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

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

Although Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of a proportion of cases of classical Hodgkin lymphoma (cHL), how the virus contributes to the pathogenesis of this disease remains poorly defined. It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required. This article reviews what is known about the contribution of EBV to the pathogenesis of cHL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Hodgkin Disease ; virology ; Humans ; Reed-Sternberg Cells

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

Hodgkin's disease (HD) is a lymphoproliferative disorder that presents as a clinically asymptomatic mass or painless lymph node swelling. Cutaneous HD is a very rare manifestation in patients with HD. A 66-year-old man complained of a maculopapular rash waxing and waning for one year. A painful mass had developed on his left axilla 7 weeks prior to presenting. The biopsy specimens of both skin and lymph node revealed Hodgkin's lymphoma with atypical lymphoid cells and Reed-Sternberg cells. We report a case of cutaneous involvement of HD, which had been presented as a maculopapular rash for one year.
Aged ; Axilla ; Biopsy ; Exanthema ; Hodgkin Disease ; Humans ; Lymph Nodes ; Lymphocytes ; Lymphoproliferative Disorders ; Reed-Sternberg Cells ; Skin

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

Authors report a very rare case of primary Hodgkin's lymphoma limited to the cerebellum. A 64-year-old female patient presented with headache, nausea, and vomiting. Magnetic resonance imaging of the brain revealed a nodular enhancing mass in the left cerebellar hemisphere. Tumor was removed totally with retromastoid suboccipital approach. Diagnosis was Hodgkin's lymphoma of mixed cellularity type, consisting of a dense mixed inflammatory infiltrate containing scattered large atypical mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells. Systemic work-up for the Hodgkin's lymphoma was followed with negative result. Postoperative radiation therapy was given and the patient is disease-free at 16 months after the operation.
Brain ; Cerebellar Neoplasms ; Cerebellum ; Diagnosis ; Female ; Headache ; Hodgkin Disease* ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Nausea ; Reed-Sternberg Cells ; Vomiting

OBJECTIVETo study the expression of FHIT protein and its potential application in diagnosing classic Hodgkin lymphoma.

METHODSImmunohistochemical study using EnVision method for FHIT tumor suppressor protein, hematopoietic stem cell markers CD133/AC133 and CD34, B-cell marker CD20, T-cell marker CD3 and oncoprotein c-erbB2 was performed on 33 cases of classic Hodgkin lymphoma.

RESULTSThirty-three of the Hodgkin lymphoma cases (90.9%) expressed FHIT protein. The antigen was mainly located in the cytoplasm, nucleus and membrane of classic Reed-Sternberg and Reed-Sternberg-like cells. Normal B and T lymphocytes, as well as their malignant counterparts, were negative for FHIT protein; whereas monocytes, histiocytes and dendritic cells were positive. All the cases studied were negative for CD133/AC133, CD34, CD3 and c-erbB-2. Two of the 33 cases showed positive staining for CD20 in some of the Reed-Sternberg cells.

CONCLUSIONThe expression of FHIT protein can be used as a useful adjunct in diagnosing classic Hodgkin lymphoma.

AC133 Antigen ; Acid Anhydride Hydrolases ; metabolism ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, CD20 ; metabolism ; Biomarkers, Tumor ; metabolism ; Cell Nucleus ; metabolism ; Child ; Child, Preschool ; Cytoplasm ; metabolism ; Female ; Glycoproteins ; metabolism ; Hodgkin Disease ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Peptides ; metabolism ; Reed-Sternberg Cells ; metabolism ; Sensitivity and Specificity

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