Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study.

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

Combined Reverse-Transcriptase Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing Analyses to Assign Unclassified BCL2-/BCL6- Nonrearranged Small B-Cell Lymphoid Neoplasms as Follicular or Nodal Marginal Zone Lymphoma.

Distinguishing between follicular lymphoma (FL) and nodal marginal zone lymphoma (NMZL) can be difficult when morphologic and phenotypic features are unusual and characteristic cytogenetic rearrangements are absent. We evaluated the diagnostic contribution of ancillary techniques-including fluorescence in situ hybridization (FISH)-detected 1p36 deletion; reverse-transcriptase, multiplex, ligation-dependent probe amplification (RT-MLPA); and next-generation sequencing (NGS)-for tumors that remain unclassified according to standard criteria. After review, 50 CD5-negative small B-cell lymphoid neoplasms without BCL2 and BCL6 FISH rearrangements were diagnosed as FLs (n = 27), NMZLs (n = 5), or unclassified (n = 18) based on the 2016 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. FISH helped identify the 1p36 deletion in 3 FLs and 1 unclassified tumor. Most classified FLs had an RT-MLPA germinal center B-cell (GCB) signature (93%) or were noncontributive (7%). Classified NMZLs had an RT-MLPA activated B-cell signature (20%), had an unassigned signature (40%), or were noncontributive (40%). Among unclassified tumors, the RT-MLPA GCB signature was associated with mutations most commonly found in FLs (CREBBP, EZH2, STAT6, and/or TNFRSF14) (90%). An RT-MLPA-detected GCB signature and/or NGS-detected gene mutations were considered as FL identifiers for 13 tumors. An activated B-cell signature or NOTCH2 mutation supported NMZL diagnosis in 3 tumors. Combining the RT-MLPA and NGS findings successfully discriminated 89% of unclassified tumors in favor of one or the other diagnosis. NGS-detected mutations may be of therapeutic interest. Herein, we detected 3 EZH2 and 8 CREBBP mutations that might be eligible for targeted therapies.

ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment.

ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3' region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment.

Parallel evolution of two distinct lymphoid proliferations in clonal haematopoiesis.

AIMS: Angioimmunoblastic T-cell lymphoma (AITL) is genetically characterized by TET2 and DNMT3A mutations occurring in haematopoietic progenitor cells, and late events (e.g. the RHOA-G17V mutation) associated with malignant transformation. As TET2/DNMT3A-mutated progenitor cells can differentiate into multilineage progenies and give rise to both AITL and myeloid neoplasms, they may also have the potential to lead to other metachronous/synchronous neoplasms. We report two cases showing parallel evolution of two distinct potentially neoplastic lymphoid proliferations from a common mutated haematopoietic progenitor cell population. METHODS AND RESULTS: Both cases presented with generalized lymphadenopathy. In case 1 (a 67-year-old female), an initial lymph node (LN) biopsy was dismissed as reactive, but a repeat biopsy showed a nodal marginal zone lymphoma (NMZL)-like proliferation with an increase in the number of T-follicular helper (TFH) cells. Immunohistochemistry, and clonality and mutational analyses by targeted sequencing of both whole tissue sections and microdissected NMZL-like lesions, demonstrated a clonal B-cell proliferation that harboured the BRAF-G469R mutation and shared TET2 and DNMT3A mutations with an underlying RHOA-G17V-mutant TFH proliferation. Review of the original LN biopsy showed histological and immunophenotypic features of AITL. In case 2 (a 66-year-old male), cytotoxic T-cell lymphoma with an increase in the number of Epstein-Barr virus-positive large B cells was diagnosed on initial biopsy. On review together with the relapsed biopsy, we identified an additional occult neoplastic TFH proliferation/smouldering AITL. Both T-cell proliferations shared TET2 and DNMT3A mutations while RHOA-G17V was confined to the smouldering AITL. CONCLUSIONS: In addition to demonstrating diagnostic challenges, these cases expand the potential of clonal haematopoiesis in the development of different lineage neoplastic proliferations.

Sustained Response to Imatinib in a Pediatric Patient with Concurrent Myeloproliferative Disease and Lymphoblastic Lymphoma Associated with a CCDC88C-PDGFRB Fusion Gene.

BACKGROUND: The WHO defined myeloid and lymphoid neoplasms (MLN) with eosinophilia associated with PDGFRB, PDGFRA, FGFR1 rearrangements as a new entity in 2016. PDGFRB-rearranged MLN sensitive to imatinib were described in adult patients. We report the first pediatric patient with PDGFRB-rearranged myeloproliferative disorder associated with T-lymphoblastic lymphoma bearing the t(5; 14)(q33;q32) translocation who was successfully treated with imatinib only. Methods/Aims: Analysis of bone marrow and peripheral blood cells by fluorescent in situ hybridization identified the PDGFRB partner as CCDC88C. Whole genome sequencing of the patient's DNA identified the exact junction site, confirmed by PCR amplification and Sanger sequencing. A real-time quantitative PCR assay was designed to quantify the fused CCDC88C-PDGFRB product. RESULTS: A 2.5-year-old boy was diagnosed with myeloproliferative disorder and eosinophilia associated with lymphoblastic lymphoma both bearing the CCDC88C-PDGFRB fusion. Imatinib therapy resulted in rapid clinical, hematological, and cytogenetic response. Molecular response to treatment was monitored by a real-time PCR assay specific for the CCDC88C- PDGFRB fusion. CONCLUSION: This is the first description of MLN with eosinophilia in the pediatric age group. Response to treatment with imatinib only was monitored by specific quantitative PCR assay with sustained remission lasting 5.5 years from diagnosis.

Cryoglobulinemic Glomerulonephritis Associated With Nodal and Renal Infiltration by T-Cell Lymphoma of T-Follicular Helper Phenotype: A Case Report.

We present a unique case of cryoglobulinemic glomerulonephritis associated with nodal and renal infiltration by T-cell lymphoma of T-follicular helper phenotype. The patient presented with transient neurologic symptoms, severe nephritic syndrome with nephrotic-range proteinuria, and acute kidney injury. He had elevated double-stranded DNA levels, low complement levels, detectable cryoglobulin, and detectable immunoglobulin M (IgM) paraprotein. The kidney biopsy showed cryoglobulinemic glomerulonephritis with a membranoproliferative pattern and diffuse interstitial infiltrates on light microscopy; IgM, C3 but weak IgG, C1q, and negative C4d staining on immunofluorescence; and deposits with organized substructures on electron microscopy. Positron emission tomography showed diffuse uptake in bilaterally enlarged kidneys and a localized group of lymph nodes. Subsequent lymph node biopsy revealed Epstein-Barr virus-negative nodal T-cell lymphoma, which was also proven in renal tissue. The association between T-cell lymphoma, autoantibodies, and cryoglobulinemia may represent a paraneoplastic phenomenon. His renal prognosis has been excellent, but overall prognosis and survival is dictated by the clinical course of T-cell lymphoma.

Morbidity and mortality after total splenectomy for lymphoid neoplasms.

BACKGROUND: Splenectomy is indicated for selected patients with lymphoid neoplasms. We examined surgical morbidity and mortality in this high-risk patient population using a contemporary national cohort, with attention to hospitalization status before surgery. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2005-2013) was queried for patients with lymphoid malignancies undergoing splenectomy. Stepwise statistical analyses were performed to identify factors associated with increased risk of death and serious morbidity (DSM). A risk scoring system was developed to predict DSM. RESULTS: In 456 patients, morbidity rate was 24.1%, and mortality rate was 2.4%. Albumin <3 g/dL (odds ratio [OR] = 2.6, P = 0.005), hematocrit <30% (OR = 2.8, P < 0.0001), and a history of chronic obstructive pulmonary disease (OR = 3.4 P = 0.009) were independent predictors of DSM. Rates of DSM were stratified by these risk factors (RFs): 13.5% (0 RF), 34.4% (1 RF), and 58.5% (2-3 RF), P < 0.0001. Patients admitted before surgery (IP) were more likely to have RF compared with those undergoing surgery on the day of admission (SDS); 74.6 versus 26.4%, P < 0.001. Morbidity (39.7% versus 18.2%, P < 0.0001) and mortality (7.1% versus 0.6%, P < 0.0001) were significantly increased in the IP group. CONCLUSIONS: Splenectomy for lymphoid neoplasm in hospitalized patients is associated with substantial morbidity and mortality. Risk stratification in this group may aid in perioperative management to mitigate DSM.

Gender and ethnic differences in incidence and survival of lymphoid neoplasm subtypes in an Asian population: Secular trends of a population-based cancer registry from 1998 to 2012.

Descriptive epidemiology on incidence and survival by lymphoid neoplasm (LN) subtypes using the 2008 World Health Organisation (WHO) classification remained limited in Asia. The aim of this study was to evaluate whether gender and ethnic differences in incidence and survival of LN subtypes existed using the Singapore Cancer Registry (SCR) from 1998 to 2012. We derived age standardised incidence rates (ASIRs) by the direct standardisation method and 5-year relative survival (RSR) by the Ederer II method and period approach. Five-year observed survival (OS) was obtained for each ethnicity. Malays had the highest ASIR of total LNs among the three ethnicities for each time period. The largest increase in 5-year RSR subtypes was follicular lymphoma from 43.8% in 1998-2002 to 82.3% in 2008-2012; followed by chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) from 48.1% in 1998-2002 to 77.9% in 2008-2012. Although males had higher incidence than females in each time period, females had greater 5-year RSR for follicular lymphoma (89.8% in 2008-2012 for females vs. 76.6% in 2008-2012 for males) and CLL/SLL (78.7% in 2008-2012 for females vs. 76.7% in 2008-2012 for males). All three ethnicities experienced an overall increase in 5-year OS for mature B-cell lymphoma, with Indians experiencing the greatest increase (37.1% in 1998-2002 to 61.1% in 2008-2012), followed by Malays (30.8% in 1998-2002 to 48.7% in 2008-2012) and then Chinese (36.4% in 1998-2002 to 51.3% in 2008-2012). Our study demonstrated that improved mature B-cell lymphoma survival was not only observed in the West, but also in Singapore.

New classifications of B-cell neoplasms: a comparison of 5th WHO and International Consensus classifications.

In 2024, the World Health Organization (WHO) launched a new classification of lymphoid neoplasms, a revision of the previously used Revised 4th Edition of their classification (WHO-4R). However, this means that two classifications are now in simultaneous use: the 5th Edition of the WHO classification (WHO-5) and the International Consensus Classification (ICC). Instead of a comprehensive review of each disease entity, as already described elsewhere, this review focuses on revisions made in both the WHO-5 and ICC from WHO-4R and discrepancies between them regarding B-cell neoplasms. Similarities include cutaneous marginal zone lymphoma, cold agglutinin disease, non-primary effusion lymphoma-type effusion-based lymphoma, and gray zone lymphoma. Differences include plasma cell neoplasms, high-grade B-cell lymphoma (double hit lymphoma), follicular lymphoma, LPD with immune deficiency and dysregulation, extranodal large B-cell lymphoma, transformations of indolent B-cell lymphomas, and diffuse large B-cell lymphoma, not otherwise specified. Understanding the similarities and differences between the two latest classifications will aid daily diagnostic practice and future research on lymphoid neoplasms.

Hematological Neoplasms with Eosinophilia.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.

Trends in risk for therapy-related myelodysplastic syndrome/acute myeloid leukemia after initial chemo/immunotherapy for common and rare lymphoid neoplasms, 2000-2018.

