Association of both BCL2 positive and negative follicular lymphoma to clasical Hodgkin lymphoma and/or gray zone lymphoma.

We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.

Actionable mutational profiling in solid tumors using hybrid-capture-based next-generation sequencing in a real-world setting in Spain.

OBJECTIVE: This study aimed to describe the performance of a next-generation sequencing (NGS) panel for the detection of precise genomic alterations in cancer in Spanish clinical practice. The impact of tumor characteristics was evaluated on informative NGS and actionable mutation rates. MATERIALS AND METHODS: A cross-sectional study was conducted at the Fundación Jiménez Díaz University Hospital (May 2021-March 2022) where molecular diagnostic of 537 Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples of diverse solid tumors (lung, colorectal, melanoma, gastrointestinal stromal, among others) was performed using AVENIO Tumor Tissue Targeted Kit. A descriptive analysis of the features of all samples was carried out. Multivariable logistic analysis was conducted to assess the impact of sample characteristics on NGS performance defined by informative results rate (for all tumors and for lung tumors), and on actionable mutations rate (for lung tumors only). RESULTS: AVENIO performance rate was 75.2% in all tumor samples and 75.3% in lung cancer samples, and the multivariable analysis showed that surgical specimens are most likely to provide informative results than diagnostic biopsies. Regarding the mutational findings, 727 pathogenic, likely pathogenic, or variant of unknown significance mutations were found in all tumor samples. Single nucleotide variant was the most common genomic alteration, both for all tumor samples (85.3% and 81.9% for all solid tumors and lung samples, respectively). In lung tumors, multivariable analysis showed that it is more likely to find actionable mutations from non-smokers and patients with adenocarcinoma, large cell, or undifferentiated histologies. CONCLUSION: This is the largest cohort-level study in Spain to profile the analyses of biopsy samples of different tumors using NGS in routine clinical practice. Our findings showed that the use of NGS routinely provides good rates of informative results and can improve tumor characterization and identify a greater number of actionable mutations.