Journal of Hematopathology最新文献

Distinct bone marrow morphology is considered the primary basis for the diagnosis of BCR::ABL1-negative myeloproliferative neoplasms (MPNs). However, presence of a mutually exclusive classical driver mutation in JAK2, CALR, or MPL aids in diagnosing and determining the prognosis of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Few recent studies have reported presence of dual mutations in MPNs and double mutations in patients with PMF have been rarely described. We present two PMF patients with concurrent MPL and atypical JAK2 mutations. Patient-P1 harbored MPL: p.W515L and JAK2: p.R867Q mutations and exhibited morphologic and clinical features consistent with PMF, overt fibrotic stage. Patient-P2 harbored MPL: p.W515L, JAK2: p.R683S, and ASXL1: p.G660Rfs*9 and presented with features consistent with PMF, early fibrotic phase. Both patients initially presented with isolated, increasing thrombocytosis, and never displayed the leukocytosis seen in many PMF cases. These cases highlight dynamic emergence of these co-mutations during MPN development and progression. They also illustrate the utility of broad molecular profiling in detecting canonical and atypical oncogenic mutations across genetically heterogeneous MPN that could assist in selecting treatment approaches to improve clinical outcomes.

Here, we present a challenging diagnostic case of a B-cell acute lymphoblastic leukemia (B-ALL) presenting as a rare extramedullary and extranodal presentation without bone marrow or peripheral blood involvement, also classified as B-cell lymphoblastic lymphoma (B-LBL). Our case demonstrated a lack of expression for typical immature B-ALL markers CD34, TdT, and CD99 and instead showed positive expression for CD5, SOX11, BCL-6, and c-MYC, which are markers more often seen in mature aggressive B-cell lymphomas. A distinction between B-ALL and the aggressive B-cell lymphomas, high-grade B-cell Lymphoma (HGBL), and mantle cell lymphoma (MCL), which can show a blastoid morphology, could not be made based on our immunohistochemistry (IHC), flow cytometry, and FISH studies. The diagnosis of B-ALL in our case eventually required extensive molecular methods, with next generation sequencing (NGS)-based DNA and RNA fusion genomic profiling studies to achieve an accurate diagnosis and classification. The molecular studies identified a positive MEF2D::BCL9 gene fusion, a recently described rare abnormality in high-risk B-ALL. These rare B-ALL cases with a MEF2D::BCL9 gene fusion have been categorized as specific B-ALL subtypes in the newest World Health Organization (WHO) 5th edition classification of hematolymphoid tumors and lymphoid neoplasms. We want to share the challenges we faced in making this new diagnosis and the results of our studies, since complete expression profiles for this rare entity have not yet been extensively described.

Castleman disease is a clinicopathological entity that shares features with hematological, rheumatological, and infectious diseases, making accurate diagnosis essential. The objective of this study is to characterize the clinical and pathological characteristics of CD in a Mexican cohort. A retrospective study was conducted on adult Mexican patients diagnosed with unicentric (UCD) and multicentric (MCD) Castleman disease from 1985 to 2023. Clinical and histopathological characteristics typical of UCD and MCD were observed. POEMS-associated MCD showed a higher relapse rate. The mixed histopathological variant was more prevalent in MCD. Immunohistochemical expression of VEGF-A was elevated in all CD cases. A multidisciplinary diagnostic approach is crucial for accurately categorizing CD. The mixed histopathological variant was more common than previously reported, especially in MCD. Further studies are needed to validate VEGF-A as a biomarker for CD.

Acid sphingomyelinase deficiency type B (ASMD-B), also known as Niemann-Pick type B (NPB), is caused by inherited mutations in acid sphingomyelinase that results in accumulation of sphingomyelin and other lipids in monocytes/macrophages leading to splenomegaly, hepatomegaly, and/or cytopenias that typically manifest in mid-childhood. Microscopic examination of bone marrow aspirate and core biopsy specimens frequently reveals the presence of foamy histiocytes. In this case report, we describe a case of a 21-year-old woman who presented with progressive hepatosplenomegaly, gastroparesis, weight loss, and a neutrophilic leukocytosis who was found to have foamy histiocytes with engulfed nucleated cells compatible with emperipolesis or hemophagocytosis. Based on the constellation of clinicopathologic findings, a lysosomal storage disorder was suspected and subsequent genetic testing revealed the presence of two SMPD1 variants, one known pathogenic (c.1829_1831del, p.Arg610del) and one variant of unknown significance (VUS) (c.872G > A, p.Arg291His) (Table 1). Follow-up testing found that acid sphingomyelinase (ASM) activity was low (0.11 nmol/h/mg, reference value > 0.32 nmol/h/mg), consistent with enzyme dysfunction and supportive of the diagnosis of NPB. The patient was started on enzyme replacement therapy with olipudase alfa. To our knowledge, this is the first reported case of NPB in which foamy histiocytes with engulfed nucleated cells were a prominent feature in the bone marrow aspirate. One recent study reported finding emperipolesis in some cases of ASMD. Thus, this may be an uncommon but recurrent finding in some NPB patients.

Translocation (14;14)(q11;q32) with immunoglobulin heavy chain (IGH) (14q32) and CCAAT enhancer-binding protein (CEBPE) (14q11) involvement is a rare cytogenetic aberration in B-cell acute lymphoblastic leukemia/lymphoma (B-ALL) associated with a favorable prognosis. This study compares the genetic profile and outcome of a new case with previously reported cases of B-ALL with t(14;14)(q11;q32). In the context of routine diagnostic procedure, a case of B-ALL with t(14;14)(q11;q32) and IGH-CEBPE fusion was identified in a 53-year-old female. The patient achieved complete remission (CR) during induction chemotherapy and remained stable on maintenance therapy for 8 months before passing away from infectious complications, without evidence of leukemic disease. The rapid and sustained treatment response supports the concept that t(14;14)(q11;q32) with IGH and CEBPE involvement may represent a novel B-ALL subgroup distinguished by a favorable prognosis.

Myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) classification requires integration of mutational and cytogenetic data. MDS with biallelic TP53 inactivation (biTP53) is an established category, and MDS and MDS/MPN with biallelic TET2 (biTET2) inactivation is an emerging one. Biallelic genetic inactivation is established by both a mutation and copy loss or copy-neutral loss of heterozygosity (CNLOH) of the other allele, or it can be inferred by identifying multiple or single mutations at a sufficiently high variant allele fraction (VAF). The purpose of this study was to determine whether CNLOH genotyping data is needed to assign patients to biTP53 or biTET2 categories. We studied 157 patients with MDS or MDS/MPN who had sequencing, karyotype, and microarray performed at our institution and assigned patients to biTP53 and biTET2 categories using thresholds established in prior studies. We identified 24 biTP53 and 27 biTET2 patients. In the biTP53 group, 8 patients had > 1 mutation, 9 had a single mutation with 17p loss identified by karyotype and microarray, 2 had a single mutation with 17p loss identified only by microarray, and 3 had a single mutation and 17p CNLOH. All patients with 17p CNLOH had TP53 mutant VAF > 55%. In the biTET2 group, 24 patients had > 1 TET2 mutation with VAFs summing to > 50% and 3 had 4q CNLOH. All patients with 4q CNLOH had TET2 mutant VAF > 50%. In this cohort, CNLOH in 17p and 4q by microarray did not provide information in addition to that provided by inferring the allelic status of TP53 and TET2 using the VAF. This supports that platforms such as optical genome mapping that do not readily detect CNLOH would, in conjunction with sequencing, be adequate to identify MDS and MDS/MPN patients in the biTP53 and biTET2 categories in the great majority of cases.

