Lymphoid follicular hyperplasia (LFH) is a benign lymphoproliferative disease. Although it can occur within the thoracic cavity, LFH originating from the chest wall has not been reported. A 79-year-old woman was incidentally found to have a well-defined mass on the left posterior chest wall during a preoperative examination for aortic valve replacement. The mass had slowly grown over 6 years. Thoracoscopic surgical resection was performed without complications. Pathological examination ruled out lymphoproliferative diseases, such as Castleman disease or malignant lymphoma, and a diagnosis of LFH was made. Although LFH generally has a good prognosis, surgical resection is recommended for diagnostic and therapeutic purposes owing to the possibility of malignancy masquerading as a reactive lesion. This is the first report of an LFH arising from the chest wall with imaging findings similar to other benign tumours. Its potential as a differential diagnosis for tumours with similar imaging findings is highlighted.

T-large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder. The diagnosis is established by identifying an abnormally high number of clonal granular T lymphocytes in the peripheral blood and eventually in the bone marrow, in cases with medullary infiltration. The majority of patients present with symptoms related to neutropenia and this condition may be associated with autoimmune diseases in up to a third of cases. The authors describe the case of a 26-year-old patient admitted with subacute high fever and bullous dermatitis with necrotic lesions with central bullae. Analytically, she presented anemia and leukopenia with severe neutropenia of 200 cells/L. Skin lesions were compatible with ecthyma and the skin biopsy revealed aspects compatible with leukocytoclastic vasculitis. The myelogram and bone biopsy revealed hypoplasia of the myeloid line and a pathological T population of CD8+, TIA-1+ and granzyme B+, which were associated with compatible flow cytometry (CD3+, T-cell receptor (TCR) Alpha-Beta+, CD5+, CD2+, with loss of CD7 antigen expression) established the diagnosis of T-LGLL. The patient had a favorable evolution, with cytopenias almost returning to normal after two months. She began follow-up at a Hematology Reference Center, remaining asymptomatic without specific treatment considering the indolent course of the disease.

BACKGROUND: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020.
RESULTS: Median time from ibrutinib initiation was 6.6 [3-18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5-11] vs. 4 [3-7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1-2] vs. 0 [0-2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups.
CONCLUSIONS: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.

T-cell lymphoma in the gastrointestinal tract (intestinal T-cell lymphoma, [ITCL]) is rare. ITCL, not otherwise specified (ITCL, NOS) which is a type of ITCL is particularly rare. There are few case reports of ITCL, NOS but no previous reports describe its endoscopic features. In this report, the 69-year-old man was diagnosed with ITCL, NOS. Colonoscopy revealed the elevated legion and edematous mucosa with focal depressions in the lower rectum. On the depressed legions, magnifying endoscopy combined with narrow-band imaging detected the disappearance of glandular structure and branching abnormal blood vessels like a tree. These findings were similar to the tree-like appearance, which has been described as a unique feature of gastric mucosal-associated lymphoid tissue lymphoma. The targeted biopsy of the tree-like appearance showed abnormal histopathological findings which fit the definition of ITCL, NOS. He was treated with chemotherapy and achieved complete remission. As is the case of gastric mucosal-associated lymphoid tissue lymphoma, the tree-like appearance is possibly the unique sign of ITCL, NOS. We report the endoscopic features of ITCL, NOS and show characteristic findings by magnifying endoscopy combined with narrow-band imaging.

OBJECTIVE: Epstein-Barr virus (EBV) causes multiple human cancers, including B-cell lymphomas. In cell culture, EBV converts healthy human B-cells into immortalized ones that grow continuously, which model post-transplant lymphomas. Constitutive signaling from two cytoplasmic tail domains of the EBV oncogene latent membrane protein 1 (LMP1) is required for this transformation, yet there has not been systematic analysis of their host gene targets. We identified that only signaling from the membrane proximal domain is required for survival of these EBV-immortalized cells and that its loss triggers apoptosis. We identified key LMP1 target genes, whose abundance changed significantly with loss of LMP1 signals, or that were instead upregulated in response to switching on signaling by one or both LMP1 domains in an EBV-uninfected human B-cell model. These included major anti-apoptotic factors necessary for EBV-infected B-cell survival. Bioinformatics analyses identified clusters of B-cell genes that respond differently to signaling by either or both domains.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is an extremely rare, indolent skin malignancy that can be difficult to distinguish from autoimmune disease-associated panniculitides. Here, we describe a 12-year-old boy who was diagnosed at age 7 years with dermatomyositis with classical manifestations, including poikiloderma, Gottron\'s sign, and symmetric muscle weakness. Recently, the boy presented multiple subcutaneous nodules and fever. Histopathological examination and immunohistochemical staining revealed coexistence of SPTL. To our knowledge, this is the first case of dermatomyositis accompanied with SPTL. This case alert clinical physicians of the possibility of SPTL should be considered when a patient with dermatomyositis has new lesions presenting as nodules and unknown fever.

