Journal of Hematopathology最新文献

Background: The Triple A model has recently been developed and validated in essential thrombocythemia (ET) and polycythemia vera (PV). However, external validation in diverse populations remains unclear.

Purpose: The purpose of this study was to externally validate the Triple A prognostic model in a Turkish cohort of patients with ET and PV.

Methods: A retrospective analysis was conducted at two centers in Bursa, Türkiye, involving patients diagnosed with ET or PV under the World Health Organization (WHO) 2016/2022 criteria between 2014 and 2024.

Results: While the Triple A model has significantly separated the ET patients with a median follow-up of 47 months (p = 0.015), no significant difference was observed in PV patients in terms of survival (p = 0.87). For thrombosis-free survival (TFS), Fine and Gray's competing risk analysis showed a significant separation with the Triple A model in ET (p = 0.017).

Conclusion: While the Triple A model was validated as a practical prognostic tool in ET, it demonstrated limited utility in PV. Further multicenter studies are needed to refine risk stratification in PV.

Background: 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans have largely replaced bone marrow biopsy in the staging workup for diffuse large B-cell lymphoma (DLBCL).

Purpose/methods: Here, we highlight a pitfall of FDG PET/CT for assessing bone marrow involvement, detailing the clinical course of a patient diagnosed with otherwise limited-stage DLBCL who exhibited diffuse bone marrow FDG uptake, felt to be compatible with extensive lymphomatous infiltration. In accordance with current National Comprehensive Cancer Network guidelines, this finding circumvented the need for a formal staging bone marrow biopsy procedure.

Results: Subsequent clinical developments revealed extensive bone marrow involvement by a second, unexpected malignancy (multiple myeloma), casting doubt on the assumption that the initial diffuse marrow uptake was attributable to DLBCL.

Conclusion: The presented case emphasizes the challenges of interpreting diffuse FDG uptake within the bone marrow compartment and highlights the inherent contribution of histomorphology for the accurate diagnosis and classification of hematolymphoid neoplasms.

Background: Myeloid and/or lymphoid neoplasms with eosinophilia PDGFRA gene fusions usually occur with FIP1L1 as the partner gene; however, novel partners have been described. These novel partners are sometimes responsive to tyrosine kinase inhibitor therapy.

Purpose: We describe here a patient with a PDGFRA fusion with a previously undescribed partner gene, BMP2K.

Methods: RNA sequencing with the Archer Fusion Plex Pan Solid Tumor Panel (IDT) was used to detect fusions. DNA sequencing using a custom IDT panel was also performed.

Results: An in-frame BMP2K::PDGFRA fusion was detected in a patient who had an ill-defined myeloid neoplasm with eosinophilia. The myeloid neoplasm had a prominent mast cell component and myeloid blast component in the lymph node, while the bone marrow showed hypercellularity, eosinophilia, and myelofibrosis. DNA NGS revealed a pathogenic TP53 mutation but was negative for mutations in other genes including KIT, JAK2, CALR, and MPL.

Conclusions: Given that PDGFRA fusions with novel fusion partners may respond to tyrosine kinase inhibitor therapy, partner agnostic testing methods should be considered either up front or as reflex testing in patients with myeloid and/or lymphoid neoplasms with blood, bone marrow, or tissue eosinophilia.

Trephine bone marrow biopsies (TBMB) are standard specimens for diagnostics and follow-up of myeloid and precursor cell neoplasms, usually as part of a multimodal approach including complete blood count (CBC) tests, cytologic assessment of BM aspirate smears, flow cytometry, cytogenomics, and molecular genetics. Incorporating the results of all the above methods or running all tests within one specialized lab and providing an integrative report is ideally desirable. However, in reality, in many countries, (1) diagnostic (hemato-)pathologists may not have access to information on the results obtained by other technologies except for a CBC, (2) individual procedures may not be available at all, (3) specimens may not be submitted to specialized labs, or (4) particular technologies may fail yielding results (e.g., dry taps or specimens with destroyed nucleic acids), so that the TBMB might remain the only analytic sample. The detailed description of our approach to handling TBMB including classic histopathology, immunohistochemistry, fluorescence in situ hybridization, and sequencing techniques in the setting of myeloid and precursor neoplasms may help the readership to achieve a comprehensive TBMB diagnostic approach reaching more definite and robust conclusions to improve patient care.

Background: The interpretation of lymph node biopsy is influenced by factors inherent to the type of biopsy. In recent times, core needle biopsies (CNB) have increasingly been preferred over whole node excision (WNE) for sampling lymph nodes.

Purpose: To compare the diagnostic efficacy of CNB and WNE in diagnosing lymph node pathologies and to evaluate the diagnostic challenges in interpreting CNB.

Material and methods: Lymph node biopsies (CNB and WNE) received over 5.5 years were analyzed using hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC). The percentage of cases diagnosed on morphology alone and with IHC in each group was evaluated. Cases that did not have a definitive diagnosis, even after the application of IHC, were analyzed.

Results: A total of 751 lymph node biopsies were studied, comprising 222 CNB and 529 WNE. Based on morphology alone (± special stains), the diagnosis could be established in 63/222 (28.4%) cases on CNB and 308/529 (58.2%) of WNE. After IHC, a diagnosis could be rendered in 65.8% of CNB, compared to 95.8% of WNE. Thus, 17.6% of CNB remained inconclusive even after IHC, and 16.7% of CNB had inadequate or nonrepresentative tissue. CNB was more prone to fragmentation, cellular distortion, crushing, and shrinkage, thereby challenging the interpretation.

Conclusion: WNE offers a significantly higher diagnostic yield and provides complete nodal architecture and fewer tissue artefacts, making it a superior sampling technique to CNB for diagnosing lymph node lesions. Inconclusive diagnoses on CNB are due to a lack of architectural pattern, limited tissue, nonrepresentative sampling, and procedural artefacts.

We collected 97 cases of myeloid neoplasia with the rare cytogenetic event of isolated trisomy 19 (+19), with the aim to characterize this group clinically and pathologically. 51 patients with myelodysplastic syndrome (MDS +19) and 11 patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN +19) presented with +19 at disease onset and were further analyzed. Patients with insufficient data were excluded. We collected additional clinical and laboratory data and performed mutation analysis on available bone marrow biopsies. The 62 patients of both disease groups turned out to be remarkably homogeneous in terms of male sex (85%), the presence of anemia with increased numbers of ring sideroblasts (RS, 80%), the absence of an SF3B1 mutation (95%), and the overall rather consistent presence of SRSF2 (61%) or ASXL1 (39%) mutations. MDS +19 patients with available follow-up (1 month to 7.5 years) presented or progressed with significant fibrosis (45%), leuko- or monocytosis (13%) or acute leukemia (28%). Compared to a control cohort of 23 patients with MDS and an SRSF2 mutation, but without isolated +19 (MDS-SRSF2), the 16 MDS +19 patients with SRSF2 mutation and the 12 MDS +19 patients with an ASXL1 mutation showed a striking difference in the presence of ≥ 15% RS (73% and 67% versus 17% in MDS-SRSF2) and the occurrence of fibrosis (44% and 57% versus 4% in MDS-SRSF2). Although all individual features observed in the MDS +19 and MDS/MPN +19 cohorts are seen in MDS and MDS/MPN in general, their combination is rather unique and provides clues regarding disease evolution in this rare, cytogenetically defined group of myeloid neoplasia.

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.