Extranodal classical Hodgkin lymphoma involving the spinal cord: case report and review of the literature.

Primary CNS involvement is very rare in Hodgkin lymphoma. Here we present two cases of spinal cord dissemination. Two women of 40 and 65 years of age presented symptoms of spinal cord injury; imaging showed an intramedullary mass in T10 and T2, respectively, without vertebral involvement and upper diaphragmatic lymph nodes. Lymph-node biopsy confirmed the diagnosis of classical Hodgkin lymphoma in both patients. The first patient received four cycles of chemotherapy (escalated BEACOPP and ABVD) with intrathecal therapy, and the second four cycles of doxorubicin, vinblastine, dacarbazine (AVD) and local irradiation after surgery decompression. Complete metabolic response was obtained at the end of treatment. After 5 and 7 years of follow-up respectively, neurological deficits persisted in both.

Lymph-node infiltration is the most common presentation in Hodgkin lymphoma at diagnosis. Primary extranodal involvement is rare and spinal cord infiltration exceptional. Back pain, tingling and vesico-sphincter dysfunctions are the main symptoms. 18F-fluorodeoxyglucose (FDG) PET and MRI can detect the location and extension of neurological involvement. We present here two cases of tumoral myelitis and a review of the literature. Local treatment (surgery/radiotherapy) is often administered together with chemotherapy to optimize local control and to avoid long-term sequelae.

Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21).

Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (BCL2/IGH), mutated IGHV, deletion 17p, and mutations in BCL2, NOTCH1 (subclonal), and TP53 (subclonal). Quite strikingly, a novel PAX5 mutation that was predicted to be loss of function was also seen. Exome sequencing identified, in addition, a potentially actionable BRAF mutation, together with novel somatic mutations affecting the homeobox transcription factor NKX2-3, known to control B-lymphocyte development and homing, and the epigenetic regulator LRIF1, which is implicated in chromatin compaction and gene silencing. Neither NKX2-3 nor LRIF1 mutations, predicted to be loss of function, have previously been reported in B-CLL. Sequencing confirmed the presence of these mutations together with BCL2, NOTCH1, and BRAF mutations, with the t(14;18)(q32;q21) translocation, in the initial diagnostic sample obtained 12 yr prior. This is suggestive of a role for these novel mutations in B-CLL initiation and stable clonal evolution, including upon treatment withdrawal. This case extends the spectrum of atypical B-CLL with t(14;18)(q32;q21) and highlights the value of more global precision genomics for patient follow-up and treatment in these patients.

First-line treatment of double-hit and triple-hit lymphomas: Survival and tolerance data from a retrospective multicenter French study.

Historically, double or triple hit lymphoma (DHL and THL) have poor outcomes with conventional chemotherapy, but there is currently no guideline. We report the French experience in managing DHL and THL in first line using collective data on both survival and tolerance. All consecutive patients with newly diagnosis of large B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements, as determined by FISH between January 2013 and April 2019 were included. Based on the eligibility criteria, 160 patients were selected among the 184 patients identified. With a median follow-up of 32 months, 2- and 4-year progression free survival (PFS) rates were 40% and 28% with R-CHOP compared with 57% and 52% with intensive chemotherapy (P = .063). There was no difference in overall survival (OS). For advanced stages, PFS was significantly longer with intensive chemotherapy than with R-CHOP (P = .029). There was no impact of autologous stem cell transplantation among patient in remission. For patients with central nervous system (CNS) involvement, the 2-year PFS and OS rate was 21% and 39%, vs 57% and 75% without CNS disease (P = .007 and P < .001). By multivariate analysis, elevated IPI score and CNS disease were strongly and independently associated with a poorer survival, whereas treatment was not significantly associated with OS. This is the largest series reporting the treatment of DHL and THL in Europe. The PFS was significantly longer with an intensive regimen for advanced stage, but no difference in OS, supporting the need for a prospective randomized trial.

First Case of Human Primary Vertebral Cystic Echinococcosis Due to Echinococcus Ortleppi.

Cystic echinococcosis (CE) is a cosmopolitan parasitic zoonosis affecting more than one million people worldwide. In humans, primary bone CE is rare and involvement of E. ortleppi is very uncommon. We report here the first case of primary vertebral cystic echinococcosis due to E. ortleppi in Burgundy, France.

Venous thromboembolic events during warm autoimmune hemolytic anemia.

Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ≥ 40 µmol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x10(9)/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined.