Journal of Hematopathology最新文献

Background: Flow cytometric identification of plasma cells can be confounded by therapeutic anti-CD38 antibodies, a phenomenon commonly encountered during measurable residual disease (MRD) assessment after chemo/immunotherapy. Less frequently, loss of plasmacell gating markers may occur due to the disease process itself. In low-resource settings, diagnostic and MRD flow cytometry panels are tailored for cost-effective use of CD markers. At baseline diagnosis, CD38, CD138, and CD45 are usually sufficient as backbone plasma-cell gating markers, and alternate markers are not routinely required.

Case description: We present a case of plasma cell leukemia in which standard diagnostic flow cytometry panels were challenged by variable CD138 expression. Given the difficulty in identifying plasma cells using conventional markers, an expanded flow cytometry panel incorporating antibody CD319 (SLAMF7) was employed.

Results: The inclusion of CD319 enabled reliable detection of clonal plasma cells despite predominant loss of CD138 expression. This approach allowed identification of circulating malignant plasma cells outside the setting of therapeutic anti-CD38 antibody interference.

Conclusion: Use of alternate plasma-cell gating markers beyond the conventional backbone can be critical even in upfront diagnostic settings. Incorporating multiple, non-overlapping plasma-cell markers-including antibodies designed to avoid therapeutic masking-improves plasma-cell detection in both MRD assessment and initial diagnostic flow cytometry panels.

Background: Acute myeloid leukemia with erythroid and megakaryocytic differentiation (AML-EMD) is a rare and aggressive presentation of AML characterized by overlapping morphologic, immunophenotypic, and genetic features of erythroid and megakaryocytic lineages. The classification, pathogenesis, and clinical behavior of this entity remain poorly defined.

Methods: We report a series of three patients in conjunction with a systematic review of reported cases in published literature with AML-EMD.

Results: Cytogenetic and molecular studies revealed frequent abnormalities including complex karyotypes, TP53 mutations, and JAK1/2 mutations. Clinically, patients demonstrated a poor-risk profile.

Conclusions: Collective phenotypic and genetic features suggest that AML-EMD represents a high-risk subgroup of either TP53-mutated AML or AML with myelodysplasia-related genetics, likely reflecting leukemic transformation from multipotent progenitors retaining erythro-megakaryocytic potential. Despite shared biologic features, current classification systems for AML-EMD are diagnostically incongruent. Recognition of this entity will allow for consistent subclassification, prognostication, and future studies aimed at defining its molecular underpinnings and therapeutic vulnerabilities.

Background: Expression of TRBC1 and TRBC2 is increasingly assessed in the evaluation for clonal T-cell populations. While flow cytometry has repeatedly shown utility in evaluating TRBC 1/2 expression, immunohistochemical (IHC) methods have not been extensively examined, particularly in immature T-cell populations.

Purpose: This study evaluated TRBC1 IHC staining in formalin-fixed paraffin-embedded (FFPE) tissue, encompassing benign thymic tissue, thymomas, and T-lymphoblastic leukemias/lymphomas (T-LL).

Methods: IHC for TRBC1, CD3, TCR-BF1, and TCR-δ was performed in all cases; TdT was performed on all T-LLs. TRBC1 was scored as positively restricted (≥ 85%), negatively restricted (≤ 15%), or polytypic (16-84%) in T cells, using CD3 and/or TdT staining as the denominator.

Results: All thymic tissues (n = 6) and thymomas (n = 5) showed polytypic TRBC1 staining patterns. Twenty-four T-LL specimens were identified from 21 patients, including bone marrow (n = 16), lymph node (n = 7), and bone (n = 1) biopsies. All T-LL cases showed positively (n = 3 patients, 14%) or negatively (n = 18 patients, 86%) restricted TRBC1 expression. Patients with multiple specimens showed consistent TRBC1 staining across tissue sites and sampling time points. Coexpression analysis of TRBC1, TCR-BF1, and TCR-δ staining revealed frequent TRBC1-negative cases with either TCR-δ + (n = 6, 29%) or TCR null (n = 7, 33%) phenotypes. TRBC1 IHC restriction and molecular methods for clonality assessment were concordant in 13 of 15 evaluated cases (87%).

