Features of non-Hodgkin's lymphoma diagnosed in minor salivary gland biopsies from primary Sjögren's syndrome patients.

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.

Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice.

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.

In situ BCL2 expression is an independent prognostic factor in HIV-associated DLBCL, a LYMPHOVIR cohort study.

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.

What is the Prognostic Value of a Discordant Radiologic and Pathologic Response in Patients Undergoing Resection of Colorectal Liver Metastases After Preoperative Chemotherapy?

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.

IgG4-related disease: rare presentation as a soft-tissue mass in the thigh of an adolescent.

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.

A comprehensive analysis of Lymphoma-associated haemophagocytic syndrome in a large French multicentre cohort detects some clues to improve prognosis.

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.

High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence.

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.

Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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.

Clinical relevance of RORγ positive and negative subsets of CD161+CD4+ T cells in primary Sjögren's syndrome.

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.

Prognostic Value of Sterilized Lymph Nodes After Preoperative Chemoradiotherapy for Patients with ypN0 Rectal Cancer.

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.

Cytometry by time-of-flight immunophenotyping identifies a blood Sjögren's signature correlating with disease activity and glandular inflammation.

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.

Squared ligament of the elbow: anatomy and contribution to forearm stability.

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.

Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome.

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.

Immune Checkpoint Inhibitor-induced Sicca Syndrome.

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.

Complete remission after a single bisphosphonate infusion in isolated bone Langerhans cell histiocytosis lesion: a case report and a narrative review of the literature.

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH.

Design of a specific colonic mucus marker using a human commensal bacterium cell surface domain.

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.

Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors.

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.

Understanding a mass in the paraspinal region: an anatomical approach.

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.

p52 Activation in monomorphic B-cell posttransplant lymphoproliferative disorder/diffuse large B-cell lymphoma without BAFF-R expression.

Posttransplantation lymphoproliferative disorders (PTLD) are associated with Epstein-Barr virus (EBV) and activate the NF-κB pathway. B-cell activating factor (BAFF) modulates cell growth and survival in non-Hodgkin's lymphomas. However, there are few studies of EBV, BAFF/BAFF-R signaling, and NF-κB1 and NF-κB2 pathway activation in PTLD. Diffuse large B-cell lymphomas (DLBCL) in two different clinical contexts, immunocompetent patients (DLBCL/IC; n = 30) or posttransplantation solid-organ recipients (DLBCL/PTLD; n = 21), were characterized histogenically as germinal center (GC) or non-germinal center (NGC). Expression of BAFF, BAFF-R, and NF-κB proteins p50 and p52 and the presence or absence of EBV were compared in these clinical contexts. Regardless of the GC or NGC pattern of DLBCL, BAFF-R was expressed in 37% of DLBCL/IC but in only 4.8% of DLBCL/PTLD. p52 was expressed in DLBCL/PTLD/NGC (12 of 19 cases) as compared with DLBCL/IC/NGC (0 of 18 cases). This pattern might be related to the presence of EBV and latent membrane protein 1 because p52 expression was observed primarily in EBV-positive DLBCL/PTLD cases expressing latent membrane protein 1. Thus, the activation profile or NGC pattern of DLBCL/PTLD was not associated with BAFF/BAFF-R expression, whereas nuclear p52 related to NF-κB2 pathway activation might be linked to EBV.

Management of chordoma of the sacrum and mobile spine.

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.