Maximum disease diameter is associated with outcomes in stage II follicular lymphoma treated with radiation therapy alone.

Purpose: The optimal management of stage II follicular lymphoma (FL) is unclear. Radiation therapy (RT) alone has been the gold standard treatment, but a proportion of patients relapse. We sought to characterize outcomes and prognostic factors for stage II FL treated with RT alone to identify a high-risk subgroup of patients who may benefit from treatment intensification. Methods: This was a population-based, province-wide, retrospective study. Included patients had grade 1-3A, non-mesenteric, stage IIA or IIAE FL diagnosed between 1986 and 2016 and treated with curative-intent (≥20 Gy) RT alone. Results: 102 patients were included. Median follow-up was 10.4 years (range, 0.3-22.3). Median age was 59 years (range, 33-86). Median greatest disease diameter was 3.6 cm (range, 1.5-11.5). Freedom from progression (FFP) was 60.3% at 5 years and 40.7% at 10 years. Overall survival (OS) was 89.2% at 5 years and 81.8% at 10 years. Greatest disease diameter of >3.6 cm was associated with inferior FFP (10-year FFP 34% vs. 47%, p = 0.013) on univariable analysis and inferior FFP (hazard ratio [HR] 1.87, p = 0.019) and inferior OS (HR 2.12, p = 0.027) on multivariable analysis (MVA). Older age was associated with inferior OS (HR 1.08, unit = 1 year, p < 0.001) on MVA. Conclusions: 40.7% of stage II FL patients treated with RT alone remained disease-free at 10 years. Greatest disease diameter >3.6 cm was associated with inferior FFP and OS, representing a novel prognostic indicator in this population that may help in the decision-making process on whether to complement RT with systemic therapy.

[The clinical features, survival analysis, and geriatric assessment of 85 patients with follicular lymphoma: a single-center study].

Objective: To retrospectively analyze the clinical characteristics and prognosis of 85 newly diagnosed patients with follicular lymphoma (FL), as well as the prognostic value of comprehensive geriatric assessment (CGA) in patients with FL aged ≥ 60 years old. Methods: The clinical data and prognosis of 85 newly diagnosed FL patients admitted from August 2011 to June 2022 were collected. The clinical features, laboratory indicators, therapeutic efficacy, survival and prognostic factors of patients were statistically analyzed, and the prognosis of patients was stratified using various geriatric assessment tools. Results: ① The patients with FL were mostly middle-aged and older, with a median age of 59 (20-87) years, including 41 patients (48.2%) aged ≥60 years. The ratio of male to female was 1∶1.36. Overall, 77.6% of the patients were diagnosed with Ann Arbor stage Ⅲ-Ⅳ, and 17 cases (20.0%) were accompanied by B symptoms. Bone marrow involvement was the most common (34.1%). ②Overall, 71 patients received immunochemotherapy. The overall response rate was 86.6%, and the complete recovery rate was 47.1% of 68 evaluated patients. Disease progression or relapse in the first 2 years was observed in 23.9% of the patient. Overall, 14.1% of the patients died during follow-up. ③Of the 56 patients receiving R-CHOP-like therapies, the 3-year and 5-year progression-free survival (PFS) rates were 85.2% and 72.8%, respectively, and the 3-year and 5-year overall survival (OS) rates were 95.9% and 88.8%, respectively. The univariate analysis showed that age ≥60 years old (HR=3.430, 95% CI 1.256-9.371, P=0.016), B symptoms (HR=5.030, 95% CI 1.903-13.294, P=0.016), Prognostic Nutritional Index (PNI) <45.25 (HR=3.478, 95% CI 1.299-9.310, P=0.013), Follicular Lymphoma International Prognostic Index (FLIPI) high-risk (HR=2.918, 95% CI 1.074-7.928, P=0.036), and PRIMA-prognostic index (PRIMA-PI) high-risk (HR=2.745, 95% CI 1.057-7.129, P=0.038) significantly predicted PFS. Moreover, age ≥60 years old and B symptoms were independent risk factors for PFS. Progression of disease within 24 months (POD24) significantly predicted OS in the univariate analysis. Conclusions: FL is more common among middle-aged and older women. Age, B symptoms, PNI score, FLIPI high-risk, PRIMA-PI high-risk, and POD24 influenced PFS and OS. The CGA can be used for treatment selection and risk prognostication in older patients with FL.

[Clinical features and outcomes of newly diagnosed follicular lymphoma concurrent with diffuse large B-cell lymphoma component].

Objective: To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component. Methods: 1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis. Results: 146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) (P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS (P=0.006) , while LDH higher than normal was an independent risk factor for OS (P=0.031) . Conclusion: FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

The outcome of watchful waiting in patients with previously treated follicular lymphoma.

Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low-tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow-up from the first progression was 79.8 months (range, 2.1-227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4-30.2), and 76.5% (95% CI, 68.0-84.1) of the patients subsequently underwent the second-line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6-94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4-38.8) (HR, 2.13; 95% CI, 1.48-3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first-line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7-NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0-25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes.

Fludarabina en el tratamiento del linfoma no Hodgkin folicular / Fludarabine in the treatment of follicular non-Hodgkin lymphoma

RESUMEN Fundamento: el linfoma no Hodgkin folicular ocupa el segundo lugar entre los linfomas no Hodgkin de estirpe B, se caracterizan por un patrón de remisiones y recaídas continuas. La fludarabina constituye una opción de tratamiento del mismo al lograr una rápida remisión, con disminución del porciento de recaída. Objetivo: evaluar la fludarabina como tratamiento de rescate del linfoma no Hodgkin folicular. Métodos: se realizó un estudio observacional analítico de cohortes, longitudinal prospectivo concurrente. El universo de estudio lo conformaron los pacientes que acudieron a la consulta de Hematología con diagnóstico de linfoma no Hodgkin folicular y quedó constituido por 63 pacientes, de los cuales 21 seleccionados mediante muestreo no probabilístico intencionado que recibieron tratamiento con fludarabina, conformaron cohorte de expuestos, que se compararon con 42 pacientes con similares características que recibieron otros esquemas de poliquimioterapia que no incluyó la fludarabina y que constituyó la cohorte de no expuestos. Resultados: fue mayor el número de pacientes con más de 50 años y del sexo masculino, perteneciente al estadio IV de Cotswold y los que tuvieron un riesgo de recaída de bajo - intermedio. El tiempo de sobrevida libre de enfermedad fue mayor en los tratados con fludarabina quienes presentaron menos complicaciones. Conclusiones: en los pacientes tratados con la fludarabina como tratamiento de rescate del linfoma folicular el tiempo de sobrevida libre de la enfermedad fue mayor y se presentaron menos complicaciones, lo que demuestra su utilidad como tratamiento de primeria línea en ausencia del rituximab.

ABSTRACT Background: follicular non-Hodgkin's lymphoma occupies the second place among non-Hodgkin's lymphomas of line B, they are characterized by a pattern of continuous remissions and relapses. Fludarabine constitutes a treatment option for the same as it achieves a rapid remission, with a decrease in the percentage of relapse. Objective: to evaluate fludarabine as a rescue treatment for follicular non-Hodgkin lymphoma. Methods: a concurrent prospective longitudinal, analytical, observational cohort study was conducted. The study universe was made up of patients who attended the Hematology consultation with a diagnosis of follicular non-Hodgkin's lymphoma and consisted of 63 patients, of which 21 were selected by intentional non-probabilistic sampling who received treatment with fludarabine, made up a cohort of exposed, these were compared with 42 patients with similar characteristics who received other poly-chemotherapy regimens that did not include fludarabine and they constituted the unexposed cohort. Results: the number of male patients over 50 years of age, belonging to Cotswold stage IV, and those with a low-intermediate risk of relapse was greater. The disease-free survival time was longer in those treated with fludarabine, who had fewer complications. Conclusions: in patients treated with fludarabine as rescue treatment for follicular lymphoma, the disease-free survival time was longer and there were fewer complications, which show its usefulness as a first-line treatment in the absence of rituximab.

[Clinicopathological characteristics of pediatric-type follicular lymphomas: an analysis of 37 cases].