Conclusions: T-LL showed restricted patterns of TRBC1 expression by IHC, whereas benign immature T-cell populations showed polytypic staining. The observed TCR and TRBC1 phenotypes of T-LL are distinct from those of mature T-cell neoplasms and warrant further study.

Mantle cell lymphoma (MCL) is a mature B cell neoplasm characterized by the CCND1::IgH t(11;14) translocation. The process of MCL clonal evolution remains poorly understood. In this report, we describe a rare case of a patient with blastoid variant MCL who developed clonally related classic Hodgkin lymphoma (CHL), following CD19 chimeric antigen receptor T cell (CAR T cell) therapy. A 65-year-old man was initially diagnosed with blastoid variant MCL with a concurrent TP53 deletion. He was treated with chemotherapy followed by CD19 CAR T cell therapy with significant clinical response. Eight months later, he developed a recurrence with numerous CD19-negative, pleomorphic cells with Hodgkin and Reed-Sternberg-like (HRS-like) phenotype. The previously described blastoid MCL component was eradicated. Fluorescence in situ hybridization (FISH) testing confirmed CCND1::IgH t(11;14) in the HRS-like tumor cells, indicating a clonal relationship to the original MCL. Loss of CD19 expression is a known mechanism of resistance in CD19 CAR T cell therapy in B cell lymphomas. A notable feature of the HRS-like cells in this case is the gain of markers associated with CHL, such as CD30 and CD15. This immunophenotypic shift highlights the concept of lymphoma plasticity, where the tumor cells evolve in response to selective pressures, such as CAR T cell therapy.

Background: Acute promyelocytic leukemias (APL) with variant translocations involving the RARA gene at 17q21.2 with non-PML partners constitute a rare and diverse subset of APLs, accounting for approximately 5% of total cases. Variant APLs present considerable diagnostic challenges, as standard testing methodologies targeting the PML::RARA fusion protein are unrevealing, leading to a lack of diagnosis.

Case presentation: We present the case of a 54-year-old patient with APL harboring a TBL1XR1::RARA fusion, an exceptionally rare APL variant that showed distinctive morphologic, phenotypic, and clinical attributes. Unlike conventional APL, the neoplastic promyelocytes lacked pathognomonic Auer rods and bilobed nuclei and were accompanied by marked granulocytic dysplasia and significant monocytosis. Phenotypically, the blasts were negative for CD117 and showed an associated expanded monocyte population with aberrant CD56 and CD23 expression, features highly uncharacteristic of classic APL. Cytogenetic analysis and targeted PCR yielded negative results for PML::RARA fusion; however, the break-apart probe analysis tested positive for a RARA rearrangement, ultimately facilitating an accurate diagnosis. The patient did not respond to all-trans retinoic acid (ATRA) and succumbed to the disease 24 days after the initial presentation.

Conclusions: This case brings to light the diagnostic challenges posed by variant APLs that may demonstrate divergent morphologic and phenotypic features and carry translocations that render the routine PML::RARA fusion-based methodologies futile. Accurate diagnosis requires a high index of suspicion and a comprehensive multifaceted diagnostic strategy that encompasses morphologic assessment, immunophenotypic analysis, RARA break-apart probe analysis supplementing traditional fusion probe techniques, conventional karyotyping, and advanced molecular fusion testing.

ALK-positive anaplastic large cell lymphoma (ALCL) may show sinusoidal involvement, but exclusive intrasinusoidal infiltration of lymph nodes is exceptionally rare. We describe a 39-year-old woman with isolated stage I inguinal lymphadenopathy, in whom the lymph node architecture was preserved despite massive intrasinusoidal infiltration by CD30- and ALK-positive atypical cells. This pattern can closely mimic metastatic carcinoma, creating a significant diagnostic challenge. Its recognition is crucial, as ALK-positive ALCL generally responds well to therapy. Further studies are required to better define the clinical and prognostic implications of this presentation.

A 22-month-old previously healthy girl presented with profound microcytic anemia and severe thrombocytopenia due to iron deficiency. Following transfusions and iron supplementation, her platelet count rose dramatically, peaking at 3.5 million/µL before gradually normalizing over several months. This case highlights the rare presentation of iron deficiency with severe thrombocytopenia, which can mimic bone marrow disorders. It also illustrates the phenomenon of rebound thrombocytosis after iron repletion, emphasizing the need for close platelet monitoring to mitigate potential thrombotic risk.

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.