Background: Historically, survivors of common lymphoid neoplasms (LNs) had increased risks for therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Despite major treatment advances in the treatment of LNs over the last two decades, a comprehensive evaluation of tMDS/AML trends following both common and rare LNs treated in this contemporary period is lacking. Methods: In US cancer registries during 2000-2018, we identified 1496 tMDS/AML cases among 186,503 adults who were treated with initial chemo/immunotherapy for first primary LN and survived ≥1 year. We quantified tMDS/AML standardized incidence ratios (SIRs), excess absolute risks (EARs, per 10,000 person-years), and cumulative incidence. Findings: The highest tMDS/AML risks occurred after precursor leukemia/lymphoma (SIR = 39, EAR = 30), Burkitt leukemia/lymphoma (SIR = 20, EAR = 24), peripheral T-cell lymphoma (SIR = 12, EAR = 23), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; SIR = 9.0, EAR = 27), and mantle cell lymphoma (SIR = 8.5, EAR = 25). Elevated risks (SIRs = 4.2-6.9, EARs = 4.9-15) also were observed after all other LN subtypes except hairy cell leukemia and mycosis fungoides/Sézary syndrome. Among patients treated more recently, tMDS/AML risks were significantly higher after CLL/SLL (SIR2000-2005 = 4.8, SIR2012-2017 = 10, Ptrend = 0.0043), significantly lower after Hodgkin (SIR2000-2005 = 15, SIR2012-2017 = 6.3, Ptrend = 0.024) and marginal zone (SIR2000-2005 = 7.5, SIR2012-2017 = 2.3, Ptrend = 0.015) lymphomas, and non-significantly lower after mantle cell lymphoma (SIR2000-2005 = 10, SIR2012-2017 = 3.2, Ptrend = 0.054), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR2000-2005 = 6.9, SIR2012-2017 = 1.0, Ptrend = 0.067), and plasma cell neoplasms (SIR2000-2005 = 5.4, SIR2012-2017 = 3.1, Ptrend = 0.051). EAR and cumulative incidence trends generally were similar to SIR trends. Median survival after tMDS/AML was 8.0 months (interquartile range, 3.0-22.0). Interpretation: Although tMDS/AML risks are significantly elevated after initial chemo/immunotherapy for most LNs, patients treated more recently have lower tMDS/AML risks, except after CLL/SLL. Though rare, the poor prognosis following tMDS/AML emphasizes the importance of continued efforts to reduce treatment-associated toxicity. Funding: This research was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. LMM, GMD, REC, and CBS verified the data, and all authors had access to the data and made the decision to submit for publication.

Pemigatinib for the treatment of myeloid/lymphoid neoplasms with FGFR1 rearrangement.

INTRODUCTION: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangements (MLNFGFR1) are rare entities with aggressive features and poor prognosis. Presentation is heterogeneous, ranging from myeloproliferative neoplasms (with or without eosinophilia) to T-cell lymphoma and acute leukemia. Historical treatments have been guided by the presenting phenotype with induction chemotherapy frequently used. Pemigatinib is a FGFR1-3 tyrosine kinase inhibitor that has demonstrated high complete hematologic and cytogenetic response rates in MLNFGFR1. AREAS COVERED: We discuss the pathogenesis, presentation, and historical treatments for MLNFGFR1, in addition to clinical data using pemigatinib and other targeted therapies. Discussion of the mechanism of action and adverse events is also included. EXPERT OPINION: Pemigatinib represents a significant advance in the management of MLNFGFR1. High rates of complete hematologic and cytogenetic response have been observed. While direct comparative data are unavailable, outcomes appear favorable compared to conventional approaches. Long-term efficacy and tolerability are not yet known, and allogeneic hematopoietic stem cell transplant (alloHSCT) continues to be the treatment with the highest chance of long-term disease free survival in responding patients. Combinations of pemigatinib and chemotherapy, particularly for more aggressive phenotypes, warrant future investigation as does the use of pemigatinib maintenance following alloHSCT.

Clinicopathologic characteristics, genetic features, and treatment options for acute lymphoblastic leukemia with JAK2 rearrangement-A 10-case study and literature review.

JAK2 rearrangement (JAK2-R) in acute lymphoblastic leukemia (ALL) is rare and often categorized as B-ALL with BCR::ABL1-like features based on the World Health Organization classification. We report 10 patients with JAK2-R ALL, 9 males and 1 female, with a median age 40.5 years. Eight patients presented with marked leukocytosis (median WBC, 63 × 10 9/L) and hypercellular (>95%) bone marrow with increased lymphoblasts (72%-95%). There was no evidence of bone marrow fibrosis or hypereosinophilia. Immunophenotypic analysis showed 9 B-cell and 1 T-cell neoplasms. Using fluorescence in situ hybridization (FISH) and RNA sequencing analysis, JAK2 partners were identified for 7 cases and included PCM1 (n = 4), ETV6 (n = 2) and BCR (n = 1). All patients received upfront polychemotherapy. Additionally, 2 patients received ruxolitinib, 2 received allogeneic stem cell transplant, and 1 received CAR-T therapy. The 1- and 3-year overall survival rates were 55.6% and 22.2%, respectively. A literature review identified 24 B-ALL and 4 T-ALL cases with JAK2-R reported, including 16 males, 6 females and 6 gender not stated. Many JAK2 partner-genes were reported with the most common being PAX5 (n = 7), ETV6 (n = 5), BCR (n = 4) and PCM1 (n = 2). Survival data on 13 reported cases showed 1- and 3-year overall survival rates of 41.7% and 41.7%, respectively. In summary, JAK2-R ALL occurs more often in adult males, are mostly of B-cell lineage, and associated with an aggressive clinical course. Absence of eosinophilia and bone marrow fibrosis and no evidence of preexisting/concurrent JAK2-R myeloid neoplasms distinguish JAK2-R ALL from other myeloid/lymphoid neoplasms with eosinophilia and JAK2-R.

Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement Presenting with Polycythemia Vera and T-cell Acute Lymphoblastic Leukemia.

Myeloid/lymphoid neoplasm with fibroblast growth factor 1 rearrangements (MLN-FGFR1) represents a rare group of hematologic neoplasms, with approximately 100 cases reported to date. A 69-year-old woman with a history of polycythemia and leukocytosis, with negative molecular testing for JAK2, CALR, and MPL, presented with diffuse adenopathy. A lymph node (LN) biopsy revealed effacement by T-lymphoblasts, consistent with T-cell acute lymphoblastic lymphoma (T-ALL). A staging bone marrow (BM) biopsy demonstrated trilineage hyperplasia, which, taken together with the patient's elevated hemoglobin and low serum erythropoietin level, fulfilled diagnostic criteria for polycythemia vera. Karyotype and fluorescence in situ hybridization on both the BM and LN demonstrated a FGFR1 rearrangement due to t(8;13), consistent with MLN-FGFR1. Whole genome sequencing on the LN additionally identified a pathogenic frameshift mutation of ASXL1 NC_000020.11:g32434646dup NM_015338.6(ASXL1):c.1934dup p.(Gly646Trpfs) predicted to result in loss of protein function, a finding also observed in 8.1% of BM reads. Both the BM and LN harbored missense variants in HDAC4 NM_001378414.1(HDAC4):c.[2763G>A]; [2763=] p.(Met921Ile) and CHEK2 NM_007194.4(CHEK2):c.[538C>T];[538=] p.(Arg180Cys), with an unknown significance. Despite initial response to Mini-CVD + venetoclax, the patient subsequently experienced rapid clinical deterioration and death. We report the second case of MLN-FGFR1 with an ASXL1 mutation and the first case with HDAC4 and CHEK2 variants.

The 2022 classifications of lymphoid neoplasms : Keynote.

