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Hypereosinophilia (HE) can be caused by a wide variety of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders. Diagnosing hypereosinophilia/hypereosinophilic syndrome (HE/HES) is challenging due to the complex nature of disease manifestations and numerous underlying etiologies. Knowing that only rare cases are clonal, it is wise to rule out reactive conditions and proceed with molecular and other advanced tools. The exclusion of secondary causes needs a detailed clinical evaluation followed by a wide range of serological and imaging investigations. Once reactive eosinophilia has been ruled out, the diagnosis of primary HE/HES is made using a combination of morphologic examination of the blood and bone marrow, conventional cytogenetics, fluorescent in situ hybridization, flow-cytometry, and T-cell clonality evaluation to look for histopathologic or clonal evidence of an underlying hematological disorder. The accurate diagnosis of clonal eosinophilia-causing myeloid and lymphoid neoplasms and the identification of numerous gene rearrangements significantly enhance patient outcomes, because a proportion of these patients (such as PDGFRA and PDGFRB rearrangements) responds well to tyrosine kinase inhibitors. Considering the complex etiopathologies, the cost of testing, and the time involved, the workup needs to be tailored according to the urgency of the situation and the resources available. In urgent situations with organ damage, it is crucial to initiate appropriate management without waiting for the results of investigations. In contrast, in a resource-limited situation, it is acceptable to employ step-by-step rather than comprehensive testing to rule out the most common causes first. Here, we discuss various laboratory investigations employed in diagnosing HE/HES, highlighting their importance in different situations. [ABSTRACT FROM AUTHOR]

Introduction: The categorization of mature B cell neoplasms (MBN) infiltrating blood and bone marrow are met with difficulties. The inclusion of CD148 and CD180 in the routine flow cytometry/FCM panels has been suggested to refine the diagnosis. We studied the discriminatory ability of CD148 and CD180 median fluorescence intensity(MFI), CD148/CD180 ratio and their expression relative to T cells (CD148ab/T, CD180ab/T), neutrophils (CD148ab/gr, CD180ab/gr) and normal B cells (CD148ab/n, CD180ab/n) in the differentiation of mature B cell neoplasms (MBN) especially non‐chronic lymphocytic leukaemia (CLL). Methodology: The flow cytometric (FCM) expression of CD148 and CD180 was studied prospectively in 102 patients (non‐CLL; n = 72); diagnosed by a comprehensive panel of immunophenotypic and cytogenetic studies. The MFI and ratios were statistically compared across MBNs by Mann‐Whitney U test. Cut‐off values, sensitivity and specificity were calculated for significant parameters by receiver operator characteristic curve. Results: CD180MFI > 4.35 showed 100% sensitivity and 90.9% specificity for a diagnosis of marginal zone lymphoma (MZL) while, CD148/180 > 5.15 was 100% specific and 81.8% sensitive for lymphoplasmacytic lymphoma. CD148ab/T(>4.3; 100% specificity, 83.4% sensitivity) and CD148ab/gr(>1.1; 100% sensitivity, 90% sensitivity) were useful for differentiating blastoid‐mantle cell lymphoma/MCL from diffuse large B cell lymphoma; while CD148MFI (≥20.25), CD148ab/T(>3.35) and CD148ab/gr(>0.95) showed >90% specificity and sensitivity for distinguishing MCL from CLL. Pairwise analysis also showed a good discriminant function of various parameters for distinguishing SMZL from other MBNs like FL, MCL as well as CLL. Conclusions: The current study shows an excellent utility of CD148MFI, CD180MFI, their ratio and relative expression levels in the subcategorization of immunophenotypically related MBNs. [ABSTRACT FROM AUTHOR]

Background: Philadelphia chromosome (Ph)–like B‐acute lymphoblastic leukemia (B‐ALL) is a clinically significant, high‐risk genetic subtype of B‐ALL cases. There are few data on the incidence, characterization, and treatment outcomes of Ph‐like ALL cases from low‐ and middle‐income countries. There is a pressing need to establish a well‐organized/cost‐effective approach for identifying Ph‐like ALL instances. Methods: Multiplex reverse transcriptase polymerase chain reaction, nCounter NanoString, and fluorescence in situ hybridization were used to detect and characterize Ph‐like ALL cases among recurrent genetic abnormalities (RGA)neg B‐ALL cases. At the end of induction therapy, flow cytometry‐minimal residual disease (MRD) assay was used to quantify MRD positivity in Ph‐like ALL cases. Results: Of 130 newly diagnosed B‐ALL cases, 25% (BCR::ABL1), 4% (ETV6::RUNX1), 5% (TCF3::PBX1), 2% (KM2TA::AFF1), and 65% RGAneg B‐ALL cases were revealed by multiplex reverse transcriptase polymerase chain reaction. Among RGAneg B‐ALL cases, 24% Ph‐like ALL cases using nCounter NanoString were identified, with 48% CRLF2high cases with 45% CRLF2::P2RY8 and 18% CRLF2::IGH rearrangements(∼r) revealed by fluorescence in situ hybridization. In 52% of CRLF2low cases, 17% ABL1 and JAK2∼r 8% EPOR::IGH & PDGRFB∼r were identified. Ph‐like ALL cases had higher total leukocyte count (p <.05), male preponderance (p <.05), and high MRD‐positivity/induction failure compared with RGAneg B‐ALL cases. Furthermore, in Ph‐like ALL cases, 11 significant genes using quantitative polymerase chain reaction were identified and validated. CRLF2, IGJ, CEACAM6, MUC4, SPATS2L and NRXN3 genes were overexpressed and show statistical significance (p <.05) in Ph‐like ALL cases. Conclusions: This study showed the high incidence of Ph‐like ALL cases with kinase activating alterations and treatment outcomes from low‐ and middle‐income region. Furthermore, a surrogate cost‐effective multiplex panel of 11 overexpressed genes for the prompt detection of Ph‐like ALL cases is proposed. Plain Language Summary: Identification of recurrent gene abnormalities (RGA)neg B‐acute lymphoblastic leukemia (B‐ALL) cases using multiplex‐reverse transcriptase polymerase chain reaction.Identification and characterization of Philadelphia (Ph)–like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization.Furthermore, Ph‐like ALL cases were characterized according to CRLF2 expression and kinase‐activating genomic alterations. Minimal residual disease of Ph‐like ALL cases were quantified using flow cytometry‐minimal residual disease assay.A surrogate molecular approach was established to detect Ph‐like ALL cases from low‐ and middle‐income countries. A surrogate approach for the rapid baseline detection of Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia cases, followed by its kinase gene alterations. Early detection of Ph–like acute lymphoblastic leukemia cases is extremely important to start personalized treatments to improve the overall survival/outcomes of these cases. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging revealed an epidural soft tissue mass lesion involving the dorsolumbar and sacral region with extension into the neural foramina [Figure 1]a and [Figure 1]b. A 28-year-old female presented with conus-cauda syndrome. [Extracted from the article]

Background: Immunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real‐world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders. Materials and Methods: A retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure. Results: Immunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with <10% PCs and 318/352 (90.3%) with ≥10% PCs in BM aspirate; P =.003). Among cases with unsuccessful IMCS (<10% PCs; n = 21 and ≥10% PCs; n = 34), an alternate source could be used successfully in 34 (62%) patients and includes air‐dried trephine biopsy imprint smears (n = 28) with aggregates or sheets of PCs, fine‐needle aspiration smears/biopsy from plasmacytoma (n = 5), and ascitic fluid (n = 1). 284/395 (71.9%) patients with successful IMCS and all 34 cases with an alternate source of PCs showed at least one cytogenetic abnormality on four‐probe FISH. Conclusion: Variations in the sample quality together with significant variation in the number of PCs between BM aspirate and the trephine biopsy imprint smears/biopsy reduce the success rate of IMCS in a real‐world scenario and necessitate utilization of patient‐specific alternate sources of PCs like a trephine biopsy imprint or cytology smears from extramedullary sources for successful FISH testing in PC neoplasms. [ABSTRACT FROM AUTHOR]

The overexpression of cytokine receptor-like factor-2 (CRLF2) identified by anti-thymic stromal lymphopoietin receptor/TSLPR flow cytometry (FCM) has been reported as a screening tool for the identification of BCR-ABL1-like B-cell acute lymphoblastic leukemia/B-ALL with CRLF2 re-arrangement. TSLPR expression was studied prospectively in consecutive 478 B-ALLs (≤ 12 years (n = 244); 13–25 years (n = 129); > 25 years (n = 105)) and correlated with various hematological parameters and end-of-induction measurable residual disease (day 29; MRD ≥ 0.01% by 10-color FCM). TSLPR positivity in ≥ 10% leukemic cells was detected in 14.6% (n = 70) of B-ALLs. CRLF2 re-arrangement was detected in eight cases (11.4%) including P2RY8-CRLF2 (n = 6), and IgH-CRLF2 (n = 2) with a median TSLPR positivity of 48.8% and 99% leukemic cells, respectively. Recurrent gene fusions/RGF (BCR-ABL1 (17.1%); ETV6-RUNX1 (4.2%), TCF3-PBX1 (1.4%)), other BCR-ABL1-like chimeric gene fusions/CGFs (PDGFRB-rearrangement (2.9%), IgH-EPOR (1.4%)), CRLF2 extra-copies/hyperdiploidy (17.1%), and IgH translocation without a known partner (10%) were also detected in TSLPR-positive patients. CD20 positivity (52.9% vs 38.5%; p = 0.02) as well as iAMP21 (4.3% vs 0.5%; p = 0.004) was significantly more frequent in TSLPR-positive cases. TSLPR-positive patients did not show a significantly higher MRD, compared to TSLPR-negative cases (37% vs 33%). Increasing the threshold cut-off (from ≥ 10 to > 50% or > 74%) increased the specificity to 88% and 100% respectively in identifying CRLF2 translocation. TSLPR expression is not exclusive for CRLF2 translocations and can be seen with various other RGFs, necessitating their testing before its application in diagnostic algorithms. In patients with high TSLPR positivity (> 50%), the testing may be restricted to CRLF2 aberrancies, while patients with 10–50% TSLPR positivity need to be tested for both CRLF2- and non-CRLF2 BCR-ABL1-like CGFs. [ABSTRACT FROM AUTHOR]

The article focuses on utility of fluorescence in situ hybridization testing in patients has suspected of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myeloproliferative neoplasm overlap (MDS/MPN) is limited in the absence of significant morphological dysplasia. Topics include the MDS/MPN are clonal disorders of hematopoietic stem cells has characterized by progression to acute myeloid leukemia, and the cytogenetic information is essential for their prognostic assessment.

The article discusses that genetic abnormalities have significantly contributed to disease stratification in B‐ALL. It mentions the detection of iAMP21 can easily be achieved by multiplex ligation‐dependent probe amplification (MLPA); and also mentions that iAMP21 is reported to be a primary genetic event in B‐ALL subgroup arising due to complex structural rearrangements and is associated with a dismal outcome.