Progress of angioimmunoblastic T-cell lymphoma / 白血病·淋巴瘤

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) that originates from follicular helper T cells (TFH). It has the highest incidence in PTCL which is second only to PTCL-not otherwise specified (PTCL-NOS). Its clinicopathological diagnosis is difficult, it is easy to be misdiagnosed and missed, and the prognosis is poor. This article reviews the pathogenesis, clinical and pathological characteristics as well as treatment progress of AITL, in order to provide a reasonable basis for clinical diagnosis and treatment of the disease.

Angioimmunoblastic T-cell lymphoma complicated with Epstein-Barr virus-positive diffuse large B-cell lymphoma: report of two cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinicopathological features, treatment and prognosis of patients with angioimmunoblastic T-cell lymphoma (AILT) complicated with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 2 cases of AILT with EBV-positive DLBCL in the Fifth Medical Center of PLA General Hospital were retrospectively analyzed, and the literature was reviewed.Results:One case of complex lymphoma (CL) developed from low fever with systemic superficial lymphadenopathy, the right axillary tumor biopsy showed that AILT complicated with EBV-positive DLBCL. After 8 cycles of chemotherapy, the patient reached unconfirmed complete remission, then received maintenance treatment with chidamide and survived until the deadline. Another case of discordant lymphoma began with subcutaneous nodules and then developed progressive enlargement of superficial lymph nodes. The pathological examination of subcutaneous nodule diagnosed as DLBCL, and the pathological examination of right inguinal lymph node diagnosed as AITL. After 7 cycles of chemotherapy, the patient died of hemophagocytic syndrome.Conclusions:AILT with EBV-positive DLBCL is rare. The main clinical symptom is AITL and the immunophenotypic characteristic indicates the presence of T cells and B cells. At the same time, the prognosis is poor, and the treatment strategy mainly depends on the lymphoma type with unfavorable prognosis.

Expressions of CD200 and inducible costimulator in angioimmunoblastic T-cell lymphoma and their significances / 白血病·淋巴瘤

Objective:To investigate the expressions of CD200 and inducible costimulator (ICOS) protein in angioimmunoblastic T-cell lymphoma (AITL) and the relationship with prognosis as well as their significances in the differential diagnosis of AITL.Methods:A total of 39 AITL patients in the First People's Hospital of Chenzhou, the Fourth People's Hospital of Chenzhou, Xiangnan College Affiliated Hospital and Chenzhou 3rd People's Hospital from June 2012 to December 2019, and 10 patients with classic Hodgkin lymphoma (CHL) and 10 patients with peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) from August 2016 to July 2019 in the First People's Hospital of Chenzhou were selected. Immunohistochemistry was used to detect the expressions of CD200, ICOS, CD10, programmed death 1 (PD-1), bcl-6 and CXC chemokine receptor-13 (CXCL13) proteins, and the correlation of CD200 and ICOS with clinicopathological features and prognosis of AITL patients was analyzed, and the diagnostic significance of both in differentiating AITL from PTCL-NOS and CHL was also analyzed.Results:The positive rates of CD200 and ICOS in 39 AITL patients were 71.79% (28/39) and 61.54% (24/39), respectively. There were 7 cases of CD200 weak and moderate positive in 10 CHL patients, and ICOS proteins were all negative. Among 10 PTCL-NOS patients, 4 patients had CD200 positive and 1 patient had ICOS positive. The differences in positive rates of ICOS protein between AITL patients and CHL, PTCL-NOS patients were statistically significant (all P < 0.05); the differences in positive rates of CD200 protein between AITL patients and CHL, PTCL-NOS patients were not statistically significant ( χ2=0.013, P=0.911; χ2=3.551, P=0.060). The positive rate of CD200 in AITL patients with elevated lactate dehydrogenase (LDH) and international prognostic index (IPI) score of 3-4 was higher than that in AITL patients with normal LDH and IPI score of 0-2 (both P < 0.05); The positive rate of ICOS in AITL patients with elevated LDH and PD-1 positive was higher than that in AITL patients with normal LDH and PD-1 negative (both P < 0.05). CD200 negative AITL patients had better 3-year overall survival (OS) rate (4.2% vs. 66.7%) and 3-year progression-free survival (PFS) rate (5.3% vs. 77.1%) compared with those in CD200 positive AITL patients, and the differences between both groups were statistically significant (both P < 0.01); there was a statistically significant difference in 3-year OS rate between ICOS positive AITL patients and ICOS negative AITL patients (15.3% vs. 38.6%, P=0.011), while there was no statistically significant difference in 3-year PFS rate of both groups (18.6% vs. 41.5%, P=0.059). Multivariate analysis showed CD200 ( HR=0.076, 95% CI 1.555-79.497, P=0.001), extranodal involvement or not ( HR=11.117, 95% CI 1.555-79.497, P=0.016) and LDH ( HR=2.147, 95% CI 0.844-5.459, P=0.109) were independent influencing factors of OS in AITL patients; CD200 ( HR=0.075, 95% CI 0.016-0.357, P=0.001) and LDH ( HR=2.335, 95% CI 0.929-5.870, P=0.071) were independent influencing factors of PFS in AITL patients. Conclusions:CD200 and ICOS can be used as immunohistochemical indicators to assist the diagnosis of AITL patients. ICOS protein helps to differentiate AITL from CHL and PTCL-NOS; CD200 can be used as indicators to judge the prognosis and deterioration of AITL patients.

Angioimmunoblastic T-cell lymphoma with fever, arthritis and skin pigmentation: A case report / 北京大学学报(医学版)

Angioimmunoblastic T-cell lymphoma is a rare T-cell lymphoma. The clinical manifestations are not specific. In addition to the common clinical manifestations of lymphomas such as fever, weight loss, night sweats and lymphadenopathy, it may also have skin rashes, arthritis, multiple serous effusions, eosinophilia and other systemic inflammatory or immune symptoms. The lymphoma cells of angioimmunoblastic T-cell lymphoma originates from follicular helper T cells, and the follicular structure of lymph nodes disappears. In the tumor microenvironment, in addition to tumor cells, there are a large number of over-activated immune cells, such as abnormally activated B cells, which produce a series of systemic inflammation or immune-related symptoms. This disease is rare and difficult to diagnose. This article reports a 36-year-old female. She got fever, joint swelling and pain, skin pigmentation, accompanied by hepatomegaly, splenomegaly, lymphadenopathy, anemia and other multiple-systems manifestations. The clinical manifestations of this patient were similar to autoimmune diseases such as adult onset Still's disease, rheumatoid arthritis, and systemic sclerosis, which made the diagnosis difficult. At the beginning of the disease course, the patient got arthritis and fever. And her white blood cells were significantly increased. Adult onset Still's disease should be considered, but her multiple-systems manifestations could not be explained by adult onset Still's disease. And her arthritis of hands should be distinguished with rheumatoid arthritis. However, the patient's joint swelling could get better within 3-7 days, and there was no synovitis and bone erosion on joint imaging examination. The rheumatoid factor and anti-CCP antibody were negative. The diagnostic evidence for rheumatoid arthritis was insufficient. The patient's skin pigmentation and punctate depigmentation were similar to those of systemic sclerosis. But the patient had no Raynaud's phenomenon, and her sclerosis-related antibody was negative. The diagnostic evidence for systemic sclerosis was also insufficient. After 3 years, she was finally diagnosed with angioimmunoblastic T-cell lymphoma by lymph node biopsy aspiration. This case suggests that the clinical manifestations of angioimmunoblastic T-cell lymphoma are diverse, and some symptoms similar to immune diseases may appear. When the patient's clinical symptoms are atypical and immune diseases cannot explain the patient's condition, and further evidence should be sought to confirm the diagnosis.

The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens. MATERIALS AND METHODS: Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen. RESULTS: Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response. CONCLUSION: Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

A Case of Angioimmunoblastic T-cell Lymphoma Involving the Ipsilateral Parotid and Lateral Neck / 대한두경부종양학회지

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of malignant lymphoma (ML), accounting for only 1 to 2% of all non-Hodgkin's lymphoma (NHL). Although ML of the parotid gland is rare, the majority are B-cell types. The AITL occurring synchronously in the parotid gland and lateral neck has not been reported earlier. It is classified as a high-grade malignancy with aggressive clinical features, and the prognosis is worse than any other type of NHL. We recently encountered a 72-year-old man with multiple mass on the ipsilateral parotid tail and lateral neck, and he was finally diagnosed as AITL. We report the unique and rare disease entity with a brief literature review.

The progress of pathogenesis and treatment in angioimmunoblastic T-cell lymphoma / 中国肿瘤临床

Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of peripheral T-cell lymphomas. It is a fol-licular T-helper-derived neoplasm, and characterized by the presence of some genetic alterations, such as mutations in TET2, DN-MT3A, IDH2, and RHOA. Anthracycline-containing regimens represent the most widely adopted first-line option; however, new biolog-ic agents should be designed and incorporated to improve treatment response. The elucidation of the specific roles of these genetic al-terations in AITL will facilitate the development of molecularly targeted therapies to treat this disease.

Acute myeloid leukemia secondary to angioimmunoblastic T-cell lymphoma: report of three cases and review of literature / 白血病·淋巴瘤

Objective To investigate the clinical characteristics, pathogenesis, diagnosis, treatment and prognosis of acute myeloid leukemia secondary to angioimmunoblastic T-cell lymphoma. Methods The clinical data of 3 patients with acute myeloid leukemia secondary to angioimmunoblastic T-cell lymphoma including immunohistochemistry and flow cytometer analysis were analyzed retrospectively, then the literature was reviewed. Results All the 3 patients were elderly men and the initial diagnosis was angioimmunoblastic T-cell lymphoma. The 3 cases developed secondary acute myeloid leukemia in 8 months, 14 months and 34 months after treating primary neoplasms respectively. After diagnosed acute myeloid leukemia, one case died 10 months later without treatment, one case died 13 months later despite aggressive treatment and one case lost follow-up. Conclusion Angioimmunoblastic T-cell lymphoma has risk to developing acute myeloid leukemia, and there is a poor survival and the pathogenesis is unclear.

Therapeutic efficacy of first-line CHOP or CHOP-like chemotherapy on patients with advanced staged angioimmunoblastic T-cell lymphoma / 白血病·淋巴瘤

Objective To evaluate the efficacy of first-line CHOP or CHOP-like regimen on patients with advanced staged angioimmunoblastic T-cell lymphoma (AITL).Methods Between Aug 2006 and Sep 2014,twenty-nine AITL patients who were newly diagnosed without prior treatment were included in study.The clinical features,efficacy and survival were analyzed retrospectively.Results Median age of these patients was 59 years old.All patients had stage Ⅲ/Ⅳ disease.17 (58.6 ％) cases presented with B symptoms.26 (89.7 ％) cases had an international prognostic index (IPI) score ≥2,and 20 (69.0 ％) cases had elevated LDH,9 (31.0 ％) cases had ≥2 extranodal involvements.The median follow-up time was 20 months.Overall response rate was 69.0 ％ (20/29).Five (17.2 ％) patients achieved complete remission (CR+CRu),15 (51.7 ％) patients achieved partial remission,and 3 (10.3 ％) patients had stable disease (SD),6 (20.7 ％) patients had progressive diseases(PD).Median progression-free survival (PFS) was 6 months.1-and 2-year PFS rates were 39.0 ％ and 20.0 ％.1-,2-and 5-year overall survival (OS) rates for all patients were 76.8 ％,53.4 ％ and 17.1％,respectively.PFS was significantly better in chemotherapy-sensitive patients (P ＜ 0.001).The responses to chemotherapy had a tendency of affecting the OS,but it failed to reach statistical significance (P ＞ 0.05).Conclusions The CHOP or CHOP-like regimen maybe induce unfavorable efficacy in AITL patients.Further therapeutic options are required to improve the outcome.

Unusual Presentation of Angioimmunoblastic T-cell Lymphoma as a Solitary Lymph Node.

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) characterized by systemic disease. It is a rare subtype of non-Hodgkin’s lymphomas. However, it forms a major subset of PTCL. Lymph node is the primary site of disease and virtually all patients present with generalized lymphadenopathy. Case report: A 42-year-old male presented with fever of short duration and a solitary axillary lymph node swelling on the right side. Systemic examination revealed moderate ascites and hepatosplenomegaly. Hematological investigations showed pancytopenia and abnormal liver function. Axillary lymph node showed histological features suggesting AITL and was confirmed by a panel of immunohistochemistry (IHC). Conclusion: AITL presenting as solitary axillary lymph node enlargement is unusual. Such atypical presentation mandates careful clinical and laboratory evaluation. IHC is an effective ancillary tool for confirmation of diagnosis of this distinct clinicopathological entity.

