Lymph node excisions provide more precise lymphoma diagnoses than core biopsies: a French Lymphopath network survey.

According to expert guidelines, lymph node surgical excision is the standard of care for lymphoma diagnosis. However, core needle biopsy (CNB) has become widely accepted as part of the lymphoma diagnostic workup over the past decades. The aim of this study was to present the largest multicenter inventory of lymph nodes sampled either by CNB or surgical excision in patients with suspected lymphoma and to compare their diagnostic performance in routine pathologic practice. We reviewed 32 285 cases registered in the French Lymphopath network, which provides a systematic expert review of all lymphoma diagnoses in France, and evaluated the percentage of CNB and surgical excision cases accurately diagnosed according to the World Health Organization classification. Although CNB provided a definitive diagnosis in 92.3% and seemed to be a reliable method of investigation for most patients with suspected lymphoma, it remained less conclusive than surgical excision, which provided a definitive diagnosis in 98.1%. Discordance rates between referral and expert diagnoses were higher on CNB (23.1%) than on surgical excision (21.2%; P = .004), and referral pathologists provided more cases with unclassified lymphoma or equivocal lesion through CNB. In such cases, expert review improved the diagnostic workup by classifying ∼90% of cases, with higher efficacy on surgical excision (93.3%) than CNB (81.4%; P < 10-6). Moreover, diagnostic concordance for reactive lesions was higher on surgical excision than CNB (P = .009). Overall, although CNB accurately diagnoses lymphoma in most instances, it increases the risk of erroneous or nondefinitive conclusions. This large-scale survey also emphasizes the need for systematic expert review in cases of lymphoma suspicion, especially in those sampled by using CNB.

Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Key performance indicators in Tour de France sailing.

This study aimed to determine the key performance indicators of inshore sailing during the sailing Tour de France. Technical and physical parameters were investigated to determine the discriminating factors between successful and less successful international level sailors. Measurements from 21 sailors (mean ± SD; age = 23.81 ± 4.18 years) were conducted prior to the sailing Tour de France. Global Positioning System data of all participating teams (n = 23) was analysed. Sailors were divided into two groups (i.e. successful and less successful) according to qualifying performance percentage. The differences between successful and less successful sailors were explored by means of independent t-tests. Results indicate that successful boats displayed higher maximal speed, higher average speed and more efficient starting performance per race than less successful boats. Successful sailors have stronger handgrip strength, higher isometric maximal voluntary force relative to bodyweight (isometric mid-thigh pull) and more powerful submaximal pulling (bench pull) actions than their less successful counterparts. The results of this study suggest that multiple sailing, physical and physiological variables are related to sailing performance in inshore sailing. Therefore, we emphasize the importance of integrating specific testing protocols to evaluate the performance potential of inshore sailors participating in the sailing Tour de France.

[Thymoma and squamous thymic carcinoma diagnosis; experience from the RYTHMIC network]. / Diagnostic des thymomes et carcinomes thymiques malpighiens ; expérience du réseau RYTHMIC.

The RYTHMIC network, supported by the French National Cancer Institute is dedicated to the management of patients with thymic epithelial tumors through regional and national multidisciplinary tumor boards. Tumor board decisions are based on the initial pathology diagnoses. However, following clinical inclusion in the network, a central pathology review is organized, implicating a panel of pathologists, for histotype and stage classification, which is different from a classical second opinion from pathologist to pathologist for a difficult case. Thanks to the participation of all French pathologists, more than 1000 cases have been reviewed by the panel. The aim of this review is to share with the French pathology community, the experience of the group. It underlines the importance of macroscopy and surgeon-pathologist involvement to allow a good central review, the main histopathological and immunophenotypical patterns of the most frequent thymomas and thymic carcinoma types, the differential diagnoses, as well as the difficulties for the panel to reproducibly assess on slides, stage, for some cases.

Cutaneous Involvement in Waldenström's Macroglobulinaemia.

Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the follow-up of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation).

Influence of Weekly Workload on Physical, Biochemical and Psychological Characteristics in Professional Rugby Union Players Over a Competitive Season.

Dubois, R, Lyons, M, Paillard, T, Maurelli, O, and Prioux, J. Influence of weekly workload on physical, biochemical and psychological characteristics in professional rugby union players over a competitive season. J Strength Cond Res 34(2): 527-545, 2020-This study aimed to (a) quantify the physical workload (P-WL) during training and games throughout the professional rugby season and (b) analyze the influence of the season period and weekly-WL, at short (acute) and moderate (chronic) terms, on physical, biochemical, and psychological responses during the season. Physiological (physical and biochemical) responses to P-WL were analyzed by examining changes in the individual Z score of the Yo-Yo intermittent recovery test (YYIRT), submaximal aerobic tests (5'/5'-test), strength tests, countermovement jump tests, blood sampling, and "recovery-stress" scores (RESTq) in 14 professional players (26.9 ± 1.9 years). Changes throughout the season were analyzed using a linear mixed model to identify changes in P-WL, whereas repeated-measures analysis of variance was used to analyze changes in physiological responses across the season. The relationship between P-WL and physiological responses was analyzed using Pearson's correlation coefficient (r). The results showed that the preseason period comprised the highest level of P-WL compared with all other blocks across the season (p < 0.001). The acute P-WL, acute competitive-WL, and number of impacts seemed to be the WL parameters, which most influenced the physiological responses (changes in testosterone [T], cortisol [C], T/C ratio, IGF-1/C ratio, strength, and RESTq index). The chronic P-WL, particularly conditioning-WL, induced positive changes in fitness characteristics (YYIRT and 5'/5'-test). Finally, this study provides information to players and coaches alike as to the influence of P-WL on as well as adaptations in physiological and psychological indices throughout a playing season. This information can greatly inform the training and preparation of future players in different levels.

Effects of Precompetitive Preparation Period on the Isokinetic Muscular Characteristics in World Class Handball Players.

Maurelli, O, Bernard, PL, Dubois, R, Ahmaidi, S, and Prioux, J. Effects of precompetitive preparation period on the isokinetic muscular characteristics in world class handball players. J Strength Cond Res 33(4): 1065-1074, 2019-The aim of this study was to describe the effects of 8 weeks of precompetitive preparation period (Pc2P) on the isokinetic muscular characteristics in world-class handball players. Nineteen male professional players (age, 26.6 ± 5.4 years) participated in the study. Two bilateral isokinetic tests of knee joint flexors (H; hamstring) and extensors (Q; quadriceps) were performed before and after Pc2P to determine the peak torque (PT), the mean power (MP), and the ratios (agonist-antagonist, dominant-nondominant, and combined). For the PT, Q at low angular velocity (60°·s) in concentric mode revealed no significant increase for the dominant or nondominant legs. For H, results showed a significant increase for both legs (p < 0.001). At the higher angular velocity (240°·s), Q was significantly increased for the dominant (p < 0.005) and nondominant (p < 0.002) legs and also H for both sides (p < 0.001). Eccentric mode (30°·s) showed a significant increase for dominant (p < 0.005) and nondominant (p < 0.01) legs. For MP, results showed significant increase at low angular velocity (p < 0.003) and high angular velocity (p < 0.01) for both legs. In eccentric mode, values showed a significant increase after Pc2P for dominant (p < 0.001) and nondominant (p < 0.02) legs. The ratios showed significant increase for the agonist-antagonist ratio at 60°·s for dominant leg (p < 0.003) and the nondominant leg (p < 0.01). At 240°·s, the values showed a significant difference for both side (p < 0.02). From an injury risk perspective, in addition to optimizing performance, these results demonstrated that 8 weeks of Pc2P increased the maximum strength and muscle power of international handball players, even if the ratios of the knee joint muscles did not change during this period.

Effects of the Competitive Season on the Isokinetic Muscle Parameters Changes in World-Class Handball Players.

Maurelli, O, Bernard, PL, Dubois, R, Ahmaidi, S, and Prioux, J. Effects of the competitive season on the isokinetic muscle parameters changes in world-class handball players. J Strength Cond Res 33(10): 2778-2787, 2019-The aim of this study is to investigate the effects of the competitive season on isokinetic muscular parameters of the lower limbs in world-class handball players. Nineteen, male, world-class, handball players (age, 26.6 ± 5.4 years) participated in the study. Two bilateral isokinetic tests of knee joint flexors (H; hamstring) and extensors (Q; quadriceps) were performed in the beginning and end of the competitive season to determine the peak torque (PT), the mean power, and agonist-antagonist ratio, dominant-nondominant ratio (DNDR), and combined ratio. The results showed a significant decrease in PT values at low angular velocity (60°·s) in concentric mode for Q on dominant leg (p < 0.001). The other PT values for dominant and nondominant legs at low and high angular velocities (240°·s) and in eccentric mode (30°·s) were not significantly different for Q and H. For mean power, values did not change at 60°·s. At 240°·s, we found a significant decrease in H for dominant leg (p < 0.001) but not for nondominant leg. In eccentric mode, the results showed a significant increase on both legs (p < 0.001). For the ratios, values significantly decreased for DNDR at 60°·s for Q (p < 0.03) and for agonist/antagonist ratio at 240°·s for the dominant leg (p < 0.01). The present results highlight the importance of integrating regular strength training sessions during the competitive season in world-class handball players. Accordingly, this study should help trainers to modify their planning to maximize strength and power qualities of the lower limbs of their players in addition to avoiding injuries.

[Pervasive refusal syndrome: study of a clinical case]. / Syndrome de refus global : étude d'un cas clinique.

The clinical presentation of pervasive refusal syndrome is marked by a refusal to eat, walk, talk, firm resistance and an aggressive refusal to accept help and care. The management of patients with this syndrome is physically and emotionally draining for caregivers. The quality of the relationship can be quickly affected as it is so unusual and singular. Training, communication and support from the team are essential to be able to continue to provide compassionate care.

A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.

JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in patients with relapsed/refractory Hodgkin lymphoma. The primary objective was overall response rate according to the International Harmonization Project 2007 criteria. Thirty-three patients with advanced disease (median number of prior lines of treatment: 5; refractory: 82%) were included; nine (27.3%) received at least six cycles of ruxolitinib and six (18.2%) received more than six cycles. The overall response rate after six cycles was 9.4% (3/32 patients). All three responders had partial responses; another 11 patients had transient stable disease. Best overall response rate was 18.8% (6/32 patients). Rapid alleviation of B-symptoms was common. The median duration of response was 7.7 months, median progression-free survival 3.5 months (95% CI: 1.9-4.6), and the median overall survival 27.1 months (95% CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%). One event led to treatment discontinuation, while 87.5% of patients recovered without sequelae. Twenty-five adverse events were grade 3 or higher. These events were mostly anemia (n=11), all considered related to ruxolitinib. Other main causes of grade 3 or higher adverse events included lymphopenia and infections. Of note, no cases of grade 4 neutropenia or thrombocytopenia were observed. Ruxolitinib shows signs of activity, albeit short-lived, beyond a simple anti-inflammatory effect. Its limited toxicity suggests that it has the potential to be combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005.

Running and Metabolic Demands of Elite Rugby Union Assessed Using Traditional, Metabolic Power, and Heart Rate Monitoring Methods.

The aims of this study were (1) to analyze elite rugby union game demands using 3 different approaches: traditional, metabolic and heart rate-based methods (2) to explore the relationship between these methods and (3) to explore positional differences between the backs and forwards players. Time motion analysis and game demands of fourteen professional players (24.1 ± 3.4 y), over 5 European challenge cup games, were analyzed. Thresholds of 14.4 km·h-1, 20 W.kg-1 and 85% of maximal heart rate (HRmax) were set for high-intensity efforts across the three methods. The mean % of HRmax was 80.6 ± 4.3 % while 42.2 ± 16.5% of game time was spent above 85% of HRmax with no significant differences between the forwards and the backs. Our findings also show that the backs cover greater distances at high-speed than forwards (% difference: +35.2 ± 6.6%; p<0.01) while the forwards cover more distance than the backs (+26.8 ± 5.7%; p<0.05) in moderate-speed zone (10-14.4 km·h-1). However, no significant difference in high-metabolic power distance was found between the backs and forwards. Indeed, the high-metabolic power distances were greater than high-speed running distances of 24.8 ± 17.1% for the backs, and 53.4 ± 16.0% for the forwards with a significant difference (+29.6 ± 6.0% for the forwards; p<0.001) between the two groups. Nevertheless, nearly perfect correlations were found between the total distance assessed using the traditional approach and the metabolic power approach (r = 0.98). Furthermore, there is a strong association (r = 0.93) between the high-speed running distance (assessed using the traditional approach) and the high-metabolic power distance. The HR monitoring methods demonstrate clearly the high physiological demands of professional rugby games. The traditional and the metabolic-power approaches shows a close correlation concerning their relative values, nevertheless the difference in absolute values especially for the high-intensity thresholds demonstrates that the metabolic power approach may represent an interesting alternative to the traditional approaches used in evaluating the high-intensity running efforts required in rugby union games.

A Vision Transformer-Based Framework for Knowledge Transfer From Multi-Modal to Mono-Modal Lymphoma Subtyping Models.

Determining lymphoma subtypes is a crucial step for better patient treatment targeting to potentially increase their survival chances. In this context, the existing gold standard diagnosis method, which relies on gene expression technology, is highly expensive and time-consuming, making it less accessibility. Although alternative diagnosis methods based on IHC (immunohistochemistry) technologies exist (recommended by the WHO), they still suffer from similar limitations and are less accurate. Whole Slide Image (WSI) analysis using deep learning models has shown promising potential for cancer diagnosis, that could offer cost-effective and faster alternatives to existing methods. In this work, we propose a vision transformer-based framework for distinguishing DLBCL (Diffuse Large B-Cell Lymphoma) cancer subtypes from high-resolution WSIs. To this end, we introduce a multi-modal architecture to train a classifier model from various WSI modalities. We then leverage this model through a knowledge distillation process to efficiently guide the learning of a mono-modal classifier. Our experimental study conducted on a lymphoma dataset of 157 patients shows the promising performance of our mono-modal classification model, outperforming six recent state-of-the-art methods. In addition, the power-law curve, estimated on our experimental data, suggests that with more training data from a reasonable number of additional patients, our model could achieve competitive diagnosis accuracy with IHC technologies. Furthermore, the efficiency of our framework is confirmed through an additional experimental study on an external breast cancer dataset (BCI dataset).

Micronodular thymic epithelial tumors with lymphoid hyperplasia and mimicking lesions.

Micronodular arrangement of epithelial cells and lymphoid B-cell hyperplasia with follicles are both peculiar histological features in thymic tissue. Such features may especially occur in thymic epithelial tumors. The most common form is called micronodular thymoma with lymphoid stroma. We have recently described some characteristics of thymic micronodular carcinoma with lymphoid hyperplasia, highlighting how this carcinomatous counterpart should not be misdiagnosed as a thymoma. In this review, we discuss these two entities but also other mimics, which may occur in the anterior mediastinum. These mimics include various types of cellular micronodules and lymphoid backgrounds encompassing a wide range of mediastinal lesions. Non-neoplastic lesions, such as thymic nodular epithelial hyperplasia, thymic lymphoid hyperplasia, or sarcoidosis, as well as tumors of very varying aggressiveness, such as micronodular thymic epithelial tumors, low-grade lymphoma, seminoma, or lymphoepithelial carcinoma, are discussed. We show how these lesions may be misleading and we describe how a correct diagnostic may be obtained in current practice.

Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression.

ABSTRACT: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.