title: Perforin and granzyme expression in cytotoxic T-cell lymphomas.
abstract: We studied the morphologic and immunohistochemical features of 10 peripheral T-cell lymphomas of a cytotoxic phenotype (CD3+/CD4-/CD8+), encountered among 98 peripheral T-cell lymphomas (PTCLs). Nine tumors were positive for both cytotoxic molecules, namely perforin (Pf) and granzyme B (GrB), and strong positivity was seen in the majority of the malignant cells. We also studied the expression of these molecules in 92 other cases of T-cell and natural killer (NK) cell neoplasms; 18 anaplastic large cell lymphomas (ALCLs); 63 CD4+ PTCLs; 10 CD56+ nasal lymphomas; and 1 NK-cell leukemia. Most of the CD4+ PTCLs (62 of 63) were negative for GrB, but all of the nasal lymphomas and the NK cell leukemia were positive for both Pf and GrB. Variable expression was seen among the 18 ALCLs. Within the 10 CD8+ PTCLs, 4 involved the skin, 3 of which were diagnosed as primary cutaneous lymphomas. Five patients died within 1 year of diagnosis. According to the Revised European-American Classification of Lymphoid Neoplasms, seven cases were categorized as "PTCL, unspecified," and three as "angioimmunoblastic T-cell lymphoma," "adult T-cell lymphoma/leukemia," or "small cell lymphoma," respectively. Three cases had characteristic morphologic features consisting of large lymphomatous cells with massive necrosis and nuclear fragmentation. Epstein-Barr virus mRNA was detected by in situ hybridization in three cases. Although the degree of apoptosis varied, apoptotic cells were detected in all cases by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick end labeling. We conclude that CD8+ PTCLs are relatively rare, often involve extranodal sites, have an aggressive clinical course, and are often associated with Epstein-Barr virus. Compared with ALCLs, which have recently been considered as neoplasms of cytotoxic T-cells, we think that CD8+ PTCLs are more lineage-specific neoplasms of mature, cytotoxic, T lymphocytes.
authors.affiliation: First Department of Pathology, Nagoya University School of Medicine, Japan. k46581anucc.cc.nagoya-u.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Yatabe
authors.forename: T
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: A
authors.initials: A
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: N
authors.initials: N
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015139:Blotting, Southern; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000821:virology; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005821:Genetic Techniques; D053804:Granzymes; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016411:Lymphoma, T-Cell, Peripheral / Q000737:chemistry* / Q000235:genetics / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D012697:Serine Endopeptidases / Q000032:analysis* / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry* / Q000378:metabolism / Q000821:virology
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases