Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive malignancy that has been associated with thiopurines during the treatment of inflammatory bowel disease (IBD). We present a case of a 26-year-old man with Crohn's disease on infliximab without prior thiopurine exposure who developed HSTCL. His diagnosis was confirmed through flow cytometry, fluorescence in situ hybridization, and bone marrow biopsy. This is the sixth case of HSTCL in patients with IBD without prior thiopurine exposure and highlights the need for a comprehensive risk-benefit discussion with patients on the various treatment modalities for IBD.

This research study was conducted to examine the clinical characteristics and post-splenectomy survival outcomes of patients diagnosed with hepatosplenic T-cell lymphoma (HSTCL).

A total of 10 cases of HSTCL patients admitted to the Hematology Department of Fudan University Affiliated Huadong Hospital between January 2012 and December 2021 were included. In addition, we also included 30 other cases reported from domestic and international sources. All pathological specimens were stained with hematoxylin and eosin (H&E) and immunohistochemistry, with color development using DAB staining. Survival analysis was conducted using Kaplan-Meier curves and log-rank tests.

In the 10 HSTCL patients, Epstein-Barr virus (EBV) infection was confirmed. Six patients had died, with 5 of them within 1 year of disease onset. Survival analysis showed poorer prognosis in patients with hemophagocytic syndrome and thrombocytopenia. Patients who underwent splenectomy followed by chemotherapy had a higher median and average survival time compared to those who only received chemotherapy. The study included a total of 40 HSTCL patients, with 29 males and 11 females, and an average age of onset at 42.3 years. All patients presented with fever, with some exhibiting emaciation and/or hemophagocytic syndrome. Splenomegaly, hepatomegaly, lymphadenopathy, and bone marrow involvement were found in the patients. Common laboratory findings included leukopenia, anemia, and thrombocytopenia. All patients exhibited elevated ferritin levels and decreased blood calcium levels.

Those patients suffering from hemophagocytic syndrome at the onset of this disease face greater treatment-related difficulties and a higher risk of mortality. Combined chemotherapy after splenectomy may improve HSTCL patient survival.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes, representing less than one percent of non-Hodgkin lymphomas. Given its rarity, the true incidence of HSTCL is unknown and most data have been extrapolated through case reports. To the best of our knowledge, the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014, with a sample size of 122 patients.

To paint the most updated epidemiological picture of HSTCL.

A total of 186 patients diagnosed with HSTCL, between 2000 and 2017, were ultimately enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of HSTCL. Variables with a P value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio of greater than 1 representing adverse prognostic factors.

Male gender was the most represented. HSTCL was most common in middle-aged patients (40-59) and less common in the elderly (80+). Non-Hispanic whites (60.75%) and non-Hispanic blacks (20.97%) were the most represented racial groups. Univariate Cox proportional hazard regression analysis of factors influencing all-cause mortality showed a higher OM among non-Hispanic black patients. CSM was also higher among non-Hispanic blacks and patients with distant metastasis. Multivariate Cox proportional hazard regression analysis of factors affecting CSM revealed higher mortality in patients aged 80 or older and non-Hispanic blacks.

Overall, the outlook for this rare malignancy is very grim. In this retrospective cohort study of the United States population, non-Hispanic blacks and the elderly had a higher CSM. This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group, such as treatment delays, which have been shown to increase mortality in this racial/ethnic group for other cancers.

T-cell lymphomas (TCLs) are a group of rare subtypes of non-Hodgkin lymphoma derived from mature T-lymphocytes. Recent updates in lymphoma classification based on the cell-of-origin pathogenesis have shed new light on TCL epidemiology and outcomes. Contemporary regional consortia and international studies, including those conducted recently in Asia and South America, have provided an updated delineation of the major subtypes across various global regions.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), remains the most common subtype globally except in Asia, where extra-nodal NK-T cell lymphoma (ENKTL) has emerged as the most prevalent. Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype globally except in South America where its incidence falls behind adult T-cell leukemia/lymphoma (ATLL) and ENKTL. ALK-negative anaplastic large cell lymphoma (ALCL) has been recognized as the second most common subtype in some parts of South America. Studies on the newly classified breast implant-associated ALCL (BIA-ALCL) are beginning to reveal its distribution and risk factors. Deciphering the epidemiology of TCLs is a challenging endeavor due to the rarity of these entities and ongoing refinement in classification. Collaborative efforts on prospective registries based on the most current WHO classifications will help capture the true epidemiology of TCL subtypes to better focus resources for diagnostic, prognostic, and therapeutic efforts.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients. Fifty-three patients with HSTCL were included in the study. Thirty-six patients received an allo-HCT and 17 received an auto-HCT. Thirty-five (66%) were males. Median age at diagnosis was 38 (range 2 to 64) years. Median follow-up for survivors was 75 months (range 8 to 204). The median number of prior lines of therapy was 1 (range 1 to 4). Median OS and progression-free survival (PFS) for the entire cohort were 78.5 months (95% CI: 25 to 79) and 54 months (95% CI: 18 to 75), respectively. There were no significant differences in OS (HR: 0.63, 95% CI: 0.28 to 1.45, P = .245) or PFS (HR: 0.7, 95% CI: 0.32 to 1.57, P = .365) between the allo-HCT and auto-HCT groups, respectively. In the allo-HCT group, the 3-year cumulative incidence of relapse was 35% (95% CI: 21 to 57), while 3-year cumulative incidence of NRM was 16% (95% CI: 7 to 35). In the auto-HCT group, the 3-year cumulative incidence of relapse and NRM were 43% (95% CI: 23 to 78) and 14% (95% CI: 4 to 52), respectively. Both Auto-HCT and Allo-HCT are effective consolidative strategies in patients with HSTCL, and patients should be promptly referred for HCT evaluation.

Hepatosplenic T cell lymphoma is a rare subtype of non-Hodgkin lymphoma affecting younger adult men and immunocompromised individuals. The neoplastic cells typically express surface CD3, CD2 and CD7. We report a rare case of hepatosplenic T cell lymphoma with an aberrant loss of sCD3 at diagnosis.This case report is written based on reviewing electronic health data, liver biopsy histology, bone marrow biopsy and conventional cytogenic analysis. Literature search for case reports were conducted on PubMed database and Google Scholar.Our case presents a de novo hepatosplenic T cell lymphoma with loss of surface CD3 expression on immunohistochemistry and flow cytometry. The unusual immunophenotype has been reported in three previous cases, and likely contributed to a delay in diagnosis of our patient.Hepatosplenic T cell lymphoma with loss of surface CD3 expression is a rare histological presentation which warrants further research into its prognostic significance. This unusual presentation can cause delay in diagnosis.

T Cells comprise many subtypes of specified lymphocytes, and their differentiation and function take place in different tissues. This cellular diversity is also observed in the multiple ways T-cell transformation gives rise to a variety of T-cell neoplasms. This review covers the main types of T-cell malignancies and their specific characteristics, emphasizing recent advances at the cellular and molecular levels as well as differences and commonalities among them.

TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers.

We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, N = 10,263). Skin cancer cases [nonmelanoma skin cancer (NMSC, N = 501), basal cell carcinoma (BCC, N = 161), squamous cell carcinoma (SCC, N = 150)] and cancer-free controls (N = 30,475) were selected from Medicare beneficiaries residing in SEER areas. Cases and controls had prior Medicare claims-based evidence for rheumatoid arthritis, and TNFi exposure was ascertained from part B and part D claims. Logistic regression was used to estimate adjusted odds ratios (aOR).

TNFi exposure was present in 16.2% of controls and 12.8% to 33.7% of cancer cases, varying by site. TNFi use was associated with increased risk of NMSC overall (aOR 1.32, 95% confidence interval 1.06-1.63), non-Hodgkin lymphoma (NHL) overall (1.28, 1.06-1.56) and, specifically, follicular lymphoma (2.63, 1.63-4.24). TNFi exposure was not associated with other SEER cancer sites, BCC or SCC specifically, or other common NHL subtypes.

Among older adults with rheumatoid arthritis, TNFi exposure was associated with elevated risk of NMSC and NHL, driven specifically by follicular lymphoma. Exposure was not associated with increased risk for other cancer sites.

Our results support a role for TNF in lymphomagenesis. Given the association with NMSC, patients initiating TNFi therapy may benefit from skin cancer screening and sun protection measures.

The discrimination of benign from malignant lymphoproliferative disorders is sometimes difficult because there can be overlap in their histological and immunophenotypic features. In such situations, molecularly based clonality testing is often used to discriminate benign (polyclonal) from malignant (monoclonal) processes. Clonality testing by polymerase chain reaction (PCR) has a number of pitfalls that may result in spurious results. Here we report the case of a woman diagnosed by 2 major academic institutions with hepatosplenic T-cell lymphoma based on a dense infiltration of the spleen by a γδ T-cell population with mild cytologic atypia, resulting in expansion of the splenic red pulp, and a positive T-cell receptor clonality test by PCR. There was likewise mild involvement of the liver and bone marrow by the "atypical" T-cell population. Close attention to her uncharacteristically well clinical appearance led to repeat T-cell receptor clonality testing using next-generation sequencing. Definitive demonstration of polyclonality by this test showed that she in fact did not have hepatosplenic T-cell lymphoma but rather a reactive condition, and allogeneic stem cell transplantation could be safely avoided. As molecular clonality testing is widely used in the practice of hematology, this case brings attention to the pitfalls of clonality testing by PCR that practitioners may encounter. It is therefore a cautionary tale highlighting the need for critical interpretation of test results in full clinical context.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma accounting for less than 1% of non-Hodgkin lymphomas. It is generally associated with poor prognosis.

We performed a cohort study of patients with HSTCL treated at the Mayo Clinic between 1996 and 2020 exploring the clinical characteristics and therapeutic outcomes.

Twenty-two cases of HSTCL were identified with a median (range) age at diagnosis of 45.5 (15.5-80.6) years and a male predominance (15/22, 68.2%). Clinical characteristics include massive splenomegaly in 16 patients (73%), hepatic involvement in 13 (59%), and chronic immunosuppressed state in 8 (36%). Phenotypically, lymphoma cells had gamma/delta T-cell receptor expression in 18 (82%) and alpha/beta in 4 patients. Cytogenetic abnormalities included isochromosome 7q (i7q) in 8 (62%) of 13 and trisomy 8 in 4 (44%) of 9. The median (range) follow-up of surviving patients was 33 (2.5-137) months. The median progression-free and overall survival were 9.5 months (95% CI, 1.8, 16.3) and 12.4 months (95% CI, 4.9, 18.5), respectively. Long-term survival was seen in 4 (18%) of 22 patients, with survival of 55, 74, 95, and 137 months. Moreover, 3 of 4 long-term survivors had splenectomy as part of initial treatment, and 2 of 4 long-term survivors received an allogeneic hematopoietic cell transplant (allo-HCT).

Liver involvement and chronic immunosuppression were associated with shorter survival. Although splenectomy and allo-HCT have anecdotal benefit in the literature, our data do not show a statistically significant benefit of splenectomy and/or allo-HCT, likely as a result of our small sample size.

A 45-year-old woman was diagnosed with hepatosplenic T-cell lymphoma (HSTCL), a rare subtype of peripheral T-cell lymphoma. She received different types of chemotherapy, but disease progression was observed. To reduce the tumor burden before an unrelated bone marrow transplantation, combination chemotherapy consisting of the gemcitabine, carboplatin, and dexamethasone (GCD) was administered as bridging therapy, resulting in a reduction in the number of lymphoma cells. We were then able to perform bone marrow transplantation. Although she experienced some adverse events, she successfully achieved long-term remission. We herein report a successful case of HSTCL treated with unrelated stem cell transplantation following the GCD regimen as bridging chemotherapy.

Hepatosplenic gamma-delta T-cell lymphoma with concurrent hemophogocytic lymphohistiocytosis is a rare but well-recognized clinical scenario, associated with a grim prognosis. Clinicians must be aware of this aggressive type of lymphoma so that a prompt diagnosis can be made with timely initiation of systemic therapy and referral for bone marrow transplant.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that arises most often in adolescents and young adults. Patients with HSTCL commonly present with B-symptoms and cytopenias, which may suggest a diagnosis of acute leukemia initially. Patients present with extranodal disease involving the spleen, liver and bone marrow; lymphadenopathy is usually absent. The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage, often negative for CD4 and CD8 and positive for T-cell receptor γδ or, less often, αβ. Recent studies have identified gene mutations in oncogenic pathways that are likely involved in pathogenesis and may be targets for therapy. Mutations in STAT3 or STAT5B lead to activation of the JAK/STAT pathway, and mutations involving SETD2, IN080 and ARID1 are involved in chromatin modification. Currently, there is no consensus standard of care for HSTCL patients, although several studies support a role for allogeneic hematopoietic stem cell transplant. Although patients with HSTCL are best treated in the context of clinical trials, the rarity of these neoplasms likely necessitates a multi-institutional approach. In this review, we focus on the clinicopathologic and genetic characteristics of HSTCL. We also discuss the differential diagnosis and therapeutic approaches.