Journal of Hematopathology最新文献

Somatic IKZF1 alterations are common in B-lymphoblastic leukemia (B-ALL) and are generally associated with poor outcomes. However, rare germline missense and nonsense variants were found to predispose individuals to leukemia. We report a case of B-ALL in a female patient with a germline IKZF1 deletion. The deletion was detected with diagnostic fluorescence in situ hybridization studies and persisted after treatment at a high percentage of nuclei discordant to that of the residual disease. A chromosomal microarray analysis was subsequently performed on a peripheral blood specimen which indicated that the deletion was most likely germline in origin and was confirmed by buccal and skin fibroblast analysis. This report emphasizes the increased predisposition of leukemia for individuals who have germline deletions of IKZF1.

Hypereosinophilia is uncommon in the pediatric population and may be associated with either primary or secondary conditions. In a very small proportion of cases (less than 1%), it forms part of the initial presentation of acute lymphoblastic leukemia (ALL). More frequently, hypereosinophilia appears before overt leukemia symptoms develop, which can delay diagnosis and place affected children at increased risk due to the lack of early intervention. We recently reviewed a case of 6½-year-old female who presented with hypereosinophilia and no circulating blasts. Bone marrow aspirate showed significant prominence of eosinophils and their precursors with ~ 2% blasts on morphology. Bone marrow biopsy was received for review and showed a significant burden of immature cells/blasts which on immunohistochemistry was revealed as B-acute lymphoblastic leukemia (B-ALL). Cytogenetics by fluorescence in situ hybridization (FISH) showed IGH rearrangement while the routine karyotyping as well as next-generation sequencing (NGS) were both negative for any genetic aberrancy. This case highlights the importance of a thorough marrow evaluation in pediatric eosinophilia and discusses the challenges in identifying cryptic rearrangements that are not evident on standard cytogenetic and molecular panels.

Granulomas in a bone marrow biopsy are like gold dust. Numerous studies have reported that the incidence of granulomas in bone marrow biopsies ranges from 0.3 to 2.2%. In developing countries such as India, tuberculosis is the most common cause of bone marrow granulomas; nonetheless, the etiologic spectrum includes a broad range of disorders. To better understand granulomatous inflammation in the bone marrow and prevent its misinterpretation, this study aims to highlight the variety of disorders, including infectious and non-infectious causes, that are linked to this finding. This is a retrospective study which was conducted in the Department of Pathology and Laboratory Medicine at All India Institute of Medical Sciences, Rishikesh. Bone marrow biopsies with granulomatous inflammation reported over a period of 3 years, from 2022 to 2024, were reviewed for their clinical and laboratory features and included in this study. We identified 22 cases among 3485 bone marrow biopsies, representing an incidence of 0.63% in the series. Among the 22 patients, the most common etiology was infectious (59.1%), followed by malignancy (36.34%), and sarcoidosis (4.5%). Marrow granulomas should prompt a thorough investigation into the underlying cause. It is hoped that this article would help in guiding the investigation for potential causes.

POEMS syndrome is a rare paraneoplastic disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Although Castleman disease (CD) is observed in up to 30% of POEMS cases, it is typically of the multicentric subtype (MCD) and identified during the initial diagnostic workup. Unicentric Castleman disease (UCD), by contrast, is rarely associated with POEMS and has not been previously reported following POEMS remission. We present the case of a 39-year-old woman who was diagnosed with POEMS syndrome based on clinical, radiographic, and histopathologic findings, including an IgA lambda-restricted plasma cell neoplasm, sclerotic bone lesions, thrombocytosis, and markedly elevated VEGF levels. She achieved clinical and biochemical remission after 17 cycles of daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Eighteen months later, she developed a tender inguinal lymph node with no systemic signs of relapse. Excisional biopsy revealed histopathologic features consistent with UCD, including IgA lambda-restricted plasma cells, alternating hyperplastic and atretic follicles, and a "lollipop" lesion. To our knowledge, this is the first reported case of UCD arising after remission of POEMS syndrome. The presence of clonally restricted plasma cells within the lymph node, matching the original neoplastic clone, raises the possibility of localized residual disease rather than a de novo process. This case highlights the need for ongoing vigilance in POEMS patients, as late-onset lymphoproliferative disorders such as UCD may emerge in the absence of traditional disease markers or systemic relapse.

Familial erythrocytosis type 3 (ECYT3) is a rare condition caused by loss of function germline mutations in the prolyl hydroxylase domain-2 (PHD2), a regulator in the hypoxia-sensing pathway. Although mutations in PHD2 have been previously described, this particular variant lacks clinical characterization and presents with an aggressive course. We report the case of a patient with vasomotor symptoms and elevations in hematocrit (HCT) and hemoglobin (Hgb) despite frequent therapeutic phlebotomy. He had a family history of erythrocytosis spanning four generations. Germline genetic testing revealed a rare pathogenic variant of PHD2, confirming a diagnosis of ECYT3. Therapeutic phlebotomy yielded only transient Hgb and HCT reductions and only partial symptomatic control. This case highlights the diagnostic challenges and limitations of current treatments for hereditary erythrocytosis and underscores the need for symptom-centered management strategies. Furthermore, we highlight a gap in the literature around the pathophysiology and management of ECYT3.

Factor XII (FXII) deficiency is a rare autosomal recessive disorder characterized by prolonged activated partial thromboplastin time (APTT) without bleeding diathesis. Genetic diagnosis is critical to avoid unnecessary interventions. An 8-year-old boy with incidentally prolonged APTT (> 170 s) was referred for preoperative evaluation. FXII activity was 7.7%. No personal/family history of bleeding or thrombosis was reported. Genetic testing revealed F12: c.1092dup homozygous mutations in F12, inherited from his parents. Familial segregation confirmed autosomal recessive transmission. The identification of these mutations expands our understanding of the genetic basis of factor XII deficiency and emphasizes the importance of genetic diagnosis in such cases.

Given its strong correlation with disease progression and risk stratification, CD200 has emerged as a pivotal biomarker in chronic lymphocytic leukemia (CLL). Elevated CD200 expression, strongly linked to CLL progression, underscores its diagnostic and therapeutic potential. In this case-control study, we evaluated CD200 expression levels in CLL patients and analyzed their correlation with key clinicopathological features, investigating its potential as a critical biomarker for diagnosis and follow-up strategies. Peripheral blood samples from 27 CLL patients and five healthy individuals were stained by fluorochrome-conjugated antibodies against CD19 and CD200 markers, followed by flow cytometry. Data analysis compared CD200 expression levels among CLL patients at four stages and in the healthy control group. CD200 expression levels in CLL patients' lymphocytes significantly exceeded those observed in the healthy control group (P < 0.0001). Within the patient group, expression levels progressively increased from low-risk to high-risk classifications, with statistically significant differences between each category (P < 0.0001). Furthermore, a strong positive association was identified between CD200 expression and disease clinical stage (r = 0.758, P < 0.0001), WBC count (r = 0.705, P < 0.0001), and lymphocyte percentage (r = 0.544, P = 0.009). Conversely, a strong inverse correlation was observed with neutrophil count (r =  - 0.55, P = 0.008). Overall, CD200 assessment may serve as a valuable prognostic marker in CLL, providing insight into disease progression and aiding in treatment monitoring.

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.