Follicular Peripheral T-cell Lymphoma Expands the Spectrum of Classical Hodgkin Lymphoma Mimics

Abstract

Epstein-Barr virus (EBV)-infected B cells with Reed-Sternberg-like cell (RS) features may occur in peripheral T-cell lymphomas (PTCLs), especially in angioimmunoblastic T-cell lymphoma. Here, we report 5 patients presenting with lymphadenopathy whose first biopsies demonstrated nodular lymphoid proliferations containing scattered CD30+, CD15+, EBV+ Hodgkin and Reed-Sternberg-like cells, which led to an initial diagnosis of lymphocyte-rich classical Hodgkin lymphoma. However, the uncommon clinical features and/or the occurrence of relapse as PTCL prompted review of the biopsies with expanded immunohistologic and molecular studies and revision of the diagnoses to follicular variant of PTCL (F-PTCL). All cases had atypical small to medium-sized CD3+ T cells that expressed CD10 (4/5) and the follicular helper T-cell (TFH) antigens BCL6, PD1, CXCL13, and ICOS. All demonstrated clonal T cells with a similar pattern in multiple samples from 4 patients. In 2 cases, flow cytometry demonstrated circulating lymphocytes with an abnormal sCD3+, CD4+, ICOS+ immunophenotype. Two patients had a skin rash at presentation, and 1 had B symptoms. Two of the 4 patients treated with polychemotherapy are alive at 3 and 6 years after first diagnosis. These cases highlight how some F-PTCLs may closely mimic lymphocyte-rich classical Hodgkin lymphoma requiring careful assessment of the T cells before rendering the latter diagnosis. The functional properties of TFH cells might lead to the presence of EBV-positive B blasts with RS-like features in TFH-derived PTCL such as angioimmunoblastic T-cell lymphoma and F-PTCL.

Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed–Sternberg cells

“…Based on this idea, understanding the mechanisms involved in fusion-based RS cell formation might lead to new therapeutic interventions making use of this process. Finally, our present findings have implications beyond HL, given that RS and RS-like cells are also regularly seen in other lymphoproliferative disorders, including infectious mononucleosis, B-cell chronic lymphocytic leukemia, and T-cell lymphomas (7,47,48). In these disorders, the RS-like cells may be generated in a similar way as we have described here.…”

The 2016 revision of the World Health Organization classification of lymphoid neoplasms

“…In some cases, the atypical B-cell blasts simulate Hodgkin-Reed-Sternberg cells, leading to a mistaken diagnosis of classical Hodgkin lymphoma (CHL). 93,94 Progression to EBV 1 , and more rarely EBV 2 , B-cell neoplasms may occur in a subset of cases. 95 Nevertheless, although the neoplastic cells share a TFH phenotype and share many genetic changes, clinical and pathological differences remain, so that both diagnoses are retained in the classification.…”

Thomas Hodgkin and Hodgkin lymphoma

“…Less commonly, peripheral T cell lymphoma, NOS [74], and rarely adult T cell leukemia/lymphoma (HTLV1+) [74,75] contain Reed-Sternberg-like B cells. Recently, cases of the follicular variant of peripheral T cell lymphoma, NOS, which has a less polymorphous composition, and may also contain EBV+ Reed-Sternberg-like B cells have been described that have been mistaken initially for LRCHL [76]. Clues to the correct diagnosis in such cases include clinical and pathological features that would be unusual for CHL.…”

“…In addition, T cell receptor gene rearrangement studies usually disclose a clonal T cell population in T cell lymphomas, while clonal T cells are nearly always absent in Hodgkin lymphoma. Unusual clinical features such as widespread disease or involvement of extranodal sites typically spared by Hodgkin lymphoma may also raise suspicion that Hodgkin lymphoma is not the correct diagnosis [76].…”