Cases Of Hepatosplenic T-cell Lymphoma Research Articles

Clinical Value of Gene Copy Number Variation Detection in Peripheral Blood in the Diagnosis and Treatment of Lymphoma

Objective To investigate the consistency between the results of gene copy number variation (CNA) in peripheral blood and bone marrow or tissue samples of lymphoma patients with curative and its clinical value in diagnosis and treatment. Methods A total of 5 patients with lymphoma were selected. Case 1 was diffuse large B-cell lymphoma (DLBCL) without bone marrow invasion. Tissue samples and peripheral blood samples were collected at the same time point before treatment. Case 2 was high-grade B-cell lymphoma (HGBL) stage IV, tissue samples were collected before treatment at the initial diagnosis and peripheral blood samples were collected after treatment. Case 3 was DLBCLIV, tissue samples were collected at initial diagnosis and peripheral blood samples were collected during remission after treatment. Case 4 was DLBCL-IV B stage. Peripheral blood samples were collected before treatment at initial diagnosis and bone marrow samples were collected during remission after treatment. Case 5 was a case of hepatosplenic T-cell lymphoma (HSTL). Tissue samples before treatment and peripheral blood samples after treatment were collected at initial diagnosis and analyzed in combination with clinical efficacy. Results 2p -, 2q-, 3p-, 4p -, 6q-, 9p+, 10q-, 11q+, 19p + and 19q+ chromosome abnormalities were detected in the tissues and peripheral blood CNA of case 1, and the 3p -, 6q-, 9p +, 11q+ and 19q+ abnormalities were consistent. In case 2, 4p -, 9P +, 9p-, 16p+, 16q- and +X gene variants were detected in peripheral blood CNA than in tissue CNA at initial diagnosis. In case 3, obvious abnormal signals were detected in tissues at initial diagnosis, but no abnormal signals were detected in peripheral blood samples during remission. In case 4, obvious abnormal signals were detected in peripheral blood at initial diagnosis, but no abnormal signals were detected in bone marrow during remission. In case 5, obvious abnormal signals were detected in tissues at initial diagnosis, and a small amount of abnormal signals were detected in peripheral blood after treatment. The results of CNA detection in 5 patients were consistent with the clinical efficacy. All 3 DLBCL patients showed 6q-chromosome abnormalities in CNA test before treatment. Conclusion The results of CNA detection in peripheral blood are consistent with those in tissue and bone marrow. The dynamic monitoring results of in peripheral blood CNA can be used as a basis for monitoring the curative effect of lymphoma.

Hepatosplenic T-Cell Lymphoma Mimicking Acute Onset of Cholestatic Hepatitis in a Young Immunocompetent Man: A Case Report

We herein report a case of hepatosplenic T-cell lymphoma (HSTCL) incidentally found in a 30-year-old man who came to the emergency department after an ankle trauma. At admission, laboratory tests revealed abnormal liver enzymes and pancytopenia, and imaging showed mild hepatosplenomegaly. During hospitalization, the patient’s clinical condition worsened rapidly, with a concomitant increase in cholestatic enzymes, severe jaundice, and the worsening of pancytopenia. Causes of liver injury, including many infectious diseases, were explored until the diagnosis of HSTCL was made by liver and bone marrow biopsies. Subsequently, the patient underwent six cycles of chemotherapy with a CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) regimen and one with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) but, despite this aggressive treatment, died due to disease progression 2 months after diagnosis. This rare disease should be considered in the diagnostic workup of acute cholestatic hepatitis presenting with concomitant hepatosplenomegaly and cytopenia.

Expression pattern and diagnostic utility of BCL11B in mature T- and NK-cell neoplasms

BCL11B is an essential transcription factor for T-cell lineage commitment and differentiation, and its dysregulation has been shown to be associated with T-cell tumourigenesis. In this study, we investigated BCL11B expression by immunohistochemical analysis in 120 cases of mature T-cell lymphoma, 34 B-cell lymphomas, 11 NK-cell neoplasms and 17 reactive cutaneous conditions. All cases of mycosis fungoides (n=23), primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (n=8) and T-prolymphocytic leukaemia (n=6) were positive for BCL11B and the staining intensity was higher than that of reactive T-cells. Fourteen of 15 (93%) cases of angioimmunoblastic T-cell lymphoma, 10 of 12 (83%) T-large granular lymphocytic leukaemia and 14 of 20 (70%) peripheral T-cell lymphoma, not otherwise specified, were also positive for BCL11B with an intensity comparable to reactive T-cells. Other T-cell neoplasms were uncommonly positive including one of three (33%) cases of primary cutaneous gamma delta T-cell lymphoma, one of four (25%) cases of subcutaneous panniculitis-like T-cell lymphoma, one of four (25%) cases of hepatosplenic T-cell lymphoma, and one of 20 (5%) cases of anaplastic large cell lymphoma (8 ALK-positive, 12 ALK-negative). T-cells in reactive cutaneous infiltrates were also positive for BCL11B, but staining intensity was much weaker than in mycosis fungoides. All NK-cell (n=11) and B-cell neoplasms (n=34) were negative for BCL11B. In conclusion, BCL11B shows a distinct expression pattern in various T-cell neoplasms. BCL11B appears to have utility as another T-cell marker and may be useful in the differential diagnosis of lymphoid neoplasms.

