Aged ; Female ; Hodgkin Disease ; diagnosis ; pathology ; Humans ; Reed-Sternberg Cells ; pathology

OBJECTIVETo detect the clonal relationship, the rearrangement, and the mutational status of IgVH gene; the influence of these molecular characteristics on the clinical outcome in Hodgkin variant of Richter syndrome; and the possible molecular pathogenesis in this transformation.

METHODSThe clonal rearrangements and mutational status of IgVH genes were analyzed in Hodgkin variant of Richter syndrome and B-CLL with Reed-Stemberg (R-S)-like cells by GeneScan analysis and sequencing. Semi-nest PCR based on laser capture microdissection was utilized to compare the clonal relationship between B-CLL and R-S/R-Slike cells. Immunohistochemical staining was used to detect the different expressions of ZAP70, p53, IRF-4 and LMP1 in the two components.

RESULTS(1) 5/6 B-CLL cases transformed to Hodgkin lymphoma (HL)/R-S-like cells carried the mutated IgVH genes; (2) 2 cases of R-S cells and 1 case of R-S-like cells were clonally distinct from B-CLL clone and express LMP1, whereas 1 case of R-S-like cells was relating to the surrounding B-CLL cells and did not express LMP1; (3) 2/6 B-CLL cases transformed to HL convey VH4-34 and VH3-48 respectively.

CONCLUSIONS(1) Richter transformation to HL/R-S-like cells evolves from the B-CLL which originates from the germinal center or post germinal center B cells, indicating that different lymphoma cells of different subtypes in Richter syndrome come from different B cell lineage and possibly involve a different pathogenesis and pathway; (2) HL and R-S-like cells evolve from either the B-CLL clone or may develop as a clonally unrelated lymphoma, the independent secondary malignancies are appear to be EBV-positive, possibly as a consequence of the underlying immunodeficiency; (3) The biased usage of IgVH genes suggested a role of antigens involved in the HL variant of Richter syndrome.

Aged ; Aged, 80 and over ; Clone Cells ; pathology ; Female ; Herpesvirus 4, Human ; Hodgkin Disease ; classification ; genetics ; pathology ; virology ; Humans ; Immunoglobulin Variable Region ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Reed-Sternberg Cells ; pathology ; Syndrome

OBJECTIVETo study the clinicopathologic features and pathologic diagnosis and differential diagnosis of angioimmunoblastic T-cell lymphoma with HRS-like cells.

METHODSSix cases of angioimmunoblastic T-cell lymphoma with HRS-like cells were examined histologically and immunohistochemically (EliVision method) and in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER), and the literature was reviewed.

RESULTSThe cytologic and microscopic features of these imprints and lymph node samples showed a heterogeneous population of hematolymphoid cells, including small to intermediate lymphoid cells, immunoblasts, plasma cells, dendritic cells, and eosinophils, as well as small vessels that were surrounded by some of the abnormal cells. The neoplastic T-cells expressed CD3 and CD5 and partly positive for CD10 and bcl-6, CD21 showed expanded and irregular follicular dendritic cell (FDC) meshworks that surrounding the high HEV. The HRS-like cells were positive for MUM-1 and Ki-67, variable intensity positive for CD30, CD20, and PAX-5, but negative for CD15. EBV-positive cells included HRS-like cells and small to large-sized neoplastic T-cells, which formed small clusters or scattering in the background of the disease.

CONCLUSIONSThe clinical course of angioimmunoblastic T-cell lymphoma with HRS-like cells is aggressive. Which present with histomorphology overlap with classical Hodgkin lymphoma (CHL), similar to CHL in EBER and immunophenotype, however, it is easy to misdiagnosis as HL. Thus, angioimmunoblastic T-cell lymphoma pathology diagnosis should comprehensive analysis of different kinds of materials, including clinical features, and histological structure, and EBER, and immunophenotype, and gene rearrangement.

Diagnosis, Differential ; Herpesvirus 4, Human ; Hodgkin Disease ; pathology ; Humans ; Immunoblastic Lymphadenopathy ; diagnosis ; pathology ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; Lymphoma, T-Cell ; diagnosis ; pathology ; RNA, Viral ; Reed-Sternberg Cells ; pathology ; T-Lymphocytes ; pathology

Cell Proliferation ; Cell Transformation, Neoplastic ; Epigenesis, Genetic ; Hodgkin Disease ; genetics ; immunology ; metabolism ; pathology ; Humans ; Immunophenotyping ; NF-kappa B ; metabolism ; Receptor, Notch1 ; metabolism ; Reed-Sternberg Cells ; immunology ; metabolism ; pathology ; Transcription Factor AP-1 ; metabolism

