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1.
Ann Hematol ; 99(2): 241-253, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31897674

RESUMEN

This study aims to investigate the clinicopathological features of in situ follicular neoplasm (ISFN) in Japan. ISFN is a rare condition formerly considered as an early precursor of follicular lymphoma (FL). This is a first original report of ISFN from Asian country. We reviewed 19 biopsy samples of ISFN. ISFNs were categorized into two groups: (1) ISFN, consisting of ISFN with strong positivity for BCL-2 immunohistochemical staining (IHC), and obvious translocation of BCL-2; and (2) ISFN-like FL, featuring cases without obvious translocation but having morphological features and characteristic IHC findings of ISFN. As control, we adopted obvious FL. For some cases showing coexisting ISFN and FL lesions in the same lymph node, we could conduct further clonality analysis for each lesion. Nine of the 19 cases of ISFN coexisted with FL or had a history of overt B- or T-cell lymphoma including FL. Statistical comparison among ISFN-like FL and FL showed no significant differences in pathological features. Molecular analysis suggested that ISFN lesion and FL lesion in the same lymph node each have a different clonality. ISFN coexists or associates with other overt lymphomas frequently.


Asunto(s)
Ganglios Linfáticos/metabolismo , Linfoma Folicular , Neoplasias Primarias Secundarias , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Japón , Ganglios Linfáticos/patología , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/metabolismo , Neoplasias Primarias Secundarias/patología
2.
Hematol Oncol ; 38(1): 67-73, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31724191

RESUMEN

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m2 for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was -20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (-12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Antineoplásicos Inmunológicos/farmacocinética , Biosimilares Farmacéuticos/farmacocinética , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/patología , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Pronóstico , Rituximab/farmacocinética , Distribución Tisular
4.
Ann Hematol ; 99(2): 391-393, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31858188
6.
Virchows Arch ; 475(6): 771-779, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31686194

RESUMEN

The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)-associated markers stathmin and LLT-1 were positive in most of the cases (12/13 and 12/13, respectively). Interestingly, FOXP-1 was uniformly positive in PTFL (12/13 cases) in contrast to reactive GCs in FH, where only a few isolated positive cells were observed. FISH revealed no evidence of BCL2, BCL6, or MYC rearrangements in the examined cases. By PCR, clonal immunoglobulin gene rearrangements were detected in 100% of the tested PTFL cases. Our study confirmed the unique morphological and immunophenotypic features of PTFL and suggests that FOXP-1 can represent a novel useful diagnostic marker in the differential diagnosis between PTFL and FH.


Asunto(s)
Factores de Transcripción Forkhead/metabolismo , Linfoma de Células B/patología , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Proteínas Represoras/metabolismo , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Humanos , Inmunohistoquímica/métodos , Inmunofenotipificación/métodos , Linfoma de Células B/diagnóstico , Linfoma de Células B/metabolismo , Linfoma Folicular/diagnóstico , Masculino , Estatmina/metabolismo , Adulto Joven
7.
Indian J Pathol Microbiol ; 62(4): 586-588, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31611445

RESUMEN

The follicular variant of peripheral T-cell lymphoma, not otherwise specified, is very rare. Primary epiglottic follicular variant of peripheral T-cell lymphoma is extremely rare in clinical practice. Here, we report the first case of a follicular variant of peripheral T-cell lymphoma not otherwise specified in a 44-year-old Chinese man, who presented with a tumor in the middle of the epiglottis tongue surface. Microscopically, the tumor had a vague nodular growth pattern and the morphology of the nodules was different from each other at low power. Atypical lymphoid cells were medium to large in size and had round nuclei, with an irregular nuclear membrane, distinct nucleoli, and rapid mitotic activity. Plasma cells were found surrounding the nodules. The tumor cells were positive for follicular helper T-cell markers (CD10, PD-1, CXCL13, and BCL-6). The EBER was negative by in situ hybridization. Polymerase chain reaction-based analysis showed monoclonal rearrangements of TCRß, TCRγ, and polyclonal rearrangements of IgH, IgK, and IgL. The clinical and imaging features and the prognostic factors of FV PTCL-NOS remain poorly understood. Thus, investigation of more cases and longer follow-up is necessary to understand the disease and to identify the best treatment to improve prognosis.


