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The aim of this paper is to present a unique, to the best of our knowledge, case of a patient with a fracture of the first lumbar vertebra (L1), which occurred through a pre-existing Schmorl's node (SN), with histopathological characteristics mimicking a low-grade chondrosarcoma that initially led to a false diagnosis. A 54-year-old woman tripped and fell to the ground, sustaining a fracture of the L1 vertebral body. She was treated conservatively with gradual mobilization using a thoracolumbar brace for six weeks. Due to persistent pain and her inability to achieve full mobilization, she was offered vertebral kyphoplasty. During the same operative session and just before the kyphoplasty, she underwent a core-needle biopsy of the affected area. Following her operation, she reported a gradual, yet quick and full remission of her symptoms. The pathology report indicated findings consistent with a low to mid-grade chondrosarcoma. A re-evaluation of the specimen by a different pathologist confirmed the diagnosis of low-grade chondrosarcoma. Subsequently, she underwent full oncological staging, which was negative for metastases. Additional imaging studies failed to show signs of local disease progression. Due to the discordance between the pathology reports and the imaging and clinical findings, her case was referred to our specialized center for spinal tumor surgery. A new pathological re-evaluation of the biopsy samples was performed, and the diagnosis of low-grade chondrosarcoma was once again confirmed. However, during the multidisciplinary tumor (MDT) meeting that followed, and after careful evaluation of subsequent imaging studies that showed signs of local improvement and due to the complete lack of symptoms, the histopathological findings were re-evaluated and attributed to the fracture occurring through a pre-existing SN penetrating the cancellous bone of the vertebra. This complex situation contributed to histopathological findings consistent with a well-differentiated chondrosarcoma. The patient remains symptom-free 10 months following her operation and has fully returned to her previous activities. Our unique case highlights the importance of an MDT meeting when evaluating patients with musculoskeletal tumors and emphasizes the need for increased awareness when clinical findings and imaging studies are in discordance with histopathology reports., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Papavasiliou et al.)

The development of sicca in patients treated with immune checkpoint inhibitors (ICIs) is undoubtedly an underestimated complication, but one whose functional consequences and impact on quality of life are significant for patients. This update aims to review the frequency of this complication and different clinical pictures. The authors also propose a diagnostic and therapeutic approach to guide clinicians in daily practice., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The paraspinal region encompasses all tissues around the spine. The regional anatomy is complex and includes the paraspinal muscles, spinal nerves, sympathetic chains, Batson's venous plexus and a rich arterial network. A wide variety of pathologies can occur in the paraspinal region, originating either from paraspinal soft tissues or the vertebral column. The most common paraspinal benign neoplasms include lipomas, fibroblastic tumours and benign peripheral nerve sheath tumours. Tumour-like masses such as haematomas, extramedullary haematopoiesis or abscesses should be considered in patients with suggestive medical histories. Malignant neoplasms are less frequent than benign processes and include liposarcomas and undifferentiated sarcomas. Secondary and primary spinal tumours may present as midline expansile soft tissue masses invading the adjacent paraspinal region. Knowledge of the anatomy of the paraspinal region is of major importance since it allows understanding of the complex locoregional tumour spread that can occur via many adipose corridors, haematogenous pathways and direct contact. Paraspinal tumours can extend into other anatomical regions, such as the retroperitoneum, pleura, posterior mediastinum, intercostal space or extradural neural axis compartment. Imaging plays a crucial role in formulating a hypothesis regarding the aetiology of the mass and tumour staging, which informs preoperative planning. Understanding the complex relationship between the different elements and the imaging features of common paraspinal masses is fundamental to achieving a correct diagnosis and adequate patient management. This review gives an overview of the anatomy of the paraspinal region and describes imaging features of the main tumours and tumour-like lesions that occur in the region., (© 2023. The Author(s).)

Background and Aims: Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors., Methods: We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally., Results: Between January 2021 and March 2022, nine women and one man, aged 50-90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis., Conclusion: BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon., (© 2022 John Wiley & Sons Ltd.)

Lymphomas localized in the kidney are a rare entity that may be challenging to diagnose. We analyzed data from 10 patients with renal involvement of lymphoma diagnosed between 2009 and 2019 on fine needle biopsy from our tertiary center, and compared these with findings of 160 cases reported in the literature. Diffuse large B-cell lymphoma was the main histology subtype (40 and 38% in our sample and in the literature, respectively), followed by low-grade B-cell lymphomas, mostly from the marginal zone (MZ). Altogether, 106 patients had urological inaugural symptoms and 64 had general symptoms. Patients with urological presentation more often had renal masses than diffuse infiltration (p < 0.001), unilateral tumors (p = 0.0036) and low-grade B-cell lymphomas (17 vs 6%, p = 0.043). In both groups, nearly one-fourth of patients had diffuse (stage IV) lymphomas. Overall survival did not differ by the presence of urological/systemic symptoms, stage or aggressive lymphoma status. Notably, 3 of 10 patients from our series had MZ lymphomas associated with primary Sjögren syndrome revealed by acute kidney injury, including one where the autoimmune disease was detected. Lymphoproliferative disorders localized in the kidney are a challenging condition that can lead to detection of aggressive or diffuse lymphomas., (© 2022. Japanese Society of Hematology.)

Objective: To evaluate the contribution of minor salivary gland biopsy (mSGB) histology in diagnosing primary SS (pSS)-associated non-Hodgkin B-cell lymphoma (NHL)., Methods: pSS patients with mSGB at NHL diagnosis were included., Results: Among the 24 patients (92.3% female, mean age 61.3 years) with an mSGB at NHL diagnosis, 13 (54.2%) had mSGB histology-revealed NHL (mSGB+); it was the only site enabling NHL diagnosis in 10/13 (76.9%) patients. Mucosa-associated lymphoid tissue (MALT) lymphoma was found in 23/24 (95.8%) patients; 100% of mSGB+ identified MALT lymphomas. pSS and lymphoma characteristics were comparable for mSGB+ and mSGB- patients. Eight (61.5%) of the 13 mSGB+ patients and all 11 mSGB- patients were treated for lymphoma. Between diagnosis and 1 year of follow-up, the ESSDAI without the NHL item remained stable (7.4 vs 5.0; P = 0.33) for the five untreated patients, while it decreased significantly for the 19 treated patients (15.8 vs 5.1; P = 0.004)., Conclusion: For pSS patients with suspected NHL, mSGB histology enabled NHL diagnosis in half of them, MALT was found in 95.8% and all mSGB+ were MALT lymphomas, thereby avoiding more invasive biopsy. Our results suggest that mSGB should be obtained at pSS diagnosis and repeated during follow-up when NHL is suspected., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The well documented association between obesity and the severity of SARS-CoV-2 infection raises the question of whether adipose tissue (AT) is impacted during this infection. Using a model of SARS-CoV-2 infection in cynomolgus macaques, we detected the virus within subcutaneous AT (SCAT) but not in visceral AT (VAT) or epicardial AT on day 7 post-infection. We sought to determine the mechanisms responsible for this selective detection and observed higher levels of angiotensin-converting-enzyme-2 mRNA expression in SCAT than in VAT. Lastly, we evaluated the immunological consequences of SARS-CoV-2 infection on AT: both SCAT and VAT T cells showed a drastic reduction in CD69 expression, a standard marker of resident memory T cell in tissue, that is also involved in the migratory and metabolic properties of T cells. Our results demonstrate that in a model of mild infection, SCAT is selectively infected by SARS-CoV-2 although changes in the immune properties of AT are observed in both SCAT and VAT., (© 2022. The Author(s).)

Chordoma is a very rare, poorly known malignancy, with slow progression, mainly located in the sacrum and spine. All age groups may be affected, with a diagnostic peak in the 5th decade of life. Clinical diagnosis is often late. Histologic diagnosis is necessary, based on percutaneous biopsy. Specific markers enable diagnosis and prediction of response to novel treatments. New radiation therapy techniques can stabilize the tumor for 5 years in inoperable patients, but en-bloc resection is the most effective treatment, and should be decided on after a multidisciplinary oncology team meeting in an expert reference center. The type of resection is determined by fine analysis of invasion. According to the level of resection, the patients should be informed and prepared for the expected vesico-genito-sphincteral neurologic sequelae. In tumors not extending above S3, isolated posterior resection is possible. Above S3, a double approach is needed. Anterior release of the sacrum is performed laparoscopically or by robot; resection uses a posterior approach. Posterior wall reconstruction is performed, with an associated flap. Spinopelvic stabilization is necessary in trans-S1 resection. Total or partial sacrectomy shows high rates of complications: intraoperative blood loss, infection or mechanical issues. Neurologic sequelae depend on the level of root sacrifice. No genital-sphincteral function survives S3 root sacrifice. Patient survival depends on initial resection quality and the center's experience. Immunotherapy is an ongoing line of research., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objectives: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence., Methods: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma., Results: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma., Conclusion: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA., Competing Interests: Competing interests: PD: participation to clinical trials and punctual interventions for BMS and Roche. CM: reports outside the submitted work personal fees from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Sanofi. PG: honoraria from AbbVie, Amgen, Biogaran, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, MEDAC, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB. BF: research grants from AbbVie, Lilly, MSD and Pfizer, and honoraria from AbbVie, Amgen, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, SanofiAventis, SOBI, UCB. PP: participation in clinical trials and punctual honoraria from MSD Pfizer ABBvie Sanofi Novartis Sandoz. BC: honoraria from AbbVie, BMS, Gilead, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, RocheChugai and research grants from Novartis, Pfizer, and Roche. GN: received honorarium from Novartis, Lilly and UCB. RS: received honorarium from Pfizer, BMS and UCB. XM: received honorarium from BMS, Gilead, Pfizer, UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of tumor necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month-old BAFF-Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF antibodies increase the risk of lymphoma in B cell-driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF antibodies., (© 2021 British Society for Immunology.)

