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1.
Ann Hematol ; 99(2): 223-228, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853704

RESUMO

Limited-stage (Ann Arbor stage I or II) mantle cell lymphoma (MCL) is an extremely rare disease. Thus, there is little data on the clinical features and treatment outcomes of patients with early-stage MCL. We examined consecutive stage I or II MCL 41 cases diagnosed between 2000 and 2016 in 16 institutions of the Consortium for Improving Survival of Lymphoma group. All cases were pathologically confirmed and systemic evaluation was performed for staging. The clinical features were reviewed, and the treatment outcomes were analyzed. The median age of patients was 66 years (range 19-85 years); there were more men (n = 31, 75.6%) than women. Most patients (n = 28, 68.3%) had stage 2 disease, and 29 (70.7%) were symptomatic. The elevation of lactate dehydrogenase (n = 2, 4.9%) was not common; thus, 39 patients (95.1%) had a low-risk score (0 or 1) for the International Prognostic Index, and 28 (68.3%) had a low-risk score (1-3) for the MCL International Prognostic Index. Most patients (n = 37, 90.1%) received chemotherapy as the first therapeutic strategy, while some received radiotherapy (n = 2), surgical resection (n = 1), or no treatment (n = 1). Of the patients who received chemotherapy, 23 (56.9%) received a rituximab-containing regimen, and R-CHOP (n = 17) and R-bendamustine (n = 5) were commonly used. The best response was noted in 97.4% (n = 38) of patients, including 32 who showed a complete response (78%). With a median follow-up duration of 40.6 months, the 42 months relapse-free survival was 59.1%, and the 5-year overall survival rate was 80.4%. Limited-state MCL showed indolent clinical and low-risk prognostic features. Chemotherapy could be effective for controlling localized MCL lesions, with high complete response rates.


Assuntos
Linfoma de Célula do Manto , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Radioterapia , Estudos Retrospectivos , Fatores de Risco , Rituximab/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagem
2.
Anticancer Res ; 39(8): 4179-4184, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366503

RESUMO

BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), possesses histone N-methyltransferase (HMT) activity and plays an essential role in cancer initiation and development. The aim of the present study was to investigate the potential of Wedelolactone (WL) to inhibit the methylation activity of EZH2. MATERIALS AND METHODS: The mantle cell lymphoma (MCL) cell line, Mino, was treated with WL, while untreated cells were used as control. HMT activity and EZH2 amount were measured in nuclear extracts from WL-treated and control Mino cells. RESULTS: WL was found to target EZH2-mediated histone H3K27 methylation. Along with the inhibition of H3K27 methylation in vitro (IC50=0.3 µM), WL suppressed HMT activity in Mino cells with an IC50 value of 3.2 µM. We detected a reduced amount of EZH2 in Mino cells treated with WL, compared to untreated control cells. CONCLUSION: This is the first study to show that WL induces inhibition of H3K27 methylation via EZH2 modulation and decreases cell proliferation in MCL, in vitro. WL is proposed as a promising agent and a novel epigenetic approach in MCL investigation and treatment.


Assuntos
Cumarínicos/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Código das Histonas/genética , Linfoma de Célula do Manto/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Código das Histonas/efeitos dos fármacos , Histona Metiltransferases/genética , Histona Metiltransferases/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Metilação/efeitos dos fármacos , Complexo Repressor Polycomb 2/genética
3.
Surg Pathol Clin ; 12(3): 719-731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352984

RESUMO

Technical advances in diagnostic modalities have led to the characterization of indolent lymphoid disorders similar to the in situ lesions described in epithelial malignancies. These early and indolent lymphoid lesions share clinicopathologic characteristics with well-characterized lymphoid malignancies such as chronic lymphocytic leukemia and follicular lymphoma. The in situ lesions have an indolent clinical course with only a minor subset shown to progress to frank malignancies. In addition to the in situ lesions, new indolent lymphoproliferative disorders have been recently characterized. Diagnosis and characterization of these indolent lesions is necessary to prevent overtreatment with aggressive therapeutic regimens.


Assuntos
Linfoma Folicular/patologia , Transtornos Linfoproliferativos/patologia , Linfócitos B/patologia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfocitose/patologia , Linfoma de Célula do Manto/patologia , Prognóstico
5.
Medicine (Baltimore) ; 98(30): e16180, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348229

RESUMO

Mantle cell lymphoma (MCL) exhibits a heterogenous clinical course. The MCL International Prognostic Index (MIPI) is the most commonly used risk classification system in MCL. However, it does not contain a parameter associated with the tumor microenvironment. The aim of this study was to develop a more powerful prognostic index by evaluating the absolute monocyte count (AMC), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) at diagnosis in conjunction with the clinical and laboratory parameters.The data of 96 MCL patients with newly diagnosed from January 2014 to December 2018 were retrospectively evaluated in this study. The AMC, NLR, and PLR cut-off values were determined using the receiver operating characteristic (ROC) analysis.The clinical behavior and results of the disease exhibited significant variation in high and low value groups at the time of diagnosis. In univariate analysis, the AMC ≥ 580, NLR ≥ 2.43, and PLR ≥ 120.85 were determined as negative prognostic factors for 5-year progression free survival (PFS) (AMC: PFS, P < .001; NLR: PFS, P < .001; PLR: PFS, P < .001) and for 5-year overall survival (OS) (P < .001, P < .001, P < .001, respectively). Beta-2 microglobulin (B2-MG), and MIPI for PFS, and for OS were found to be independent risk factors in the multivariate analysis (for PFS: P = .006, P = .002, respectively; and for OS: P = .007, P = .001, respectively). The 5-year OS was 20% in the group with B2-MG ≥ 3.5. The patients in high-risk MIPI group had poorer 5-year OS (median OS: 40 months, P < .001).The results stated that the use of B2-MG in conjunction with MIPI was a more sensitive method in determining the prognosis in MCL (median OS: 12 months in high-risk MIPI group with a B2-MG ≥3.5, P < .001). Additionally, it was found that parameters reflecting the tumor microenvironment such as AMC, NLR, and PLR increased the risk of progression in MCL. In view of these findings, in addition B2-MG to the MIPI to create a more sensitive prognostic scoring system may provide an insight into personalization of treatment with early recognition of patients with poor prognosis.


Assuntos
Linfócitos/patologia , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Monócitos/patologia , Neutrófilos/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Contagem de Linfócitos , Linfoma de Célula do Manto/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Microambiente Tumoral
10.
Med Sci Monit ; 25: 2599-2608, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30964854

RESUMO

BACKGROUND Mantle cell lymphoma (MCL) is a high-grade B-cell lymphoma with poor prognosis. Fludarabine is used alone or in combination for relapsed and advanced-stage MCL. The expression of the signal transducer and activator of transcription 5B (STAT5B) gene is associated with tumorigenesis in solid tumors, but its role in MCL remains unknown. The aims of this study were to investigate the role of STAT5B in GRANTA-519 human mantle cell lymphoma cells and drug resistance. MATERIAL AND METHODS GRANTA-519 human mantle cell lymphoma cells were cultured with and without 10 µM fludarabine dephosphorylated 9-ß-D-arabinofuranosyl-2-fluoroadenine, (2-F-araA) or 10 µM 4-hydroperoxycyclophosphamide (4-HC). The MTT assay assessed cell proliferation. Flow cytometry was used to investigate the cell cycle in MCL cells treated with the specific inhibitor of the Akt pathway, LY294002, and assessed cell cycle and cell apoptosis. Western blot was used to detect the expression levels of p-Akt/Akt and STAT5B/p-STAT5B. The gene expression profiles of lymph node (LN)-derived MCL cells were compared with peripheral blood (PB)-derived lymphocytes using bioinformatics and hierarchical cluster analysis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to determine the expression of the marker of proliferation Ki-67 (MKI67) gene. RESULTS STAT5B was significantly upregulated in LN-derived MCL cells compared with PB lymphocytes. Increased expression of STAT5B was associated with increased MCL cell proliferation and reduced cell apoptosis and was associated with drug resistance and activation of Akt. CONCLUSIONS STAT5B promoted cell proliferation and drug resistance in human MCL cells by activating the Akt signaling pathway.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT5/genética , Transdução de Sinais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/patologia , Linfócitos/metabolismo , Linfoma de Célula do Manto/enzimologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT5/metabolismo
11.
Arch Ital Urol Androl ; 91(1): 49-50, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30932430

RESUMO

Primary urethral lymphoma is a rare entity without a standardized treatment protocol. We report a case of an elderly woman presenting with a caruncle associated with vaginal spotting and intermittent dysuria. She underwent surgical excision of the lesion. Histological analysis revealed a blastoid variant of mantle cell lymphoma, a previously unreported subtype. The patient received chlorambucil assisting a rapid local disease progression. She died of disseminated disease 6 months after diagnosis. A review of the lymphomas of the urethra is included.