Asunto(s)
Epiglotis/patología , Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/patología , Adulto , Quimiocina CXCL13/genética , Epiglotis/diagnóstico por imagen , Humanos , Masculino , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-6/genética , Linfocitos T/citología , Tomografía Computarizada por Rayos X
8.
Medicine (Baltimore) ; 98(41): e17567, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31593142

RESUMEN

RATIONALE: Pediatric-type follicular lymphoma (PTFL) is a rare neoplasm with features that differ from those of adult-type follicular lymphoma. Compared to patients with adult-type follicular lymphoma, PTFL patients often show an excellent response. Preoperative diagnosis is challenging and, therefore, an accurate diagnosis is based on the findings of postoperative pathological examination and immunohistochemistry. PATIENT CONCERNS: A 13-year-old boy presented with a slow-growing mass on the right side of his neck. DIAGNOSES: The patient was diagnosed with PTFL based on the findings of histopathological examination and immunohistochemistry. INTERVENTION: The mass was completely resected. OUTCOMES: After 12 months of postoperative follow-up, the patient achieved good recovery without recurrence. LESSONS: The optimal treatment for PTFL has not yet been defined. However, patients with PTFL always show satisfactory prognoses, regardless of treatment strategy (targeted radiotherapy, multiagent chemotherapy, or "watch and wait" strategy). Clinically, pathological and immunohistochemical analyses are necessary in the diagnoses of PTFL cases, especially for distinguishing PTFL from reactive follicular hyperplasia, to avoid unnecessary treatment.


Asunto(s)
Linfoma de Células B/patología , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Cuello/patología , Adolescente , Cuidados Posteriores , Humanos , Inmunohistoquímica/métodos , Linfoma de Células B/diagnóstico , Linfoma de Células B/inmunología , Linfoma de Células B/cirugía , Linfoma Folicular/diagnóstico , Linfoma Folicular/cirugía , Masculino , Cuello/diagnóstico por imagen , Cuello/cirugía , Resultado del Tratamiento , Ultrasonografía
9.
Cancer Immunol Immunother ; 68(11): 1791-1804, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31620858

RESUMEN

The perspective of combining cancer vaccines with immunomodulatory drugs is currently regarded as a highly promising approach for boosting tumor-specific T cell immunity and eradicating residual malignant cells. The efficacy of dendritic cell (DC) vaccination in combination with lenalidomide, an anticancer drug effective in several hematologic malignancies, was investigated in a follicular lymphoma (FL) model. First, we evaluated the in vitro activity of lenalidomide in modulating the immune responses of lymphocytes co-cultured with a new DC subset differentiated with IFN-α (IFN-DC) and loaded with apoptotic lymphoma cells. We next evaluated the efficacy of lenalidomide and IFN-DC-based vaccination, either alone or in combination, in hu-PBL-NOD/SCID mice bearing established human lymphoma. We found that lenalidomide reduced Treg frequency and IL-10 production in vitro, improved the formation of immune synapses of CD8 + lymphocytes with lymphoma cells and enhanced anti-lymphoma cytotoxicity. Treatment of lymphoma-bearing mice with either IFN-DC vaccination or lenalidomide led to a significant decrease in tumor growth and lymphoma cell spread. Lenalidomide treatment was shown to substantially inhibit tumor-induced neo-angiogenesis rather than to exert a direct cytotoxic effect on lymphoma cells. Notably, the combined treatment with the vaccine plus lenalidomide was more effective than either single treatment, resulting in the significant regression of established tumors and delayed tumor regrowth upon treatment discontinuation. In conclusion, our data demonstrate that IFN-DC-based vaccination plus lenalidomide exert an additive therapeutic effect in xenochimeric mice bearing established lymphoma. These results may pave the way to evaluate this combination in the clinical ground.


Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Células Dendríticas/inmunología , Sinergismo Farmacológico , Factores Inmunológicos/inmunología , Interferón-alfa/inmunología , Lenalidomida/farmacología , Linfoma Folicular/terapia , Animales , Terapia Combinada , Femenino , Humanos , Factores Inmunológicos/farmacología , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID
10.
Nat Methods ; 16(10): 1007-1015, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31501550

RESUMEN

Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to large datasets, mapping approaches require purified or pre-annotated data and both are prone to batch effects. To overcome these issues, we present CellAssign, a probabilistic model that leverages prior knowledge of cell-type marker genes to annotate single-cell RNA sequencing data into predefined or de novo cell types. CellAssign automates the process of assigning cells in a highly scalable manner across large datasets while controlling for batch and sample effects. We demonstrate the advantages of CellAssign through extensive simulations and analysis of tumor microenvironment composition in high-grade serous ovarian cancer and follicular lymphoma.


Asunto(s)
Perfilación de la Expresión Génica , Linfoma Folicular/patología , Probabilidad , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Microambiente Tumoral , Humanos , Linfoma Folicular/inmunología
11.
Trials ; 20(1): 544, 2019 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-31470902

RESUMEN

BACKGROUND: Large field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera® and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30-40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects. Immune modulating radiation therapy alone using low-dose radiotherapy (LDRT) of 2 × 2 Gy has been shown to be effective in FL. The GAZAI (GAZyvaro and response Adapted Involved-site Radiotherapy) trial aims to prove the efficacy of LDRT in combination with a novel anti-CD20 therapy. METHODS/DESIGN: The GAZAI trial is a non-randomized, open, non-controlled, German, multi-center phase II trial that includes patients with early-stage (I and II) nodular FL (grades 1 and 2) confirmed by central histological review. A maximum of 93 patients will be included in the trial. Patients will receive a combined approach of immunotherapy with the fully humanized anti-CD20 antibody obinutuzumab (Gazyvaro®) and involved site radiotherapy (IS-RT) with 2 × 2 Gy. The primary endpoint of the trial is the rate of metabolic complete response (CR), based on fludeoxyglucose positron emission tomography/computed tomography, after obinutuzumab and 2 × 2 Gy IS-RT in week 18. Secondary endpoints are morphologic CR rate in weeks 7 and 18 and month 6, progression-free survival, toxicity, recurrence patterns, overall survival, and quality of life. Additionally, minimal residual disease response is assessed. The risk for a potentially higher recurrence rate after LDRT will be minimized by additional salvage radiation up to the "full dose" of 40 Gy for patients who have less than a metabolic CR and morphologic partial response/CR, which will be evaluated in week 18, offering a response-adapted approach. DISCUSSION: The goal of this trial is a further reduction of the radiation dose in patients with nodal early-stage FL showing a good response to a combination of LDRT and anti-CD20 immunotherapy and a comparison with the currently published MIR trial. TRIAL REGISTRATION: EudraCT number: 2016-002059-89. ClinicalTrials.gov identifier: NCT03341520 .


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/radioterapia , Terapia Combinada , Humanos , Linfoma Folicular/patología , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Proyectos de Investigación
12.
Hematol Oncol ; 37(5): 564-568, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31475375

RESUMEN

Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous.


Asunto(s)
Biomarcadores de Tumor/genética , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/genética , Anciano , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Estimación de Kaplan-Meier , Linfoma Folicular/mortalidad , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Mutación , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento
14.
Presse Med ; 48(7-8 Pt 1): 850-858, 2019.
Artículo en Francés | MEDLINE | ID: mdl-31447334

RESUMEN

Follicular lymphoma, the second most common lymphoma, is characterized by its slow growth and is often considered incurable in advanced stages. Progresses in biology have contributed to better understand the complex and successive mechanisms of development of this pathology, whose diagnosis is based on a lymph node biopsy. However, the prognosis of the patients is heterogeneous and several indexes have been proposed to identify groups of patients with a similar life expectancy, in order to guide the therapeutic choices. The treatment has been modified in the last 20 years by the emergence of anti-CD20 monoclonal antibodies which constitute, alone or in combination, of the cornerstone of therapeutic management. After staging using, in particular, 18-fluorodeoxyglucose positron emission tomography, the therapeutic strategy will be adapted for each patient, ranging from simple watchful waiting to a combination of chemotherapy and anti-CD20 antibodies. Relapses (which often require a new lymph node biopsy to eliminate a possible histological transformation into an aggressive lymphoma with poorer prognosis) remain common but are still accessible to effective therapeutic interventions. Thanks to these advances, the median life expectancy of patients with follicular lymphoma now exceeds 15 years.