Splenectomy is indicated in cases of trauma to the spleen or hematological and immunological diseases (hereditary spherocytosis, autoimmune cytopenia). Less frequently, splenectomy is performed for diagnostic purposes to complement unsuccessful prior etiological investigations. The splenectomy remains a surgery at risk of complications and should be considered as a last-resort procedure to make the diagnosis and to be able to treat patients. We studied the medical files of 142 patients who underwent a splenectomy for any reason over a 10-year period and identified 20 diagnostic splenectomies. Diagnostic splenectomies were mainly performed to explore unexplained splenomegaly for 13 patients and fever of unknown origin for 10. The other patients had surgery for other causes (cytopenia, abdominal symptoms, suspicion of relapsing malignant hemopathies). Splenectomy contributed to the final diagnosis in 19 of 20 cases, corresponding mostly to lymphoid hemopathies (14/20). The most frequent disease was diffuse large B-cell lymphoma (8/20). Splenectomy did not reveal any infectious disease. The most relevant pre-operative procedures to aid the diagnosis were 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and immuno-hematological examinations. Diagnostic splenectomy is useful and necessary in certain difficult diagnostic situations. Highlights: Diagnostic splenectomy is still useful in 2020 to diagnose unexplained splenomegaly or fever of unknown origin. Lymphoma was the most common final diagnosis. FDG PET/CT was the most useful tool to aid in the diagnosis.

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France). The primary endpoint was progression-free rate (PFR) at 4 months; secondary endpoints were: best response (according to RECIST v1.1), progression-free survival (PFS), overall survival (OS) and safety. With a median follow-up of 9.8 months, 37 patients were eligible for this analysis: 68% males, median age 42 (range: 21-75), 19% with synchronous metastases, 92% with lung metastases, median PS: 1 (range: 0-3). Median number of previous treatment lines in the metastatic setting was 1 (range: 0-4). Progression-free rate at 4 months was 40.3% (95% CI: 24.5-56.2). Best response was partial response in 11% and stable disease in 35% of patients (disease control rate: 46%). Median PFS was 3.1 months (95% CI: 2.5-4.7) and median OS was 9.8 months (95% CI: 5.1-12.3). Toxicity profile was acceptable, with 13% grade 3 haematological toxicities (anaemia and neutropenia), without any grade 3-4 non-haematological toxicity. In our experience, oral metronomic etoposide demonstrated effective palliation along with acceptable toxicity in patients with progressive metastatic osteosarcoma., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The clinical significance of discordant radiological and pathological response to preoperative chemotherapy of colorectal liver metastases (CLM) is unknown., Methods: From 2011 to 2016, all eligible patients undergoing resection for CLM after preoperative chemotherapy were included at two centres. Patients were categorized according to radiologic response using RECIST as Rad-responders (complete/partial response) or Rad-non responders (stable disease) and according to Blazer et al. pathologic response grade as Path-responders (complete/major response) or Path-non responders (minor response). Survival outcome was analysed according to radiologic and pathologic response., Results: Among 413 patients undergoing resection of CLM, 119 fulfilled the inclusion criteria. Among these, 52 (44%) had discordant radiologic and pathologic response including 27 Rad-non responders/path responders and 25 Rad-responders/Path-non responders. Rad-non responders/path responders and Rad-responders/Path-non responders had similar characteristics except for the proportion receiving more than 6 cycles of preoperative chemotherapy (7/27 vs 16/25; P = 0.017). Median disease-free survival was not different in patients with or without discordant radiologic and pathologic responses (P = 0.195) but the type of discordance had an impact on oncologic outcome as median disease-free survival was 13.9 months (95% CI 5.7-22.2 months) in Rad-non responders/Path responders and 8.6 (6.2 - 10.9 months) in Rad-responders/Path-non responders (P = 0.034). Univariate and multivariate analysis showed that major pathologic response was associated with improved disease-free survival (OR 0.583, 95% CI 0.36-0.95, P = 0.031)., Conclusion: A discordant radiologic and pathologic response is common after preoperative chemotherapy for CLM. In these patients, pathologic response drives oncologic outcome.

The prognostic value of cell of origin (COO) classification and BCL2 expression is not well established in diffuse large B-cell lymphoma (DLBCL) patients with human immunodeficiency virus (HIV) infection in the recent era. Phenotypic patterns were determined by immunohistochemistry (IHC) of pathological samples from patients with HIV-associated DLBCL prospectively enrolled in the French AIDS and Viral Hepatitis CO16 Lymphovir cohort between 2008 and 2015. Molecular subgroup classification into germinal centre B-cell (GCB) and non-GCB subtypes was determined using the Hans algorithm. Among 52 samples of systemic DLBCL subjected to centralized pathological analysis, 25 of the 42 tested for BCL2 expression were positive. Samples were further classified into GCB (n = 19) and non-GCB (n = 16) subtypes and 17 remained unclassified. In multivariable analysis, BCL2 expression was an independent pejorative prognostic biomarker [4-year progression-free survival (PFS): 52% for BCL2 + vs. 88% for BCL2 - , P = 0·02] and tended to reduce 4-year overall survival (OS) (63% for BCL2 + vs. 88% for BCL2 - , P = 0·06). The difference between CGB and non-GCB subtypes on PFS and OS did not reach significance (4-year PFS: 79% for GCB vs. 53% for non-GCB, P = 0·24 and 4-year OS: 78% for GCB vs. 69% for non-GCB, P = 0·34). BCL2 expression determined by IHC is an independent pejorative prognostic biomarker in HIV-associated DLBCL in the recent era. This supports the investigation of new therapeutic strategies in patients with BCL2 expression., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

