INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) in western countries are uncommon tumors with unfavorable prognosis. They may be subclassified as anaplastic large-cell lymphomas (ALCLs), angioimmunoblastic-T-cell lymphomas (AITLs), or unspecified peripheral T-cell lymphomas (PTCLs-U). It has recently been demonstrated that AITLs originate from germinal center follicular helper T cells (TFH), whereas the normal counterparts of other PTCLs remain essentially unknown. The aim of this study was to establish whether other PTCL subgroups also express TFH cell markers. MATERIALS AND METHODS: One hundred forty-six PTCLs were analyzed for programmed death-1 (PD-1) expression in tissue microarrays using a new monoclonal antibody called NAT-105. PD-1-positive cases, which did not fulfill all the criteria for AITL, were further evaluated in whole-tissue sections for another 12 immunohistochemical markers, including the TFH cell markers CXCL13, CD10, and BCL6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic, clinical, and follow-up data were reviewed. RESULTS: Twenty-five out of 87 non-AITL cases (28.75%) showed PD-1 immunostaining. CXCL13, BCL6, and CD10 expression was found in 24/25 (96%), 16/25 (64%), and 6/25 (24%) cases, respectively. All cases expressed at least 2 TFH cell markers. Moreover, 5 cases were positive for all 4 markers. Most cases (17/25, 68%) displayed some AITL-like features. Of the remainder, 1 was considered to be early AITL, 1 was diagnosed as ALCL-anaplastic lymphoma kinase-negative, and 4 of the other 6 PTCLs-U had morphology consistent with lymphoepithelioid (Lennert's) lymphoma. Three AITL-like cases showed IgH clonal rearrangement, 2 of which were associated with Epstein-Barr virus expression. Our series of patients did not differ significantly in their clinical presentation from most reported PTCL cases in the literature: 55% of them were alive and 35% were in complete remission after a median follow-up of 15 months after cyclophosphamide, dexorubicin, vincristine, and prednisone-based chemotherapy. CONCLUSIONS: TFH cell markers, especially PD-1, were expressed in a subset of PTCLs not classified as AITL, although most of them shared some morphologic features with AITL. This suggests that the spectrum of AITL may be wider than previously thought, possibly including cases of lymphoepithelioid (Lennert's) lymphoma. Additionally, the results suggest that a subgroup of PTCLs-U, distinct from AITL and including some cases denominated as ALCL, may also be derived from TFH cells, although they develop along a distinct pathogenic pathway.
INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) in western countries are uncommon tumors with unfavorable prognosis. They may be subclassified as anaplastic large-cell lymphomas (ALCLs), angioimmunoblastic-T-cell lymphomas (AITLs), or unspecified peripheral T-cell lymphomas (PTCLs-U). It has recently been demonstrated that AITLs originate from germinal center follicular helper T cells (TFH), whereas the normal counterparts of other PTCLs remain essentially unknown. The aim of this study was to establish whether other PTCL subgroups also express TFH cell markers. MATERIALS AND METHODS: One hundred forty-six PTCLs were analyzed for programmed death-1 (PD-1) expression in tissue microarrays using a new monoclonal antibody called NAT-105. PD-1-positive cases, which did not fulfill all the criteria for AITL, were further evaluated in whole-tissue sections for another 12 immunohistochemical markers, including the TFH cell markers CXCL13, CD10, and BCL6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic, clinical, and follow-up data were reviewed. RESULTS: Twenty-five out of 87 non-AITL cases (28.75%) showed PD-1 immunostaining. CXCL13, BCL6, and CD10 expression was found in 24/25 (96%), 16/25 (64%), and 6/25 (24%) cases, respectively. All cases expressed at least 2 TFH cell markers. Moreover, 5 cases were positive for all 4 markers. Most cases (17/25, 68%) displayed some AITL-like features. Of the remainder, 1 was considered to be early AITL, 1 was diagnosed as ALCL-anaplastic lymphoma kinase-negative, and 4 of the other 6 PTCLs-U had morphology consistent with lymphoepithelioid (Lennert's) lymphoma. Three AITL-like cases showed IgH clonal rearrangement, 2 of which were associated with Epstein-Barr virus expression. Our series of patients did not differ significantly in their clinical presentation from most reported PTCL cases in the literature: 55% of them were alive and 35% were in complete remission after a median follow-up of 15 months after cyclophosphamide, dexorubicin, vincristine, and prednisone-based chemotherapy. CONCLUSIONS: TFH cell markers, especially PD-1, were expressed in a subset of PTCLs not classified as AITL, although most of them shared some morphologic features with AITL. This suggests that the spectrum of AITL may be wider than previously thought, possibly including cases of lymphoepithelioid (Lennert's) lymphoma. Additionally, the results suggest that a subgroup of PTCLs-U, distinct from AITL and including some cases denominated as ALCL, may also be derived from TFH cells, although they develop along a distinct pathogenic pathway.
Authors: Sarah H Beachy; Masahiro Onozawa; Yang Jo Chung; Chris Slape; Sven Bilke; Princy Francis; Marbin Pineda; Robert L Walker; Paul Meltzer; Peter D Aplan Journal: Blood Date: 2012-06-21 Impact factor: 22.113