In:
Histopathology, Wiley, Vol. 70, No. 4 ( 2017-03), p. 595-621
Abstract:
We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma ( DLBCL sn ) in a series of 240 cases of DLBCL not otherwise specified [ DLBCL all ( NOS ) ], including DLBCL sn training set ( n = 11) and validation set ( n = 18), and DLBCL non‐sn ( n = 211). Methods and results In the training set, 82% had a non‐germinal center B‐cell‐like (Hans’ Classifier) (non‐ GCB ) phenotype and 18% were Epstein–Barr virus‐encoded small RNA s ( EBER ) + . The genomic profile showed gains (+) of 1q21.3q31.2 (55%), 10q24.1 (46%), 11q14.1 (46%) and 18q12.1q23 (46%); losses (−) of 6q26q27 (55%) and 9p21.3 (64%); and copy number neutral loss of heterozygosity (LOH) (acquired uniparental disomy, UPD) at 6p25.3p21.31 (36%). This profile is comparable to DLBCL NOS ( GSE 11318, n = 203.) and closer to non‐ GCB /activated B‐cell‐like subtype ( ABC ). Nevertheless, +1q31, −9p21.3 and −10q11.1q26.2 were more characteristic of DLBCL sn ( P 〈 0.001). Array results were verified successfully by fluorescence in situ hybridization ( FISH ) on +1q21.3 ( CKS 1B) , −6q26 ( PARK 2 ), +8q24.21 ( MYC ), −9p21.3 ( MTAP , CDKN 2A/B ), −17p13.1 ( TP 53 ) and +18q21.33 ( BCL 2 ) with 82–91% agreement. Minimal common regions included biologically relevant genes of MNDA (+1q23.1), RGS 1 and RGS 13 (+1q31.2), FOXP 1 (+3p13), PRDM1 (BLIMP1) and PARK 2 (−6q21q26) , MYC ( + 8q24.21), CDKN 2A (−9p21.3), PTEN (−10q23.31), MDM 2 (+12q15), TP 53 (−17p13.1) and BCL 2 (+18q21.33). Correlation between DNA copy number and protein immunohistochemistry was confirmed for RGS 1, RGS 13, FOXP 1, PARK 2 and BCL 2. The microenvironment had high infiltration of M2‐like tumour associated macrophages ( TAM s) and CD 8 + T lymphocytes that associated with higher genomic instability. The DLBCL sn validation set confirmed the clinicopathological characteristics, all FISH loci and immunohistochemistry ( IHC ) for RGS 1. RGS 1 , one of the most frequently altered genes, was analysed by IHC in DLBCL all and high RGS 1 expression associated with non‐ GCB , EBER + and unfavourable overall survival (hazard ratio = 1.794; P = 0.016). Conclusions DLBCL sn has a characteristic genomic profile. High RGS 1 IHC expression associates with poor overall survival in DLBCL all ( NOS ) .
Type of Medium:
Online Resource
ISSN:
0309-0167
,
1365-2559
DOI:
10.1111/his.2017.70.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2006447-0
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