IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas

Falini, Brunangelo; Agostinelli, Claudio; Bigerna, Barbara; Pucciarini, Alessandra; Pacini, Roberta; Tabarrini, Alessia; Falcinelli, Floriana; Piccioli, Milena; Paulli, Marco; Gambacorta, Marcello; Ponzoni, Maurilio; Tiacci, Enrico; Ascani, Stefano; Martelli, Maria Paola; Favera, Riccardo Dalla; Stein, Harald; Pileri, Stefano

doi:10.1111/j.1365-2559.2012.04289.x

Cited by 97 publications

(76 citation statements)

References 35 publications

(66 reference statements)

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“…73 In a similar way, immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) was shown to be expressed on marginal zone and monocytoid B cells, 74 and also subsequently on MZLs. 75 In the latter study, 73% of NMZLs were IRTA1-positive in contrast to none of 320 FLs.…”

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confidence: 91%

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Brand

Krieken

2013

Haematologica

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The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n . Epidemiology and etiology NMZL is a rare lymphoma, accounting for 1.5-1.8% of lymphoid neoplasms. 9,10 The incidence of NMZL appears to be increasing, which is most likely due to a 'real' increase, rather than better recognition.11 Most studies report a median age around 60 years with a wide age distribution ranging from adolescence to patients over 90 years old. [9][10][11][12][13][14][15][16][17][18][19][20] Both sexes are affected with approximately equal frequency.Morphologically, NMZL resembles EMZL. EMZL is well known for its association with conditions that provide a chronic stimulation to the immune system, including chronic infections (e.g. Helicobacter pylori infection in gastric EMZL) and autoimmune conditions (e.g. salivary gland EMZL in Sjögren's syndrome). From this, one could hypothesize that NMZL, or a subset of NMZLs, might also be caused by specific chronic inflammatory conditions. Indeed, infections and autoimmune disorders have been reported in association with NMZL, but this evidence remains far from sufficient to establish a definitive role for these stimuli in lymphomagenesis. Recently, we encountered a case of what we had referred to as NMZL lymphoma in an axillary lymph node. However, we detected H. pylori by PCR analysis and a gastric biopsy revealed EMZL. This case implies that without extensive workup, including gastric biopsies, one cannot be sure that a case of NMZL really represents this entity.Hepatitis C virus (HCV) has been reported in a subset of NMZL patients. In an early but small study, monocytoid B-cell lymph...

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confidence: 91%

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Brand

Krieken

2013

Haematologica

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“…IRTA1 positivity, reported on the neoplastic cells in cases of extranodal MZL (EMZL), is barely present in SMZL. 22 …”

Section: Histologymentioning

confidence: 99%

“…26 Finally, secondary splenic localization of EMZL presents a pattern that overlaps with that of SMZL, but clinical dissemination is crucial for differentiation. Splenic involvement virtually excludes a diagnosis of nodal MZL; apart from the differential expression of IRTA1, which is negative in SMZL, 11,22 clinical correlation is critical for reaching a correct diagnosis when dealing with a BM biopsy.…”

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confidence: 99%

Splenic marginal zone lymphoma: from genetics to management

Arcaini

Rossi

Paulli

2016

Blood

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138

132

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Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.

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“…1 Among MZL, only EMZL of the MALT represents a well-defined entity in terms of clinicopathologic presentation, genetics, and treatment. Conversely, the lack of typical markers, with the exception of IRTA1 expression in a fraction of NMZL, 2,3 and the absence of clear consensus criteria for diagnosis, make the pathologic classification of NMZL and SMZL difficult, laborious, and not easily reproducible. 4 NMZL and SMZL share similar morphology and phenotype and are distinguished solely by the different pattern of dissemination.…”

Section: Introductionmentioning

confidence: 99%

The genetics of nodal marginal zone lymphoma

Spina

Khiabanian

Messina

et al. 2016

Blood

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147

123

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Key Points• PTPRD lesions are among the most recurrent alterations in NMZL and appear to be enriched in this lymphoma type across mature B-cell tumors.• NMZL and SMZL genetics overlap with the exceptions of PTPRD lesions, supporting their distinction as independent entities.Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, wholetranscriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ‡3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%).Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification. (Blood. 2016;128(10):1362-1373

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IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas

Cited by 97 publications

References 35 publications

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Splenic marginal zone lymphoma: from genetics to management

The genetics of nodal marginal zone lymphoma

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