Cryoglobulinaemia vasculitis can present with a variety of symptoms and there is limited data on the incidence and presentation of cryoglobulinaemia vasculitis in haemodialysis patients. We report a case of a 63-year-old male who had a series of presentations with rash, visual changes, abdominal pain, weight loss, fevers and digital ischaemia. This is on a background of a congenital single kidney with end-stage renal failure secondary to diabetes and hypertension, receiving haemodialysis for nearly 5 years. He initially experienced a leukocytoclastic vasculitis rash confirmed on skin biopsy, followed by multiple hospital presentations for undifferentiated abdominal pain and fever of unknown source. Jejunal biopsy revealed intestinal vasculitis. His peripheral blood flow cytometry and bone marrow biopsy were consistent with marginal zone lymphoma (indolent subtype, IgM kappa clone). Further testing revealed a type II cryoglobulinaemia consisting of an IgM kappa monoclonal band with polyclonal IgG (cryocrit 5%). A diagnosis of cryoglobulinaemia vasculitis was established and he was treated with pulsed methylprednisolone and rituximab therapy. However, after receiving three doses of rituximab the patient developed a presumed vasculitis-associated pulmonary haemorrhage for which he received treatment with five sessions of plasma exchange. His symptoms resolved and cryocrit reduced to < 1% after his final dose of rituximab. The clinical features of cryoglobulinaemia may be difficult to detect in chronic haemodialysis patients and vigilance is required.

UNASSIGNED: This case report shows a unique case of Castleman\'s disease in the context of histopathological diagnosis of cutaneous melanoma where clinical and radiological features of Castleman\'s disease were masked by presumptive diagnosis of metastatic melanoma. The disease is part of a group of lymphoproliferative disorders with characteristic histopathological features that can occur in any lymph node in the body, characterised by slow growing painless masses which are asymptomatic until mass effect occurs. This case highlights the need for caution when considering management of lymphadenopathy with clinically/radiologically suspicious nodes.
METHODS: A 65 year old man with metastatic melanoma of the left elbow presented for axillary sentinel node mapping and was found to have a hypoechoic enlarged node on ultrasound. This was further investigated and found to be a lymphoproliferative growth pathognomonic for Castlemans disease.
CONCLUSIONS: Whilst clinically detected lymphadenopathy in the draining node basin of a primary cutaneous melanoma is highly suspicious for nodal metastasis, it is sometimes not possible to confirm or exclude this diagnosis without complete histological examination of the node. Multidisciplinary input from the surgeon, histopathologist and radiologist is a key step in confirming diagnosis.
CONCLUSIONS: Alternative diagnoses must be considered in the context of lymphadenopathy, even in the context of malignant melanoma.

UNASSIGNED: There is little information on diagnosis and management of small bowel lymphomas, and optimal management strategies are still undefined. This study aims to describe their main clinical and pathological characteristics and identify poor prognostic factors.
UNASSIGNED: A retrospective observational study of all patients with histological diagnosis of small bowel lymphoma between January 2010 and December 2020 was performed.
UNASSIGNED: We included 40 patients, with male predominance (60%) and mean age of 60.7 years. The ileum was the most common location, and the most common histological subtypes were follicular lymphoma and diffuse large B-cell lymphoma. Clinical presentation was variable from asymptomatic patients (30%) to acute surgical complications (35%) including perforation, intestinal obstruction, ileal intussusception, or severe bleeding. Diagnosis was established by endoscopy in 22 patients (55%), and the most common findings included polyps, single mass, diffuse infiltration, or ulceration, whereas 18 (45%) required surgery because of acute presentations or tumor resection, and lymphoma was diagnosed postoperatively. Surgery was curative in one-third of those patients. Median survival was 52 months. Acute presentation (P = 0.001), symptomatic disease (P = 0.003), advanced stage (P = 0.008), diffuse large B-cell lymphoma (P = 0.007), anemia (P = 0.006), hypoalbuminemia (P < 0.001), elevated lactate dehydrogenase (P = 0.02), elevated C-reactive protein (P < 0.001), and absence of treatment response (P < 0.001) were significant predictors of mortality.
UNASSIGNED: Small bowel lymphoma is a rare malignancy with diverse clinical and endoscopic presentations that require a high index of suspicion. Primary factors associated with worse outcome included acute presentation, advanced stage, histological subtype, biochemical abnormalities, and absence of treatment response.

The Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1) mimics CD40 signaling and is expressed by multiple malignancies. Two LMP1 C-terminal cytoplasmic tail regions, termed transformation essential sites (TES) 1 and 2, are critical for EBV transformation of B lymphocytes into immortalized lymphoblastoid cell lines (LCL). However, TES1 versus TES2 B-cell target genes have remained incompletely characterized, and whether both are required for LCL survival has remained unknown. To define LCL LMP1 target genes, we profiled transcriptome-wide effects of acute LMP1 CRISPR knockout (KO) prior to cell death. To then characterize specific LCL TES1 and TES2 roles, we conditionally expressed wildtype, TES1 null, TES2 null or double TES1/TES2 null LMP1 alleles upon endogenous LMP1 KO. Unexpectedly, TES1 but not TES2 signaling was critical for LCL survival. The LCL dependency factor cFLIP, which plays obligatory roles in blockade of LCL apoptosis, was highly downmodulated by loss of TES1 signaling. To further characterize TES1 vs TES2 roles, we conditionally expressed wildtype, TES1 and/or TES2 null LMP1 alleles in two Burkitt models. Systematic RNAseq analyses revealed gene clusters that responded more strongly to TES1 versus TES2, that respond strongly to both or that are oppositely regulated. Robust TES1 effects on cFLIP induction were again noted. TES1 and 2 effects on expression of additional LCL dependency factors, including BATF and IRF4, and on EBV super-enhancers were identified. Collectively, these studies suggest a model by which LMP1 TES1 and TES2 jointly remodel the B-cell transcriptome and highlight TES1 as a key therapeutic target.