Objective: To study the clinicopathologic features, immunophenotype and prognosis of pediatric-type follicular lymphoma (PTFL). Methods: Thirty-seven cases of PTFL at the Beijing Friendship Hospital, Capital Medical University, from January 2012 to March 2018 were analyzed using light microscopy, immunohistochemistry, and polymerase chain reaction (PCR), and 13 cases were also examined using fluorescence in situ hybridization (FISH). Results: The male to female ratio was 35∶2. The median age was 16 years. Thirty-one patients were clinical stage Ⅰ and 6 were stage Ⅱ, displaying enlargement of lymph node in the head and neck regions. Follow-up information was available in 32 patients. Only two patients received low-dose chemotherapy, and none of these patients had relapse or disease progression at the latest follow-up (ranging from 16 to 79 months; median, 37 months). Morphologically, the lymph node architecture was partially or totally effaced by expansile follicles lacking polarization, with a prominent "starry sky" appearance. The cytologic composition was dominated by monotonous medium to large-sized blastoid cells with round to oval nuclei, finely clumped chromatin, small nucleoli, and scant cytoplasm. Immunophenotypically, all cases were positive for CD20, CD10, and bcl-6, but negative for bcl-2, MUM1 and C-MYC. Tumor cells were restricted to the follicles. The Ki-67 immunohistochemistry demonstrated a high proliferation (50% to 90%). Moreover, the tumor cells in the examined 28 cases were negative for CD43, CD5 and CD23. PCR analysis revealed monoclonal Ig gene rearrangements in all specimens. Thirteen cases being subjected to the FISH testing lacked bcl-2 and bcl-6 translocations. Conclusion: PTFL is different from conventional follicular lymphoma in their distinct morphology, immunophenotypic and molecular features, and behaves like an highly indolent or benign tumor.

Criterios diagnósticos y nuevas opciones terapéuticas para los pacientes con diagnóstico de linfoma no Hodgkin / Diagnostic criteria and new therapeutic options for patients diagnosed with non-Hodgkin lymphoma

RESUMEN Fundamento: las hemopatías malignas día a día aumentan su incidencia y proliferación dentro de la población, entre ellas el síndrome linfoproliferativo ocupa un lugar importante, es un grupo de trastornos de origen clonal, que afecta a las células linfoides, con características heterogéneas desde el punto de vista clínico, histológico y molecular. Objetivo: agrupar diferentes criterios diagnósticos y divulgar nuevas opciones terapéuticas para los pacientes con diagnóstico de linfoma no Hodgkin. Métodos: se realizó una búsqueda bibliográfica en las plataformas de acceso a bases de datos de la red de información de salud cubana Infomed, dentro de ellas en EBSCOhost, PubMed/Medline y SciELO. Se utilizaron los siguientes descriptores: síndromes linfoproliferativos, linfomas, linfoma no Hodgkin. Resultados: se aborda la evolución histórica de los síndromes linfoproliferativos desde su descripción inicial hasta el momento actual, así como las diferentes clasificaciones, los tratamientos convencionales utilizados y una panorámica de las investigaciones que se realizan en busca de nuevos tratamientos. Conclusiones: la clasificación de los linfomas no Hodgkin ha cambiado a lo largo del tiempo, la extensión de la enfermedad tiene un papel fundamental en la selección del tratamiento y posible sobrevida del paciente. Existe una amplia variedad de prometedores agentes en desarrollo disponibles para el tratamiento del linfoma folicular.

ABSTRACT Background: malignant haemopathies increase their incidence and proliferation within the population, among them the lymphoproliferative syndrome occupies an important place, it is a group of disorders of clonal origin, which affects the lymphoid cells, with heterogeneous characteristics from the point of clinical, histological and molecular view. Objective: to group different diagnostic criteria and to disclose new therapeutic options for patients diagnosed with non-Hodgkin's lymphoma. Methods: a bibliographic search was carried out in the access platforms to databases of the Infomed Cuban health information network, within them in EBSCOhost, PubMed / Medline and SciELO. The following descriptors were used: lymphoproliferative syndromes, lymphomas, non-Hodgkin's lymphoma. Results: the historical evolution of the lymphoproliferative syndromes is addressed from its initial description to the present time, as well as the different classifications, the conventional treatments used and an overview of the research carried out in search of new treatments. Conclusions: the classification of non-Hodgkin lymphomas has changed over time; the extent of the disease has a fundamental role in the selection of treatment and possible survival of the patient. There is a wide variety of promising developing agents available for the treatment of follicular lymphoma.

[Clinicopathological features and molecular genetics of paediatric-type follicular lymphoma: report of eight cases].

Objective: To investigate the clinical presentation pathological diagnostic features and molecular genetics of paediatric-type follicular lymphoma (PTFL). Methods: Eight cases of PTFL at Fujian Cancer Hospital between January 2003 and May 2018 were analyzed by hematoxylin-eosin stain, immunohistochemistry, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). The relevant literature review was performed. Results: All patients were male with age ranging from 12 to 27 years (median age of 18 years and average age of 19 years). Clinical manifestations included painless lymph adenopathy, primarily involving head and neck lymph nodes (6/8). According to Ann Arbor stage, there were 7 patients at stage Ⅰ A and 1 patient at stage Ⅱ A. Histologically, the structure of the lymph nodes was effaced with pushing borders visible at the tumor periphery. The lesions consisted of expanding, irregular follicles that were arranged in back to back fashion along with thinning or disappearing sleeves. The starry sky phenomenon in the follicle was prominent with loss of polarity. Under high power magnification, the follicles were composed of uniform, medium-sized blastic cells in 5 cases or centroblast in 3 cases. The neoplastic cells were positive for B cell markers and germinal center markers primarily confined to the germinal center. Bcl-2 was negative in 7 cases and 1 case showed weak bcl-2 staining. MUM1 was negative in all cases. Ki-67 demonstrated a high proliferation index of great than 70% in 7 of 8 cases. Eight cases showed Ig clonal rearrangement. No bcl-2, bcl-6, and IRF4/MUM1 gene rearrangements by FISH were detected in all cases. One patient was treated with 6 cycles of CHOP after surgical resection. Other patients underwent only simple surgical resection. All patients were alive upon clinical follow-up. Conclusion: PTFL is a rare subtype of B cell lymphoma with unique clinical and pathological features. It should be distinguished from reactive follicular hyperplasia, nodal marginal lymphoma in children, large B-cell lymphoma with IRF4 rearrangement and usual follicular lymphoma.

[Prognostic study of 229 follicular lymphoma patients treated with rituximab combined with chemotherapy].

Objective: To explore the clinical characteristics of follicular lymphoma (FL) in the era of rituximab combined with chemotherapy and the prognostic significance of the follicular lymphoma international prognostic index (FLIPI), follicular lymphoma international prognostic index 2 (FLIPI2), international prognostic index (IPI), revised international prognostic index (R-IPI), National Comprehensive Cancer Network international prognostic index (NCCN-IPI) among Chinese patients. Methods: 229 FL patients who were treated initially with rituximab combined with CHOP-like (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy from November 2008 to April 2018 were analyzed retrospectively and all were scored by the above clinical index. Univariate and multivariate survival analysis were performed on 201 patients who completed the treatment and were followed regularly. Results: In the univariate survival analysis, age>60 years, hemoglobin<120 g/L, elevated serumß(2)- macroglobulin, involvement of bone marrow and elevated CRP were the risk prognostic factors for overall survival (OS) and progression free survival (PFS). Moreover, the analysis of the OS and PFS between rituximab (R) maintenance (RM) group and non-maintenance (non-RM) group showed that the OS and PFS of RM group were better than those of non-RM. In the multivariate analysis of OS, hemoglobin<120 g/L, involvement of bone marrow, elevated CRP and non-RM were independent prognostic factors. In the multivariate analysis of PFS, hemoglobin<120 g/L, CRP and non-RM were independent prognostic factors. When FLIPI2 was included in the multivariate analysis, CRP and FLIPI2 were independent prognostic factors in both OS and PFS, and non-RM was independent prognostic factors in PFS. Conclusion: FLIPI2 is the better risk stratification in FL patients in the era of rituximab.

[Clinicopathological features of follicular lymphoma in children].

Objective: To investigate the clinicopathologic features of follicular lymphoma (FL) in children. Methods: One female and one male patients with FL diagnosed in the First College of Clinical Medical Science, China Three Gorges University and Beijing Friendship Hospital of the Capital University of Medical Science in February 2016 and June 2015 were studied by HE immunohistochemistry, EBER in situ hybridization, IgH and IgK gene rearrangement analysis and IRF4 fusion gene detection. Results: The two patients' age were 6.3 and 12 years, respectively. The lesions involved head and neck lymph nodes with duration of more than 2 months. Histopathologically, the lesions consisted of nodular proliferation of lymphoid follicles with diffuse distribution of large cells. Starry sky phenomenon was seen in one of the two cases. Immunohistochemistry showed that one case was positive for bcl-2 and MUM1, but negative for bcl-6 and CD10. Ki-67 index was>50% and oligoclonal IgK rearrangement was observed. The second case showed positivity for bcl-6, and CD10 but negative for bcl-2. Ki-67 index was>50% and clonal IgH FR1-JH and IgH FR2-JH rearrangements were detected. Both cases showed no evidence of IRF4 gene fusion. Conclusions: Childhood FL is a rare B-cell lymphoma with characteristic features and high-grade histomorphology. However, its immunophenotype and molecular genetic characteristics are divergent.

[Pathological features of duodenal-type follicular lymphoma].

Objective: To investigate the clinicopathological features, treatment and prognosis of duodenal-type follicular lymphoma. Methods: Four cases of duodenal-type follicular lymphoma diagnosed at Guangdong General Hospital from 2014 to 2015 with detailed clinical data were included. The histomorphology, immunophenotype, treatment and prognoses were analyzed. Results: The patients' age ranged from 51 to 57 years (mean 54 years), and there were 2 males and 2 females. The involved sites were gastric fundus in one case, second portion of the duodenum in two cases and terminal ileum in one case. All patients presented with multiple mucosal granules or nodules at endoscopy. Microscopically, there were multiple mucosal neoplastic follicles, constituting grade 1-2 disease based on nodal follicular lymphoma grading system. The tumor cells were positive for CD20, CD10, bcl-6 and bcl-2. CD21 highlighted the follicular dendritic meshwork mainly at the periphery of the follicles. Proliferation index was low. Three patients received rituximab monotherapy for 4 cycles, leading to complete remission. One patient refused therapy and the disease progressed to systemic lymphoma 15 months after the initial diagnosis. Conclusions: Duodenal-type follicular lymphoma is a special variant of follicular lymphoma with indolent clinical course. The tumor exhibits morphology of low grade follicular lymphoma with characteristic dendritic meshwork at the periphery of the follicles and a low proliferation index. Prognosis is excellent. Rituximab monotherapy is treatment of choice, but a small minority of patients may progress to systemic disease.

[Clinical characteristics and survival analysis of de novo grade 3 or transformed follicular lymphoma patients].

Objective: To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL). Methods: Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed. Results: ① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022). Conclusion: De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.

[Cut-off value of Ki-67 labeling index in the pathologic grading of follicular lymphoma].

Objective: To determine the cut-off values of Ki-67 labeling index (LI) in the histological grading of follicular lymphoma (FL). Methods: Clinicopathological data of 350 FL patients diagnosed at Beijing Friendship Hospital from June 2014 to January 2016 were analyzed retrospectively by quantitative evaluation and statistical analysis of Ki-67 LI. Results: Of the 350 patients with FL, the male and female ratio was 1.1 and the average age was (50.2±14.0) years with a median age of 51 years (range 4 to 82 years). The tumors were graded as grade Ⅰ-Ⅱ in 215 cases (61.4%), grade Ⅲ A in 105 cases (30.0%), and grade Ⅲ B in 30 cases (8.6%). The average Ki-67 values were (22.8%±8.3%) for the FL low (grade Ⅰ-Ⅱ) and (50.4%±10.7%) for high grade (Ⅲ A and Ⅲ B) and were statistically significant by Mann Whitney U test (P<0.01). Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of low grade FL was 35% (sensitivity of 96.3% and specificity of 93.3%) with the largest area under curve (AUC=0.990, P<0.01, 95%CI for 0.982-0.998). According to the analysis of four lattice diagnostic tests, Ki-67 LI >40% was an important factor (χ2=230.733, P<0.01) in predicting high grade FL. When the cut-off value of Ki-67 LI was set at 40%, high grade LF could be diagnosed with the greatest sensitivity (98.1%) and specificity (87.7%). Moreover, a significant correlation between the Ki-67 LI and the pathological grade of FL (r=0.836, P<0.01) was observed. Conclusions: Ki-67 LI of below a cut-off value of 35% is a reliable indicator of low grade FL.Ki-67 over 40% is consistent with high grade FL. These Ki-67 cut-off values may serveas an important auxiliary indicator in the grading of FL.

[Detection and application of bcl-2/IgH gene translocation and immunoglobulin gene rearrangement in follicular lymphoma].

Objective: To evaluate the application of FISH testing of bcl-2/IgH gene translocation and IgH/L gene rearrangement in different stages of follicular lymphoma. Methods: In 32 follicular lymphoma cases, which were collected at Guangdong General Hospital from September 2014 to December 2016, the bcl-2/IgH gene ectopic state was detected by FISH while the IgH/L gene rearrangement was tested using PCR-GeneScan to analyze the relationship between bcl-2/IgH gene translocation, different stages of follicular lymphoma and clonal immunoglobulin (IgH/L) gene rearrangements. Results: From the paraffin sections of all 32 follicular lymphomas, 17 cases showed bcl-2/IgH gene translocation, and the percentages of FL1, FL2 and FL3 translocation were 12/13, 3/5 and 2/14, respectively. Among the 24 cases of IgH/L gene arrangements identified from the total sample, the occurrence rates of FL1, FL2 and FL3 gene arrangement were 7/13, 4/5 and 13/14, respectively. Spearman's rank correlation analysis and χ(2) analysis showed that bcl-2/IgH gene translocation was negatively correlated with follicular lymphoma stage and the association was statistically significant. In more advanced stages of follicular lymphoma, the occurrence of bcl-2/IgH gene translocation tended to decrease with distinct FL1, FL2 and Fl3 gene expression (P<0.05). As IgH/L gene rearrangement in FL3 was higher than that in FL1 and FL2, its detection may be complimentary to FISH test for bcl-2/IgH gene translocation in diagnosing follicular lymphoma. Conclusions: The combined use of FISH and PCR-GeneScan increases the positive rate of follicular lymphoma diagnosis, and this combination is more sensitive than FISH or clonal analysis only to detect the chromosomal abnormality or the gene rearrangement.

Primary Colonic Follicular Lymphoma Presenting as Four Diminutive Sessile Polyps Found Incidentally During Colonoscopy.

Follicular lymphomas, which typically arise in the lymph nodes with spleen, liver, and bone marrow involvement, have generally low occurrence rates in Asian countries as compared with Western countries. Follicular lymphomas of the gastrointestinal tract are rare, and primary colonic follicular lymphomas are particularly rare compared with others found in the small intestine and duodenum. Colonoscopic imaging of colonic lymphomas, including follicular lymphoma, may reveal mucosal ulcerations, erosions, indurations, polypoid mass-like lesions, and diffuse mucosal nodularity. Herein, we report a unique case of a follicular lymphoma of the transverse colon characterized by four sessile diminutive polyps located intermittently with multiple lymph node involvement in a 62-year-old man.

Transformed follicular lymphoma.

Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment. Although t-FL is considered a devastating complication, as it is associated with treatment-refractory disease and a dismal outcome, recent data in the rituximab era have suggested that not only is the prognosis less severe than reported in the previous literature but the risk of transformation is also lower. Thus, this study aimed to review the most recent research on t-FL in an attempt to better understand the clinical meaning of transformation from FL to diffuse large B cell lymphoma (DLBCL) and the impact of current treatment strategies on the curability of this intriguing subentity of lymphoma.

Rituximab Maintenance Strategy in Advanced Follicular Lymphoma: Facts and Controversies

Rituximab is a chimeric monoclonal CD20 antibody used in the treatment of CD20 positive non-Hodgkin lymphomas and has revolutionized treatment approach to these hematologic malignancies in the last decade. The main aim of this review is to present data on the use of rituximab in the treatment of follicular lymphoma (FL). We will focus on rituximab maintenance strategies in the first and second line treatment. This approach has improved the outcome in FL patients with better progression-free survival in all patients and better overall survival in relapsed setting. Regardless of good results, this strategy has generated controversies in medical community in the range from the lack of overall survival benefit in first line setting, adverse effects of possible overtreatment and toxicities to its unknown role in the era of novel agents. The existing data suggest that rituximab maintenance should be a rational therapeutic option for all patients with FL responding to fi rst line therapy and transplant-ineligible patients responding to reinduction.

Clinical Significance of VEGF-A and Microvessel Density in Diffuse Large B-Cell Lymphoma and Low-Grade Follicular Lymphoma.

Angiogenesis is essential for the development, growth and progression of tumors. Although vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor, its impact on lymphoma has not yet been fully clarified. The aim of this study was to evaluate VEGF-A -expression and microvessel density (MVD) in aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL), in indolent lymphomas such as low-grade follicular lymphoma (FL), and in lymph node reactive follicular hyperplasia (FH). In 80 prospective and retrospective cases (30 DLBCL, 30 FL and 20 FH), CD31 was analyzed by immunohistochemical staining assessing density of blood vessels, as well as the total number of CD31 positive endothelial cells. The results were compared with relevant clinical data. MVD was 85% in FH, followed by 60% in DLBCL and 43% in low-grade FL. VEGF-A was significantly higher in DLBCL than in low-grade FL and FH. A statistically significant association of MVD and VEGF-A with the International Prognostic Index (IPI) was found in DLBCL. High MVD and VEGF-A expression was observed in DLBCL patients with high IPI, while there was no statistically significant association between MVD and VEGF-A with the Follicular Lymphoma International Prognostic Index in low-grade FL. Our results suggested an important relationship between angiogenesis and high-grade lymphoma.

Primary cutaneous follicle center lymphoma simulating basal-cell carcinoma on the nasal ala

Primary cutaneous B-cell lymphomas (PCBCLs) constitute 25% of all primary cutaneous lymphomas. They present in the skin with no evidence of systemic or extracutaneous disease at the time of diagnosis, after adequate staging. Primary cutaneous B-cell lymphomas differ significantly from their nodal counterparts in relation to both clinical behavior and prognosis. The distinction between primary and secondary B-cell lymphomas is essential for defining prognosis/course of action. Such distinction is also very difficult to make, since primary and secondary B-cell lymphomas are clinically and histologically indistinguishable. We report the case of a patient with primary cutaneous follicle center lymphoma who underwent surgical excision.

Linfoma folicular primario intestinal no polipósico: reporte de un caso y revisión de la literatura / Primary non-polipoid intestinal folicular lymphoma: case report and review of the literature

El linfoma folicular primario intestinal es un desorden raro descrito en la última clasificación de linfomas de la WHO. Es una entidad localizada con excelente pronóstico. En el presente artículo, reportamos una mujer peruana de 64 años de edad diagnosticada con linfoma folicular primario intestinal. Ella tuvo dos años con dolor abdominal y vómitos tardíos. Ella desarrolló una obstrucción intestinal y tuvo una resección completa del tumor. Se describe el caso y se realiza una revisión de la literatura de esta entidad.

The primary intestinal follicular lymphoma is a rare disease described in the last classification of lymphomas from WHO. It is a localized disease with excellent prognosis. We describe in this article ,a 64 year-old Peruvian female with abdominal pain and delayed vomiting for the last two years, has undergone a partial intestinal resection due to bowel obstruction. There was a well-circumscribed annular tumor. A diagnosis of non-polypoid primary intestinal follicular lymphoma was made. We report the case and review the literature in this article.