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Introduction and objectives: The main objective of this article is to present and discuss a case of localized ulcerative nodular amyloidosis with deep involvement clinically manifesting as ulcerative panniculitis and discuss its impact on the choice of treatment. Methods and results: We present a 73-year-old woman with a history of painful ulcerated nodules on the inferior limbs. Microscopy confirmed amyloid deposits deep in the dermis and subcutaneous fat. No systemic involvement was found. Considering that skin-directed treatments often are not able to reach subcutaneous fat or were contraindicated because of the ulcers, she was successfully treated with cyclophosphamide and prednisone. Conclusion: Localized ulcerative nodular amyloidosis with deep involvement is a rare clinical presentation that can present as ulcerative panniculitis. Such a clinical manifestation might be misleading. Systemic treatment might be necessary to control symptoms when conventional skin-directed therapies are contraindicated.

Total liquid ventilation (TLV) using perfluorocarbons has shown promising results for the management of neonatal respiratory distress. However, one important safety consideration for TLV is a better understanding of the early events during the transition to TLV, especially regarding the fate of residual air in the non-dependent-lung regions. Our objective was to assess perflubron distribution during transition to TLV using electrical impedance tomography, complemented by fluoroscopy, in a neonatal lamb model of induced surfactant deficiency. Eight lambs were anesthetized and ventilated in supine position. Surfactant deficit was induced by saline lung lavage. After deflation, lungs were filled with 25 ml/kg perflubron over 18 s, and TLV was initiated. Electrical impedance tomography data was recorded from electrodes placed around the chest, during the first 10 and at 120 min of TLV. Lung perfusion was also assessed using hypertonic saline injection during apnea. In addition, fluoroscopic sequences were recorded during initial lung filling with perfluorocarbons, then at 10 and 60 min of TLV. Twelve lambs were used as controls for histological comparisons. Transition to TLV involved a short period of increased total lung volume (p = 0.01) secondary to recruitment of the dependent lung regions. Histological analysis shows that TLV was protective of these same regions when compared to gas-ventilated lambs (p = 0.03). The non-dependent lung regions filled with perflubron over at least 10 min, without showing signs of overdistention. Tidal volume distribution was more homogenous in TLV than during the preceding gas ventilation. Perflubron filling was associated with a non-significant increase in the anterior distribution of the blood perfusion signal, from 46 ± 17% to 53 ± 6% (p = 0.4). However, combined to the effects on ventilation, TLV had an instantaneous effect on ventilation-perfusion relationship (p = 0.03), suggesting better coupling. Conclusion: transition to TLV requires at least 10 min, and involves air evacuation or dissolution in perflubron, dependent lung recruitment and rapid ventilation-perfusion coupling modifications. During that time interval, the total lung volume transiently increases. Considering the potential deleterious effect of high lung volumes, one must manage this transition phase with care and, we suggest using a real-time monitoring system such as electrical impedance tomography.

Bronchial inflammation contributes to a sustained elevation of airway hyperresponsiveness (AHR) in asthma. Conversely, omega‐3 fatty acid derivatives have been shown to resolve inflammation in various tissues. Thus, the effects of docosapentaenoic acid monoacylglyceride (MAG‐DPA) were assessed on inflammatory markers and reactivity of human distal bronchi as well as in a cultured model of guinea pig tracheal rings. Human bronchi were dissected and cultured for 48 h with 10 ng/mL TNF‐α or IL‐13. Guinea pig tracheas were maintained in organ culture for 72 h which was previously shown to trigger spontaneous AHR. All tissues were treated with increasing concentrations of MAG‐DPA (0.1, 0.3, and 1 μmol/L). Pharmacomechanical reactivity, Ca2+ sensitivity, and western blot analysis for specific phosphoproteins and transcription factors were performed to assess the effects of both cytokines, alone or in combination with MAG‐DPA, on human and guinea pig airway preparations. Although 0.1 μmol/L MAG‐DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG‐DPA (0.3 and 1 μmol/L) blunted the activation of the TNF‐α/NF κB pathway and abolished COX‐2 expression in human and guinea pig tissues. Moreover, 0.3 and 1 μmol/L MAG‐DPA consistently decreased the Ca2+ sensitivity and pharmacological reactivity of cultured bronchial explants. Furthermore, in human bronchi, IL‐13‐stimulated phosphorylation of CPI‐17 was reversed by 1 μmol/L MAG‐DPA. This effect was further amplified in the presence of 100 μmol/L aspirin. MAG‐DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca2+ sensitivity and contractile reactivity.

T-acute lymphoblastic leukemia (T-ALL) represents 25 % of cases of acute lymphoblastic leukemia (ALL) in adults. The clinical presentation is dominated by a elevated number of white blood cells and in immunophenotype the lymphoblasts are generally Tdt positive and variably express CD1a, CD2, CD3, CD4, CD5, CD7, and CD8. NK/T non Hodgkin lymphoma is presented as a single lesion often ulcerated with torpid evolution affecting the nasal cavity, nasopharynx and/or palate. CD56 expression is while characteristic of NK-cells, and is also expressed on a subset of normal T cells. Its expression in ALL does not exclude the diagnosis and seems to be a prognostic factor of this disease. We report the case of a young woman with nasal cavity tumor which was initially diagnosed as T-cell lymphoma. This diagnosis was finally revised to conclude to T-ALL with CD56 aberrant expression.

Large granular lymphocyte (LGL) leukemia is a spectrum of rare lymphoproliferative disorders, classified into T-cell LGL leukemia, chronic lymphoproliferative disorder of NK-cells and aggressive NK-cell leukemia; chronic NK-cell leukemia is a provisional diagnosis. However, we identified fourteen cases of aggressive T-LGL leukemia retrieved in the literature. Considering this unusual and rare clinical presentation, we are reporting a literature review and presenting an additional case. Leukemic cells of T-LGL leukemia have a characteristic phenotype (CD3+CD8+CD16+CD57+) and show clonal TCR gene rearrangement, while leukemic cells of aggressive NK cell leukemia show a distinguishable phenotype (CD3-CD4-CD8-CD16+CD56+CD57-) and are EBV-related. In contrast with the aggressive NK cell leukemia, the chronic lymphoproliferative disorder of T-cell is not EBV-associated and has a distinguishable immunophenotype (CD16+CD56−CD57+). While T-LGL leukemia and chronic lymphoproliferative disorder of NK-cells have a more chronic disease (years), mainly reported with autoimmune disease (rheumatoid arthritis), numerous infections due to neutropenia and a mild-to-moderate splenomegaly, aggressive NK-cell leukemia is characterized by systemic manifestations and a disseminated disease after a few weeks of presentation despite treatment instauration. In contrast to the T-LGL leukemia, aggressive T-LGL leukemia has a clinical presentation similar to the aggressive NK-cell leukemia, characterized by constitutional symptoms, rapidly progressive hepatosplenomegaly, cytopenia and organ infiltration. The atypical clinical presentation and pathological findings of the aggressive T-LGL leukemia explain the diagnostic challenge of this entity for clinicians. In fact, cases of aggressive T- LGL leukemia retrieved atypical size, irregular nuclei and atypical immunophenotype. Some cases had features similar to those described for patients with NK-cell leukemia (CD56+CD57-) while others did not present neither NK nor T-cell classical immunophenotype (CD56-57-). Facing the heterogeneity of aggressive LGL leukemia, the rapidly evolutive disease (multi-organic infiltration) and the absence of randomized trials on large numbers of patients, no consensus on the treatment approach exists. (Table 1) Our patient presented, at the age of 24 yo, with transitory and autonomous resolution of hepatosplenomegaly and pancytopenia. Almost 30 years later, the patient developed a similar and persistent episode, which lead to a diagnosis of aggressive T-cell LGL leukemia. Was this first episode the early and indolent presentation of his T- LGL leukemia or was it only related to an indolent and transitory etiology? Considering the clinical evolution of previously reported case and of our patient, LGL leukemia tends to evolve in many ways; resolution, indolent and chronic or aggressive evolution and transformation into a lymphoma. As the cases retrieved in literature, the diagnosis of our patient was complicated by atypical clinical presentation and unusual pathological findings; massive medullary involvement without real images of intra-sinusal lymphocytosis and atypical T- LGL based on their small-medium size with slightly irregular nuclei and the lack of expression of CD56/CD57. Facing the heterogeneity of treatments attempted for aggressive T-LGL leukemia and their unpredictable response, we believe that the treatments given to our patient were consistent with the current literature and did not add an additional mortality risk (3 cycles of CHOP, 4 cycles of ESHAP, methotrexate, splenectomy). As reported in literature, even though our patient was treated with varying regimens, his disease rapidly evolved into a multi-organic infiltration (skin, lungs, liver, kidney, facial cranial nerves, conus medullaris and bone marrow involvement) Large granular lymphocyte (LGL) leukemia represent a spectrum of indolent and aggressive diseases, whereby an indolent form can evolve into an aggressive form. Aggressive T-cell LGL leukemia are characterized by a multisystem disease, an atypical immunophenotype (CD56-CD57- or CD56+CD57-) and are associated with an uncertainty regarding therapeutics.Our case report of an aggressive T-cell LGL leukemia adds to the few available studies on the subject. Disclosures Pavic: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Pulmonary hypertension (PH) is a rare disease in which pathophysiology is characterized by an increase in proinflammatory mediators, chronic endothelial dysfunctions, and a high migration rate of smooth muscle cells (SMC). Over the course of the last decade, various treatments have been proposed to relax the pulmonary arteries, none of which have been effective in resolving PH. Our hypothesis is that artery-relaxing drugs are not the long-term solution, but rather the inhibition of tissue inflammation, which underlies human pulmonary artery (HPA) dysfunctions that lead to abnormal vasoconstriction. The goal of the present study was to assess the anti-inflammatory effects of resolvin E1 (RvE1) with concomitant effects on SMC migration and on HPA reactivity. The role and mode of action of RvE1 and its precursor, monoacylglyceride eicosapentaenoic acid were assessed on HPA under proinflammatory conditions, involving a combined pretreatment with 10 ng/ml TNF-α and 10 ng/ml IL-6. Our results show that TNF-α and IL-6 treatment induced hyperreactivity and Ca2+ hypersensitivity in response to pharmaco-mechanical stimuli, including 80 mM KCl, 1 μM phorbol 12–13-dibutyrate, and 30 nM U-46619. Furthermore, the proinflammatory treatment increased the migration rate of SMC isolated from HPA. The phosphorylation level of regulatory contractile proteins (CPI-17, MYPT-1), and proinflammatory signaling pathways (c-Fos, c-Jun, NF-κB) were also significantly increased compared with control conditions. Conversely, 300 nM RvE1 was able to normalize all of the above abnormal events triggered by proinflammation. In conclusion, RvE1 can resolve human arterial hyperreactivity via the resolution of inflammatory markers.

Introduction Le lymphome intravasculaire est caracterise par la presence exclusive ou predominante de cellules lymphoides dans la lumiere des petits vaisseaux. Malgre qu’il y ait des cas de lymphome intravasculaire a cellules T rapportes, cette malignite est, selon la classification de l’Organisation mondiale de la sante (OMS) un sous-type des lymphomes diffus a grandes cellules B. Le lymphome intravasculaire est une maladie agressive, disseminee et habituellement fatale, touchant principalement les populations plus âgees. Sa presentation clinique varie selon la geographie. Le lymphome intravasculaire « classique », principalement rencontre en Europe, est rapporte avec des atteintes cutanees et/ou neurologiques ; lorsque l’atteinte est exclusivement cutanee, nous parlons de la « variante cutanee » du lymphome intravasculaire « classique ». Le lymphome intravasculaire a « variante asiatique », principalement rencontre en Asie, est majoritairement associe a un syndrome hemophagocytaire, un envahissement de la moelle osseuse, une fievre, une hepatosplenomegalie et/ou une thrombopenie. L’heterogeneite de la presentation clinique du lymphome intravasculaire entraine souvent un retard de diagnostic et de traitement. En l’absence d’etudes nord-americaines d’envergure, le lymphome intravasculaire a ete majoritairement etudie par des etudes retrospectives europeennes et asiatiques a nombre restreint de patients. Notre comprehension clinicopathologique et therapeutique de cette maladie est donc limitee. Patients et methodes Nous rapportons la plus grande etude retrospective nord-americaine sur le lymphome intravasculaire. Nous avons revise l’ensemble des cas de lymphome intravasculaire dans la grande majorite des centres hospitaliers de la province du Quebec, Canada de 1990 a 2015 (n = 21). L’objectif etait de dresser le portrait de la presentation clinique, de la prise en charge diagnostique et therapeutique et des issues cliniques de notre population et, ainsi, comparer le phenotype de nos cas a celui des etudes europeennes et asiatiques. Resultats Dans notre cohorte, le lymphome intravasculaire se presentait par une atteinte disseminee (100 % Ann Arbor stade IV), touchant les populations âgees (âge median 65,9 ans [51,5–90,8]). La presentation clinique etait caracterisee par des symptomes constitutionnels (100 %), un mauvais score ECOG-PS (100 % ≥ 2), des cytopenies (90 % anemie) et des elevations des lactates deshydrogenases (100 %), de la vitesse de sedimentation (90) et de la proteine C-reactive (95 %). Tel qu’observe dans la litterature europeenne, nos patients presentaient principalement des atteintes cutanees et neurologiques. Cependant, les atteintes neurologiques etaient predominantes dans notre cohorte (76 %) et aucun cas de « variante cutanee » pure n’a ete observe ; cela differe de la litterature europeenne, dans laquelle le lymphome intravasculaire « classique » est plus souvent rapporte avec des anomalies cutanees. Deux de nos patients (10 %) avaient un lymphome intravasculaire a « variante asiatique » ; cette constatation est rapportee dans la litterature, alors qu’on observe des cas « classiques » chez les Asiatiques et des cas a « variante asiatique » chez les Europeens. Tous les patients ont ete classifies en fonction de leurs caracteristiques immunophenotypiques en 3 sous-groupes (CD5+ ou CD5− CD10+, CD5− CD10– et CD5 + CD10–). La seule difference statistiquement significative etait la splenomegalie (p = 0,006), qui etait plus frequente dans le sous-groupe CD5 + CD10–que dans le sous-groupe CD5− CD10–. Finalement, 52 % des patients de notre cohorte ont recu une chimiotherapie a base d’anthracycline et 45 % des patients traites ont eu une reponse complete. Cinq patients ont eu un diagnostic post-mortem. La survie globale des patients pris en charge etait de 322 jours. Conclusion Contrairement aux etudes europeennes realisees sur la forme « classique » du lymphome intravasculaire, notre etude demontre que sa presentation canadienne est plus frequemment associee a une atteinte neurologique que cutanee. Puisque deux de nos patients caucasiens ont ete atteints d’un lymphome intravasculaire a « variante asiatique », nous croyons que la nomenclature devrait utiliser « lymphome intravasculaire classique » et « lymphome intravasculaire associe a un syndrome hemophagocytaire », plutot que de se baser sur les distinctions « lymphome intravasculaire europeen » et « lymphome intravasculaire a variante asiatique ». Le diagnostic reste difficile avec pres de 25 % de diagnostic autopsique.

Introduction:Intravascular large B-cell lymphoma (IVL) is an extremely rare malignancy, mainly studied through European and Asian series. Due to the low incidence of this condition, our understanding of the clinical presentation as well as the management of IVL relies on a limited number of

Nous rapportons le cas d'un patient marocain de 40 ans, suivi pour aplasie medullaire sous traitement immunosuppresseur et ayant presente 6 mois apres le debut du traitement une MK iatrogene. L'histologie cutanee a permis de poser le diagnostic et etait en faveur d'une MK. Le traitement consistait a des cures de Bleomycine avec une evolution favorable. Notre cas illustre l'interet d'un suivi regulier des patients sous immunosuppresseurs. Cette forme particuliere de MK constitue un vrai defi therapeutique pour le praticien.

Inflammation is a major burden in respiratory diseases, resulting in airway hyperresponsiveness. Our hypothesis is that resolution of inflammation may represent a long-term solution in preventing human bronchial dysfunctions. The aim of the present study was to assess the anti-inflammatory effects of RvD2, a member of the D-series resolving family, with concomitant effects on ASM mechanical reactivity. The role and mode of action of RvD2 were assessed in an in vitro model of human bronchi under pro-inflammatory conditions, induced either by 1 μM LTD4 or 10 ng/ml TNF-α pre-treatment for 48h. TNF-α and LTD4 both induced hyperreactivity in response to pharmacological stimuli. Enhanced 5-Lipoxygenase (5-LOX) and cysteinyl leukotriene receptor 1 (CysLTR1) detection was documented in LTD4 or TNF-α pre-treated human bronchi when compared to control (untreated) human bronchi. In contrast, RvD2 treatments reversed 5-LOX/β-actin and CysLTR1/β-actin ratios and decreased the phosphorylation levels of AP-1 subunits (c-Fos, c-Jun) and p38-MAP kinase, while increasing the detection of the ALX/FPR2 receptor. Moreover, various pharmacological agents revealed the blunting effects of RvD2 on LTD4 or TNF-α induced hyper-responsiveness. Combined treatment with 300 nM RvD2 and 1 μM WRW4 (an ALX/FPR2 receptor inhibitor) blunted the pro-resolving and broncho-modulatory effects of RvD2. The present data provide new evidence regarding the role of RvD2 in a human model of airway inflammation and hyperrresponsiveness.