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Lymphoma, T-Cell, Peripheral/pathology* ; Reed-Sternberg Cells/pathology* ; Epstein-Barr Virus Infections ; Hyperplasia/pathology* ; Retrospective Studies ; Herpesvirus 4, Human/genetics* ; Immunoblastic Lymphadenopathy/pathology* ; Hodgkin Disease/pathology* ; Germinal Center/pathology* ; Receptors, Antigen, T-Cell

Aged ; Antigens, CD20 ; analysis ; Gene Rearrangement ; Humans ; Immunoblastic Lymphadenopathy ; genetics ; metabolism ; pathology ; Immunoglobulin Heavy Chains ; genetics ; Immunohistochemistry ; Lymph Nodes ; metabolism ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Male ; Polymerase Chain Reaction ; RNA, Viral ; analysis ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; Reed-Sternberg Cells ; metabolism ; pathology

OBJECTIVETo explore the origin and clonality of H/RS cells.

METHODSImmunohistochemical method was used to detect the expression of B-cell-specific activator protein (BSAP) and CD(20) in 33 paraffin-embedded tissues of classical Hodgkin lymphoma (cHL). IgH gene rearrangement was detected in 33 paraffin-embedded cHL tissue and 6 microsectioned H/RS cell samples. The PCR products of a case of cHL and its microsectioned cells were sequenced.

RESULTSH/RS cells were positive for BSAP in 30 of 33 (90.91%) cHL cases and positive for CD(20) in 10/33 (30.30%) cases. There was a significant difference between the expression of BSAP and CD(20) in H/RS cells (P = 0.000). BSAP and CD(20) were positive in almost all B cells of lymph node reactive hyperplasia and malignant cells in B-cell lymphomas while were negative in all malignant cells of T-cell lymphomas. 16 of 33 cHL were positive for gene rearrangement, and microsectioned H/RS cells in 14 of 19 tubes displayed clonal bands of rearrangement. There was no significant difference among the rearrangement rates in tubes containing different numbers of H/RS cells (P = 0.280). Sequencing analyses of the PCR products from both paraffin-embedded tissue and microsection of the same patient revealed the rearranged V segments, but the sequences were not identical.

CONCLUSIONH/RS cells were originated from B cells of different differentiation stage.

Adolescent ; Adult ; Antigens, CD20 ; analysis ; Base Sequence ; Child ; Child, Preschool ; DNA-Binding Proteins ; analysis ; Female ; Gene Rearrangement ; Hodgkin Disease ; genetics ; immunology ; pathology ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Sequence Data ; PAX5 Transcription Factor ; Reed-Sternberg Cells ; cytology ; Sequence Analysis, DNA ; Transcription Factors ; analysis

OBJECTIVETo investigate the apoptosis-related genes and protein expression patterns in relation to classical Hodgkin lymphomas (CHL) and the origin of H/RS cell.

METHODSSixty-two cases of CHL were retrieved from Shanxi Tumor Hospital files. An ABC method was used to detect the expression of bcl-2, CD3, CD20, CD30, CD15 and CD10, a double immunohistochemical method to study the H/RS cells P53 expression, a double immunohistochemical ABC-DNA end labeling technique to detect the apoptosis, a double immunohistochemical ABC- in situ hybridization technique to detect the expression of kappa mRNA and lambda mRNA, and a multiple mark techniques to detect the distribution of background non-neoplastic T and B cells.

RESULTOf 62 CHL, 14 (22.58%) were p53 positive and 35 (56.45%) bcl-2 positive. Apoptosis was found in the background non-neoplastic cells in all of the cases, but in H/RS cells in only 10 of 62 cases. There was a significant reverse correlation between bcl-2 expression and apoptosis in H/RS cells (P = 0.02). CD30 positive H/RS cells were observed in all cases, whereas CD15 positive in only 41 cases, and CD20 positive in 8 cases. None was positive for CD3, MPO, bcl-6, CD10, kappa RNA and lambda RNA in H/RS cells. The H/RS cells were surrounded by non-neoplastic T cells looked like a rosette and the outer periphery was B cells.

CONCLUSIONSThe H/RS cell of classical Hodgkin lymphoma has a great variety of B lineage markers. The characteristic distributions of T, B and H/RS cells may serve as a reference for the diagnosis. Multiple marker technique is able to highlight the critical cells, and facilitate the study of H/RS cells. Abnormal expression of P53 may not play a major role in CHL. Over expression of bcl-2 may be linked to blockage of apoptosis in CHL.

Adolescent ; Adult ; Aged ; Antigens, CD20 ; genetics ; metabolism ; Apoptosis ; Biomarkers, Tumor ; genetics ; metabolism ; CD3 Complex ; genetics ; metabolism ; Child ; Child, Preschool ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; In Situ Nick-End Labeling ; Ki-1 Antigen ; genetics ; metabolism ; Lewis X Antigen ; genetics ; metabolism ; Middle Aged ; Neprilysin ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Reed-Sternberg Cells ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult