Background: The aim of the current study was to elucidate the histology, immunophenotype, and differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with a vague nodular pattern. The heterogeneity of DLBCL is widely acknowledged. T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) is an uncommon aggressive variant of DLBCL. It has both nodal and extranodal presentation. The diagnosis of T/HRBCL is difficult as it may share several morphological and immunophenotypic similarities to other lymphoid diseases, such as nodular lymphocytic predominance Hodgkin’s lymphoma (NLPHL) and classic Hodgkin’s lymphoma. Thus, histologic subclassification of DLBCL is useful to avoid the risk of treatment failure. Accurate diagnosis therefore requires a careful immunohistochemical analysis.
Patients and methods: A total of 332 cases diagnosed with DLBCL with vague nodularity were reviewed between 2009 and 2012. They were reclassified as DLBCL, T/HRBCL, or NLPHL according to the 2008 WHO classification of lymphoid neoplasms. Immunohistochemical studies were carried out on paraffin-embedded tissue to study the immunophenotype of the large neoplatic cells (CD20, CD15, CD30, EMA, Bcl-2) and the background of non-neoplastic cells (CD3, CD20).
Results: In total, 332 cases diagnosed with DLBCL with vague nodularity were reviewed. Of which 318 (95.7%) cases were diagnosed as DLBCL, whereas 12 (3.6%) were reclassified as T/HRBCL and two (0.6%) were reclassified as NLPHL. There was male predominance (75.0%) among cases of T/HRBCL. Most patients with T/HRBCL were diagnosed at a younger age in comparison with patients with DLBCL, with a mean age of 46.50±14.2 years. Cervical lymph nodes were the most frequently involved lymph node type in both DLBCL (56.6%) or in T/HRBCL (50.0%).
In terms of disease stage, there was a statistically significant difference (P=0.031) between T/HRBCL and DLBCL patients. Most patients [eight (66.7%)] with T/HRBCL presented at an advanced stage. All patients with DLBCL were CD3− and showed a diffuse positive reaction for CD20. However, patients with T/HRBCL showed a positive reaction for CD3 in 80–90% of the reactive cells and showed a positive reaction for CD20 in 10–20% of the large neoplastic cells. In NLPHL cases, lymphocytic and/or histiocytic cells showed positivity for EMA and CD20 and were surrounded by reactive T cells positive for CD3. There was a statistically significant difference between patients with T/HRBCL and DLBCL in the mean Bcl-2 expression (16.3±7.1 and 43.2±18.2, respectively).
Conclusion: T/HRBCL is an uncommon clinicopathologic subtype of DLBCL. Careful attention must be paid at the time of diagnosis because it may be confused with other lymphoid neoplasms characterized by a marked host immune reaction such as Hodgkin’s disease (NLPHL). Immunophenotyping analysis is essential in establishing the diagnosis of T/HRBCL in all cases.