Classification of hematological neoplasms in the past 25 years has been generated through international efforts to achieve broad consensus among professionals. In recent years, the understanding of lymphoid neoplasms has advanced notably, particularly with the impact of genomic studies. Two classifications of these neoplasms were produced in 2022. The International Consensus Classification (ICC) was generated following the same successful process used for the third, fourth, and updated fourth editions of the World Health Organization (WHO) Classification of Hematologic Neoplasms, coordinated by a steering committee approved by the Executive Committees of the European Association for Haematopathology and the Society of Hematopathology. The topics were prepared by different working groups and subsequently discussed in the clinical advisory committee (CAC) meeting with the participation of a large group of pathologists, clinicians, and scientists who all approved the classification after reaching consensus on all topics. Simultaneously, the International Agency for Cancer Research (IARC) of the WHO has produced the fifth edition of the classification of these neoplasms with a group of professionals appointed by the agency who discussed the proposed classification in different meetings. The definition and criteria for diagnosis of many entities have been refined in both proposals. Terminology for some diseases has been adapted to the current knowledge of their biology. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many entities. Although most categories are similar in both classifications, there are also conceptual differences and differences in the diagnostic criteria for some diseases.

Myeloid/lymphoid neoplasm with ZMYM2::FGFR1 rearrangement: A complex trilineage phenotypic and clonal evolution with associated genomic alterations.

We report a case of myeloid/lymphoid neoplasm with ZMYM2::FGFR1 rearrangement (MLNZMYM2::FGFR1) exhibiting a complex disease evolution. This neoplasm initially presented as T-lymphoblastic lymphoma (T-LBL) in lymph node and myeloproliferative neoplasm (MPN) with eosinophilia in bone marrow, then transitioned to systemic mastocytosis (SM) likely accompanied by additional JAK3 and other mutations and finally transformed to acute myeloid leukemia (AML) accompanied by additional/secondary genetic abnormality (gain of chromosome 21, der(13)t(8;13), and RUNX1 mutation). To our knowledge, this is the first case of MLNZMYM2::FGFR1 with a complex trilineage/phenotypic [T-cell (T-LBL), mast cell (SM), and myeloid (MPN and AML)] lineage evolution.

Updates on eosinophilic disorders.

This review addresses changes and updates in eosinophilic disorders under the International Consensus Classification (ICC). The previous category of myeloid/lymphoid neoplasm with eosinophilia (M/LN-eo) and a specific gene rearrangement is changed to M/LN-eo with tyrosine kinase gene fusions to reflect the underlying genetic lesions. Two new members, M/LN-eo with ETV6::ABL1 fusion and M/LN-eo with various FLT3 fusions, have been added to the category; and M/LN-eo with PCM1::JAK2 and its genetic variants ETV6::JAK2 and BCR::JAK2 are recognized as a formal entity from their former provisional status. The updated understanding of the clinical and molecular genetic features of PDGFRA, PDGFRB and FGFR1 neoplasms is summarized. Clear guidance as to how to distinguish these fusion gene-associated disorders from the overlapping entities of Ph-like B-acute lymphoblastic leukemia (ALL), de novo T-ALL, and systemic mastocytosis is provided. Bone marrow morphology now constitutes one of the diagnostic criteria of chronic eosinophilic leukemia, NOS (CEL, NOS), and idiopathic hypereosinophilia/hypereosinophilic syndrome (HE/HES), facilitating the separation of a true myeloid neoplasm with characteristic eosinophilic proliferation from those of unknown etiology and not attributable to a myeloid neoplasm.

A Case of Atypical Hairy Cell Leukemia With CD10+ and CD38+: Diagnosis and Treatment.

Hairy cell leukemia (HCL) is a rare disease of mature B-cell neoplasms. Its name comes from the hair-like strands surrounding the cytoplasm of the cells, which are observed on peripheral blood or bone marrow smears. Leukemic cells mainly involve the spleen, peripheral blood, and bone marrow. The classical immunophenotyping of HCL includes overexpression of the B-cell surface antigens such as CD19, CD20, and CD22 and co-expression of CD25, CD103, CD11c, and CD123. Other markers including CD5, CD10, and CD38 are usually negative, in which CD38 is considered a poor prognostic factor. Herein, we report a case of HCL with atypical morphology and abnormal expression of both CD38 and CD10.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.