Journal of Hematopathology最新文献

The pluripotency of malignant blasts in acute leukemias is a growing area of scientific and clinical interest. Mixed-phenotype acute leukemias (MPALs) are defined by the presence of blasts showing evidence of differentiation along at least two lineages. Curiously, MPALs exhibit some of the same recurrent cytogenetic abnormalities (e.g., BCR::ABL1, KMT2A rearrangements) that are seen in single-lineage acute leukemias. Factors that contribute to phenotypic selection and divergence of blast populations in single-lineage and mixed-phenotype acute leukemias are incompletely understood. Optimal therapeutic management of MPAL also remains a matter of debate. Herein, we present a case of MPAL with BCR::ABL1 fusion that showed distinct T-lymphoblastic and B-lymphoblastic/myeloblastic populations at different anatomic sites (tonsil and bone marrow, respectively). Both blast populations showed clonally related TRG rearrangements with evidence of clonal evolution. The patient initially responded to tyrosine kinase inhibitor therapy, but he quickly relapsed and expired a year after diagnosis. To our knowledge, this is the first time an MPAL has been shown to have different blast lineages segregated to distinct anatomic sites in a treatment-naïve patient. This case emphasizes the importance of a multifaceted diagnostic approach to acute leukemias and highlights what is left to learn about the biology and management of these poorly understood neoplasms.

In situ follicular neoplasia (ISFN) is characterized by a monoclonal proliferation of BCL2-positive B cells harboring the translocation t(14;18)(q32;q21). These cells are confined to follicle centers and are usually identified incidentally, with a very low risk of progression to follicular lymphoma. Sebaceous lymphadenoma is a rare, benign salivary gland tumor, most commonly arising in the parotid gland, and is histologically defined by solid epithelial nests and cysts with sebaceous differentiation in a hyperplastic lymphoid stroma. We report an unusual case of ISFN arising within a sebaceous lymphadenoma. To the best of our knowledge, this association has not previously been reported.

Background: Current classification systems for myelodysplastic syndromes (MDS) incorporate morphologic findings, blast percentage, and some genetic features such as del(5q) and SF3B1 and TP53 mutations. A recent comprehensive molecular taxonomy proposed by the MDS-International Working Group (MDS-IWG) categorizes MDS into 16 molecular groups and two residual groups and describes associations with various clinicopathological features and differing overall survival among groups.

Purpose: In this study, we attempt to validate the findings described in the MDS-IWG classification in an independent cohort.

Methods: We applied the MDS-IWG classification to 484 cases of MDS and myelodysplastic-type chronic myelomonocytic leukemia.

Results: We verified numerous findings and associations described in the MDS-IWG molecular taxonomy paper, including the association of monocytosis with the bi-TET2 group, lower bone marrow blast percentage in the SF3B1 group, and higher bone marrow blast percentage in the TP53-complex and the IDH-STAG2 groups. This study confirms the poor prognosis of the EZH2-ASXL1 group despite low blast counts. Blast counts tended to affect prognosis most in the low-risk molecular groups, with little impact in the high-risk molecular groups. Within the MDS-IWG TP53-complex group, we find significant survival differences between TP53-mutated and unmutated cases, suggesting that this group is clinically and biologically heterogeneous.

Conclusion: The MDS-IWG molecular taxonomy of MDS is clinically applicable in routine practice and exhibits clinicopathologic and prognostic significance.

This study evaluated immune cell subset variations in immune thrombocytopenia (ITP) by comparing frequencies at diagnosis with controls and assessing changes post-therapy. A single-center prospective observational study enrolled 25 untreated acute and chronic ITP patients and 20 matched controls from January 2018 to January 2019. Immune cell subsets, including CD4+, CD8+, NK cells, NK-T cells, and T regulatory cells (Tregs), were analyzed using flow cytometric immunophenotyping. Patients received standard therapy, with responses assessed after 1 month using international criteria. The median age of patients was 43 years, with 52% female. At diagnosis, patients exhibited significantly lower Tregs (p = 0.001) and NK-T cells (p = 0.017), higher CD8+ cytotoxic T-cells, and a reduced CD4/CD8 ratio (p = 0.001) compared to controls. Following therapy, 85% of patients responded: 45% achieved complete response, and 40% partial response. However, post-treatment immune cell subsets did not differ significantly from baseline, nor could they predict response. ITP patients display notable immune cell abnormalities compared to controls, though these differences do not serve as reliable predictors of treatment outcomes. Further large-scale studies with functional analyses are essential to elucidate ITP pathogenesis and identify therapeutic targets.

