Primary testicular diffuse large B‐cell lymphomas have activated B‐cell‐like subtype characteristics

Booman, Marije; Douwes, Jenny; Glas, Annuska M.; Jong, Daphne de; Schuuring, Ed; Kluin, Philip M.

doi:10.1002/path.2033

Cited by 44 publications

(47 citation statements)

References 56 publications

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“…Looking at other reports, the definition of primary testicular lymphoma was different and therefore showing other phenotype rates of DLBCLs (7). In our investigation, a heterogeneous differentiation of DLBCLs of primary testicular lymphomas was detected using immunohistochemistry and being in line with the observations of Booman et al (4). Interestingly, all cases with a GC-phenotype were positive for CD10 with parallel co-expression of MUM-1 being in line the with the used algorithm (9).…”

Section: Discussionsupporting

confidence: 75%

“…Nevertheless, heterogeneous results are published, if AID is directly linked to somatic hypermutation (16,21). Since we are not able to carry out somatic hypermutation analysis and cDNA microarray hybridization due to missing frozen tissue samples, we cannot exclude that all of our DLBCL with 'classical' GC phenotype are indeed of an ambiguous immunophenotype as concluded by Booman et al (4).…”

Section: Discussionmentioning

confidence: 99%

“…As only 1% of testicular neoplasms and about 5% of all lymphoma presentations are due to primary testicular lymphomas, most of the publications dealing with testicular lymphomas are case reports (1). Newer publications tried to characterize this rare testicular entity on larger series systematically in retrospective analyses (2)(3)(4). Patients usually present with enlargement of testis caused by a homogeneous tumor mass.…”

Section: Introductionmentioning

confidence: 99%

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Primary testicular lymphoma: A strictly homogeneous hematological disease?

Kemmerling

Stintzing²,

Mühlmann³

et al. 2010

Oncol Rep

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Abstract. Primary testicular lymphomas display mostly aggressive diffuse large cell B-cell lymphomas, which could be further subclassified into germinal center B-cell-like and an activated B-cell phenotype via immunohistochemistry. A retrospective analysis of primary testicular lymphomas diagnosed at the Institute of Pathology, Salzburger Landeskliniken (SALK) between January 1997 and December 2008 was done. Immunohistochemical staining and complete clinical data evaluation was carried out and linked to overall survival time. We found 18 cases of primary testicular lymphoma diagnosed in elderly patients showing no side predilection and having an aggressive clinical behavior with short overall survival independent of treatment. The lymphomas could for the most be classified into diffuse large cell B-cell lymphomas [15/18 (83.3%)] showing a nonsignificant prevalence of activated B cell phenotype [9/15 (60%)] compared to the germinal centre phenotype [6/15 (40%)]. Two of the cases were mantle cell lymphomas consisting of the infrequent pleomorphic subtype. The survival analysis revealed no significant difference for any of the investigated antigens. Primary testicular lymphomas are for the most DLBCL, but subtype classification reveal molecular heterogeneity inside this lymphoma entity. A distinction between those subtypes is necessary because of different clinical behavior and treatment.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Primary testicular lymphoma: A strictly homogeneous hematological disease?

Kemmerling

Stintzing²,

Mühlmann³

et al. 2010

Oncol Rep

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“…29,30 The distribution in the nodal and the heterogeneous other extranodal diffuse large BCL groups was also consistent with earlier reports. 2,4 Remarkably, no significant differences in expression levels for any of the 15 B-cell related miRNAs were found between the germinal and nongerminal center cases in our total group of diffuse large BCL.…”

Section: Testicular Diffuse Large B-cell Lymphomasupporting

confidence: 80%

Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma

et al. 2009

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Recent studies have shown that certain non-coding short RNAs, called miRNAs, play an important role in diffuse large B-cell lymphomas. Patients with diffuse large B-cell lymphoma have great diversity in both clinical characteristics, site of presentation and outcome. The aim of our study is to validate the differential expression in germinal center and non-germinal center diffuse large B-cell lymphoma,s and to study to the extent to which the primary site of differentiation is associated with the miRNA expression profile. We studied 50 cases of de novo diffuse large B-cell lymphoma for the expression of 15 miRNAs (miR-15a, miR-15b, miR-16, miR-17-3p, miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-92, miR-127, miR-155, miR-181a and miR-221). Apart from 19 nodal cases without extranodal dissemination (stages I and II), we selected two groups with unambiguous stages I and II extranodal presentation; 9 cases of primary central nervous system, 11 cases of primary testicular and 11 cases of other primary extranodal diffuse large B-cell lymphomas. All cases were analyzed with qRT-PCR. In situ hybridization for the most differentially expressed miRNAs was performed to show miRNA expression in tumor cells, but not in background cells. MiR-21 and miR-19b showed the highest expression levels. No significant differences were seen between germinal center and non-germinal center diffuse large B-cell lymphomas in either the total or the nodal group for any of the 15 miRNAs. Two miRNAs showed significant differences in expression levels for diffuse large B-cell lymphoma subgroups according to the site of presentation. MiR-17-5p showed a significant higher expression level in the central nervous system compared with testicular and nodal diffuse large B-cell lymphomas (Po0.05). MiR-127 levels were significantly higher in testicular than in central nervous system and in nodal diffuse large B-cell lymphomas (Po0.05). We conclude that the location of diffuse large B-cell lymphoma is an important factor in determining the differential expression of miRNAs. Modern Pathology (2009) 22, 547-555; doi:10.1038/modpathol.2009 published online 13 March 2009 Keywords: diffuse large B-cell lymphoma; miRNA; CNS; testicular Diffuse large B-cell lymphoma (BCL) accounts for approximately 40% of all adult non-Hodgkin lymphomas. Diffuse large BCL is a clinically heterogeneous group of lymphomas, which presents at different anatomical sites, either nodal or extranodal. Anatomical sites, such as the testis and central nervous system, show marked differences in genetic aberrations, morphology and clinical behavior.

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“…16 It is also consistent with the observation that this isotype predominates in rare and aggressive forms of lymphomas, such as primary central nervous system, 15 primary testicular 17 and primary cutaneous DLBCL, 18,19 which all have an ABC-like phenotype. 20 Isotype class switching in DLBCL P Ruminy et al…”

Section: Discussionmentioning

confidence: 99%

The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma

et al. 2011

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Gene expression profiling has identified two major molecular subtypes of diffuse large B-cell lymphoma (DLBCL) that are histologically indistinguishable but differ in cure rates. Here, we investigated whether the isotype of the B-cell receptor (BCR) expressed by the tumoral cells correlated with the molecular subtype and survival. Gene expression analysis clustered the 53 patients included in this study into three subgroups, 17 germinal center B-cell-like (GCB) cases, 26 activated B-celllike (ABC) cases and 10 intermediate cases. The molecular subtype was correlated with the isotype, as 15/17 GCB cases expressed a secondary isotype (immunoglobulin (Ig)G or IgA), whereas 24/26 ABC cases expressed a primary isotype (IgM or IgD) (Po0.0001). There was a trend toward a worse outcome for patients with an ABC DLBCL and a shorter overall survival for patients with IgM þ tumor (P ¼ 0.21 and 0.014, respectively). Finally, fluorescence in situ hybridization (FISH) analysis revealed a striking asymmetric pattern, as the IGHM gene is conserved only on the productive IGH allele in most IgM þ tumors. Taken together, these data indicate that the isotype of the BCR is a reliable indicator for the GCB and ABC subtypes in DLBCL, and suggest that the conservation of an IgM is required for ABC DLBCL lymphomagenesis to occur.

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Primary testicular diffuse large B‐cell lymphomas have activated B‐cell‐like subtype characteristics

Cited by 44 publications

References 56 publications

Primary testicular lymphoma: A strictly homogeneous hematological disease?

Primary testicular lymphoma: A strictly homogeneous hematological disease?

Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma

The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma

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