Bing–Neel syndrome presenting with bilateral lumbar radiculopathy: A case report of a rare clinical entity / Síndrome de Bing-Neel que se presenta con radiculopatía lumbar bilateral: reporte de caso de una entidad clínica rara

The differential diagnosis of bilateral lower extremity weakness is broad. We present a very rare case of a 48-year old male patient, with walking difficulties due to Bing–Neel syndrome. On clinical examination, there was a significant loss of muscle power in all his lower extremities key-muscle groups. The lumbar spine magnetic resonance imaging (MRI) showed only mild degenerative changes, whereas the MRI of the head indicated a diffuse meningeal thickening at the right temporal region, characterized by significant enhancement after contrast administration. Serum protein electrophoresis detected an IgM-kappa monoclonal protein. The patient received intrathecal chemotherapy with methotrexate and cytarabine, and was started on oral ibrutinib 420mg daily. In conclusion, a past medical history of Waldenstrom macroglobulinemia in conjunction with neurological manifestations should alert the treating physician for Bing–Neel syndrome. A complete diagnostic imaging and serologic protocol helps in setting the final diagnosis. Steroids are part of the treatment, but should be given after the diagnosis is set. Neurosurgical intervention is indicated for histologic confirmation in the case of diagnostic uncertainty (AU)

El diagnóstico diferencial de la debilidad bilateral de las extremidades inferiores es amplio. Presentamos un caso muy raro de un paciente masculino de 48 años, con dificultad para caminar debido al síndrome de Bing-Neel. El examen clínico reveló una pérdida significativa de fuerza muscular en todos los grupos de músculos clave de sus extremidades inferiores. La resonancia magnética de la columna lumbar reveló solamente cambios degenerativos leves. Sin embargo, la resonancia magnética de cerebro detectó engrosamiento meníngeo difuso en la región temporal derecha caracterizado por realce significativo tras la administración del contraste. La electroforesis de proteínas en suero detectó una proteína monoclonal IgM-Kappa. Inicialmente, el paciente recibió dexametasona y su situación neurológica mejoró excepcionalmente. Además, se le administró quimioterapia intratecal con metotrexato y citarabina y empezó a tomar ibrutinib oral 420mg a diario. En conclusión, un historial médico anterior de macroglobulinemia de Waldenström junto con manifestaciones neurológicas debe alertar al médico tratante sobre síndrome de Bing-Neel. Un protocolo completo de diagnóstico por imágenes y serológico ayuda a establecer el diagnóstico final. Los esteroides son parte del tratamiento, pero deben administrarse después de establecer el diagnóstico. La intervención neuroquirúrgica está indicada para confirmación histológica en caso de incertidumbre diagnóstica (AU)

Bing-Neel syndrome presenting with bilateral lumbar radiculopathy: A case report of a rare clinical entity.

The differential diagnosis of bilateral lower extremity weakness is broad. We present a very rare case of a 48-year old male patient, with walking difficulties due to Bing-Neel syndrome. On clinical examination, there was a significant loss of muscle power in all his lower extremities key-muscle groups. The lumbar spine magnetic resonance imaging (MRI) showed only mild degenerative changes, whereas the MRI of the head indicated a diffuse meningeal thickening at the right temporal region, characterized by significant enhancement after contrast administration. Serum protein electrophoresis detected an IgM-kappa monoclonal protein. The patient received intrathecal chemotherapy with methotrexate and cytarabine, and was started on oral ibrutinib 420mg daily. In conclusion, a past medical history of Waldenstrom macroglobulinemia in conjunction with neurological manifestations should alert the treating physician for Bing-Neel syndrome. A complete diagnostic imaging and serologic protocol helps in setting the final diagnosis. Steroids are part of the treatment, but should be given after the diagnosis is set. Neurosurgical intervention is indicated for histologic confirmation in the case of diagnostic uncertainty.

Real-life Experience With Rituximab-CHOP Every 21 or 14 Days in Primary Mediastinal Large B-cell Lymphoma.

BACKGROUND/AIM: Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL), whose prognosis has greatly improved since the incorporation of the anti-CD20 monoclonal antibody rituximab into current therapeutic regimens. Evidence, however, on the optimal time interval between consecutive chemoimmunotherapy (CIT) cycles is still scarce. This study aimed to evaluate the efficacy outcomes of the more commonly administered 3-weekly regimens to the biweekly ones in a PMLBCL patients' population, who were mostly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP-21) or R-CHOP-14. PATIENTS AND METHODS: We retrospectively studied our cohort of consecutively treated PMLBCL patients, focusing on their treatment density, in order to determine possible differences in treatment outcomes. RESULTS: CIT, in the form of both R-CHOP-21 as well as R-CHOP-14 (or similar regimens), is highly active in PMLBCL, with low rates of early treatment failure. In our cohort of patients, R-CHOP-14 did not result in a meaningful improvement of freedom from progression (FFP) or overall survival (OS). CONCLUSION: Both R-CHOP-14 and R-CHOP-21 are probably equally effective in PMLBCL, yet further, prospective, randomized studies are warranted to clarify whether dose-dense regimens can be associated with better disease control and long-term results.

Bing-Neel syndrome presenting with bilateral lumbar radiculopathy: A case report of a rare clinical entity.

The differential diagnosis of bilateral lower extremity weakness is broad. We present a very rare case of a 48-year old male patient, with walking difficulties due to Bing-Neel syndrome. On clinical examination, there was a significant loss of muscle power in all his lower extremities key-muscle groups. The lumbar spine magnetic resonance imaging (MRI) showed only mild degenerative changes, whereas the MRI of the head indicated a diffuse meningeal thickening at the right temporal region, characterized by significant enhancement after contrast administration. Serum protein electrophoresis detected an IgM-kappa monoclonal protein. The patient received intrathecal chemotherapy with methotrexate and cytarabine, and was started on oral ibrutinib 420mg daily. In conclusion, a past medical history of Waldenstrom macroglobulinemia in conjunction with neurological manifestations should alert the treating physician for Bing-Neel syndrome. A complete diagnostic imaging and serologic protocol helps in setting the final diagnosis. Steroids are part of the treatment, but should be given after the diagnosis is set. Neurosurgical intervention is indicated for histologic confirmation in the case of diagnostic uncertainty.

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP.

BACKGROUND: R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. MATERIALS AND METHODS: We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients ≤65 years treated with R-CHOP ± radiotherapy in a multicenter setting in Greece and Cyprus. RESULTS: With a median follow-up of 69 months, 5-year freedom from progression (FFP) was 78% and 5-year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) ≥2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%-27% of patients [pts]) with approximately 19%-23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. CONCLUSION: The combination of E/IV with either bulky disease or LDH ≥2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. IMPLICATIONS FOR PRACTICE: By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R-CHOP and do not need more intensive regimens such as R-da-EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age-adjusted IPI).

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner.

BAFF, APRIL and their receptors regulate the survival, maturation and homeostasis of mature B-cells. Despite the lack of a functional role of BAFF/APRIL system during normal early B-cell development, previous studies indicated a contribution of these molecules in the pathogenesis of B-lineage acute lymphoblastic leukemia (B-ALL). Here, we evaluated the expression of this system in B-ALL and its involvement in spontaneous and drug-induced apoptosis of B-lymphoblasts, taking into consideration the distinct disease subtypes. We found that BAFFR is the most predominant aberrantly expressed receptor in B-ALL and that its expression, along with BCMA and APRIL, positively correlates with the maturation stage of B-lymphoblasts. Moreover, the binding of the E2A-PBX1 chimeric protein to the BAFFR promoter suggests that the transcriptional activator promotes the increase in BAFFR expression observed in about 50% of pre-B-ALL patients carrying the t (1, 19) translocation. BAFF binding to BAFFR led to the processing of NF-κB2 p100 in pre-B ALL cells suggesting that BAFFR can activate the NF-κB2 pathway in pre-B ALL cells. Surprisingly, we found that BAFF treatment promotes the cell death of primary BCR-ABL+ BAFFR+ pre-B-lymphoblasts in adult B-ALL. It also enhances glucocorticoid-induced apoptosis in the E2A-PBX1+ pre-B-ALL cell line 697. These data suggest that BAFF/BAFFR signaling in B-ALL cells differs from normal B cells and that it may affect the pathogenesis of the disease.

Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma. The Hellenic experience.

This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety-five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty-seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease. The median number of prior treatments was 4 and 44% of the patients were refractory to their most recent therapy. The median number of BV cycles was 8 (range, 2-16), and the median time to best response was the fourth cycle. Fifty-seven patients achieved an objective response: twenty-two (23%), a complete response (CR), and 35 patients (37%), a partial, for an overall response rate of 60%. Twelve patients (13%) had stable disease, and the remaining twenty-six (27%) had progressive disease as their best response. At a median follow-up of 11.5 months, median progression-free survival and overall survival were 8 and 26.5 months, respectively. Multivariate analysis showed that chemosensitivity to treatment administered before BV was associated with a significantly increased probability of achieving response to BV (P = .005). Bulky disease (P = .01) and response to BV (P <.001) were significant for progression-free survival, while refractoriness to most recent treatment (P = .04), bulky disease (P = .005), and B-symptoms (P = .001) were unfavorable factors for overall survival. Among the 22 CRs, 5 remain in CR with no further treatment after BV at a median follow-up of 13 months. In conclusion, our data indicate that BV is an effective treatment for R/R HL patients even outside clinical trials. Whether BV can cure a fraction of patients remains to be seen.

TACI expression and signaling in chronic lymphocytic leukemia.

TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL), including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches.

A primary hepatic lymphoma treated with liver resection and chemotherapy.

Primary hepatic lymphoma (PHL) is a rare malignancy, which is frequently misdiagnosed. Although chemotherapy is the treatment of choice there are reports that a combination of surgery and adjuvant chemotherapy can offer better results. Herein we present an interesting case of a large primary non-Hodgkin lymphoma originating from liver was treated with a liver which resection and chemotherapy.

Metabolism-related cytokine and hormone levels in the serum of patients with myelodysplastic syndromes.

BACKGROUND: A number of cytokines secreted from the bone marrow stromal cells and circulating hormones related to bone, adipose tissue and glucose metabolism might be involved in the pathogenesis of myelodysplastic syndromes (MDS). METHODS: Serum levels of cytokines related to the metabolism of bone tissue [osteocalcin and parathyroid hormone (PTH)], adipose tissue (adiponectin, leptin and ghrelin) and glucose [insulin and insulin-like growth factor-1 (IGF-1)] were determined in 72 patients suffering from MDS, mostly of the low-risk group according to FAB classification, and 41 healthy individuals (controls). RESULTS: Adiponectin and osteocalcin serum levels were significantly elevated in the MDS patients. Leptin, insulin and IGF-1 serum levels were reduced. No difference was found in the serum levels of PTH and ghrelin. Leptin levels were reversibly associated with patient blast count. CONCLUSION: Increased serum levels of adiponectin and low levels of IGF-1 in MDS patients may counterbalance the increased rate of apoptosis in the pool of hematopoietic progenitors. Osteocalcin secreted by osteoblasts regulates the renewal and proliferation of hematopoietic stem cells. Hormones and cytokines either secreted by the cells of the bone marrow stroma or transferred by the microcirculation act on hematopoietic progenitors and may regulate their differentiation, apoptosis and proliferation rate in MDS.