We report a case of a 16-year-old boy who presented a soft-tissue mass in the anterior compartment of the right thigh discovered by positron emission tomography/computed tomography within the work-up of unexplained prolonged inflammatory syndrome. The mass has no calcification. Subsequently, magnetic resonance imaging of the femoral triangle was carried out. Axial short tau inversion recovery images showed a 3.5-cm ill-defined mass in the femoral triangle with focal areas of hypointensity, which suggests that there might be fibrosis or hemosiderin within the tumor. Axial T1-weighted images showed a slight hyperintense mass involving the iliopsoas muscle. Contrast-enhanced fat-suppressed T1-weighted imaging showed a heterogeneous solid enhancement. Adjacent thick fascia enhancement of the vastus intermedius and the vastus lateralis muscles extending from the mass as a tail-like margin suggested the infiltrative spread of the tumor along the fascial plane. The mass and the lymphadenopathy were excised. Immunohistochemically, tumor cells were staining for muscle actin and desmin. Many plasma cells were IgG4+ (175per high-power field) with a ratio IgG4+/IgG+ of 50%. The diagnosis of IgG4-related disease (IgG4-RD) was made. Although a diffuse array of musculoskeletal symptoms has been observed in IgG4-related disease, reports of biopsy-proven musculoskeletal involvement of the limb are rare. We showed the radiological features of IgG4-RD presenting as a soft-tissue mass of the thigh. Musculoskeletal involvement, clinical significance, and treatment of IgG4-RD are also discussed.

The quality of pathologic assessment of rectal cancer specimens is crucial for treatment efficiency and survival. The Royal College of Pathologists (RCP) recommends evaluating the quality of the pathology report in routine practice using three quality indicators (QIs): the number of lymph nodes (LNs) analyzed (≥ 12), the rate of venous invasion (VI ≥ 30%), and peritoneal involvement (pT4a ≥ 10%). In this study, we evaluated the three QIs of the French national pathology reports and compared them with British guidelines and assessed the influence of neoadjuvant radiochemotherapy on QIs. From January 1 to December 31, 2016, all pathology reports for rectal adenocarcinoma were collected from French departments. Neoadjuvant radiochemotherapy included long-course radiotherapy with concomitant 5-FU-based chemotherapy. A total of 983 rectal cancer pathology reports were evaluated. A median of 15 LNs were analyzed and 81% of centers had ≥ 12 LNs. The rate of VI was 30% and 41% of centers had ≥ 30% VI. The rate of pT4a was 4% and 18% of centers reported ≥ 10% pT4a. None of the centers reached the threshold for the three QIs. All three QIs were lower after radiochemotherapy compared to surgery alone. In conclusion, in French routine practice, the values of two of the three QIs (LNs analyzed and VI) were globally in line with RCP guidelines. However, the rate of pT4a was very low, particularly after radiochemotherapy, suggesting its low value in rectal cancer.

Lymphoma-associated haemophagocytic syndrome (LAHS) accounts for most cases of secondary haemophagocytic syndrome (HS) and has been extensively described in Asian populations. However, little is known about the epidemiology of LAHS in Western countries. We herein report a case series of 71 LAHS patients in which the lymphomas were mainly of the aggressive type. Diagnoses included non-Hodgkin B cell lymphoma (46·5%) including human herpes virus 8-associated non-Hodgkin lymphoma (12·7%), T cell lymphoma (28·2%) and Hodgkin lymphoma (23·9%). An underlying immunodeficiency was described in 30 patients (42·3%). Early mortality within the 30 days following HS diagnosis was observed in 26·8% of cases. The overall survival was estimated at 45·7% [95% confidence interval, CI (35·4-59·0)] at 6 months, and 34·3% [95% CI (24·8-47·4)] at 2 years. Concurrent infection, age over 50 years, ethnicity and etoposide treatment were independently associated with mortality. While it appears that certain types of lymphomas were more prone to trigger HS, LAHS were not restricted to a few types of lymphoma. The overall prognosis was poor, with a particularly high rate of early mortality, highlighting the importance of both early recognition and choice of initial therapeutic management., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

Neutrophils represent the most abundant immune cells recruited to inflamed tissues. A lack of dedicated tools has hampered their detection and study. We show that a synthesized peptide, MUB 40 , binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactoferrin is specifically produced by neutrophils among other leukocytes, making MUB 40 a specific neutrophil marker. Naive mammalian neutrophils (human, guinea pig, mouse, rabbit) were labeled by fluorescent MUB 40 conjugates (-Cy5, Dylight405). A peptidase-resistant retro-inverso MUB 40 (RI-MUB 40 ) was synthesized and its lactoferrin-binding property validated. Neutrophil lactoferrin secretion during in vitro Shigella infection was assessed with RI-MUB 40 -Cy5 using live cell microscopy. Systemically administered RI-MUB 40 -Cy5 accumulated at sites of inflammation in a mouse arthritis inflammation model in vivo and showed usefulness as a potential tool for inflammation detection using non-invasive imaging. Improving neutrophil detection with the universal and specific MUB 40 marker will aid the study of broad ranges of inflammatory diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Surgical reconstruction of ligaments and tendons is frequently required in clinical practice. The commonly used autografts, allografts, or synthetic transplants present limitations in terms of availability, biocompatibility, cost, and mechanical properties that tissue bioengineering aims to overcome. It classically combines an exogenous extracellular matrix with cells, but this approach remains complex and expensive. Using a rat model, we tested a new bioengineering strategy for the in vivo and de novo generation of autologous grafts without the addition of extracellular matrix or cells, and analyzed their biomechanical and structural properties., Methods: A silicone perforated tubular implant (PTI) was designed and implanted in the spine of male Wistar rats to generate neo-transplants. The tensile load to failure, stiffness, Young modulus, and ultrastructure of the generated tissue were determined at 6 and 12weeks after surgery. The feasibility of using the transplant that was generated in the spine as an autograft for reconstruction of medial collateral ligaments (MCL) and Achilles tendons was also tested., Findings: Use of the PTI resulted in de novo transplant generation. Their median load to failure and Young modulus increased between 6 and 12weeks (respectively 12N vs 34N and 48MPa vs 178MPa). At 12weeks, the neo-transplants exhibited collagen bundles (mainly type III) parallel to their longitudinal axis and elongated fibroblasts. Six weeks after their transfer to replace the MCL or the Achilles tendon, the transplants were still present, with their ends healed at their insertion point., Interpretation: This animal study is a first step in the design and validation of a new bioengineering strategy to develop autologous transplants for ligament and tendon reconstructions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4 + T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4 + T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4 + T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: The study aimed to evaluate the accuracy of imaging for measurement of the length of the ileocolic segment affected by Crohn's disease., Method: Fifty-four consecutive patients who underwent resection between 2011 and 2014 for ileocolic Crohn's disease were prospectively studied. All had preoperative MR or CT enterography. Two independent radiologists measured the length of the diseased intestinal segment. The measurements were compared with the length of disease assessed on pathology of the non-fixed surgical specimen., Results: The median preoperative length of the Crohn's disease segment on imaging was 20.5 (2-73) cm and 20 (3-90) cm, as measured by the two radiologists. Interobserver agreement was substantial (κ = 0.69) with a correlation coefficient (r) of 0.82 (P < 0.001). The median length of the Crohn's disease segment on pathological examination was 16.5 (2-75) cm and was closely correlated with the radiological measurement (r = 0.76, P < 0.001). The length of the Crohn's disease segment on imaging was correct to within 5 cm of the value on pathology. It was correct in 30 (55%) patients and was underestimated and overestimated in 6 (11.1%) and 18 (33.3%). A length of disease of less than 20 cm found on imaging in 26 patients was confirmed in 25 (96%) on pathology, whereas a length of more than 20 cm found on imaging in 28 patients was confirmed in 18 (64%) on pathology. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of imaging for predicting a length of less than 20 cm were 71%, 95%, 96%, 64% and 79%., Conclusion: Imaging accurately identifies the length of the ileocolic segment of Crohn's disease when it is 20 cm or less on pathological examination. In patients with more extensive disease, imaging tends to overestimate the length and should be interpreted with caution., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Background: Patients with ypN0 rectal cancer who have received preoperative chemoradiotherapy can be divided into those who initially were node negative and those whose positive nodes have been sterilized by preoperative therapy. The long-term prognosis for ypN0 patients with sterilized lymph nodes (LNS) is unknown. This study aimed to assess the prognostic value of LNS after preoperative chemoradiotherapy for patients with ypN0 rectal cancer., Methods: From January 2007 to March 2014, 206 patients with ypN0 tumors of the mid or lower rectum treated by chemoradiotherapy and radical surgery were enrolled in the study. Of these 206 patients, 49 had ypN0 tumors with LNS (LNS+ group), and 157 had ypN0 tumors without LNS (LNS- group). The patients in both groups were comparable in terms of tumor characteristics, type of chemoradiotherapy, type of surgery, R0 resection rate, and postoperative complication rate., Results: The mean follow-up period was 40.5 ± 27 months. The 1- and 3-year OS rates in the LNS+ group were respectively 100 and 95.5% versus 99.4 and 91.6% in the LNS- group (P = 0.549). The 1- and 3-year DFS rates in the LNS+ group were respectively 100 and 94.2% versus 94.7 and 87.1% in the LNS- group (P = 0.117). The multivariate analysis showed that the presence of LNS did not affect OS (P = 0.918) or DFS (P = 0.209)., Conclusions: The prognosis is excellent for patients with ypN0 rectal cancer who have LNS after preoperative chemoradiotherapy. The presence of LNS in ypN0 rectal cancer patients after chemoradiotherapy should not be considered a factor for a poor prognosis.

