CD30 expression in neoplastic T cells of follicular T cell lymphoma is a helpful diagnostic tool in the differential diagnosis of Hodgkin lymphoma

Abstract

Follicular T cell lymphoma is derived from follicular T-helper cells. In many cases, neoplastic T cells form rosettes around Hodgkin-Reed-Sternberg-like cells, which can lead to the misdiagnosis of classical Hodgkin lymphoma. The aim of the present study was to obtain a better understanding of this rosetting phenomenon and to recognize features that are helpful in the differential diagnosis of classical Hodgkin lymphoma. Sixteen mostly elderly follicular T cell lymphoma patients (mean 66 years) were analyzed. Fifteen of the 16 follicular T cell lymphoma cases presented with Hodgkin-Reed-Sternberg-like cells, which were CD20-positive in 27% of the cases and Epstein-Barr virus-infected in nearly all cases. Frequently, the immunophenotype of rosetting neoplastic T cells differed from the bulk neoplastic cells with less numerous T-follicular helper cell markers expressed, suggesting a modulation of T-follicular helper cell marker expression in the neoplastic T cells. In 75% of the cases, variable CD30 expression was encountered in the neoplastic T cells, likely reflecting an activation state in these cells. Hodgkin-Reed-Sternberg-like cells were positive for CCL17, and follicular T cell lymphoma tumor cells expressed its receptor CCR4 at variable intensity, thus potentially explaining the phenomenon of the tumor cells' rosetting around Hodgkin-Reed-Sternberg-like cells. In summary, this study confirms the presence of Hodgkin-Reed-Sternberg-like cells in a high number of cases of follicular T cell lymphoma, suggesting that Hodgkin-Reed-Sternberg-like cells may contribute to the development of this lymphoma. Hodgkin-Reed-Sternberg-like cells in follicular T cell lymphoma cannot reliably be differentiated from the Hodgkin-Reed-Sternberg cells of classical Hodgkin lymphoma based on their immunophenotype. In contrast, demonstration of a T-follicular helper cell phenotype with CD10 and frequent CD30 expression in the neoplastic T cell population can help to establish the diagnosis of follicular T cell lymphoma, and may even indicate CD30 as a therapeutic target for these patients.

Approach to nodal-based T-cell lymphomas

“…4). 48,52 One study found that the neoplastic cells had at least partial expression of CD30 in 75% of their case series. 52 A component of large blastic EBV-positive or -negative B cells is often identified, frequently with RS-like morphology and immunophenotype ( Fig.…”

“…4). 24,48,52,53 A chromosomal translocation t(5;9)(q33;q22) involving ITK and SYK tyrosine kinases is found in about 20% of F-PTCL, and has been reported thus far in only one case of typical AITL. 48,54,55 The ITK-SYK fusion may be detected by fluorescence in situ hybridisation (FISH) assays, but its diagnostic value is rather limited.…”

“…Careful examination of the CD30 immunostain can be helpful because in TFH lymphomas and PTCL-NOS, expression of CD30 is often detected in the small and medium-sized neoplastic T cells as well, whereas in classic Hodgkin lymphoma CD30 is typically mostly restricted to the RS cells. 20,52 The clue to AITL diagnosis lies in immunohistochemistry showing expression of PD1 and other TFH markers in atypical T cells and highlighting rosettes of TFH cells around the HRS-like cells. 5,24,141 PTCL with HRS-like T cells Pleomorphic cells, including cells with HRS morphology and/or partial CD30 expression, are common features of PTCL-NOS.…”

In Situ Characterization of Follicular Helper CD4 T Cells Using Multiplexed Imaging

“…In line with this, a relatively high frequency of Tfh cells co-expressing CXCR5 and CXCL13 was found in AITL compared to tonsils, suggesting an important role for the CXCR5/CXCl13 axis as regulator of the Tfh cell trafficking and positioning in AITL LNs. CD30, a receptor found on activated T cells and widely used for diagnosis of peripheral T lymphomas (61,62,94), was readily found in AITL Tfh cells but it was almost absent in their tonsillar counterparts. Interestingly, the majority of CD30 hi Tfh cells were expressing a BCL6 hi phenotype too, indicating a possible role of CD30 in the differentiation process of AITL Tfh cells.…”

“…Approximately 5% of non-T cells in the tumor area were CD30+. Interestingly, a relatively high frequency of Tfh cells were positive for CD30, a receptor often found in AILT (61)(62)(63), in LNs (36%) while normal Tfh cells in tonsil GC very rarely coexpressed CD30 (0.04%) (Table 4). Analysis of the three aforementioned Tfh cell signatures revealed a different pattern in AITL compared to tonsils (Figure 5B).…”