Journal of Hematopathology最新文献

Alpha globin chain variants constitute a very small fraction of the total hemoglobinopathy cases. Their rarity and the often-unfamiliar elution times/patterns in high performance liquid chromatography (HPLC) that mimic those of normal hemoglobin (Hb) fractions and/or known beta globin variants render their primary diagnosis difficult. We describe here Hb Fontainebleau, a rare alpha globin chain variant, in an adult female that eluted in the HbA2 window in a less commonly used HPLC platform, Lifotronic H8, thereby causing difficulties in the diagnosis. The matter was resolved by running the sample on a more commonly used platform wherein the abnormal Hb yielded a familiar elution time and pattern known to be associated with Hb Fontainebleau. This was further confirmed by gene sequencing, which showed a Codon 21 (G → C); HBA2:c.64G > C (or HBA1) mutation. A literature search failed to reveal any published case of the unique elution pattern of Hb Fontainebleau on Lifotronic H8 HPLC platform and the associated diagnostic challenges. An increasing use of the newer HPLC platforms calls for greater awareness of these issues.

Plasma cell neoplasms encompass a spectrum of disorders characterized by the clonal proliferation of plasma cells. Plasmablastic transformation in these neoplasms poses diagnostic and clinical challenges due to its aggressive nature and morphological overlap with other malignancies, including plasmablastic lymphoma (PBL). We report a case of discordant extramedullary plasmablastic transformation in a 55-year-old HIV-negative female presenting with an oral lesion diagnosed as plasmablastic plasmacytoma. Initial imaging indicated localized disease without systemic involvement. Despite undergoing chemotherapy and achieving a partial response, the patient developed osteolytic lesions 2 years later. Subsequent pathology evaluation confirmed mature plasma cell myeloma (PCM) morphology. Whole exome sequencing (WES) and whole RNA expression analysis revealed shared mutations (PTPN13, KRAS, LTK) and a MYC::BMP6 translocation in both lesions, supporting a clonal relationship. Additionally, the oral plasmablastic lesion revealed a KLHL6 mutation and an extra MYC::IGL translocation, which were absent in the tibial lesion. The KLHL6 mutation has not been previously reported in studies of discordant extramedullary plasmacytoma with plasmablastic transformation. This case highlights the diagnostic complexity of plasmablastic plasmacytoma presenting as the initial manifestation of plasma cell myeloma. It underscores the necessity of a thorough evaluation, including bone marrow biopsy, to accurately differentiate plasmablastic transformation from PBL and ensure accurate diagnosis and appropriate management.

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.