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.

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.

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.

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.

Renal involvement of lymphomas proven by kidney biopsy: report of 10 cases from a tertiary care center and comparison with the literature.

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.

Detection of SARS-CoV-2 in subcutaneous fat but not visceral fat, and the disruption of fat lymphocyte homeostasis in both fat tissues in the macaque.

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.

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.

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.

Lymphoma complicating rheumatoid arthritis: results from a French case-control study.

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.

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.

Diagnostic Splenectomy: Characteristics, Pre-Operative Investigations, and Identified Pathologies for 20 Patients.

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 18F-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.

Efficacy and safety of oral metronomic etoposide in adult patients with metastatic osteosarcoma.

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.

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.

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.

A composite lymphoma combining a Hodgkin lymphoma and a marginal zone lymphoma transformed into a diffuse large B-cell lymphoma.

Composite lymphoma is defined as the occurrence of two or more distinct lymphoma types in a single anatomic site. We report a case of Richter syndrome with both Hodgkin lymphoma and non-Hodgkin lymphoma in the bone marrow. This diagnostic was suspected because of discrepancies between histological and cytological results.

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.