title: Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations.
abstract: The term gray zone lymphoma has been applied to tumors that demonstrate transitional morphologic and immunophenotypic features between classical Hodgkin's lymphoma and diffuse large B-cell lymphoma, especially primary mediastinal large B-cell lymphoma. Histopathological and genetic data are limited for these unusual cases. We analyzed cases of gray zone lymphoma (n=27), mediastinal composite lymphoma (n=3) and mediastinal synchronous/metachronous lymphoma (n=3) by morphology, immunophenotyping and fluorescence in situ hybridization. Mediastinal involvement was assured in 24/33 patients (73%). The patient cohort showed a male predominance (M:F ratio; 20:13) and a median age of 32 years (range, 16-91 years). Patients with mediastinal disease were significantly younger (median age: 29.5 years) than patients presenting without evident mediastinal disease (median age: 55 years). Gains including amplifications in 2p16.1 (REL/BCL11A locus) were observed in 33% of all patients, whereas alterations affecting the JAK2/PDL2 locus in 9p24.1 were present in 55%. Further studies revealed rearrangement of the CIITA locus at 16p13.13 in 8/30 cases (27%) and 7/26 cases (27%) demonstrated gains of 8q24 (MYC). Genetic aberrations involving 2p16.1, 9p24.1 and 8q24 showed a higher incidence in cases with evident mediastinal involvement. However, this was not statistically significant when compared with cases without known mediastinal involvement. Twelve of the 27 cases of gray zone lymphoma were morphologically more reminiscent of classical Hodgkin's lymphoma, whereas the other gray zone lymphomas presented with morphological features more closely resembling large B-cell lymphoma. Both morphological groups of gray zone lymphoma were similarly positive for Cyclin E (75 and 93%) and p63 (50 and 53%, respectively) expression. These findings further support a close relationship between gray zone lymphoma, classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma, and suggest that some cases of gray zone lymphoma without mediastinal disease may share similar genetic alterations.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Franziska C
authors.initials: FC
authors.lastname: Eberle
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Christian
authors.initials: C
authors.lastname: Steidl
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Summers
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Susana Ben
authors.initials: SB
authors.lastname: Neriah
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.forename: Kris
authors.initials: K
authors.lastname: Ylaya
authors.forename: David
authors.initials: D
authors.lastname: Liewehr
authors.forename: Kieron
authors.initials: K
authors.lastname: Dunleavy
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002869:Chromosome Aberrations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008223:Lymphoma / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008479:Mediastinal Neoplasms / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor