Jurnal Internasional PMBCL: diagnosis molekuler? | Jurnal Darah


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Jurnal Internasional PMBCL: diagnosis molekuler? | Jurnal Darah

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In this issue Blood Mottok et al 1 shows the usefulness of molecular tests that assess the expression of 58 genes to differentiate primary mediastinal B cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL) using routinely supplied biopsies of paraffin-embedded tissue that is routinely available (FFPET). The results can improve diagnostic accuracy for patients with PMBCL and may have important implications for selecting clinical trials and interpreting clinical results for patients with this rare lymphoma.

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The use of gene-based assay expression in the classification of large B-cell lymphoma molecules in the mediastinum becomes PMBCL and DLBCL.

PMBCL is a unique clinicopathological subtype of aggressive B cell lymphoma, dependent diagnosis on correlated clinical features and pathology and immunophenotypic features. 2 Despite improvements in the diagnostic criteria that have been developed for many subtypes of non-Hodgkin's lymphoma, distinguishing PMBCL from DLBCL and gray zone lymphoma involving the mediastinum is still a challenge when using the currently available diagnostic methods. [19659013] By utilizing the wealth of gene expression disclosure data (GEP) obtained from PMBCL samples, 3 4 the authors attempt to establish molecular tests that will be widely applicable to routine clinical diagnostic testing. An important criterion is the ability to use nucleic acids obtained from FFPET routines and use widely available diagnostic platforms. The authors discussed this challenge by developing a quantitative gene test that analyzed 58 genes using the Nanostring platform labeled Lymph3Cx.

The Mottok article describes a rigorous study using a set of training consisting of 68 cases of PMBCL and DLBCL and independent validation sets consisting of 158 cases . The authors use 30 genes to differentiate between PMBCL and DLBCL, 24 of which are expressed in PMBCL and 6 of them are overexpressed in DLBCL and represent high discriminatory power. This test also includes genes represented in Lymph2Cx, which allows for the determination of cell-of-origin (COO) in DLBCL not specified otherwise (NOS). Thus, testing can use molecular signatures to differentiate PMBCL and also assign COO assignments to DLBCL NOS (see figure). The reproducibility of test performance in 2 independent laboratories is high, supporting the possibility of this testing being clinically relevant.

Patients with PMBCL demonstrate selective responses to new therapeutic approaches such as dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) 5 or anti-programmed cell death protein 1 antibody 6 vs therapy for DLBCL. Thus, the ability to more accurately differentiate PMBCL from DLBCL has important implications for patient management.

A potential obstacle in rapid and large-scale adoption of these tests in routine clinical settings is the availability of technical platforms and the number of networks needed (core needle biopsy vs. biopsy lymph nodes) for testing to be carried out at the level reported in the Mottok article. Most importantly, the ability to translate the results of the Mottok study is limited by the fact that the test was developed using a specific technical platform, and thus the application of other GEP methods such as multiplex reverse ligation-dependent transcriptase probes 7 is unknown.

False one of the main diagnostic challenges not discussed is the difference between PMBCL and classic Hodgkin lymphoma (CHL). Given the biological overlap between these two entities, the GEP test as described in the Mottok article can provide a stronger and more accurate molecular test to distinguish PMBCL from CHL and provide quantitative gene-based expression cutoff values ​​that can be used to define diseases that truly represent gray zone lymphoma.

The Mottok study highlights the continued development of strong quantitative-based GEP molecular testing such as the DLBCL COO classification 8 and possible tests in current development for classifying peripheral lymphoma T cells. 9 This adds to the expansion of molecular armamentarium tests (for example, circulating tumor DNA, targeted generation sequencing panels, epigenetic profiles, exosomal analysis) which will be available to the diagnostic team in the near future.

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