The diagnosis of THRLBCL, particularly as it pertains to differentiating it from DLBCL and other<unk> s, depends on examining involved tissues obtained by biopsy or operation for their histology, i.e. microscopic anatomy. The tissues involved in THRLBCL commonly show an effacement of their normal architecture by a diffusely growing infiltrate of non-malignant T-cell lymphocytes,<unk> s, and neoplastic (i.e. malignant) B-cells. The malignant B-cells represent <10% of the cells in these lesions and bear resemblances to centroblast, immunoblasts, and/or the Reed–Sternberg cells found in Hodgkin disease, including in particular Hodgkin disease's nodular variant. The non-malignant T-cells generally have a reactive morphology as indicated by their larger than normal size and irregularly shaped cell nuclei. And, the<unk> s, which are not always present in these lesions, have a non-epithelial cell appearance. These infiltrates often resemble these seen in inflammation. The malignant B-cells in THRLBCL are definitively identified by immunophenotyping to detect B-cell marker proteins (e.g. CD19, CD20, CD22, CD79a, and/or PAX5). These cells may also express other identifying marker proteins such as Bcl-6 (50-90% of cases), the product of the MYC gene, c-Myc (most cases), Bcl-2 (40% of cases), MUC1 (30% of cases), and, in a minority of cases, CD10. The T-cells in these lesions are predominantly cytotoxic T cells as indicated by their expression of T-cell receptor, CD8 T-cell co-receptor, and CD5 cell surface proteins. And, the<unk> s in these lesions express CD68 and CD163 cell surface proteins. Before making a diagnosis of THRLBCL in a pediatric population, congenital and acquired immunodeficiency diseases, which can cause aberrant immune responses with a histology similar to THRLBCL, must be ruled-out. Differential diagnosis While the histological features of THRLBCL are distinctly different that those found in other DLBCL subtypes, they can closely resemble, and be mistaken for, those found in the variant form of nodular lymphocyte predominant Hodgkin<unk> . Some important histological features that favor the diagnosis of THRLBCL over NLPHL include the presence of: 1) <10% neoplastic B-cells; 2) CD163-expressing<unk> s (cases of THRLBCL in which<unk> s are absent appear to take a less aggressive course than cases in which these cells are present); 3) a diffuse rather than nodular cell infiltration pattern with any nodular infiltrates present in THRLBCL containing follicular dendritic cells; 5) PD-1-, CD4-, and CD57-expressing T-cells; 6) cells strongly expressing the BAT3/BAG6 ubiquitin domain-containing protein; and 7) few or no small lymphocytes, variant Hodgkin i.e. popcorn and Reed-Sternberg cells.
T cell/histiocyte-rich large B-cell lymphoma
Diffuse large B-cell lymphoma associated with chronic inflammation
Germinal center B-cell like diffuse large B-cell lymphoma
Extranodal NK/T-cell lymphoma, nasal type
Fibrin-associated diffuse large B-cell lymphoma
Pediatric-type follicular lymphoma
Nodal marginal zone B cell lymphoma
Marginal zone B-cell lymphoma