Hepatosplenic T-cell lymphoma diagnosed using flow cytometry. A single-center study of 12 cases from North India.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare fatal T-cell neoplasm with unique clinical and laboratory features. There is, however, significant morphological and immunophenotypic heterogeneity which may lead to diagnostic dilemma. The study was aimed to study the prevalence and clinic-pathological spectrum of this rare variant of T cell lymphoma in the Indian subcontinent. A retrospective analysis of all consecutive cases of HSTCL diagnosed over a period of 6 years was carried out. The clinical and laboratory parameters of all these patient were reviewed and analysed. A total of 12 cases of HSTCL were diagnosed during this period which accounted for 1.76% of all non-Hodgkin's lymphomas (NHLs) and 9.1% of all T-cell NHLs. The median (range) age of presentation was 23 (16-30) years.Leukocytosis, peripheral blood (PB) involvement, and a blastic morphology were noted in 41%, 67%, and 58% of the cases, respectively. FCI proved these cells to have a mature, dual-negative (CD4-/CD8-) T-cell phenotype with a gamma-delta T-cell receptor restriction. Frequent loss of CD5 expression (84%) was also noted. These patients invariably had a fatal outcome and majority died within a year of diagnosis. The incidence of leukocytosis and a blastoid morphology is quite frequent in HSTCL. Hence, a differential diagnosis of HSTCL should always be considered in young patients presenting with splenomegaly and exhibiting atypical lymphoid/blastoid cells in the PB or a marrow. An FCI can readily diagnose and differentiate them from an acute lymphoblastic leukemia/lymphoma.

Outcomes in Patients with Enteropathy-Associated T-Cell Lymphoma (EATL) and Hepatosplenic T-Cell Lymphoma (HSTCL): A Population Based Analysis Using the SEER Data

Introduction and AimHepatosplenic T-cell lymphoma (HSTCL) and Enteropathy-associated T-cell Lymphoma (EATL) are rare aggressive peripheral T-cell lymphomas with dismal outcomes. Due to their rarity there is paucity of data on disease epidemiology and survival outcomes. We analyzed these rare diseases using Surveillance, Epidemiology and End Results (SEER) data to identify patient and disease factors that impact survival.MethodsUsing the SEER data, cases of HSTCL and EATL diagnosed between 1996 and 2014 were identified based on the ICD-O3 codes 9716 and 9717, respectively. Proportions were compared using chi-squared tests. Multivariable Cox proportional hazards models and stepwise regression were used to analyze disease-specific overall survival. Computations were performed in R.ResultsWe identified 122 patients with HSTCL and 163 with EATL; both had male predominance with 69% in HSTCL and 58% in EATL (p=0.07). Median age was 38 years (range 4-83) in HSTCL and 64 years (range 23-96) in EATL patients. The HSTCL group was much younger with 79% aged <55 years compared to only 26% in the EATL group (P=<0.0001) (Table 1). Although both groups were primarily Caucasian - 61% in HSTCL and 77% in EATL, 27% of HSTCL patients were of African American race. While the majority of the HSTCL (53%) were diagnosed in 2008-2014, 55% of EATL pts were diagnosed in 1996-2008. Disease characteristics also differed between these entities with HSTCL mostly being advanced stage (81%) and EATL largely early stage (58%) at diagnosis; 79% of HSTCL patients had stage IV compared to only 31% in EATL (p<0.0001). Treatments in HSTCL pts included chemotherapy (83%) surgery (43%) radiation therapy (10%). On the contrary, surgery (70%) was the most common treatment in EATL followed by chemotherapy (55%) and radiation therapy (3%). Median OS for EATL and HSTCL were 9 (95% CI 715) and 5 months (95% CI 37), respectively (log-rank P= 0.0018 (Figure 1A). In univariate analysis, surgery (HR: 0.62, 95% CI: 0.39-0.96, p=0.032), and radiation therapy (HR: 0.3, 95% CI: 0.16-0.96, p=0.042) was associated with superior OS, while there was increased risk of mortality with advanced age (HR: 1.6, 95% CI: 1.01-2.79, p=0.043) in HSTCL patients. Sex, race, marital status, year of diagnosis, use of chemotherapy and stage failed to predict survival in HSTCL. However, in EATL advanced stage (HR: 1.48, 95% CI: 0.99-2.20, p=.052) was associated with inferior OS and use of chemotherapy (HR: 0.46, 95% CI: 0.31-0.67, p=.0001) was a positive predictor for OS. On stepwise regression analysis, surgery (HR 0.57; p=0.014) and radiation therapy (HR 0.33; p= 0.019) were associated with improved survival in patients with HSTCL, whereas in EATL patients receiving chemotherapy improved survival (HR 0.42; p<0.001) (Figure 1B) and advanced stage correlated with reduced survival (HR 1.60; p=0.01).ConclusionTo our knowledge, this is the first and largest United States population based study of patients diagnosed with HSTCL and EATL. Our analysis showed that HSTCL is commonly diagnosed in younger, males with increased incidence in African American population compared to EATL. Although surgical interventions were commonly used in both entities, it was more frequent in EATL. While surgery and radiation improved survival in HSTL, chemotherapy was the significant factor in EATL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hypercalcaemia: An Extremely Rare Presentation of Hepatosplenic T-Cell Lymphoma.

Hepatosplenic T-cell lymphoma (HSTCL) is difficult to diagnose, has a poor prognosis and usually presents with hepatosplenomegaly, B symptoms and cytopenias.Hypercalcaemia is an extremely rare clinical presentation of HSTCL.Severe hypercalcaemia is a life-threatening condition and should always be corrected and investigated.

Risk of Cancer in Pediatric-Onset Inflammatory Bowel Diseases: A Nation-Wide Study from the Epi-Iirn

Background: Pediatric-onset IBD (PIBD) is characterized by a more extensive phenotype than adults and a higher utilization of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments. Methods: PIBD cases were included from the epi-IIRN cohort , covering 98% of the Israeli population from 2005, linked to the national cancer registry. We matched PIBD cases to non-IBD children for calculating the cumulative incidence of cancer. Finding: 3,944 PIBD cases were included (2,642 [67%] Crohn's disease, 1,302 [33%] ulcerative colitis) translating into 23,635 person-years of follow-up , individually matched to 13,005 non-IBD children. By 30 years of age, 14 IBD patients (0.35%, 5.9/10,000 patient-years) were diagnosed with cancer and one (0.03%) with haemophagocytic-lymphohistiocytosis (HLH), compared with 14 (0.11%, 1.9/10,000 patient-years) cases of cancer (OR 2.5 [95%CI 1.05-6.2]; p=0.04) and no HLH in the comparison-group. There were no cases of hepatosplenic T-cell lymphoma, adenocarcinoma or cholangiocarcinoma. Cancer risk was 15.6 cases/10,000 person-years in those treated with thiopurines alone (OR compared with those never exposed to either thiopurines or anti-tumor necrosis factor (TNF) 1.8 (95%CI 0.6-6.1); p=0.2), 11.1/10,000 in those treated with anti-TNF alone (OR 1.3 [95%CI 0.3-6.6]; p=0.5), and 23.1/10,000 treated with combination therapy of anti-TNF and thiopurines (OR 2.8 [95%CI 0.6-13.8]; p=0.2). Interpretation: PIBD confers an increased risk for malignancy compared with non-IBD children. The risk was not statistically associated with treatment, likely since the absolute risk was very low. Funding Statement: None to declare. Declaration of Interests: ID- Has received consultation fee, research grant or honorarium from Janssen, Pfizer, Abbvie, Takeda, Genentech/Roche, Neopharm, Ferring, Rafa Laboratories, Falk Pharma, Nestle, Given Imaging/Medtronic, Gilead, Celgene, Arena, Sublimity, Celltrion Altman Research; DT - Has received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Biogen, Neopharm, Uniliver, Atlantic Health, Shire, Celgene, Lilly, Roche; all other authors have nothing to declare. Ethics Approval Statement: This study was approved by the local ethics committee.

Systematic review: hepatosplenic T-cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, poorly treatable malignancy associated with therapy for IBD. Current knowledge of HSTCL risk in IBD comes from an era of step-up therapy, before earlier use of biologics or combination therapy was advocated to achieve deep mucosal healing. HSTCL risk among newer biologic classes has also not been evaluated. To systematically characterise the association of HSTCL with biologic therapy for IBD. We conducted a literature search and query of the Food and Drug Administration Adverse Event Reporting System to summarise HSTCL cases among IBD patients with prior biologic exposure. Demographics and immunosuppression exposure were extracted. Patients were stratified by current regimen (combination therapy, biologic monotherapy or no biologic), and biologic class (anti-TNF, anti-integrin, anti-interleukin 12/23). Sixty-two cases of HSTCL were identified from 2486 abstracts and 181 FDA Adverse Events Reporting System reports. The median age of affected patients was 28years (range 12-81), and 83.6% were male, 84.7% had Crohn's disease. Five of 62 patients had no reported azathioprine/mercaptopurine exposure. Three patients within the cohort developed HSTCL after exposure to natalizumab, vedolizumab or ustekinumab; all three also had anti-TNF and azathioprine/mercaptopurine exposure. Forty-three of 49 (87.8%) patients with known outcomes died with a median survival of 5months. Consistent with existing data, almost all identified HSTCL cases among IBD patients on biologic therapy had azathioprine/mercaptopurine exposure, and all cases on patients exposed to biologics had anti-TNF exposure. These data suggest initiating a patient-centred discussion before starting anti-TNF therapy or other biologics.

2059 A Case of Hepatosplenic T-cell Lymphoma in a Patient on Vedolizumab for Crohn’s Disease

INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL) is a rare malignancy, most commonly affecting young males with often fatal prognosis. In patients with inflammatory bowel disease (IBD), HSTCL has been associated with thiopurine analog and tumor necrosis factor (TNF)-α inhibitor therapy; particularly when used in combination, the risk increases up to 4 fold. Development of HSTCL has not been reported in association with vedolizumab. CASE DESCRIPTION/METHODS: A 22-year-old male with severe, stricturing colonic Crohn’s disease of 10 years duration, on vedolizumab monotherapy every 4 weeks for 15 months, was incidentally noted to be pancytopenic in October 2016 and subsequently diagnosed with HSTCL by bone marrow biopsy. Previous IBD therapies included mesalamine, azathioprine, infliximab, adalimumab, intravenous immunoglobulin (IVIG), budesonide, certolizumab pegol and most recently 6 mercaptopurine (6-MP). The 6-MP was discontinued 1 year prior to HSTCL diagnosis. He achieved remission with chemotherapy, followed by autologous stem-cell transplant in September 2017. Unfortunately his disease relapsed only a few months later. He achieved a second remission with salvage chemotherapy, and proceeded to allogeneic bone marrow transplant in April 2018. Since diagnosis of HSTCL, he did not receive any therapy for Crohn’s disease and has been asymptomatic from his IBD. Colonoscopy demonstrated complete endoscopic and histologic remission as well. On last bone marrow biopsy, over 200 days post-transplant, there was no evidence of HSTCL relapse 24 months following HSTCL diagnosis. DISCUSSION: Fortunately, our case had a favorable outcome compared to those reported in the literature with a median overall survival of 10 months, and up to 17 months in patients who receive stem cell transplant. In addition, following stem cell transplant, our patient achieved cure of his Crohn’s disease. A recent review of patients with immunoregulatory disorders who developed HSTCL noted that 56% of patients were treated with TNF-α inhibitors versus 89% with immunomodulators, indicating that the latter pose higher risk. To our knowledge, there have not been reports of HSTCL associated with vedolizumab use nor is there a known mechanism by which vedolizumab could cause HSTCL. In our case, TNF-α inhibitor was stopped 5 years prior and thiopurine analog 1 year prior to diagnosis, raising the question as to how long the risk of HSTCL remains elevated after cessation of such agents.

A rare case of hepatosplenic γδ T-cell lymphoma expressing CD19 with ring chromosome 7 and trisomy 8

Hepatosplenic T-cell lymphoma (HSTL) is a rare subtype of peripheral T-cell lymphoma predominantly seen in young males. This disease presents with isolated hepatosplenomegaly and thrombocytopenia with sinusoidal infiltration of liver and sinusal infiltration of spleen. Immunophenotype shows positivity for CD3, CD7, TCRγδ or TCRαβ, CD38 and double negative for CD4, CD8, TdT, CD5, and CD56. Isochromosome 7q with or without trisomy 8 is seen in HSTL. Recently, ring chromosome 7 has also been identified as a new abnormality. We describe the clinical, immunophenotypic and cytogenetic analysis in a 24-year-old woman. We present an unusual case of TCRγδ positive T-cell lymphoma with aberrant expression of CD19, which is a B-cell lymphoid marker, with amplification of 7q region and subsequent formation of ring chromosome 7 and trisomy 8. This is the second case of HSTL, positive for CD19 and first case presenting with ring chromosome 7 and trisomy 8 in a CD19 positive HSTL which is a rare finding in T-cell lymphoma and needs to be explored further.

Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

BackgroundLymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma...

Distinguishing Between Hepatosplenic T-cell Lymphoma and γδ T-cell Large Granular Lymphocytic Leukemia: A Clinicopathologic, Immunophenotypic, and Molecular Analysis.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive T-cell lymphoma that can be challenging to diagnose. In particular, distinguishing HSTCL from T-cell large granular lymphocytic (T-LGL) leukemia of γδ T-cell receptor (TCR) type is difficult without examination of a splenectomy specimen. In this study, we systematically assessed a series of HSTCL cases for findings reported in the literature as supporting or not supporting the diagnosis of HSTCL. We also compared HSTCL with a group of cases of T-LGL of γδ TCR type. Criteria assessed in this study included: B-symptoms, massive splenomegaly, lymphadenopathy, extranodal involvement, peripheral lymphocytosis, lymphoma cells that expand bone marrow sinuses, lymphocyte azurophilic granules, immunophenotype, evidence of infection by Epstein-Barr virus, human immunodeficiency virus, or human T-cell leukemia virus type 1, isochromosome 7q, trisomy 8, and TCR gene rearrangement status. On the basis of the data of this study, we conclude that massive splenomegaly, bone marrow sinusoidal expansion by lymphoma cells, and lymphocytes devoid of azurophilic granules were significantly more common in HSTCL patients than in γδ T-LGL patients (P<0.0001), and these features help support the diagnosis of HSTCL.

Hepatosplenic T-cell lymphoma arising in patients with immunodysregulatory disorders: a study of 7 patients who did not receive tumor necrosis factor-α inhibitor therapy and literature review.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis. In 6 patients, medication history for the immune disorder was available: 6 patients received 6-mercaptopurine or azathioprine, and 2 patients received steroids; no patients received TNF-α inhibitors. In all 7 patients, the histologic, immunophenotypic, and cytogenetic findings were similar to cases of HSTCL that arise in immunocompetent patients. We reviewed the literature and identified 60 patients with immune disorders who subsequently developed HSTCL. These patients were treated with immunosuppressive drugs in 89%, TNF-α inhibitors in 56%, and both therapies in 54%, and 1 (2%) patient was treated with TNF-α inhibitors only. Our cohort and literature review indicates that TNF-α inhibitor therapy is not essential for the development of HSTCL in patients with immunodysregulatory disorders, and implies that immunosuppressive drugs or other factors (eg, genetic predisposition, chronic antigenic stimulation) may be more critical in the pathogenesis in this context. Although these data are observational, they have implications for the use of TNF-α inhibitors in patients with inflammatory bowel disease and other immunodysregulatory disorders.

Two Cases of Hepatosplenic T-Cell Lymphoma in Adolescents Treated for Autoimmune Hepatitis

We report the first 2 cases of hepatosplenic T-cell lymphoma in adolescents diagnosed with autoimmune hepatitis under long-term treatment with azathioprine. Patients presented with fatigue, hepatosplenomegaly, and pancytopenia. The diagnosis could be confirmed performing biopsies of liver and spleen or bone marrow, which demonstrated infiltration of neoplastic T lymphocytes with the typical phenotype with both markers, CD56(+) and TCRγδ(+) Thus, these cases emphasize the need to constantly reevaluate the administered dose and duration of thiopurines for autoimmune hepatitis, especially in adolescents.

The Risk of Hepatosplenic T-Cell Lymphoma (HSTCL) in Women with Inflammatory Bowel Disease (IBD) on Thiopurines

Hepatosplenic T-cell Lymphoma (HSTCL) is a rare and often fatal malignancy classically thought to affect males less than 35 years of age with Inflammatory Bowel Disease (IBD) on thiopurines. Even though HSTCL is thought to affect predominantly young males with IBD, it can occur in female patients as well. We report a case of HSTCL in a young female patient with ulcerative colitis (UC), the 6th female case of IBD-associated HSTCL reported in the literature. Although the risk of developing HSTCL may be lower in women, it remains a substantial concern given the aggressive nature of this disease.

Four hepatosplenic T-cell lymphoma cases of Japanese patients

Hepatosplenic T-cell lymphoma (HSTCL), a rare type of γδ T-cell lymphoma, is characterized by hepatosplenomegaly and cytopenias. It is associated with immunodeficiency and its age of onset is reportedly between the 20s and 30s. We herein report 4 Japanese HSTCL cases. Three of them, including an elderly case that was 74 years of age, were not at adolescence. No cases had a history of immunodeficiency. All other disease phenotypes were similar to the typical HSTCL cases. These findings suggest that there are a certain proportion of HSTCL patients who presented after middle age.

Benefits and risks of combining anti-tumor necrosis factor with immunomodulator therapy in pediatric inflammatory bowel disease.

Since the introduction of anti-tumor necrosis factor (TNF) therapy as treatment of inflammatory bowel disease (IBD), care of pediatric and adult patients with IBD has significantly improved. To further improve treatment efficacy and durability, multiple trials have compared the efficacy of combination therapy, using anti-TNF therapy combined with an immunomodulator (a thiopurine or methotrexate), with that of anti-TNF monotherapy with contradicting results. The safety of combined therapy has been questioned after several reported cases of hepatosplenic T-cell lymphoma in young patients with IBD so treated. Physicians prescribing anti-TNF therapy to patients with IBD are required to weigh the benefits of combined therapy with its risks. To inform physicians treating children with IBD of these benefits and risks, we reviewed studies in pediatric and adult patients with IBD comparing efficacy, durability, and/or safety of combined therapy with anti-TNF monotherapy.

Hepatosplenic T-cell lymphoma: Report of two cases

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Presenting with hepatosplenomegaly, fever, cytopenia without significant lymphadenopathy, most patients are young men with poor outcomes. Here is the report of two cases of HSTCL from Maharaj Nakorn Chiang-Mai Hospital, Thailand. Both patients were middle-aged men presented with prolonged fever, hepatosplenomegaly and cytopenia. Abnormal lymphoid cells, not demonstrated by flow cytometry, were microscopically revealed in the patients’ bone marrow. The diagnosis of HSTCL was based on the histopathologic section obtained from splenectomy and liver biopsy. Both patients received cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) regimen initially while one of them was salvaged with etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) and methotrexate, high-dose cytarabine, methylprednisolone (cycle B of hyperCVAD) regimen. They responded poorly to chemotherapy and succumbed to severe sepsis. The presented cases confirmed that HSTCL is very difficult to diagnose and current treatment modalities appear to be ineffective

Use of case reports and the Adverse Event Reporting System in systematic reviews: overcoming barriers to assess the link between Crohn’s disease medications and hepatosplenic T-cell lymphoma

BackgroundTo identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn’s disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn’s disease.MethodsWe identified cases of HSTCL in Crohn’s disease in studies included in a comparative effectiveness review of Crohn’s disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL.ResultsWe found 37 unique cases of HSTCL in patients with Crohn’s disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn’s disease based on the data contained in the case reports.ConclusionSystematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than ‘possible’ between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication.

A Case of Hepatosplenic T-cell Lymphoma Diagnosed by Bone Marrow Examination

환자는 34세 베트남인 여자로, 내원 2개월 전 좌상복부 통증을 주소로 베트남 현지병원 진료 후, 백혈병 추정진단 하에 methylprednisolone, 6-mercaptopurine (6-MP)을 복용하던 중, 국내 입국 하여 본원 혈액종양 내과 외래로 방문하였다. 내원 당시 환자는 오 심, 좌상복부 통증, 두통을 호소하였고, 진찰 소견상 의식은 명료 하였으나 만성 병색을 보였으며, 체온은 37.2°C였다. 복부 진찰에서 간은 우측 늑골 아래로 1 cm, 비장은 좌측 늑골 아래로 7-8 cm 만 져졌다. 그러나 경부, 액와부 및 서혜부 림프절비대는 관찰되지 않 았다. 일반혈액 검사에서 백혈구수 5.22×10/L, 헤모글로빈 12.7 g/dL, 혈소판수 30×10/L로 극심한 혈소판감소증을 보였으며, 프 로트롬빈시간(prothrombin time, PT) 15.2초, 활성화부분트롬보 플라스틴시간(activated partial thromboplastin time, aPTT) 43.5초 서 론