The most prevalent BCL2 fusion in B-cell lymphoma involves the IGH gene, attributable to the t(14;18)(q32;q21) translocation; this chromosomal abnormality is predominantly observed in follicular lymphoma (FL) and serves as one of its diagnostic hallmarks. In contrast, the fusion of BCL2 with IGL via the t(18;22)(q21;q11) translocation occurs less frequently. To investigate the clinicopathological characteristics associated with t(18;22)/IGL::BCL2, we conducted an analysis of five cases of B-cell lymphoma exhibiting the t(18;22) translocation. These patients underwent comprehensive diagnostic assessments, including pathological examination, flow cytometry, karyotyping, fluorescence in situ hybridization (FISH) testing, and genome-wide mutation analysis. Simultaneously, we conducted a literature review. All five patients in the study were male and diagnosed with chronic lymphocytic leukemia (CLL). Two patients exhibited an isolated t(18;22) chromosomal abnormality, while the remaining three presented with an additional +12 abnormality. Genetic rearrangements involving BCL2 and IGL were observed in all patients. Immunophenotypic analysis revealed no significant differences between classical CLL and cases with the t(18;22)/IGL::BCL2 translocation. Genetic testing conducted on three patients confirmed the presence of IGHV mutations. Of the three patients for whom treatment information was available, one demonstrated treatment indications at the initial diagnosis, one demonstrated treatment indications 14 months later, both of them did not respond to the Bruton's tyrosine kinase (BTK) inhibitor, and another one did not meet criteria for treatment. A comprehensive literature review identified 51 cases of the t(18;22)(q21;q11) translocation, primarily associated with CLL diagnoses. Detailed clinical trajectories were available for seven patients, among whom four required treatments at initial diagnosis, and two exhibited resistance to BTK inhibitors. Based on our case series and literature review, these cases appeared to have shorter time to first treatment (TTFT); however, more studies are needed. The t(18;22) chromosomal translocation, resulting in IGL::BCL2 fusion, is an infrequent occurrence predominantly observed in cases of CLL. This genetic anomaly frequently coexists with trisomy 12. Preliminary data suggest that these cases may have a shorter TTFT, though larger cohorts are needed for validation.

Megakaryocytes (MKs), the precursor cells of platelets, have essential roles in a variety of pathophysiological processes in the bone marrow (BM) niche. Megakaryocytes maintain hematopoietic stem cell microenvironment through inflammatory and immunological responses. The primary objective of this research was to investigate the clinical impact of BM-MK counts in high-risk myelodysplastic syndrome and acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Three hundred and forty-six patients (median age, 42 (15-71) years; male/female, 207/139) participated in the study. Based on the BM-MK counts on day + 100 of alloHSCT, the study population was classified into normal/high-MK⁺¹⁰⁰ and low-MK⁺¹⁰⁰ groups. The probabilities of progression-free survival (PFS) and overall survival (OS) were significantly better in the normal/high-MK⁺¹⁰⁰ group (p < 0.001, p < 0.001). Nonrelapse mortality was found to be reduced in the same group of patients (p = 0.012). BM-MK⁺¹⁰⁰ count, which was indicated to be a predictor for relapse after alloHSCT (p = 0.018), represented a considerable impact on PFS and OS (p = 0.017, p = 0.009). Megakaryocytes have regulatory roles in association with a comprehensive cytokine network in the BM microenvironment. Although the localization of MKs may be determinative for their spectrum of efficacy, distinct biological subgroups may also help to clarify the heterogeneity of their functional features. Prospective efforts in larger populations are required to illuminate the potential prognostic role of MKs in alloHSCT recipients.

"Dry tap" refers to the failed aspiration of bone marrow hematopoietic elements. Faulty technique is frequently blamed for a dry tap. But, often, the dry tap is associated with an underlying bone marrow pathology. This study aimed to evaluate the causes of dry tap and assess its clinical relevance. This retrospective observational study was conducted in the Department of Pathology over a period of 1 year, from 1 November 2023 to 31 October 2024. A total of 1327 bone marrow aspirates were reviewed. The definitive diagnosis was established by examining the trephine biopsy. A total of 267 aspirates, for which biopsy was not performed or which had suboptimal biopsies, were excluded from the study. A total of 1060 cases were taken for the final study. We attributed 125 (11.8%) cases that were aparticulate and grossly hemodiluted to a "dry tap." Of these, only 20 (16%) of the dry tap could be attributed to improper or faulty technique because their trephine biopsy was adequate and satisfactory for evaluation. An underlying bone marrow pathology, which could plausibly be the reason for dry tap, was identified in 105 (84%) patients. The most common cause was found to be acute leukemia, accounting for 32.8% of the cases. The laboratories should periodically review the cases yielding a dry tap, and if the corresponding biopsies are adequate, then one must focus on improving the technique of bone marrow aspiration. Moreover, a dry tap should serve as a diagnostic alert rather than a basis for disregard of the operator's technique.