Primary follicular immunoblastic lymphoma (FIBL) is an extremely rare lymphoma. The positive expression of CD10 suggests the lymphoma originating from germinal centers (GC) and CD138-positive expression generally indicates plasmablastic or plasmacytic differentiation. We report such a rare case in a Chinese female patient and analyze the clinicopathologic and immunohistochemical features of this disease. PET-CT examination was performed to detect signs of systemic lymph node metastasis. We also discussed the differential diagnosis of FIBL from follicular lymphoma (FL) and reactive follicular hyperplasia (RFH). As a rare variant of human follicular lymphoma, FIBL is featured by a neoplastic overgrowth of intrafollicular immunoblasts. Compared with FL, FIBL has a greater chance to evolve into diffuse large B-cell lymphoma with therefore a poorer prognosis.
Adult ; Female ; Humans ; Immunoblastic Lymphadenopathy ; pathology ; Lymphoma, Follicular ; pathology

Gastrointestinal Tract/pathology* ; Humans ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology*

Humans ; Plasma Cells/pathology* ; Hyperplasia/pathology* ; Immunoblastic Lymphadenopathy ; B-Lymphocytes/pathology* ; Lymphoma, T-Cell

Humans ; Immunoblastic Lymphadenopathy/pathology* ; Lymphocytes, Tumor-Infiltrating ; Lymphoma, T-Cell, Peripheral/pathology*

Humans ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Molecular Biology

To improve the recognition of angioimmunoblastic T-cell lymphoma (AITL) and to reduce misdiagnosis, a case diagnosed as AITL with large granular lymphocytosis was reported and the related articles were reviewed. A series of clinical tests, pathologic examination and immunohistochemical test, TCR gene rearrangement detection by multiple PCR and assay of lymphocyte immunophenotypes were carried out. The results indicated that the patient was characterized by fever, skin rash, generalized lymphadenopathy, splenomegaly, pleural effusion, ascites, anemia and thrombocytopenia, increase of circulating large granular lymphocytes with CD3(-) and CD16(+), CD56(+) were detected, T-cell receptor γ-chain gene was rearranged. More large granular lymphocytes with abnormal mitosis were found in ascites. The histological and immunohistochemical changes observed by the lymph node biopsy were compatible with AITL, some cells of which were CD56-positive. In conclusion, AITL is characterized by aggressive progress and generally occurs in elderly patients, its clinical prognosis is poor, the large granular lymphocytosis may be an autoimmune response to the tumor cells or originate from tumor stem/progenitor cells.
Humans ; Immunoblastic Lymphadenopathy ; complications ; immunology ; pathology ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; complications ; immunology ; pathology ; Male ; Middle Aged

OBJECTIVETo explore the clinical and pathological characteristics of angioimmunoblastic T-cell lymphoma (AITL).

METHODSSixty-four cases of AITL were retrospectively analyzed by histopathological and immunohistochemical methods.

RESULTSThere were 35 men and 29 women, the median age was 59 years (range, 25-84 ys). AITL typically presented with advanced stage, generalized lymphadenopathy, hepatosplenomegaly and systemic symptoms. Morphologically, the lymph nodes showed partial or total obliteration of the normal architecture by a polymorphic infiltration of lymphocytes, and by proliferation of follicular dendritic cells and that of high endothelial venules. Most cases contained a monoclonal T-cell population as well as clonal cytogenetic abnormalities. Immunophenotype analysis showed that neoplastic cells expressed the following markers: CXCL13 (positive rate 95.3%), PD-1 (positive rate 75.0%), CD10 (positive rate 25.0%), Bcl- 6 (positive rate 40.0%), CD2 (positive rate 96.0%), CD3 (positive rate 95.0%), CD4 (positive rate 84.0%), CD5 (positive rate 73.0%), EBER (positive rate 39.5%) and Ki-67 (average positive rate 55.0%), and frequently showed aberrant loss or reduced expression of CD7 and CD8.

CONCLUSIONThe neoplastic cells of AITL showed features of CD4+ TFH, with peculiar clinical features. Peripheral T-cell lymphomas with a follicular growth pattern may show overlapping features with focal AITL.

Adult ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; Female ; Humans ; Immunoblastic Lymphadenopathy ; diagnosis ; pathology ; Lymphoma, Follicular ; pathology ; Lymphoma, T-Cell, Peripheral ; diagnosis ; pathology ; Male ; Middle Aged ; Retrospective Studies

To evaluate the clinical, pathological characters and prognosis of patients with angioimmunoblastic T cell lymphoma (AITL), the clinicopathologic features, immunophenotypes, therapy and survival rate of 12 AITL patients which were confirmed by pathologic examination were retrospectively studied. The results indicated that main symptom was observed as general lymphadenopathy, however, 9 patients had fever. The diagnosis of AITL was based on lymph-node biopsy. The histopathologic characteristics of AITL showed the damage of normal lymphnode structure, the proliferation of immunoblastic cells and arborescent super vascularization. All immunophenotypes were mature peripheral T-cellular. CVP regimen was the most common chemotherapy regimen used for patients. 58% patients have a good initial response to chemotherapy. 3-year survival was 25%, with median survival time of 25 months. In conclusion, most cases of AITL display an aggressive course, therefore, the disease progresses rapidly and has unfavorable prognosis, further studies are required to improve its therapy regimen.
Aged ; Female ; Humans ; Immunoblastic Lymphadenopathy ; diagnosis ; pathology ; therapy ; Lymph Nodes ; pathology ; Lymphoma, T-Cell, Peripheral ; diagnosis ; pathology ; therapy ; Male ; Middle Aged ; Survival Rate

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR⁺/IG^-, 26.3% (5/19) TCR⁺/IG⁺, 10.5% (2/19) were TCR^－/IG^－, and 5.3% (1/19) TCR^－/IG⁺. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR^－/IG^－, 1 case with TCR^－/IG⁺, and 1 case with TCR⁺/IG⁺; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR^－/IG^－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.
Humans ; Epstein-Barr Virus Infections/genetics* ; Herpesvirus 4, Human/genetics* ; T-Lymphocytes, Helper-Inducer/pathology* ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Receptors, Antigen, T-Cell

OBJECTIVETo explore the vascular endothelial growth factor-C (VEGF-C) expression and its clinical significance in malignant lymphoma.

METHODSLymphoma cells were isolated by laser microdissection. VEGF-C expression in lymphoma tissue and microdissected lymphoma cells was measured by realtime quantitative PCR. Meanwhile, vessel ultrastructure was identified by transmission electron microscopy.

RESULTSComparing with that in 8 patients with reactive lymphocyte hyperplasia, VEGF-C was overexpressed in angioimmunoblastic T-cell lymphoma, both in lymphoma tissue (n = 18, P = 0.0020) and in microdissected lymphoma cells (n = 10, P < 0.0001). Increased VEGF-C level was associated with bone marrow infiltration (P = 0.0039), skin involvement (P = 0.0046) and high-risk international prognostic index (P = 0.0302). In VEGF-C overexpressed cases, ultrastructural study showed dystrophic vessels, with swelling endothelial cells and absence of pericytes.

CONCLUSIONThe value of VEGF-C expression might be a biomarker of disease progression in angioimmunoblastic T-cell lymphoma.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; Lymphoma, T-Cell ; metabolism ; pathology ; Male ; Middle Aged ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor C ; metabolism