Intravascular lymphoma (IVL) is characterized by exclusive or predominant presence of lymphoma cells in the lumina of small vessels. Even though T-cell phenotype has been reported, IVL has recently been classified by the World Health Organization (WHO) Classification as a subtype of diffuse large B-cell lymphoma (DLBCL). IVL is considered an aggressive, disseminated and usually fatal malignancy that affects older individuals. Its initial clinical presentation varies according to geography. "Classical" IVL, mainly reported in Europe, is characterized by cutaneous and/or neurological involvement. "Asian variant" IVL, mainly reported in Asia, is characterized by hemophagocytosis, bone marrow (BM) involvement, fever, hepatosplenomegaly and/or thrombocytopenia. This heterogeneous clinical presentation of IVL often causes a delay in diagnosis and treatment instauration. IVL has been mainly studied through European and Asian cases. However, the majority of these case series and cumulative reviews have been based on a restricted number of patients, limiting the clinicopathological understanding and treatment options of this disease. Given the lack of previous large North American studies, we decided to analyze a case series in our country (Canada, Québec) in order to compare our results with the European and Asian series. We report the largest North American study to date on IVL. We reviewed all IVL cases in all Quebec hospitals between 1990 and 2016 (n= 29). The aim of our study was to describe the clinical presentations, investigations, therapeutic management and clinical outcomes of IVL patients in our population and compare the disease phenotype to European and Asian cases. In our cohort, 100% of patients had stage IV IVL at diagnosis, with a median age of 66.7 years (range 47.2-90.8). Clinical presentation was characterized by constitutional symptoms (100%), poor ECOG-PS (100% ≥ 2), cytopenias (93% anemia) and elevated lactate dehydrogenase (97%) and C-reactive protein (96%). Our cohort presented with mainly cutaneous and neurological symptoms. However, neurological involvement (75.9%) was predominant and no "cutaneous variant" was observed; this differs from European literature, where "classical" IVL is reported with mainly cutaneous involvement. Two of our Caucasian patients presented "Asian variant" IVL; this observation is not unusual, as cases of "classical" IVL have been reported in Asians and "Asian variant" IVL has been reported in Europeans. All patients were classified according to their immunophenotypic features in 3 different subgroups (CD5+ or CD5-CD10+, CD5-CD10-, CD5+CD10-). According to the literature, no significant difference between these subgroups was found. Finally, 62% of our cohort received anthracycline-based chemotherapy, and within this group, 53% and 20% of patients achieved a complete and partial response, respectively. Overall survival at 3 years was 42.7% and 47.4% for the entire cohort and for the cases with in vivo diagnosis, respectively. Event-free survival at 3 years was 64.2%. Median follow-up of our cohort was 328 days (CI 181-474). Unlike European studies on "classical" IVL, our study showed that the Canadian presentation of this subtype of IVL is more frequently observed with neurological rather than cutaneous involvement. Based on the fact that two of our Caucasian patients presented "Asian variant" IVL, we suggest that the IVL nomenclature should use "classical" IVL and "IVL associated with haemophagocytic syndrome", instead of "European" IVL and "Asian variant" IVL. Disclosures Fleury: Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Lundbeck: Consultancy, Speakers Bureau.

Nous rapportons le cas d'un patient marocain de 40 ans, suivi pour aplasie médullaire sous traitement immunosuppresseur et ayant présenté 6 mois après le début du traitement une MK iatrogène. L'histologie cutanée a permis de poser le diagnostic et était en faveur d'une MK. Le traitement consistait à des cures de Bléomycine avec une évolution favorable. Notre cas illustre l'intérêt d'un suivi régulier des patients sous immunosuppresseurs. Cette forme particulière de MK constitue un vrai défi thérapeutique pour le praticien.