Assuntos
Linfoma de Célula do Manto/diagnóstico , Doenças Uretrais/diagnóstico , Neoplasias Uretrais/diagnóstico , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Clorambucila/administração & dosagem , Diagnóstico Diferencial , Progressão da Doença , Disuria/etiologia , Evolução Fatal , Feminino , Humanos , Linfoma de Célula do Manto/patologia , Doenças Uretrais/patologia , Neoplasias Uretrais/patologia
12.
J Cutan Pathol ; 46(7): 538-541, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30957249

RESUMO

Secondary cutaneous involvement by mantle cell lymphoma (MCL), an uncommon aggressive B-cell malignancy, predominantly involves the dermis, with few reports of pannicular involvement. Lymphocytic infiltration of subcutaneous tissue is associated with inflammatory panniculitides and certain T-cell lymphomas, primarily subcutaneous panniculitis-like T-Cell lymphoma (SPTCL), which is characterized by rimming of adipocytes by tumor cells. We report the case of a 69-year-old man with a history of systemic nodal MCL who presented with subcutaneous nodules on his lower extremities after receiving multi-agent chemotherapy. Biopsies showed a dense infiltrate of atypical, mitotically active, monomorphic, medium-sized lymphoid cells in the subcutaneous fat with prominent rimming of the adipocytes by the tumor cells. These features were not morphologically typical of MCL. Immunohistochemistry showed these cells to be CD20+, CD5+ B-cells with strong cyclin D1 expression; fluorescence in situ hybridization (FISH) analysis was positive for t(11;14)(q13;32), confirming the diagnosis of secondary cutaneous involvement of MCL. This represents an exceptional report of cutaneous MCL presenting clinically and histologically with a panniculitis-type pattern and adipocyte rimming, histomorphologically mimicking SPTCL. Noteworthy examples, such as this report, support the practice of utilizing clinical correlation, immunohistochemistry, and/or molecular cytogenetics to confirm the diagnosis of any case suspicious for cutaneous lymphoma.


Assuntos
Linfoma de Célula do Manto , Linfoma de Células T , Paniculite , Neoplasias Cutâneas , Idoso , Antígenos CD20/genética , Antígenos CD20/metabolismo , Linfócitos B/metabolismo , Linfócitos B/patologia , Antígenos CD5/genética , Antígenos CD5/metabolismo , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 11/metabolismo , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 14/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Diagnóstico Diferencial , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Masculino , Paniculite/diagnóstico , Paniculite/genética , Paniculite/metabolismo , Paniculite/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Translocação Genética
14.
Blood ; 133(11): 1201-1204, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30692121

RESUMO

Single-agent ibrutinib is active in patients with previously treated mantle cell lymphoma (MCL); however, nearly half of all patients experience treatment failure during the first year. We previously demonstrated that prolonged early G1 cell cycle arrest induced by the oral, specific CDK4/6 inhibitor palbociclib can overcome ibrutinib resistance in primary human MCL cells and MCL cell lines expressing wild-type Bruton's tyrosine kinase (BTK). Therefore, we conducted a phase 1 trial to evaluate the dosing, safety, and preliminary activity of palbociclib plus ibrutinib in patients with previously treated mantle cell lymphoma. From August 2014 to June 2016, a total of 27 patients (21 men, 6 women) were enrolled. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg on days 1 to 21 of each 28-day cycle. The dose-limiting toxicity was grade 3 rash. The most common grade 3 to 4 toxicities included neutropenia (41%), thrombocytopenia (30%), hypertension (15%), febrile neutropenia (15%), and lung infection (11%). The overall and complete response rates were 67% and 37%, and with a median follow-up of 25.6 months, the 2-year progression-free survival was 59.4% and the 2-year response duration was 69.8%. A phase 2 multicenter clinical trial to further characterize efficacy is now ongoing. The current trial was registered at www.clinicaltrials.gov as #NCT02159755.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Piperazinas/administração & dosagem , Prognóstico , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Pirimidinas/administração & dosagem , Taxa de Sobrevida
15.
Dig Dis ; 37(3): 194-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30677768

RESUMO

BACKGROUND: The frequency of endoscopically apparent gastrointestinal tract (GI) involvement in patients with mantle cell lymphoma (MCL) at diagnosis is thought to be in the range of 30%. While reports on GI involvement in MCL patients exist, most series lack a strict GI assessment due to the often asymptomatic nature of GI involvement. Owing to the standardized staging routine at our institution including GI assessment at diagnosis, we have analyzed the rate and prognostic impact of GI involvement in MCL. METHODS: In this retrospective single-center evaluation, we have investigated GI involvement in 85 consecutive patients with MCL. All data were collected from clinical records. RESULTS: MCL with and without endoscopically detectable GI involvement was reported in 29 (34%) patients and 56 patients (66%), respectively. The colon was involved in 21 (72%) and the stomach in 8 (28%). Eight of 29 patients (28%) had symptomatic GI involvement, and the primary diagnosis had been established in the GI tract in 3/29 (10%) of our patients. No statistical differences could be observed between both groups in terms of gender (p = 0.474), Eastern Cooperative Oncology Group (0.428), and MCL international prognostic index (0.543). Overall survival was longer in patients with GI involvement (116.0 vs. 74 months), but not statistically significant (p = 0.825). CONCLUSIONS: In our single center cohort, we did not find a clinical impact of GI involvement on the clinical course of MCL and no GI complications occurred during chemotherapy in these patients. As most patients were also asymptomatic, these data argue against a routine GI assessment in patients diagnosed with MCL.


Assuntos
Trato Gastrointestinal/patologia , Linfoma de Célula do Manto/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Úlcera Gástrica/patologia , Análise de Sobrevida
16.
Leukemia ; 33(7): 1675-1686, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30664664

RESUMO

p97 is an ATPase that works in concert with histone deacetylase 6 (HDAC6), to facilitate the degradation of misfolded proteins by autophagosomes. p97 has also been implicated in DNA repair and maintaining genomic stability. In this study, we determined the effect of combined inhibition of p97 and HDAC6 activities in mantle cell lymphoma (MCL) cells. We report that treatment with p97 inhibitors induces dose-dependent apoptosis in MCL cells. The p97 inhibitor CB-5083 induces ER stress markers GRP78 and CHOP and results in the accumulation of polyubiquitylated proteins. Co-treatment with CB-5083 and the HDAC6 inhibitor ACY-1215 result in marked downregulation of CDK4, Cyclin D1, and BRCA1 levels without inhibiting autophagic flux. Consequently, treatment with CB-5083 accentuates DNA damage in response to treatment with ACY-1215 resulting in enhanced accumulation of H2AX-γ and synergistic apoptosis. Furthermore, ATM loss severely impairs phosphorylation of 53BP1 following co-treatment with CB-5083 and ACY-1215 in response to gamma irradiation. Finally, co-treatment CB-5083 and ACY-1215 results in reduced tumor volumes and improves survival in Z138C and Jeko-1 xenografts in NSG mice. These observations suggest that combined inhibition of p97 and HDAC6 abrogates resolution of proteotoxic stress and impairs DNA repair mechanisms in MCL cells.


Assuntos
Adenosina Trifosfatases/antagonistas & inibidores , Reparo do DNA/efeitos dos fármacos , Sinergismo Farmacológico , Desacetilase 6 de Histona/antagonistas & inibidores , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Proteínas Nucleares/antagonistas & inibidores , Pirimidinas/farmacologia , Animais , Apoptose , Autofagia , Proliferação de Células , Dano ao DNA/efeitos dos fármacos , Quimioterapia Combinada , Regulação Neoplásica da Expressão Gênica , Inibidores de Histona Desacetilases/farmacologia , Humanos , Linfoma de Célula do Manto/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Clin Nucl Med ; 44(4): e298-e300, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30688737

RESUMO

Skeletal muscle involvement by lymphoma is rare, particularly for mantle cell lymphoma. We describe a 65-year-old man who presented with a rapidly growing left thigh mass. FDG PET/CT characterized the mass as malignant. Interestingly, an unusual hypermetabolic elongated tumorous extension was demonstrated arising from the intramuscular mass disseminating alongside the neurovascular bundle of the thigh up to the groin. Histopathology revealed intramuscular mantle cell lymphoma. In this case, we aim to highlight this interesting FDG PET/CT imaging finding, which can serve as a clue allowing one to strongly suggest lymphoma as the leading diagnosis.


Assuntos
Fluordesoxiglucose F18 , Linfoma de Célula do Manto/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia
18.
Medicine (Baltimore) ; 98(1): e13741, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608386

RESUMO

Mantle cell lymphoma (MCL) is an invasive B-cell lymphoma with significant individual differences. Currently, MCL international prognostic index (MIPI) score and tumor cell proliferation index Ki-67 have been proved to be the most important prognostic factors. But the prognostic effect of these factors in Asian population is uncertain. This study aimed to analyze the disease characteristics and prognostic factors of Chinese MCL patients.A total of 83 cases of newly-diagnosed MCL patients diagnosed by the Department of Pathology of our hospital between January 1, 2011, and May 31, 2016, were enrolled. The disease characteristics, treatment effects, and outcomes of the patients were collected and analyzed.According to our analysis, MCL cases accounted for 6.2% of non-Hodgkin lymphoma (NHL) cases and mainly occurred in elderly males. But the proportion of patients at stage IV by Ann Arbor staging system and high-risk group by simplified-MIPI (s-MIPI) were significantly lower than that among European patients. Immunochemotherapy containing rituximab was significantly more effective than chemotherapy (overall response rate, [ORR]: 88.5% vs 65.2%, P = .021) and significantly prolonged patient survival (progression free survival [PFS]: 45.5 m vs 16.2 m, P = .001; overall survival [OS]: 58.3 m vs 22.8 m, P = .001). The multivariate analysis showed that the B symptoms, s-MIPI and administration of immunochemotherapy were independent prognostic factors that affected PFS and OS of the patients. s-MIPI and B symptom make up s-MIPI-B stratification method, by which patients in low-risk group of s-MIPI without B symptom were classified as low-risk, patients in high-risk group of s-MIPI and patients in low-risk group of s-MIPI with B symptom as high-risk, the rest as middle-risk. 3-year PFS of the 3 groups were 74.9%, 43.4% and 16.1%, respectively (P = .001). 3-year OS were 84.4%, 62.2%, 27.6% (P <.001).Chinese MCL was male predominance. We have a minor proportion of late-stage and high-risk patients compared to European patients. Immunochemotherapy was proved to significantly improve the prognosis of MCL patients. B symptoms, s-MIPI, and administration of rituximab independently influenced the outcome. s-MIPI-B prognostic stratification method may better predict the prognosis of Asian MCL patients. Still, further confirmation in larger populations is needed.


Assuntos
Linfoma de Célula do Manto/diagnóstico , Medição de Risco/métodos , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Criança , China , Feminino , Humanos , Antígeno Ki-67/análise , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto Jovem
19.
Vet Pathol ; 56(3): 350-357, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30636524

RESUMO

Marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) belong to a subgroup of indolent B-cell lymphomas most commonly reported in the canine spleen. The goal of this study was to characterize the immunophenotype of splenic MZL and MCL in comparison to their human counterparts. Ten MCLs and 28 MZLs were selected based on morphology. A tissue microarray was generated, and expression of CD3, CD5, CD10, CD45, CD20, CD79a, Pax-5, Bcl-2, Bcl-6, cyclin D1, cyclin D3, MCL-1, MUM-1, and Sox-11 was evaluated. Neoplastic cells in all MCLs and MZLs were positive for CD5, CD20, CD45, CD79a, and BCL2 and negative for CD3, CD10, Bcl-6, cyclin D1, and cyclin D3. Positive labeling for Pax-5 was detected in 8 of 10 MCLs and 26 of 28 MZLs. Positive labeling for MUM-1 was detected in 3 of 10 MCLs, and 27 of 28 MZLs were positive for MUM-1. No MCLs but 8 of 24 MZLs were positive for MCL-1. Canine splenic MZL and MCL have a similar immunophenotype as their human counterparts. However, human splenic MCL overexpresses cyclin D1 due to a translocation. A similar genetic alteration has not been reported in dogs. In addition, in contrast to human MZL, canine splenic MZL generally expresses CD5. Following identification of B vs T cells with CD20 and CD3, a panel composed of BCL-2, Bcl-6, MUM-1, and MCL-1 combined with the histomorphological pattern can be used to accurately diagnose MZL and MCL in dogs. Expression of Bcl-2 and lack of MCL-1 expression in MCL may suggest a therapeutic benefit of BCL-2 inhibitors in canine MCL.


Assuntos
Doenças do Cão/patologia , Imunofenotipagem/veterinária , Linfoma de Células B/veterinária , Linfoma Folicular/veterinária , Neoplasias Esplênicas/veterinária , Animais , Antígenos de Diferenciação de Linfócitos T/imunologia , Doenças do Cão/imunologia , Cães , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/veterinária , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/veterinária , Estudos Retrospectivos , Baço/imunologia , Baço/patologia , Neoplasias Esplênicas/imunologia , Neoplasias Esplênicas/patologia
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