Perspective research of preliminarily diagnosed angioimmunoblastic T-cell lymphoma with dose-adjusted EPOCH regimen / 中国肿瘤临床

Objective:The effect and side effect of the dose-adjusted EPOCH regimen were evaluated perspectively for the pre-liminarily diagnosed angioimmunoblastic T-cell lymphoma. Methods: Nine cases of untreated angioimmunoblastic T-cell lymphoma were diagnosed and enrolled in our department from September 2008 to September 2012. All patients received dose-adjusted EPOCH regimen as first-line chemotherapy. Results: The median age of 9 patients was 54 years. The male-to-female ratio was 2∶1. About 88.9%of all patients were at Ann Arbor stageⅢ/Ⅳ, and 77.8%presented with B symptoms. Anemia was found in 66.7%of 9 patients, and lactate dehydrogenase elevated in 55.6%of patients. After an average of 4.7 cycles of chemotherapy of dose-adjusted EPOCH regi-men, the complete remission rate was 22.2%, and the total response rate was 66.7%. With a median follow-up of 20 months, the 4-year progression-free survival rate was 11.1%, and the overall survival rate was 33.3%. The median survival time was 19 months. The most common adverse events of EPOCH chemotherapy were hematologic toxicity. Grades 3-4 neutropenia and thrombocytopenia were re-ported in 77.8%and 33.3%of patients. Febrile neutropenia was observed in 44.4%of patients. Non-treatment-related mortality was al-so noted. Conclusion: The results of our research showed no clear benefit of treating preliminarily diagnosed angioimmunoblastic T-cell lymphoma with dose-adjusted EPOCH regimen. The main adverse events were hematologic toxicity and could be tolerated.

Diffuse Large B-cell Lymphoma in a Patient with Angioimmunoblastic T-cell Lymphoma / 대한피부과학회지

Sequential lymphoma is defined as two different types of lymphoma that occur in the same patient at different anatomic sites and times. In most cases, the two distinct histologies belong to the same lineage (B- or T-cell lymphoma), though cases with both have been observed. A few cases of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas arising in patients with angioimmunoblastic T cell lymphoma (AITL) have been reported. Immune deficits inherent in AITL, combined with the immunosuppressive effects of the therapy, may have allowed unchecked EBV-induced proliferation of latently or newly EBV-infected B cells with eventual clonal selection and progression to aggressive B-cell lymphoma. Here, we report a case of AITL in which EBV-positive diffuse large B-cell lymphoma (DLBCL) arose 9 months after the initial diagnosis of AITL.

Angioimmunoblastic T-Cell lymphoma: A critical analysis of clinical, morphologic and immunophenotypic features.

Background: Angioimmunoblastic T-cell lymphoma (AITL), a subtype of peripheral T-cell lymphoma (PTCL), is characterized by unique clinical and biological features. Its diagnosis remains a challenge as clinical presentation as well as pathologic findings are frequently misleading. Material and Methods: We retrospectively analyzed the clinical, morphological and immunophenotypic spectrum of 17 cases of histologically proven AITL. Result: The mean age was 54 years and male to female ratio was 2.4. Common clinical features included generalized lymphadenopathy (60%), hepatomegaly (70%), splenomegaly (50%), anemia (80%) and polyclonal hypergammaglobulinemia (100%). Microscopically, three architectural patterns; pattern I (6%), pattern II (41%) and pattern III (53%) were observed. Bone marrow infiltration was seen in 60% cases and 30% cases revealed plasmacytosis. Absence of follicles, polymorphous infiltrate, extra-follicular follicular dendritic cell (FDC) proliferation, high endothelial venules (HEV) prominence and neoplastic T-cells were the diagnostic features of AITL. CD10 positivity (47%), clear cells in the background (59%) admixture with large size CD20+ B-immunoblasts (35%) and bone marrow plasmacytosis (50%) were common observations. Conclusion: Awareness of various morphological and immunophenotypic complexities of AITL and distinction from reactive adenopathies and other types of lymphomas that mimic AITL is underscored in this study.

A case of angioimmunoblastic T cell lymphoma in a patient with ichthyosis / 대한내과학회지

Angioimmunoblastic T cell lymphoma (AITL), which accounts for only 1~2% of non-Hodgkin's lymphomas, is commonly accompanied by skin lesions. Those associated with AITL include erythematous plaques, nodules or rashes. Histological examination of most lesions shows infiltration by malignant lymphocytes. Ichthyosis is a generalized skin disease characterized by hyperkeratosis, in which the skin acquires an appearance resembling fish scales. Some cases may be acquired, but most have a genetic basis. We report a case of AITL with associated ichthyosis that is considered to be inherited.

Angioimmunoblastic T Cell Lymphomas: Frequent Cutaneous Skin Lesions and Absence of Human Herpes Viruses

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is a complex lymphoproliferative disorder and often mimics a viral infection with frequent skin involvement. Epstein-Barr virus (EBV) and human herpes virus (HHV)-6 are reported to be associated with AITL, but there are conflicting results. OBJECTIVE: We evaluated the association of EBV and HHV-6 with AITL. METHODS: We reviewed the clinical, histological and immunophenotypical features of 19 cases of AITL. Among them, 11 lymph node biopsies of AITL were examined for HHV-6, -7, and -8 by polymerase chain reaction (PCR) using virus-specific primers. In situ hybridization of EBV early region RNA (EBER) was performed and T cell receptor (TCR) gene rearrangement was also investigated in some cases. RESULTS: Among these 19 cases, maculopapular, plaque or nodular skin lesions accompanied AITL in 12 cases. Clonal TCR gene rearrangement was seen in 8/9 cases tested. EBER in situ hybridization was positive in 8 cases (57.1%). Among 7 cases with skin biopsies, five cases were consistent with cutaneous involvement of AITL, 1 case was a drug eruption, and the other case was Kaposi's sarcoma. Except a HHV-8 (+) case who also had Kaposi's sarcoma, all of these cases were negative for HHV-6, -7 and -8. CONCLUSION: Skin manifestation seems to be a cardinal component of AITL, be it in the context of presentation, progression or recurrent disease. Recognition of clinicopathological features of skin lesions in AITL as diagnostic clues should be stressed among dermatologists. The lack of HHV-6, -7 and -8 in lymph node biopsy of AITL argues against a pathogenic role for HHVs in AITL.

A Case of Epstein-Barr Virus-positive Diffuse, Large B-cell Lymphoma after Angioimmunoblastic T-cell Lymphoma / 대한혈액학회지

Angioimmunoblastic T-cell lymphoma (AITL) is a systemic lymphoproliferative disorder that presents with profound immune dysfunction and immunodeficiency. As in many other immunodeficiencies, Epstein-Barr virus (EBV) associated B-cell lymphoid proliferation can occur in AITL but few cases of EBV-positive B-cell lymphoma have been reported in patients with preexisting AITL. We report a case of AITL in which EBV-positive diffuse large B-cell lymphoma (DLBCL) developed 13 months after the initial diagnosis of AITL. Although the exact mechanisms remain unclear, Epstein-Barr virus may have played a role in the pathogenesis of the secondary DLBCL

Epstein-Barr Virus-Positivity in Tumor has no Correlation with the Clinical Outcomes of Patients with Angioimmunoblastic T-cell Lymphoma

BACKGROUND/AIMS: Epstein-Barr virus (EBV) is involved in the pathogenesis of angioimmunoblastic T-cell lymphoma (AILT), but its precise role and prognostic impact are not clear. This study aimed to evaluate the incidence of EBV-postitivity in the tumor and bone marrow (BM) samples from AILT patients, and their correlations with the clinical variables and patient survival. METHODS: Seventy AILT cases were identified over a period of 8 years. Twenty seven cases were investigated for their EBV tumor status, and 10 BM samples of these patients were investigated for their EBV status with using in situ hybridization (ISH). EBV PCR was performed for the BM mononuclear cells in 8 cases. RESULTS: Among the 27 tumor specimens, ten (37%) were EBV-positive. Only CD20-negativity in tumor correlated with the EBV-positivity (p=0.035). In 13 (48%) patients, gross tumor involvement was recognized by hematoxylin-eosin staining at the time of diagnosis. Among the 10 patients who had additional BM slides available, there were 3 with BM involvement, and none showed EBV positive results on ISH. EBV PCR of the BM mononuclear cells revealed one-positive case among 8 patients. This patient was negative for both BM involvement and EBV ISH. The median overall survival of the 25 treated patients was 48.9 months (95% CI: 18.6~79.2 months). Neither overall survival nor progression-free survival was related with EBV-positivity of the tumor. CONCLUSIONS: EBV-positivity of tumor had no impact on the prognosis of AILT patients.

Fine Needle Aspiration Cytological Findings of Angioimmunoblastic T-cell Lymphoma : A Brief Case Report / 대한세포병리학회지

Recently, we experienced a case of Angioimmunoblastic T-cell lymphom (AITL) in a 60-year-old man presented with lymphadenopathy, which is first cytological report in Korea. The cytological features showed a heterogeneous population of small to medium-sized lymphocytes, immunoblasts, and plasma cells. Characteristically, there were also a distinct population of follicular dendritic cells admixed with lymphoid cells, forming the so-called dendritic cell-lymphocyte complexes. Histological features showed the classic morphologic features of AITL. Recognition of the characteristic cytological features can suggest the possibility of AITL.