0.0016). This study confirms the prognostic value of CD68 in HL. We found a correlation between CD68 and iPET suggesting potential for a better stratification.


Assuntos
Antígenos CD/biossíntese , Antígenos de Diferenciação Mielomonocítica/biossíntese , Doença de Hodgkin/metabolismo , Doença de Hodgkin/terapia , Macrófagos/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Seguimentos , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Resultado do Tratamento , Adulto Jovem
6.
Eur J Hum Genet ; 22(2): 283-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23778871

RESUMO

Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1.We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGGAAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL.


Assuntos
Anormalidades Múltiplas/diagnóstico , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Paraganglioma/diagnóstico por imagem , Proteínas Proto-Oncogênicas/genética , Anormalidades Múltiplas/genética , Neoplasias do Córtex Suprarrenal/genética , Análise Mutacional de DNA , Feminino , Humanos , Mutação de Sentido Incorreto , Neoplasias Pancreáticas/genética , Paraganglioma/genética , Linhagem , Radiografia , Síndrome
7.
Ann Pathol ; 33(6): 406-9, 2013 Dec.
Artigo em Francês | MEDLINE | ID: mdl-24331723

RESUMO

A 59-year-old male, was admitted to our hospital for a tumor of the pancreatic tail. Serum CEA and CA 19-9 levels were normal. Splenopancreasectomy found a desmoid tumour. A 69-year-old male was referred to our institution for chronic anemia and inflammatory syndrome with splenomegaly. Splenectomy showed an important splenic congestion and siderosis. Both patients had a type 2 diabetes mellitus. Furthermore, histological examination revealed pancreatic endocrine microadenomas. The two patients' postoperative course was unremarkable. Eleven and 24 months respectively after the diagnosis, the patients are alive and well, with no tumor recurrence.


Assuntos
Adenoma/diagnóstico , Achados Incidentais , Neoplasias Pancreáticas/diagnóstico , Adenoma/cirurgia , Idoso , Biomarcadores Tumorais/análise , Diabetes Mellitus Tipo 2/complicações , Fibromatose Agressiva/sangue , Fibromatose Agressiva/cirurgia , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreatite Crônica/complicações , Esplenectomia , Esplenomegalia/etiologia
8.
Ann Pathol ; 33(4): 270-2, 2013 Aug.
Artigo em Francês | MEDLINE | ID: mdl-23954122

RESUMO

A 19-year-old male Caucasian, without prior medical history, noticed a painless right testicular mass. Physical examination revealed neither gynecomastia nor abnormal skin pigmentation. Serum alpha-fetoprotein, ß-HCG and testosterone levels were normal. Sonography depicted an intratesticular diffusely hyperechoic lesion with acoustic shadowing. The patient underwent right orchiectomy. Histology revealed a benign large cell calcifying Sertoli cell tumour. This tumour is rare and may be associated with genetic abnormalities.


Assuntos
Calcinose/patologia , Tumor de Células de Sertoli/patologia , Neoplasias Testiculares/patologia , Adenoma/diagnóstico , Biomarcadores Tumorais , Calbindina 2/análise , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Diagnóstico Diferencial , Humanos , Antígeno MART-1/análise , Masculino , Orquiectomia , Tumor de Células de Sertoli/química , Tumor de Células de Sertoli/diagnóstico , Tumor de Células de Sertoli/diagnóstico por imagem , Tumor de Células de Sertoli/cirurgia , Neoplasias Testiculares/química , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/cirurgia , Ultrassonografia , Vimentina/análise , Adulto Jovem
9.
Ann Pathol ; 29(5): 421-3, 2009 Oct.
Artigo em Francês | MEDLINE | ID: mdl-20004847

RESUMO

Lipomatous polyposis of the colon is a rare affection, with about 10 published cases. This affection is characterized by a great number of polyps which can reach several hundreds, of diffuse location on the entire length of the colon, with a higher density on the left colon and the sigmoid. The size of polyps varies from 1 to 10 cm. When they are voluminous, they can be cause of obstruction, ulceration or bleeding. We report a case of colonic lipomatous polyposis, associated with an ileocolic lipomatous, an ileocolic diverticulosis and adenomatous polyps in a 70-year-old man.


Assuntos
Pólipos do Colo/patologia , Polipose Intestinal/patologia , Idoso , Humanos , Lipoma/patologia , Masculino
10.
Ann Pathol ; 24(4): 368-70, 2004 Sep.
Artigo em Francês | MEDLINE | ID: mdl-15567955

RESUMO

Onychomatricoma is a rare fibroepithelial lesion of the nail matrix with peculiar clinical and histological features. Clinically, it is characterized by a longitudinal band of yellow thickening of the nail plate with transverse overcurvature and splinter hemorrhages. Nail avulsion exposes a villous tumor of the matrix with filamentous digitations extending into multiple holes of the nail plate. Histologically, a thick keratogenous zone forms a thickened nail plate. The lesion in its proximal portion is characterized by deep epithelial invaginations and by a stroma organized in two layers. The distal zone corresponds to multiple fibroepithelial projections extending into the nail plate. The diagnosis can be difficult in the presence of misleading clinical features or when the specimen is incomplete or examined with an improper orientation. Surgical resection is the recommended treatment.


Assuntos
Doenças da Unha/patologia , Neoplasias Cutâneas/patologia , Humanos , Masculino , Pessoa de Meia-Idade
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