Objective: The relevance of the Th17 pathway in primary SS (pSS) is unclear. Published studies have relied on restimulating circulating CD161 + T cells in vitro for quantitation of IL-17-producing cells. While CD161 marks all IL-17 + T cells, it is also expressed by other Th subsets. The aim of this study was to directly analyse retinoic acid receptor-related orphan nuclear receptor (ROR)-γ expressing and non-expressing subsets of CD161 + T cells to determine the relevance of the Th17 pathway in pSS., Methods: We quantitated the frequencies of both CD161 - and RORγ-expressing T cells by comparative flow cytometry in peripheral blood mononuclear cells from a well-stratified cohort of pSS patients and control subjects. We also analysed the expression of antigen D-related HLA (HLA-DR) and CD161 in labial salivary glands from nine subjects undergoing a diagnostic biopsy., Results: While the frequencies of both RORγ + and RORγ - subsets of CD161 + CD4 + T cells were increased in peripheral blood from pSS patients, the increase in the RORγ + subset positively correlated with humoral manifestations of the disease (anti-SSA/SSB autoantibodies and hypergammaglobulinaemia), but not with disease activity, and vice versa for the RORγ - subset. An increased frequency of HLA-DR + CD161 + CD4 + T cells was observed in labial salivary gland biopsies from pSS patients, suggesting chronic activation of CD161 + CD4 + T cells in the target tissue of the disease., Conclusion: In addition to pointing to CD161 as a marker of a pathogenic subset of CD4 + T cells in pSS patients, our data indicate that even though the RORγ + (Th17) CD161 + subset might contribute to humoral manifestations of the disease, the RORγ - (non-Th17) CD161 + subset is the one associated with disease activity in pSS patients., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: The study evaluated the outcome of severe acute antipsychotic (neuroleptic) drug related colitis requiring emergency surgery., Method: From 2009 to 2014, 20 patients underwent emergency surgery for acute and severe neuroleptic-related ischaemic colitis. Neuroleptic-induced colitis was defined as another cause besides inflammatory, infectious or ischaemic colitis with a relationship to treatment by antipsychotic drugs., Results: The main drugs involved were cyamemazine (n = 9, 45%), loxapine (n = 5, 25%), haloperidol (n = 4, 20%) and alimemazine (n = 4, 20%). Most (n = 14, 70%) patients presented with haemodynamic instability requiring massive resuscitation and vasopressive drugs. CT signs of digestive impairment were found in 13 (65%) patients having emergency surgery. The lesions were pancolonic in 40%; transparietal necrosis was found in 45% and 15% had colonic perforation. Twelve (60%) patients had total or subtotal colectomy and eight (40%) a segmental colectomy with colostomy or ileostomy in all cases. The postoperative mortality was 15% and morbidity was 70%, necessitating surgical reintervention in two (10%) patients. Of the 17 surviving patients, 11 (64.7%) had restoration of intestinal continuity after a median delay of 103 days, with a postoperative morbidity rate of 36.3%. In the intent-to-treat population, the permanent stoma rate was 30%., Conclusion: The morbidity and mortality of surgery for neuroleptic-drug-induced colitis is higher than for colitis due to other causes. A better knowledge of this condition should lead to early diagnosis., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas.

Background: Mass cytometry has recently emerged as a promising tool for clinical research. However, few studies have demonstrated its benefit for patient stratification and biomarker identification. Primary Sjögren's syndrome (pSS) is a prototype of chronic autoimmune disease, the pathogenesis of which remains unclear and for which treatment does not exist., Objective: This observational case-control study was designed to discover new cellular biomarkers and therapeutic targets in patients with pSS., Methods: Forty-nine patients with pSS and 45 control subjects were enrolled for clinical evaluation and mass cytometry quantification of 34 protein markers in blood. For a third of these subjects, matched labial salivary gland biopsy specimens were also analyzed by mass cytometry and immunohistochemistry., Results: In salivary gland biopsy specimens from patients with pSS, we identified a high number of activated CD8(+) T cells, terminally differentiated plasma cells, and activated epithelial cells, pointing to new pathogenic mechanisms for future clinical intervention. In blood, we identified a 6-cell disease signature defined by decreased numbers of CD4 and memory B lymphocytes, decreased plasmacytoid dendritic cell numbers, and increased representation of activated CD4 and CD8 T cells and plasmablasts. These blood cellular components correlated with clinical parameters and, when taken together, clustered patients into subsets with distinct disease activity and glandular inflammation., Conclusion: This first application of mass cytometry to a well-stratified clinical cohort and small biopsy tissues establishes the benefits of such an approach for the discovery of new biomarkers and therapeutic targets. Similar high-dimensional immunophenotyping strategies could be implemented in longitudinal and interventional clinical settings in this and other disease areas., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: The present study describes the macroscopic and microscopic features of the squared ligament of the elbow (SLE). In addition, the SLE biomechanical behavior and contribution to the forearm stability were also examined., Materials and Methods: Ten forearms from freshly frozen cadavers were used for this work. Each forearm was mounted in an experimental frame for quantification of longitudinal and transverse stability. Macroscopic features and biomechanical behavior were analyzed on dynamic videos obtained during forearm rotation. Then, the SLE was harvested from the 10 forearms for microscopic analysis on histological slices stained with hematoxylin-eosin-saffron., Results: Two main SLE configurations were identified. One in which the SLE had three distinct bundles (anterior, middle, posterior) and another in which it was homogeneous. The anterior part of the SLE had a mean length of 11.2 mm (±2.4 mm) and a mean width of 1.2 mm (±0.2 mm) while the posterior part had a mean length of 9.9 mm (±2.2 mm) and a mean width of 1 mm (±0.2 mm). Microscopic examination showed that the SLE is composed of a thin layer of arranged collagen fibers. During forearm rotation, the SLE progressively tightens upon pronation and supination by wrapping around the radial neck. Tightening of the SLE during forearm rotation provides transverse and longitudinal stability to the forearm, mainly in maximal pronation and supination., Conclusion: The SLE is a true ligament and provides forearm stability when it is stretched in pronation and supination.

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

Introduction: In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren's syndrome (pSS) and to identify predictors of response to treatment., Methods: Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index score of ≥3 points at W28., Results: After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D-positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score >1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5-0.67) to 0.50 (0.5-0.5) (p=0.06). B-cell activating factor (BAFF) staining was detected in 11 (78.6 %) of 14 patients before belimumab treatment compared with 7 (50.0 %) of 14 after belimumab therapy (p=0.10). The median percentage of BAFF-positive cells in foci significantly decreased from 27.5 % (10-40) to 5 % (0-20) (p=0.03). A systemic response was achieved in six patients (40 %). The only predictor of response was the presence of a low number of natural killer (NK) cells, both in blood (8.5 % [7-10] vs 11 % [9-21]; p=0.04) and in LSG (20.6/mm(3) [20.0-21.4] vs 30.0/mm(3) [25.0-100.0], p=0.003). Serum BAFF levels did not influence response to treatment., Conclusions: Low blood and salivary NK cell numbers are associated with a better response to belimumab. This suggests that two distinct subsets of pSS may exist: one with a predominant type I interferon (IFN)-BAFF-B-cell axis, representing good responders to belimumab; and one with a predominant type II IFN-NK cell axis, representing non-responders., Trial Registration: ClinicalTrials.gov identifier: NCT01160666 . Registered 9 July 2010.

Aim: Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC)., Methods: Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed., Results: All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent., Conclusion: Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC., (Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.)

Leishmaniasis caused by Leishmania infantum is endemic in the Mediterranean region. Its visceral form can present a diagnostic challenge owing to the disease's wide spectrum of clinical presentations. We describe the very atypical case of a 66-year-old male Caucasian patient with hepatopulmonary syndrome and an exceptionally rare expression of visceral leishmaniasis in a disseminated form with mucocutaneous involvement presenting as an autoimmune systemic disease.

Introduction: Over the past 3 decades, the appropriate management of metastatic germ cell tumours (GCT) has been defined by several phase III trials. Many follow-up recommendations have been published based on expert consensus. However, common clinical scenarios can still be vexing for clinicians who are less experienced at managing patients with testicular cancer., Case Report: We highlight the arduous diagnostic work-up of a suspected late relapsing metastatic GCT in a patient suffering from fatigue, weight loss and prominent retroperitoneal lymph nodes, 4 years after first-line chemotherapy for metastatic seminoma. The various explorations finally led to the diagnosis of Whipple's disease., Conclusion: This unusual clinical case strongly highlights the need to perform an exhaustive evaluation, with a biopsy, if a late recurrent GCT is suspected to avoid pointless and potentially harmful treatment.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis involving small vessels with deposition of immunoglobulin A (IgA) complexes, usually affecting children. Compared with children, HSP in adults is more severe and frequently associated with cancer. We report the case of a 49-year-old woman with medical history of kidney transplantation for segmental glomerular hyalinosis. Eight years after the transplantation, while taking combined immunosuppressive therapy with tacrolimus and azathioprine indicated for the prevention against transplant rejection, she developed a Henoch-Schönlein purpura. Vasculitis involves skin and sciatic peroneal nerve and she received systemic corticosteroid treatment. Because of four relapses and corticosteroid dependence, the patient was treated with rituximab (two intravenous infusions of 1000 mg given two weeks apart). Successful outcome was observed along two years of follow-up. This new case of successful use of rituximab in HSP promotes more investigations of this treatment in clinical trials.

Several autoimmune diseases, including primary Sjögren's syndrome (pSS), are associated with an increased risk for lymphoma. Polymorphisms of TNFAIP3, which encodes the A20 protein that plays a key role in controlling nuclear factor κB activation, have been associated with several autoimmune diseases. Somatic mutations of TNFAIP3 have been observed in the mucosa-associated lymphoid tissue lymphoma subtype frequently associated with pSS. We studied germline and somatic abnormalities of TNFAIP3 in 574 patients with pSS, including 25 with lymphoma. Nineteen additional patients with pSS and lymphoma were available for exome sequence analysis. Functional abnormalities of A20 were assessed by gene reporter assays. The rs2230926 exonic variant was associated with an increased risk for pSS complicated by lymphoma (odds ratio, 3.36 [95% confidence interval, 1.34-8.42], and odds ratio, 3.26 [95% confidence interval, 1.31-8.12], vs controls and pSS patients without lymphoma, respectively; P = .011). Twelve (60%) of the 20 patients with paired germline and lymphoma TNFAIP3 sequence data had functional abnormalities of A20: 6 in germline DNA, 5 in lymphoma DNA, and 1 in both. The frequency was even higher (77%) among pSS patients with mucosa-associated lymphoid tissue lymphoma. Some of these variants showed impaired control of nuclear factor κB activation. These results support a key role for germline and somatic variations of A20 in the transformation between autoimmunity and lymphoma.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.

Pancreatic perivascular epithelioid cell tumors (PEComas) are exceedingly rare neoplasms, <10 cases have been described; all were benign and occurring mostly in women. We report the first malignant pancreatic PEComa in a patient with BRCA2 mutation. A 51-year-old woman with a medical and familial history of breast adenocarcinoma, who was tested positive for BRCA2 mutation, presented with a recent history of jaundice. Imaging studies were consistent with endocrine or secondary tumor. Pathologic examination of fine needle aspiration biopsy and Whipple procedure revealed a 6-cm intrapancreatic PEComa, invading the duodenal wall with extensive necrosis and vascular invasion, leading to classify this PEComa into "malignant" category. The patient developed liver metastases 6 months after surgery. Although mostly benign, thorough sampling of the PEComa is mandatory, to rule out malignant behavior whatever the location of the tumor is.

Context: Unlike the small bowel, the colorectal mucosa is seldom the site of metastatic disease. Objective.-To determine the incidence of truly colorectal metastases, and subsequent clinicopathologic findings, in a substantial colorectal cancer population collected from 7 European centers., Design: During the last decade, 10 365 patients were identified as having colorectal malignant tumors, other than systemic diseases. Data collected included patient demographics, clinical symptoms, treatment, the presence of metastases in other sites, disease-free interval, follow-up, and overall survival. All secondary tumors resulting from direct invasion from malignant tumors of the contiguous organs were excluded, as well as those resulting from lymph node metastases or peritoneal seeding., Results: Only 35 patients were included (10 men) with a median age of 59 years. They presented with obstruction, bleeding, abdominal pain, or perforation. The leading source of metastases was the breast, followed by melanoma. Metastases were synchronous in 3 cases. The mean disease-free interval for the remaining cases was 6.61 years. Surgical resection was performed in 28 cases. Follow-up was available for 26 patients; all had died, with a mean survival time of 10.67 months (range, 1-41 months)., Conclusions: Colorectal metastases are exceptional (0.338%) with the breast as a leading source of metastases; they still represent a late stage of disease and reflect a poor prognosis. Therefore, the pathologist should be alert for the possibility of secondary tumors when studying large bowel biopsies. Any therapy is usually palliative, but our results suggest that prolonged survival after surgery and complementary therapy can be obtained in some patients.

Imaging living cells and organs requires innovative, specific, efficient, and well tolerated fluorescent markers targeting cellular components. Such tools will allow proceeding to the dynamic analysis of cells and the adaptation of tissues to environmental cues. In this study, we have identified and synthesized a novel non-toxic fluorescent marker allowing a specific fluorescent staining of the human colonic mucus. Our strategy to identify a molecule able to specifically bind to the human colonic mucus was on the basis of the mucus adhesion properties of commensal bacteria. We identified and characterized the mucus-binding property of a 70-amino acid domain (MUB(70)) expressed on the surface of Lactobacillus strains. The chemical synthesis of MUB(70) was achieved using the human commensal bacterium Lactobacillus reuteri AF120104 protein as a template. The synthesized Cy5-conjugated MUB(70) marker specifically stained the colonic mucus on fixed human, rabbit, and guinea pig tissues. Interestingly, murine tissue was not stained, suggesting significant differences in the composition of the murine colonic mucus. In addition, this marker stained the mucus of living cultured human colonic cells (HT29-MTX) and human colonic tissue explants. Using a biotinylated derivative of MUB(70), we demonstrated that this peptide binds specifically to Muc2, the most abundant secreted mucin, through its glycosylated moieties. Hence, Cy5-MUB(70) is a novel and specific fluorescent marker for mammalian colonic mucus. It may be used for live imaging analysis but also, as demonstrated in this study, as a marker for the diagnosis and the prognosis of colonic mucinous carcinomas.

Background: Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21)., Patients and Methods: Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years., Results: Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21., Conclusions: Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation.