title: Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa-associated lymphoid tissue localization.
abstract: T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa-associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T-cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T-cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: de Bruin
authors.forename: J A
authors.initials: JA
authors.lastname: Kummer
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: P
authors.initials: P
authors.lastname: van Heerde
authors.forename: P M
authors.initials: PM
authors.lastname: Kluin
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: T
authors.initials: T
authors.lastname: Radaszkiewicz
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D053804:Granzymes; D006801:Humans; D016130:Immunophenotyping; D018442:Lymphoma, B-Cell, Marginal Zone / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000145:classification / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009669:Nose Neoplasms / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases