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Several reports of concurrent MYC , BCL2 , BCL6 , and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a "quadruple-hit" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC , BCL2 , and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events. [ABSTRACT FROM AUTHOR] more...

Objectives Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We compared the efficacy of cytoplasmic immunoglobulin FISH (cIg-FISH) and fluorescence-activated cell sorting FISH (FACS-FISH) in a clinical laboratory setting. Methods The FISH analysis results of 14,855 samples from individuals with a suspected PCN subjected to cytogenetic evaluation between 2019 and 2022 with cIg-FISH (n = 6917) or FACS-FISH (n = 7938) testing were analyzed. Results Fluorescence-activated cell sorting–FISH increased the detection rate of abnormalities in comparison with cIg-FISH, with abnormal results documented in 54% vs 50% of cases, respectively (P <.001). It improved the detection of IGH::CCND1 (P <.001), IGH::MAF (P <.001), IGH::MAFB (P <.001), other IGH rearrangements (P <.001), and gains/amplifications of 1q (P <.001), whereas the detection rates of IGH::FGFR3 fusions (P =.3), loss of 17p (P =.3), and other abnormalities, including hyperdiploidy (P =.5), were similar. Insufficient PC yield for FISH analysis was decreased between cIg-FISH and FACS-FISH (22% and 3% respectively, P <.001). Flow cytometry allowed establishment of ploidy status in 91% of cases. In addition, FACS-FISH decreased analysis times, workload efforts, and operating costs. Conclusions Fluorescence-activated cell sorting–FISH is an efficient PC purification strategy that affords significant improvement in diagnostic yield and decreases workflow requirements in comparison with cIg-FISH. [ABSTRACT FROM AUTHOR] more...

Investigated attachment security and behavior in 34 physically disabled infants and 26 non-disabled infants using convergent, categorical, and continuous (Attachment Behavior Q-Set) measures of relationship, based on the same set of home observations. Proportions of attachment classifications were identical for each group, but insecure disabled infants scored consistently lower on the AQS security score than insecure non-disabled infants. (TJQ) more...

Myeloid/lymphoid neoplasms with FLT3 gene fusions have recently been included among myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) in the World Health Organization classification and International Consensus Classification. As this entity remains remarkably rare, its scope and phenotypic features are evolving. In this report, we describe a 33-yr-old male with MLN-TK. Conventional chromosome analysis revealed a t(13;14)(q12;q32). Further analysis with mate-pair sequencing (MPseq) confirmed a TRIP11::FLT3 gene fusion. A diagnosis of MLN-TK was rendered. To the best of our knowledge, we report the third case of MLN-TK with a TRIP11::FLT3 gene fusion. In contrast to previously described cases, our case exhibited distinctly mild clinical features and disease behavior, emphasizing the diverse spectrum of MLN-TK at primary presentation and variability in disease course. MLN-TK with FLT3 gene fusions are a genetically defined entity which may be targetable with tyrosine kinase inhibitors with anti-FLT3 activity. Accordingly, from diagnostic and therapeutic viewpoints, genetic testing for FLT3 rearrangements using fluorescence in situ hybridization (FISH) or sequencing-based assays should be pursued for patients with chronic eosinophilia. [ABSTRACT FROM AUTHOR] more...

Gene fusions involving NUP98 have been reported in several hematologic malignancies yet have been very rarely reported in B-acute lymphoblastic leukemia (B-ALL). Two cases of B-ALL for which chromosome banding analysis (CBA) and fluorescence in situ hybridization (FISH) suggested apparent NUP98 rearrangements were further investigated with next-generation sequencing-based methodologies to verify the findings obtained with traditional cytogenetic methodologies. In the first case, CBA revealed a hyperdiploid karyotype with multiple structural abnormalities including additional material of unknown origin at 11p15; subsequent break-apart probe (BAP) FISH for NUP98 demonstrated 2 intact fusion signals and a single separate 5'NUP98 signal. However, whole-genome sequencing found no evidence of a NUP98 gene fusion. The results obtained with conventional cytogenetic methodologies were in fact attributable to structural variants (SV) with breakpoints not within NUP98 but within the 5'NUP98 BAP probe-binding sequence. In the second case, CBA revealed several structural and numeric abnormalities including a complex translocation between chromosomes 11 (at 11p15.4) and 19 (at 19p13.3) and an insertion of unknown material at 11p15.4. BAP FISH demonstrated a typical FISH signal pattern consistent with an apparent NUP98 rearrangement. However, no evidence of a NUP98 fusion was found on RNA sequencing. In conclusion, the two cases thus presented with clinical false positive NUP98 rearrangements by FISH. In the clinical laboratory, SVs in the vicinity of genes involved in recurrent rearrangements in hematologic malignancies may result in misleading results with conventional chromosome methodologies. This may preclude an accurate definition of the genetic attributes of malignancies with ensuing impacts on risk stratification and management. Higher-resolution testing methodologies such as whole-genome sequencing and RNA sequencing may be helpful in resolving unexpected results with conventional chromosome methodologies and enhancing the accuracy of genetic characterization of hematological malignancies in the clinical laboratory., Competing Interests: Declaration of competing interest LBB serves as consultant for Genentech. George Vasmatzis is the owner of Whole Genome LLC. The remaining authors have no conflicting interests to declare., (Copyright © 2025. Published by Elsevier Inc.) more...