title: Peripheral T-cell lymphoma with follicular T-cell markers.
abstract: BACKGROUND
  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.
  
  
  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.affiliation: Lymphoma Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. smrodriguez@cnio.es
authors.forename: Socorro María
authors.initials: SM
authors.lastname: Rodríguez-Pinilla
authors.forename: Lidia
authors.initials: L
authors.lastname: Atienza
authors.forename: Cristina
authors.initials: C
authors.lastname: Murillo
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez-Rodríguez
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Giovanna
authors.initials: G
authors.lastname: Roncador
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Seoane
authors.forename: Purificación
authors.initials: P
authors.lastname: Domínguez
authors.forename: Francisca I
authors.initials: FI
authors.lastname: Camacho
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D015415:Biomarkers / Q000032:analysis*; D054382:Chemokine CXCL13 / Q000096:biosynthesis; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000145:classification* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis; D061026:Programmed Cell Death 1 Receptor; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C411984:BCOR protein, human; D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015260:Neprilysin