Intron 22 inversion (Inv22) of the factor VIII gene (F8) accounts for approximately 45% of severe hemophilia A (HA) cases. Detecting Inv22 has become the primary screening method for severe HA. Currently, agarose gel electrophoresis (AGE) following long-distance polymerase chain reaction (LD-PCR) is commonly used in clinical settings to separate the amplified fragments of Inv22. However, AGE is hindered by lengthy processing times, instability, and inaccuracies in quantifying DNA content and assessing fragment sizes. We combined LD-PCR with capillary gel electrophoresis (CGE) for the identification of Inv22 in HA. Three primers were designed for LD-PCR to differentiate between Inv22, carriers, and wild types. We optimized the reaction system and conditions for CGE to effectively separate the amplified fragments. The optimal dilution ratio and buffer conditions for detecting Inv22 using CGE were 300 × and 0.1 × TE buffer. The ideal voltage and duration were 5.0 kV for 80 min. Under these conditions, the amplified fragments could be effectively separated, allowing for the direct measurement of concentration and size of the target fragments using ProSize data analysis software. The LD-PCR combined with the CGE assay for detecting Inv22 in F8 within HA populations has been successfully established. This method reduces both the time and labor required for detecting Inv22 in clinical practice, thereby advancing genetic diagnostic technology for hemophilia.

Multiple myeloma (MM) is a malignant neoplasm of clonal plasma cells, typically associated with the production of a monoclonal protein. In 1-3% of cases, MM presents without measurable monoclonal protein (M protein) in the serum or urine and normal serum-free light chains; these cases are referred to as non-secretory MM (NSMM). This definition has changed over time according to the sensitivity of laboratory methods for detecting paraproteins. NSMM has been previously reported to have a less aggressive presentation and clinical course compared to secretory MM; however, the literature is conflicting. Recent studies have indicated that NSMM may exhibit different responses to therapy and outcomes, emphasizing the need for a tailored approach. This review consolidates the current understanding of NSMM and underscores the importance of advanced diagnostic techniques in improving patient management and outcomes.

Myelomastocytic leukemia (MML) presenting as a blast phase manifestation of Chronic Myeloid Leukemia (CML) is exceptionally rare, with limited documented cases in the literature. Understanding its distinct clinicopathologic features and treatment outcomes is crucial for optimal patient management. A 45-year-old male with a history of CML since 2016, previously treated with imatinib and dasatinib, presented after treatment interruption with leukocytosis (WBC 27.3 × 103/μL) and 58% circulating blasts showing metachromatic granulation. Bone marrow examination revealed 30% blast cells with strong CD117 and tryptase positivity. Flow cytometry identified two distinct populations: 7% myeloblasts and 27% immature myeloid cells with bright CD117 expression. BCR-ABL1 rearrangement was confirmed with a ratio of 112% (IS). The patient received combination therapy with standard "3 + 7" induction chemotherapy and dasatinib. Despite complications of febrile neutropenia, the post-induction bone marrow examination demonstrated achievement of complete morphologic remission. This case highlights the successful initial treatment of myelomastocytic transformation in CML blast phase using intensive combination therapy. The detailed morphologic, immunophenotypic and molecular characterization provides valuable insights into this rare entity, while the favorable initial response supports an aggressive treatment approach. Long-term follow-up and further studies are needed to establish optimal treatment strategies.

Alpha globin chain variants constitute a very small fraction of the total hemoglobinopathy cases. Their rarity and the often-unfamiliar elution times/patterns in high performance liquid chromatography (HPLC) that mimic those of normal hemoglobin (Hb) fractions and/or known beta globin variants render their primary diagnosis difficult. We describe here Hb Fontainebleau, a rare alpha globin chain variant, in an adult female that eluted in the HbA2 window in a less commonly used HPLC platform, Lifotronic H8, thereby causing difficulties in the diagnosis. The matter was resolved by running the sample on a more commonly used platform wherein the abnormal Hb yielded a familiar elution time and pattern known to be associated with Hb Fontainebleau. This was further confirmed by gene sequencing, which showed a Codon 21 (G → C); HBA2:c.64G > C (or HBA1) mutation. A literature search failed to reveal any published case of the unique elution pattern of Hb Fontainebleau on Lifotronic H8 HPLC platform and the associated diagnostic challenges. An increasing use of the newer HPLC platforms calls for greater awareness of these issues.

Plasma cell neoplasms encompass a spectrum of disorders characterized by the clonal proliferation of plasma cells. Plasmablastic transformation in these neoplasms poses diagnostic and clinical challenges due to its aggressive nature and morphological overlap with other malignancies, including plasmablastic lymphoma (PBL). We report a case of discordant extramedullary plasmablastic transformation in a 55-year-old HIV-negative female presenting with an oral lesion diagnosed as plasmablastic plasmacytoma. Initial imaging indicated localized disease without systemic involvement. Despite undergoing chemotherapy and achieving a partial response, the patient developed osteolytic lesions 2 years later. Subsequent pathology evaluation confirmed mature plasma cell myeloma (PCM) morphology. Whole exome sequencing (WES) and whole RNA expression analysis revealed shared mutations (PTPN13, KRAS, LTK) and a MYC::BMP6 translocation in both lesions, supporting a clonal relationship. Additionally, the oral plasmablastic lesion revealed a KLHL6 mutation and an extra MYC::IGL translocation, which were absent in the tibial lesion. The KLHL6 mutation has not been previously reported in studies of discordant extramedullary plasmacytoma with plasmablastic transformation. This case highlights the diagnostic complexity of plasmablastic plasmacytoma presenting as the initial manifestation of plasma cell myeloma. It underscores the necessity of a thorough evaluation, including bone marrow biopsy, to accurately differentiate plasmablastic transformation from PBL and ensure accurate diagnosis and appropriate management.