[Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases].

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Angioimmunoblastic T-cell Lymphoma Mimicking Systemic Lupus Erythematosus: A Case Report and Literature Review.

Objective: This study aimed to investigate the clinical features of angioimmunoblastic T-cell lymphoma (AITL) mimicking systemic lupus erythematosus (SLE) and raise awareness about AITL among rheumatologists in order to prevent misdiagnosis and missed diagnosis. The study reports on a case of AITL mimicking SLE and provides a literature review. Methods: Using key words as search terms, relevant articles published in PubMed before 2022-05 were searched, and their clinical characteristics were collected and analyzed. Results: The literature review retrieved six case reports, including four cases initially diagnosed with SLE and then with AITL. The other two case diagnoses were SLE and AITL, respectively. The two diseases are pathogenically associated and share some common features. The clinical manifestations of AITL are complex. The disease is closely associated with abnormal immune functions and is highly heterogeneous. Conclusion: Patients with AITL generally have a poor prognosis. Rarely do reported cases show AITL mimicking SLE. AITL should be considered during clinical practice to prevent missed diagnoses or misdiagnoses.

Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.

Spontaneous remission of angioimmunoblastic T-cell lymphoma in a child with ataxia-telangiectasia: a case report.

BACKGROUND: Angioimmunoblastic T-cell lymphoma is an uncommon subtype of peripheral T-cell lymphoma in children with fewer than 20 cases reported in literature. CASE PRESENTATION: A 3-year-old Omani boy was diagnosed with ataxia-talengectasia presenting with fever and generalized lymphadenopathy. His biopsy revealed atypical lymphocytic infiltrate consistent with the diagnosis of angioimmunoblastic T-cell lymphoma. Within 3 weeks from the initial presentation and without any neoadjuvant therapy, he showed complete recovery of symptoms with absence of fever and regression of all previously affected lymph nodes. He has remained in remission ever since. CONCLUSION: This is the first report of spontaneous improvement of angioimmunoblastic T-cell lymphoma in a patient with ataxia-telangiectasia who was 3 years old at presentation. Owing to the paucity of similar cases, this report adds valuable diagnostic, therapeutic, and monitoring data.

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study.

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.

Angioimmunoblastic T-Cell Lymphoma Diagnosed From Serous Effusion by Integration of Cytologic Features and Ancillary Studies.

OBJECTIVES: To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized. RESULTS: Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation. CONCLUSIONS: This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

Cytomorphological characterisation of angioimmunoblastic T cell lymphoma: a case-control study.

AIMS: Angioimmunoblastic T cell lymphoma (AITL) is often misdiagnosed in cytology. Hence, the present study was conducted to identify the distinctive cytomorphological features of AITL in lymph node fine-needle aspirates (LN-FNA). METHODS: This was a 4-year retrospective case-control study. Cases included LN-FNAs from patients with histopathologically confirmed AITL. The controls included LN-FNAs from patients with histopathologically confirmed reactive lymphoid hyperplasia (RLH; n=25). Eleven cytomorphological features were assessed in all the aspirates; the strength of association was determined by OR, Cramer's V and multiple correspondence analysis (MCA). RESULTS: Of a total of 22 cases of AITL reported on histopathology, 19 adequate aspirates from 14 patients (63.6%) were available for review. On univariate analysis, 5 of 11 cytomorphological variables were found to be significant for AITL; however, on MCA, 3 of these parameters, viz absence of tingible body macrophages (OR=0.014; V=0.74), presence of atypical lymphoid cells (OR=10.8; V=0.41) and singly scattered epithelioid cells (OR=19.3; V=0.31), were found to be the strongest predictors of AITL. CONCLUSIONS: The absence of tingible body macrophages, presence of atypical lymphoid cells and singly scattered epithelioid cells in polymorphic LN-FNAs are significant cytomorphological predictors of AITL in comparison with RLH. Knowledge of these diagnostic predictors, supplemented by clinicoradiological correlation and appropriate ancillary studies, can help diagnose AITL on aspiration cytology.

Cardiac Tamponade as a Recurrence of Angioimmunoblastic T-Cell Lymphoma with the Detection of a p.Gly17Val RHOA Mutation in the Pericardial Effusion.

Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.

Flow Cytometry Analysis Reveals a Wide Cytologic and Immunophenotypic Spectrum of Peripheral B Lymphocytes in Angioimmunoblastic T-Cell Lymphoma.

INTRODUCTION: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma commonly associated with B-cell dysregulation. Correlations involving B-cell dysregulation and clinicopathological features remain unclear. METHODS: We prospectively collected blood samples from 11 AITL patients and 17 healthy controls. The percentages of B-cell subpopulations and lymphocytes with IL-21 production were assessed using flow cytometry. Peripheral blood lymphocyte morphology was evaluated microscopically. RESULTS: Six of 11 (54.5%) patients presented with polyclonal hypergammaglobulinemia. Three of 11 (27.3%) tumor biopsies showed monoclonal immunoglobulin gene rearrangement. The patients exhibited significantly lower levels of naive (p < 0.001) and class-switched (p < 0.001) B cells than controls. The percentages of IgD-CD27- B cells (p = 0.007) and antibody-secreting cells (ASCs) (p = 0.001) were increased. Blood smears revealed atypical lymphocytes and immature plasma cells with morphological diversity. In comparison to normal controls, IL-21 production significantly increased in CD4+ (p < 0.001) and CD8+ (p = 0.020) T cells. B-cell clonality, RHOA G17V mutation, and the presence of sheets of clear cells and immature/mature plasma cells in lymph nodes were significantly associated with percentages of class-switched B cells and ASCs. The patients with circulating EBV DNA had a lower percentage of naive B cells (p = 0.009). CONCLUSIONS: Our results demonstrated a wide spectrum of peripheral B-cell morphologies and immunophenotypes of peripheral B cells in AITL. These findings correspond to dysregulated B-cell immunity and heterogeneous clinicopathological features.

Plasmacytic Pleural Effusion as a Major Presentation of Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Angioimmunoblastic T-cell lymphoma is one of the peripheral T-cell lymphomas. Reactive plasma cells can occasionally be observed in AITL patients' peripheral blood and bone marrow. Plasmacytic pleural effusion as the presentation of AITL has not been reported before. The mechanisms of plasmacytic pleural effusion are not fully understood. Here we present an 82-year-old male with exuberant plasma cells in his pleural effusion in addition to his peripheral blood and bone marrow aspiration. By presenting this case, we would like to expand the spectrum of disease presentations in AITL and discuss the significance of flow cytometry in the differential diagnosis of pleural effusion. To our knowledge, this is the first case report in the literature, which will be crucial to assist the hematopathologist in accurate diagnosis and treatment.

Angioimmunoblastic T-cell lymphoma with elevated serum IgA and infiltration of IgA-positive plasma cells into a skin lesion.

Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common types of peripheral T-cell lymphoma. Laboratory examination exhibits immunological abnormalities, such as polyclonal hypergammaglobulinemia and hemolytic anemia. Skin lesions are also observed in approximately half of AITL cases. However, the relationship of skin involvement with the clinical course and prognosis is unknown. Herein, we report the case of a patient with AITL with elevated serum immunoglobulin A (IgA) level, which was a predictive element of poor prognosis, and infiltration of IgA-positive plasma cells into the skin lesions. Based on this case, we believe that skin manifestations could be used to identify the characteristics of immune disorders and prognosis of AITL.

[A Case of Angioimmunoblastic T-cell Lymphoma (AITL)].

A 84-year-old female noticed erythema over her whole body for several months and was referred to our department for evaluation of her skin eruption. A physical examination revealed millet-sized erythematous papules and macules all over her body, a high body temperature, and a decreased level of consciousness. A laboratory examination showed an elevated white blood cell count (8200/µl), atypical lymphocytes (3%) and sIL-2R (4030U / ml). Computed Tomography showed systemic lymphadenopathy. A lymph node biopsy taken from the left inguinal lymph node revealed destruction of the lymph nodes, enlargement of the high endothelial venules, and atypical lymphocyte infiltration. Based on the clinical findings and laboratory examination, we diagnosed angioimmunoblastic Tcell lymphoma (AITL). AITL is a relatively rare peripheral T-cell lymphoma with severe systemic symptoms such as fever and lymph node swelling. While approximately half of all cases experience skin symptoms, which are one of the initial symptoms, it is difficult to determine the diagnosis due to the various clinical features or many non-specific rashes. We should keep in mind a differential diagnosis of lymphoma in cases of the presence of persistent eruption, systemic symptoms, and the existence of atypical lymphocytes in peripheral blood.

Relapsed Angioimmunoblastic T Cell Lymphoma with Fulminant Leukemic Involvement.

BACKGROUND Angioimmunoblastic T cell lymphoma (AITL) is an aggressive and rare entity that comprises about 1-2% of all non-Hodgkin lymphomas. This entity carries many challenges that start at the diagnosis, as most patients present with non-specific symptoms affecting different systems. As a result, the optimal approach, reaching the accurate diagnosis, and delivering needed treatment are delayed. Furthermore, it is not surprising that the initial set of biopsies are non-diagnostic given the heavy inflammatory background and scarcity of malignant cells in the early course of the disease. Other challenges include delivering the optimal curative therapy, as there is no such therapeutic option available yet. Although stem cell transplantation (SCT) can be considered a curative option, some patients have comorbidities and are not eligible for this option, and some other patients have relapse despite this aggressive approach, as was seen in our case. CASE REPORT We present an interesting case of AITL with florid leukemic infiltration at the time of relapse. We included a description of the patient's symptoms, diagnostic challenges, and clinical course, and provided therapy with demonstrative peripheral blood and flow cytometry images. Interestingly, there are very few reports in the literature that described leukemic infiltration of this entity. CONCLUSIONS Acknowledging the rarity of this aggressive lymphoma combined with all the challenges that face the involved health care workers, publishing this elaborative case report adds some insight and knowledge and helps improve our understanding of this entity.

Angioimmunoblastic T-Cell Lymphoma with Exuberant CD30-Positive Follicular Dendritic Cell Proliferation in a SARS-CoV-2 Patient: The Role of Mutational Analysis to Exclude an Associated Follicular Dendritic Cell Sarcoma.

Follicular dendritic cell (FDC) proliferation in angioimmunoblastic T-cell lymphoma (AITL) is still not well defined, challenging the accurate differential diagnosis between the AITL with expanded follicular dendritic cell meshwork and the combined AITL and follicular dendritic cell sarcoma (FDCS). Herein, we reported the case of a 58-year-old male with coexisting SARS-CoV-2 infection and AITL with an exuberant CD30-positive FDC proliferation, in which genetic analysis identified mutations of genes commonly involved in AITL but not in FDC sarcoma (i.e., RHOA, TET2, DNMT3A, and IDH2), thus supporting the reactive nature of the CD30-positive FDC expansion.