lewis-x-antigen and Lymphoma--T-Cell--Peripheral

Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement. We describe a series of 6 JAK2 rearrangements occurring in a cohort of 97 CD30+ ALK- PTCL (6%), assembled after identifying an index case of a novel PABPC1-JAK2 fusion in a case of ALK- anaplastic large cell lymphoma with unusual classic Hodgkin lymphoma (CHL)-like features. Fusions were identified using a comprehensive next-generation sequencing based assay performed between 2013 and 2020. Five of 6 cases (83%) showed JAK2 rearrangements with 4 novel partners: TFG, PABPC1, ILF3, and MAP7, and 1 case demonstrated a previously described PCM1-JAK2 fusion. By morphology, all cases showed anaplastic large cells and multinucleated Reed-Sternberg-like cells within a polymorphous inflammatory background with frequent eosinophilia reminiscent of CHL. By immunohistochemistry, atypical large cells expressed CD30 with coexpression of at least 1 T-cell marker, aberrant loss of at least 1 T-cell marker and, in 4 of 5 cases stained (80%), unusual CD15 coexpression. These findings suggest that a subset of CD30+ ALK- systemic PTCL with anaplastic morphology carry JAK2 rearrangements, some of which appear to show CHL-like morphologic features. The presence of JAK2 rearrangements in cases of CD30+ PTCL augments current classification and may provide a therapeutic target via JAK2 inhibition.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Gene Fusion; Gene Rearrangement; Genetic Predisposition to Disease; Humans; Janus Kinase 2; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Phenotype; Poly(A)-Binding Protein I; Retrospective Studies

Topics: Diagnosis, Differential; Fucosyltransferases; Humans; Ki-1 Antigen; Leukosialin; Lewis X Antigen; Lymph Nodes; Lymphoma, T-Cell, Peripheral; Reed-Sternberg Cells; Sclerosis

Topics: Aged; Antigens, CD20; Humans; Ki-1 Antigen; Lewis X Antigen; Lymphoma, T-Cell, Peripheral; Male; PAX5 Transcription Factor

CD15 is a useful immunohistochemical marker to identify Reed-Sternberg cells in classical Hodgkin's lymphoma (HL) and to distinguish it from HD-like neoplasms, but data from the literature concerning its expression in HL are quite variable. Using immunohistochemistry we compared the reactivity of three different anti-CD15 clones (MMA, C3D1 and BY87) and found that anti-CD15 MMA clone is a superior reagent in identifying atypical cells, detecting more numerous cells in 28.2%, and being the only positive marker in 12.8% of cases. We conclude that it is advisable to include this reagent in diagnostic immunohistochemical panels.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Neoplasm; Diagnosis, Differential; Hodgkin Disease; Humans; Immunoglobulin M; Lewis X Antigen; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Peripheral; Mice; Reed-Sternberg Cells; Sensitivity and Specificity

Although peripheral T-cell lymphoma, unspecified (PTCL/U), is the most common T-cell tumor in Western countries, no study to date has been based on the application of a wide panel of markers to a large series of patients and assessed the impact of phenotype on survival. We evaluated the expression of 19 markers in 148 PTCLs/U and 45 PTCLs of the angioimmunoblastic type (AILD).. The analysis was performed on tissue microarrays by immunohistochemistry and in situ hybridization. Clinical data were available in 93 PTCL/U patients, most of whom had been included in a previous study proposing a prognostic index (PIT).. An aberrant phenotype with frequent loss of CD5 and/or CD7 was typical for PTCLs, irrespective of whether they were U or AILD. Aberrantly expressed proteins rarely included CD20, CD15, and CD30. Positivity for Epstein-Barr virus-associated small RNAs and CD15 expression emerged as adverse prognostic factors. Among PTCLs/U, the proliferation-associated protein Ki-67 turned out to be prognostically relevant and was integrated in a new predictive score, incorporating age (> 60 years), high lactate dehydrogenase, poor performance status, and Ki-67 > or = 80%. This score was associated with the patient outcome (P < .0001) and was found to be more robust than PIT (P = .0043) in the present series.. Our retrospective analysis shows a wide range of protein expression in PTCLs and proposes a new prognostic index. The latter represents one of the first examples of mixed score (including patient- and tumor-specific factors) applied to malignant lymphomas and may be the basis for future prospective therapeutic trials.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, CD20; Antigens, CD7; Biomarkers, Tumor; CD2 Antigens; CD3 Complex; CD4 Antigens; CD5 Antigens; CD8 Antigens; Clinical Trials as Topic; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Ki-1 Antigen; Ki-67 Antigen; Lewis X Antigen; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Multicenter Studies as Topic; Neprilysin; Phenotype; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Tissue Array Analysis

Coexpression of CD30 and CD15 is typically associated with classic Hodgkin's lymphoma (HL). Peripheral T-cell lymphomas (PTCLs) can often display histologic features that simulate classic HL. However, reports of PTCLs coexpressing both CD30 and CD15 have been infrequently described. We report 11 cases of PTCL in which at least a subset of the neoplastic cells coexpressed CD30 and CD15. The patients included 4 women and 7 men and age ranged from 43 to 83 years (median, 62 years). Nine of 10 patients had advanced stage III or IV disease at presentation. Nodal involvement predominated in 8 of 11 patients, whereas 2 patients presented primarily with skin involvement. Two distinct groups were identified based on morphologic and immunophenotypic features. The first group of 5 cases had histologic features mimicking classic HL with CD30+, CD15+ Reed-Sternberg (RS)-like cells in an inflammatory background of varied extent and composition. The background lymphoid cells showed minimal cytologic atypia. The RS-like cells were negative for CD20 and CD79a in all cases, and CD45 expression was absent in 4 of 5 cases. The RS-like cells expressed CD25 and at least one T-cell-associated marker in all cases. The background T-cell population showed convincing subset predominance in 4 of 5 cases and loss of T-cell-associated antigens in 3 of 5 cases and coexpression of CD30 and CD15 in one case. The second group of 6 cases had morphologic features more in keeping with PTCL than classic HL. The proportion of neoplastic cells coexpressing CD30 and CD15 varied. Loss of T-cell antigens was noted in all cases and CD4 predominated in 4 of 5 cases. Three of the 6 cases expressed CD45. PCR analysis revealed clonal T-cell receptor gamma (TCR-gamma) chain gene rearrangements in 9 of 11 cases, but no immunoglobulin heavy (IgH) chain gene rearrangements. In situ hybridization studies for Epstein-Barr virus were negative in all cases. In some PTCL cases, the overlap with classic HL can be striking, and combined immunophenotypic and molecular studies are often necessary to confirm the diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Viral; Diagnosis, Differential; Female; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Hodgkin Disease; Humans; Immunophenotyping; In Situ Hybridization; Ki-1 Antigen; Lewis X Antigen; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Polymerase Chain Reaction