Asunto(s)
Linfoma Folicular , Biopsia , Diagnóstico Diferencial , Humanos , Inmunofenotipificación/métodos , Inmunoterapia/métodos , Inmunoterapia/tendencias , Esperanza de Vida , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiología , Linfoma Folicular/patología , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/terapia , Medicina de Precisión/métodos , Medicina de Precisión/tendencias , Pronóstico , Tasa de Supervivencia , Terapias en Investigación/métodos , Terapias en Investigación/tendencias
15.
Am J Case Rep ; 20: 1273-1278, 2019 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-31462626

RESUMEN

BACKGROUND Transformation of primary cutaneous follicle center lymphoma (PCFCL), a low-grade B-cell non-Hodgkin lymphoma (NHL), into a high-grade NHL is rare with uncertain prognosis and treatment. A case is reported of a 40-year-old man who presented with a scalp mass that was diagnosed histologically as PCFCL. Imaging of the head and neck identified diffuse large B-cell lymphoma (DLBCL) involving the parotid gland and cervical lymph nodes, which responded well to radiation therapy. CASE REPORT A 40-year-old African American man presented with a two-year history of a progressively enlarging scalp mass that measured 10.5×7.1×6.6 cm. Histology showed a low-grade lymphoma with a follicular pattern. Immunohistochemistry was positive for B-cell markers and Bcl-6, consistent with a diagnosis of PCFCL. Computed tomography (CT) identified a 4.9×3.7×3.4 cm mass in the left parotid gland with bilateral cervical lymphadenopathy that had been present for the previous two or three months. The diagnosis of DLBCL was made on histology from a needle biopsy. Treatment began with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy, followed by radiation therapy to the scalp, both sides of the neck, and left parotid gland. At four-month follow-up, combined positron emission tomography (PET) and CT showed only diffuse low-level uptake in the scalp and parotid gland. CONCLUSIONS Transformation of low-grade PCFCL to high-grade DLBCL is rare, and the approach to treatment varies. This case showed a good response to chemotherapy and radiation therapy.


Asunto(s)
Transformación Celular Neoplásica/patología , Metástasis Linfática , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias de la Parótida/patología , Neoplasias Cutáneas/patología , Adulto , Humanos , Masculino , Cuero Cabelludo/patología
17.
J Cancer Res Clin Oncol ; 145(8): 2149-2156, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31273513

RESUMEN

BACKGROUND: First-line rituximab therapy together with chemotherapy is the standard care for patients with advanced follicular B-cell lymphoma, as rituximab together with chemotherapy prolongs progression-free and overall survival (Herold et al. 2007; Marcus et al. 2005). However, as not all patient subgroups benefit from combined immuno-chemotherapy, we asked whether the microenvironment may predict benefit from rituximab-based therapy. DESIGN: To address this question, we performed a retrospective immunohistochemical analysis on pathological specimens of 18 patients recruited into a randomized clinical trial, where patients with advanced follicular lymphoma were randomized into either chemotherapy or immuno-chemotherapy with rituximab (Herold et al. 2007). RESULTS: We show here that rituximab exerts beneficial effects, especially in the subgroup of follicular lymphoma patients with low intrafollicular CD3, CD5, CD8, and ZAP70 and high CD56 and CD68 expression. CONCLUSION: Rituximab may overcome immune-dormancy in follicular lymphoma in cases with lower intrafollicular T-cell numbers and higher CD56 and CD68 cell counts. As this was a retrospective analysis on a small subgroup of patients, these data need to be corroborated in larger clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos Infiltrantes de Tumor/patología , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/inmunología , Rituximab/administración & dosificación , Linfocitos T/patología , Clorambucilo/administración & dosificación , Femenino , Humanos , Inmunoterapia , Células Asesinas Naturales/patología , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Linfocitos T/efectos de los fármacos , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología
18.
World J Surg Oncol ; 17(1): 115, 2019 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-31269981

RESUMEN

BACKGROUND: Ultrastructural and immunohistochemical differences have been described in FDCs of primary and secondary follicles, illustrating the highly compartmentalized structure of lymph follicles. Differences in FDC immunophenotype in different grades of FL may reflect some parallelism between reactive and neoplastic conditions in terms of FDC-B cell interaction and may be used as a valuable additional tool for grading FL. METHODS: A total of 60 paraffin blocks from patients with follicular lymphoma, 30 cases each of grade 1 and 3, were retrieved from our archive. Immunohistochemical analysis was carried out for CD21, CD23, cyclin A, and Ki-67. RESULTS: Our study demonstrates that during evaluation, six patterns of FDC distribution were distinguished. The intensity of stain for CD21 was not statistically significant in grade 1 and grade 3 FL (p = 0.340). In contrast, grade 3 FLs exhibited a significant decrease of CD23 expression by the FDCs (p < 0.001). By CD21 stain, there was no significant difference in the distribution of pattern 1 in grades 1 and 3 (p = 0.098). In contrast, in grade 3, this pattern was significantly less observed by CD23 stain (p = 0.016). The same was observed for pattern 2 for CD21 (p = 0.940) and CD23 (p = 0.010) and pattern 4 for CD21 (p = 0.305) and CD23 (p = 0.005), respectively. Distribution of pattern 5 was significantly different between grades 1 and 3 both for CD21 (p = 0.005) and CD23 (p < 0.001). Distribution of patterns 2 and 6 was not significantly different between grades 1 and 3 for CD21 and CD23. The values of cyclin A and Mib-1 were also significantly different between grades 1 and 3 (p < 0.001). CONCLUSIONS: The observed patterns of FDCs lead us to believe that similar to reactive lymph node follicles, neoplastic follicles in FL, at least in early stages, have an organized structure. Hypothetically, with CD21, CD23, and cyclin A immunohistochemistry, the sequence of events in FL progression may be traced.


Asunto(s)
Células Dendríticas Foliculares/patología , Lectinas Tipo C/análisis , Ganglios Linfáticos/patología , Linfoma Folicular/patología , Receptores de Complemento 3d/análisis , Receptores de IgE/análisis , Adulto , Anciano , Ciclina A/análisis , Ciclina A/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Lectinas Tipo C/metabolismo , Ganglios Linfáticos/citología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Receptores de Complemento 3d/metabolismo , Receptores de IgE/metabolismo
19.
Blood ; 134(9): 761-764, 2019 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-31300404

RESUMEN

Despite widespread use of bendamustine and rituximab (BR) as frontline therapy for advanced-stage follicular lymphoma (FL), little is known about the risk of early progression or incidence of histological transformation. We performed a retrospective analysis of a population-based cohort of 296 patients with advanced-stage FL treated with frontline BR and maintenance rituximab. As previously demonstrated, outcomes with this regimen are excellent, with 2-year event-free survival estimated at 85% (95% confidence interval [95% CI], 80-89) and 2-year overall survival 92% (95% CI, 88-95). Progression of disease within 24 months (POD24) occurred in 13% of patients and was associated with a significantly inferior outcome with 2-year overall survival of 38% (95% CI, 20-55). The only significant risk factor for POD24 at baseline was elevated lactate dehydrogenase (P < .001). Importantly, the majority of POD24 patients (76%) had transformed disease. Compared with a historical cohort treated with rituximab, cyclophosphamide, vincristine, and prednisone, event-free survival has improved and the risk of POD24 has decreased, but a higher proportion of patients with POD24 harbor transformation. The overall incidence of transformation appears unchanged. The presence of occult or early transformation is the main driver of POD24 in FL patients treated with frontline BR. Identification of biomarkers and improved management strategies for transformation will be crucial to improving outcomes.


Asunto(s)
Antineoplásicos/uso terapéutico , Clorhidrato de Bendamustina/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
20.
Surg Pathol Clin ; 12(3): 719-731, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31352984

RESUMEN

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.


Asunto(s)
Linfoma Folicular/patología , Trastornos Linfoproliferativos/patología , Linfocitos B/patología , Diagnóstico Diferencial , Humanos , Inmunofenotipificación/métodos , Leucemia Linfocítica Crónica de Células B/patología , Linfocitosis/patología , Linfoma de Células del Manto/patología , Pronóstico
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