Journal of Hematopathology最新文献

We report a 15-year-old boy from Karnataka, India, initially misdiagnosed as HbE/β-thalassemia. On follow-up, Capillary electrophoresis (CE) showed a 3.3% peak in Zone 4, with the WBC Differential Fluorescence (WDF) scattergram on the Sysmex XN 10 instrument suggesting an unstable hemoglobin. CE pattern, along with heat stability testing, mass spectrometry, and molecular sequencing, confirmed Hb Köln (β98 Val → Met), also detected in his father. This case emphasizes the need to suspect unstable hemoglobins in unexplained hemolysis and highlights the diagnostic value of CE and WDF scattergram.

Background: Acute myeloid leukemia (AML) is characterized by myeloid blasts in the bone marrow and peripheral blood, and it is a highly heterogenous disease genetically. Although our understanding of AML genetics has advanced considerably, disease relapse continues to pose a significant therapeutic hurdle.

Case presentation: Here, we report a case of relapsed AML following allogeneic stem cell transplantation (alloSCT) with a novel in-frame IKZF1::FAM3C fusion detected by RNA sequencing. Karyotype analysis revealed a pericentric inversion of chromosome 7, inv(7)(p13q32), which is the likely mechanism for this fusion. While IKZF1 deletions are a common feature in B-cell acute lymphoblastic leukemia (B-ALL) and are linked to poor outcomes, especially in children, they are rarely reported in AML. To our knowledge, gene fusions involving IKZF1 have not been previously described in AML, although deletion of the short arm of chromosome 7 involving the IKZF1 gene is relatively common.

Conclusions: This case broadens the spectrum of IKZF1 rearrangements in hematologic malignancies and suggests a potential role for disrupted Ikaros function in AML pathogenesis.

Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement in bone marrow hematopoietic stem cells, resulting in the transformation of myeloid/lymphoid cells into neoplastic growths. The clinical and laboratory features of affected individuals are influenced by the specific partner genes. Purpose This article aims to report a case of MLN-FGFR1 involving a novel CNTRL::FGFR1 splicing variant and to discuss its clinicopathological characteristics and treatment challenges. Methods/Results We report a case of MLN-FGFR1 in a 35-year-old male patient presenting with leukocytosis, lymphadenopathy, hepatosplenomegaly, and a mixed population of B lymphoblasts, T lymphoblasts, and monoblasts in the bone marrow and lymph nodes. Comprehensive molecular profiling, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), targeted transcriptome sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing, identified a novel splicing variant of the CNTRL::FGFR1 fusion, resulting from a t(8;9)(p11;q33) translocation. This novel splicing variant involves an in-frame fusion between exon 38 of CNTRL and exon 11 of FGFR1, retaining the kinase domain of FGFR1 and leading to its constitutive activation. Despite multiple treatment regimens, the patient failed to achieve complete remission (CR). Conclusion The findings highlight the urgent need for targeted therapies, such as FGFR inhibitors, to improve outcomes in patients with FGFR1-rearranged malignancies.

IgG4 plasma cells are well-known in the context of IgG4-related disease (IgG4-RD). Meanwhile, their role in other disorders remains enigmatic. In hematopathology practice, the presence of these cells can be non-specific in reactive lymphadenopathy, requiring clinicopathological correlation to exclude IgG4-RD. A high density of IgG4 plasma cells may help distinguish progressive transformation of germinal centers from early nodular lymphocyte-predominant Hodgkin lymphoma. IgG4 plasma cells are also present in a subset of classic Hodgkin lymphomas, particularly the nodular sclerosis subtype. Despite their morphological similarities, Rosai-Dorfman disease and IgG4-RD appear to be distinct entities. Idiopathic multicentric Castleman disease and IgG4-RD can be histologically indistinguishable, which necessitates clinical and laboratory differentiation. Marginal zone lymphoma and, rarely, myeloma can express IgG4, with some cases of marginal zone lymphoma having concurrent IgG4-RD. This review provides a comprehensive analysis of IgG4 plasma cells in hematopathology and discusses their diagnostic significance and associated challenges.

Castleman disease is an uncommon lymphoproliferative disorder that usually involves lymph nodes but can rarely present in extranodal sites. We describe an unusual case of Castleman disease exclusively involving the kidney. The authors also briefly discuss previously documented clinicopathological and radiological characteristics associated with Castleman disease of the kidney.We report a case of a 57-year-old female who presented with persistent abdominal pain. Imaging revealed a 1.8-cm nodule in the upper pole of the left kidney with no evidence of systemic lymphadenopathy. A nephrectomy was performed due to concerns for a primary renal neoplasm. Histopathological evaluation was consistent with hyaline vascular Castleman disease of the kidney (unicentric). The patient has remained stable for the past 3 years with no new development of lesions.Primary Castleman disease of the kidney is an uncommon entity that can present with various clinical and radiological features. Our case, along with previously reported cases, highlights the diagnostic challenges of these lesions, especially in distinguishing them from primary renal neoplasms during radiological evaluation. A comprehensive clinical and histopathological assessment is essential for establishing a diagnosis.

Introduction: Heparin-induced thrombocytopenia (HIT) is a life-threatening immunologic reaction to heparin exposure that is associated with substantial morbidity and mortality. Limited research is available on host-dependent risk factors, such as age, gender, and ethnicity. This study aims to characterize any association between age, gender, ethnicity, and mortality in HIT patients to better identify patient populations at increased risk.

Methods: This is a retrospective case control analysis of all-cause mortality in 72,935 patients with a diagnosis of HIT between 2016 and 2020. Adult patients with HIT were selected using the ICD-10 code D75.82 (HIT) for inclusion and evaluated by demographic, clinical, and hospital characteristics. Odds ratios were calculated for continuous variables using 95% confidence intervals. Multivariable logistic regression was used to ascertain the odds of binary clinical outcomes relative to patient and hospital characteristics as well as the odds of clinical outcomes over time.

Results: Our analysis indicates that hospitalized patients with HIT are at 5 times higher odds of mortality than those without HIT (OR: 5.42, 95% CI: 5.15-5.71, p < 0.001). Our data also indicates significantly higher odds of HIT-associated mortality based on patient age, gender, and ethnicity. By age, HIT patients at the highest risk of mortality were found to be between ages 46 and 60 (odds ratio (OR): 2.60, 95% CI: 1.58-4.25, p < 0.001). By gender, females with HIT are at significantly lower odds of mortality compared to males (OR: 0.90, 95% CI: 0.82-0.99, p < 0.001). By ethnicity, Hispanic patients are at the highest risk of mortality (OR: 1.52, 95% CI: 1.31-1.77, p < 0.001), followed by Black patients (OR: 1.45, 95% CI: 1.27-1.66, p < 0.001), and then Asian patients (OR: 1.31, 95% CI: 1.00-1.72, p = 0.05).

Conclusion: HIT remains a clinical diagnosis based on quantitative criteria such as thrombocytopenia relative to baseline and timing of platelet decline but does not take into consideration other clinical variables that may stratify patients by increased risk. This study elucidates the relationship between host-dependent risk factors such as age, gender, and ethnicity on the risk of all-cause mortality associated with HIT.

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.