Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma / 北京大学学报(医学版)

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.

Progressively transformed germinal center-like follicular T-cell lymphoma:a clinicopathological analysis of 14 cases / 中华病理学杂志

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.

Histopathologic findings of lymph node biopsy cases in comparison with clinical features

To determine useful and important clinical signs and symptoms for evaluation of lymphadenopathy with consideration of histopathologic findings of biopsy. This retrospective case-series study was done on patients hospital folders who came with lymphadenopathy, Informations was collected about clinical signs, symptoms, age, gender and histopathologic findings. It was then analyzed by SPSS version 13 with chi-square test. There were 208 specimens, 98 women [47.1%] and 110 men [52.9%]. Mean age was 32.94 years. There were 45 cases [21.6%] of malignancy, 33 cases [15.9%] of infectious diseases and 130 cases [62.5%] of reactive lymphadenopathy. The most common histopathologic finding in all ages was reactive lymphadenopathy. Clinical signs and symptoms had significant relationship with pathologic findings. For a decision of lymph node biopsy attention to patients symptoms and signs especially B signs, size of the lymph node >2cm, generalized lymphadenopathy, mobility of lymph node and splenomegaly seems to be the useful guide lines for physician. In this study it seems that decision to take biopsy was correct in 75% of the cases

Angioimmunoblastic T-cell lymphoma obscured by concomitant florid epithelioid cell granulomatous reaction--a case report.

Epithelioid cell granuloma occurs in association with many neoplasms including lymphoma. However they have rarely obscured the microscopic features of a lymphoma. We report on a case where a florid epithelioid cell granulomatous reaction caused difficulty in interpretation and delayed the final diagnosis of a case of peripheral T cell lymphoma of the angioimmunoblastic type. We draw attention to this unusual phenomenon because of its practical implications.

Poliartritis seropositiva como presentación de linfadenopatía angioinmunoblástica / Seropositive polyarthritis as a presentation of immunoblastic lymphadenopathy

Se presenta un paciente de sexo masculino de 59 años de edad con poliadenopatía febril, que habia desarrollado dos meses antes una poliartritis de tipo AR-símil, con una discreta mejória a pesar del uso de drogas analgésicas y antiinflamtorias no esteroideas. El estudio anatomopatológico de ganglio linfático mostró los criterios histológicos mayores para el diagnóstico de linfadenopatía angioinmunoblástica (LAA), según Jaffe: arquitectura normal del nódulo linfático distorsionada por infiltrados linfoplasmocíticos, acompañados por arborizaciones finas de los vasos sanguíneos y, a menudo, por depósitos intersticiales de material eosinofílico amorfo. El paciente fallece con infiltrados pulmonares. Los inofrmes sobre coexistencia de esta entidad con LES, síndrome de Sjögren, AR, ARJ, púrpura de Schonlein-Henoch, etc., son escasos. Si bien una poliartritis indefinida ha sido señalada, el inicio de la LAAI como una poliartritis seropositiva no se ha descripto en las principales revisiones, existiendo la posibilidad de que se trate de una manifestación de la misma o la asociación de una LAAI y una artritis reumatóide

Angioimmunoblastic lymphadenopathy with dysproteinaemia.

Angioimmunoblastic lymphadenopathy with dysproteinaemia is a rare disease. One such case is reported.

Enfermedad de Castleman generalizada: informe de dos casos / Systemic Castleman's diseases: report of 2 cases

Se presentan dos casos de enfermedad de Castleman generalizada (ECG). De ésta existen dos tipos: el hialino-vascular con hiperplasia folicular y prominente vascularidad interfolicular con vasos radiales, frecuente hialinización y ausencia de síntomas clínicos y el de células plasmáticas con grandes folículos y capas interfoliculares de células plasmáticas maduras y habitualmente con fiebre, anemia e hiperglobulinemia. Existen formas transicionales y la hipótesis de que la variedad de células plasmáticas es una etapa más temprana, más activa que la hialino-vascular. El primer caso es una forma transicional con síntomas generales y remisión completa con quimioterapia combinada; la duración de la remisión fue de siete meses. El caso dos corresponde a la variedad de células plasmáticas con síntomas generales y localización poco frecuente (mesenterio). En el tratamiento de la ECG se han utilizado con poco éxito, esteroides, esteroides más agentes anticoplásicos y cirugía. En el caso uno se utilizó MEPP (mostaza, etopósido, procarbazina y prednisona) con lo que se logró remisión completa de siete meses, así como una segunda remisión. En el caso dos, con la misma combinación, la remisión ha sido parcial. Es un hecho que, en algunos casos, esta combinación o una parecida obtienen remisiones completas o parciales

Linfadenopatía periférica: 10 años de experiencia de la biopsia ganglionar / Peripheral lymphadenopathy: 10 years experience with lymph nodes biopsy

Se presenta la experiencia de 20 años de la biopsia ganglionar, en la evaluación de la linfadenopatía periférica. Se incluyeron 576 biopsias, 59.7% fueron diagnósticas, siendo la patologia más frecuente TBC representando el 31.8%, seguido de cáncer metastásico y linforma con 11.6 y 9.5% respectivamente. Los ganglios supraclaviculares y cervicales fueron diagnósticas con más frecuencia que los ganglios de otras localizaciones, en forma significativa. En relación a edad y sexo, se observó que a partir de la sexta década de la vida y en mujeres, la biopsia ganglionar fué con más frecuencia diagnóstica. TBC se encontró en mayor frecuencia en los ganglios cervicales, en jóvenes y en sexo femenino: cáncer metastásico fué más frecuente en la localización supraclavicular en mayores de 50 años, no mostrando diferencia en relación al sexo, mientras que en linfoma no se encontró diferencias en sexo ni localización

Linfopatía angioinmunoblástica con hipogammaglobulinemia / Angioimmunoblastic lymphadenopathy with hypogammaglobulinemia

La linfopatía angioinmunoblástica es una proliferación ganglionar con una histología particular, habiendo numerosos reportes en la literatura desde 1974. Hipergammaglobulinemia policlonal se encontró en el 80% de los casos relatados. La hipogammaglobulinemia ha sido descripta excepcionalmente en esta entidad, y cuando ésta ocurre se debe sospechar transformación linfomatosa. Sin embargo, hay escasas referencias de linfopatía angioinmunoblástica con hipogammaglobulinemia desde el comienzo de la enfermedad (hipogammaglobulinemia total o déficit selectivo de IgA). El mecanismo de la hipogammaglobulinemia en la linfopatía angioinmunoblástica no está aclarado. Probablemente, estos pacientes representen un subgrupo cuyo pronóstico debe ser definido. Presentamos en este trabajo un caso de linfopatía angioinmunoblástica con hipogammaglobulinemia