Features Of Peripheral T-cell Lymphoma Research Articles

Classification and challenges in the histopathological diagnosis of peripheral T-cell lymphomas, emphasis on the WHO-HAEM5 updates.

Mature T-cell lymphomas represent neoplastic expansions of T-cell lymphocytes with a post-thymic derivation. Most of these tumors feature aggressive clinical behavior and challenging histopathological diagnosis and classification. Novel findings in the genomic landscape of T-cell lymphomas are helping to improve the understanding of the biology and the molecular mechanisms that underly its clinical behavior. The most recent WHO-HAEM5 classification of hematolymphoid tumors introduced novel molecular and histopathological findings that will aid in the diagnostic classification of this group of neoplasms. The current review article summarizes the most relevant diagnostic features of peripheral T-cell lymphomas with an emphasis on the updates that are incorporated at the WHO-HAEM5.

Clinicopathologic Features of Peripheral T-Cell Lymphoma in Sub-Saharan Africa.

Peripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare. Subtype distribution varies by geographic location; however, data from sub-Saharan Africa (SSA) are lacking. We sought to elucidate clinicopathologic features of PTCL in SSA. We reviewed PTCL consultation cases from three SSA countries. PTCL subtype was determined per 2017 World Health Organization classification. Cases with sufficient material were evaluated by polymerase chain reaction for human T-cell leukemia virus type 1 (HTLV-1) and T-cell receptor γ (TCRG) rearrangement. Among 32 cases, median age was 45 years and male-to-female ratio was 1.7. Thirty (94%) of 32 cases required additional workup for subclassification. PTCL, not otherwise specified (PTCL-NOS) was the most common subtype (13/32, 41%), followed by PTCL with T-follicular helper phenotype (6/32, 19%) and systemic anaplastic large cell lymphoma (6/32, 19%). Four (16%) of 25 cases were Epstein-Barr virus positive (EBV+) (2/2 extranodal natural killer/T-cell lymphoma, 1/13 PTCL-NOS, and 1/4 angioimmunoblastic T-cell lymphoma with EBV+ immunoblasts). Two (15%) of 13 patients with PTCL-NOS were human immunodeficiency virus positive. No cases with evaluable DNA (0/15) were HTLV-1 positive, and 9 of 10 showed clonal TCRG rearrangements. In comparison to Western studies, PTCLs from SSA show similar subtype distribution and male predominance but a younger age at diagnosis. Appropriate diagnosis of PTCL requires extensive ancillary testing not readily available in low-income countries, including much of SSA.

The microenvironment and immune status of peripheral T-cell lymphoma: focusing on AITL and ATLL

Angioimmunoblastic T-cell lymphoma (AITL) originates from follicular helper T cells and shows variable biological and clinical presentations. The survival rate of patients with AITL did not correlate with T-cell clonality, the presence of EBV-infected cells, EBV-DNA copy number, or IgH rearrangements. However, tumor-associated macrophage/M2 macrophages significantly correlated with worse overall survival (OS). Additionally, patients with composite lymphoma with diffuse large B cell lymphoma and AITL showed worse OS. We reported mutations in TET2, DNMT3A, IDH2, and RHOA. TET2 and DNMT3A mutations were identified in both programmed cell death 1 (PD1) + T cells and CD20+ cells. All RHOA and IDH2 mutations were confined to PD1+ T cells, whereas several mutations, including NOTCH1 mutations, were detected only in CD20+ cells. TET2 and DNMT3A mutations may originate in hematopoietic progenitor cells. Adult T-cell leukemia/lymphoma (ATLL) expresses CCR4 and FOXP3 of the regulatory T-cell marker. The p40tax viral protein leads to the transcriptional activation of several genes. In addition, the HTLV-1 basic leucine zipper factor is considered important for T-cell proliferation and oncogenesis. The presence of Tax-specific cytotoxic T lymphocytes is inversely correlated with FOXP3 expression. M2 macrophages were associated with worse clinical prognosis in patients with ATLL. Programmed cell death ligand 1 (PD-L1) expression showed two patterns, namely neoplastic PD-L1 (nPD-L1) and microenvironmental PD-L1 (miPD-L1). Patients with nPD-L1-positive ATLL cells had inferior OS, whereas those with miPD-L1-positive ATLL cells had superior OS. Patients with a HLA+ beta2M+ phenotype had significantly better prognosis, and those with a HLAm+ beta2Mm+ miPD-L1high phenotype demonstrated the most favorable prognosis. Thus, our study demonstrated that understanding the microenvironment is critical in discerning the clinicopathological features of peripheral T-cell lymphoma.

Clinicopathologic features of peripheral T-cell lymphoma, unspecified with follicular pattern

To study the clinicopathologic features of peripheral T-cell lymphoma, unspecified (PTL-U) with follicular pattern. The clinical data, hematoxylin and eosin-stained sections of lymph node biopsies and follow-up data of 18 cases of PTL-U associated with follicular growth pattern were reviewed and studied. Eight cases of reactive lymphoid hyperplasia were used as controls. Semi-quantitative observation by retiform micrometer rule was carried out. Immunohistochemical study was also performed in all cases. T-cell receptor and immunoglobulin heavy chain gene rearrangement studies were conducted by polymerase chain reaction-based method. The median age of the patients was 53 years. The male-to-female ratio was 1.57:1 in lymphoma group. All of the lymphoma patients presented with superficial lymphadenopathy, with (8/18) or without B symptoms. Histologically, the lymphoma was characterized by follicles of various sizes and shapes. The T zones were expanded by medium-sized lymphoma cells which contained clear cytoplasm and irregular nuclei. Mitotic figures were commonly identified. Immunohistochemical study confirmed that the lymphoma cells were of T-lineage. The proliferative index, as highlighted by Ki-67, was higher [average = (38.24 +/- 13.42)%/mm2] than that in the control group. T-cell receptor gene rearrangement was demonstrated in 71.4% (10/14) of the lymphoma cases. A definitive diagnosis of PTL-U with follicular pattern can be made on the basis of morphologic examination, immunohistochemical assessment and clinical features. Cases with atypical features can further be delineated by molecular analysis. Long-term follow up of these patients is prudent.

Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the Revised European-American lymphoma (REAL) classification

The aim of this study was to analyse the clinical characteristics and prognostic factors of peripheral T-cell lymphomas (PTCLs) according to the Revised European-American Lymphoma (REAL) classification. From 1994 to 1999, 78 patients were diagnosed with PTCLs, excluding cutaneous T-cell lymphomas and T-cell chronic lymphocytic leukaemia. The distribution of the histological subgroups were: PTCL unspecified (PTCL-U), 40%; angiocentric lymphoma, 32%; anaplastic large cell lymphoma (ALCL), 17%; angioimmunoblastic T-cell lymphoma (AILD), 6%; intestinal T-cell lymphoma, 3%; and panniculitic T-cell lymphoma, 3%. Patients with angiocentric lymphoma presented with favourable prognostic factors, whereas those with AILD presented with unfavourable prognostic factors. Most patients were treated with doxorubicin-containing combination chemotherapy (with or without radiation therapy). The overall complete remission rate was 61.2% (95% Confidence Interval (CI): 48.5–72.8%) and the 5-year probability of failure-free survival was 33.5%. Median survival of all patients was 45 months (range 0–64+ months) and the 5-year probability of survival was 36.2%. In the multivariate analysis, only the International Prognosis Index (IPI) was an independent prognostic factor for overall survival (P<0.01). Taken together, the proportion of angiocentric lymphoma in this study was higher than that in the studies of Western countries. PTCL responds poorly to treatment with low survival rates and the IPI is a useful prognostic factor for PTCL.

A clinicopathologic study of malignant lymphomas of the nose, paranasal sinuses, and hard palate, including cases of lethal midline granuloma.

Malignant lymphomas of the nose, paranasal sinuses, and hard palate show marked clinicopathologic, immunologic, and prognostic diversity. The clinical features and pathologic spectrum of these lesions were studied in 20 cases (11 female and 9 male cases) with a mean age of 51 years at initial presentation. Malignant lymphomas of the large cell type were most frequently encountered (11/20). The next largest category was malignant lymphoma, diffuse, mixed small and large cell type (six of 20). Two thirds, 13 of 20 cases, had morphologic features suggestive of peripheral T-cell lymphomas. Necrosis, an angiocentric growth pattern, and epitheliotropism were found in nine, eight, and three cases, respectively. Of ten cases immunophenotyped on fresh-frozen or fixed, paraffin-embedded tissue sections, eight had a T-cell phenotype and two had a B-cell phenotype. Of 17 patients with sufficient follow-up data, ten are alive (median follow-up 33 months) and seven are dead (median survival 12 months). Patients with clinical Stages IE and IIE did not have a superior 5-year survival to those with more advanced disease. Histologic type also did not correlate with survival but this may be due to the aggressive histologic grade of the majority of cases and the retrospective nature of this study. The authors conclude that, despite the overall high-grade histologic type, the pathologic spectrum of malignant lymphomas involving this anatomic region is broad. Furthermore, some cases do not fit well into the National Cancer Institute (NCI) Working Formulation but more closely resemble the histologic features of peripheral T-cell lymphomas described in Japan.