Bone Marrow Biopsy Research Articles

Intracapillary monoclonal IgM deposits disease with massive pseudothrombi: A clinicopathologic study of 4 cases and literature review.

Intracapillary monoclonal IgM deposits disease (ICMDD) has long been considered a hallmark of Waldenström macroglobulinemia (WM) nephropathy. Intracapillary immunoglobulin thrombi are the characteristic features of cryoglobulinemic glomerulonephritis. Here, we reported 4 cases of ICMDD with massive pseudothrombi but without WM or cryoglobulinemia. We retrospectively analyzed the clinical and pathologic features of patients diagnosed with ICMDD with massive pseudothrombi. A total of 4 patients (2 men and 2 women) aged 62 to 73 years were enrolled in this study. Microscopic hematuria, edema, and renal insufficiency were present in all patients, along with low serum C3 and C4 in 2 patients. Hematologic examination showed abnormal serum free light chain ratios in all patients and high levels of serum IgM in 3 patients. IgM-κ monoclonal band was identified by serum immunofixation electrophoresis in 3 patients. One patient was diagnosed with small B-cell lymphoma by bone marrow aspiration. Renal biopsy specimen showed massive periodic acid-Schiff-positive hyaline thrombi in the glomerular capillary lumens and also less mesangial, subendothelial, and subepithelial deposits on light microscopy. Immunofluorescence indicated positive staining for IgM (++) and κ light chain staining in the glomerular capillary lumens, capillary walls, and mesangium in all patients. By electron microscopy, the glomerular capillary lumens were filled with homogeneous high-electron-dense deposits without substructure. Two patients were treated with prednisone combined with cyclophosphamide, and 2 received plasma cell-targeted chemotherapy. One patient achieved partial renal remission. Intracapillary monoclonal IgM deposits disease is a rare disease and not always related to WM. Most patients have IgM monoclonal immunoglobulinemia; renal biopsy specimens mainly show a large number of pseudothrombi in the glomerular capillary lumens. Cyclophosphamide is effective in some patients.

Childhood Langerhans cell histiocytosis hematological involvement: severity associated with BRAFV600E loads.

Hematological involvement (HI) is one of the life-threatening risk organs (ROs) in Langerhans cell histiocytosis (LCH). Lahey criteria have defined HI since 1975 as hemoglobin <10 g/dL and/or platelets <100 G/L and/or leukopenia (white blood cell count <4 G/L) and/or neutrophils <1.5 G/. Among the 2313 patients <18 years old enrolled in the French National Histiocytosis Registry (1983-2023), 331 developed HI (median age at diagnosis: 1 year); median follow-up lasted 8.1 years. Bone-marrow aspirate smears and biopsies may show reactive histiocytes, hemophagocytosis or myelofibrosis but never confirm the diagnosis. Fifty-eight (17%) patients developed macrophage-activation syndrome, sometimes related to acute Epstein-Barr virus or cytomegalovirus infection, sometimes months before typical LCH manifestations appeared. Hemoglobin and platelet thresholds for initiating transfusion(s) appear to accurately distinguish 2 groups: mild HI (MHI; >7 g/dL and >20 G/L, respectively) and severe HI (SHI; ≤7 g/dL and ≤20 G/L). Each entity has different organ involvements, laboratory parameters, mutational status, blood BRAFV600E loads, drug sensitivities and outcomes (respective MHI and SHI 10-year survival rates: 98% and 73%). Since 1998, mortality first declined with combination Cladribine-cytarabine therapy, and then with mitogen-activated protein-kinase inhibitors since 2014. Forty-one (12%) patients developed neurodegenerative complications that have emerged as a risk for long-term survivors. These results suggest limiting the HI-RO definition to SHI, as it encompasses almost all medical complications of LCH. Future clinical trials might demonstrate that targeted-therapy approaches would be better adapted for these patients, while MHI can be managed with classic therapies.

Identification of CD141+vasculogenic precursor cells from human bone marrow and their endothelial engagement in the arteriogenesis by co-transplantation with mesenchymal stem cells

BackgroundCritical limb ischemia (CLI) is a condition characterized by insufficient blood flow to the lower limbs, resulting in severe ischemia and potentially leading to amputation. This study aims to identify novel vasculogenic precursor cells (VPCs) in human bone marrow and evaluate their efficacy in combination with bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of CLI.MethodsEx vivo cultured VPCs and BM-MSCs from bone marrow were characterized and their effects on neovascularization and long-term tissue regeneration were tested in a mouse CLI model.ResultsVPCs, expressing high levels of hepatocyte growth factor and c-MET, were identified from human bone marrow aspirates. These cells exhibited strong vasculogenic capacity in vitro but possessed a cellular phenotype distinct from those of previously reported endothelial precursor cells in circulation or cord blood. They also expressed most surface markers of BM-MSCs and demonstrated multipotent differentiation ability. Screening of 376 surface markers revealed that VPCs uniquely display CD141 (thrombomodulin). CD141+VPCs are present in BM aspirates as a rare population and can be expanded ex vivo with a population doubling time of approximately 20 h, generating an elaborate vascular network even under angiogenic factor-deficient conditions and recruiting BM-MSCs to the network as pericyte-like cells. Intramuscular transplantation of a combination of human CD141+VPCs and BM-MSCs at a ratio of 2:1 resulted in limb salvage, blood flow recovery, and regeneration of large vessels in the femoral artery-removed CLI model, with an efficacy superior to that of singular transplantation. Importantly, large arteries and arterioles in dual cell transplantation expressed human CD31 in the intima and human α-smooth muscle actin in media layer at 4 and 12 weeks, likely indicating their lineage commitment to endothelial cells and vascular smooth muscle, respectively, in vivo.ConclusionDual-cell therapy using BM-derived CD141+ VPCs and BM-MSCs holds potential for further development in clinical trials to treat peripheral artery disease and diabetic ulcers.

From Cord to Cure: Repurposing Biological Waste for UAE's Health Revolution with Umbilical Cord Stem Cell Therapy

In the UAE, current hospital policies mandate the disposal of biological waste, such as umbilical cords. However, this tissue represents a valuable source of therapeutic material like mesenchymal stem cells (MSCs) and their secretome. The disposal of this valuable therapeutic material imposes a significant burden on public health. In the United States alone, approximately 18,000 people per year are diagnosed with diseases that could be ameliorated with stem cell therapy. These individuals often remain untreated due to the lack of available stem cells, as current methods for MSC obtention, such as Bone Marrow-MSCs, require an invasive bone marrow aspirate procedure, which is painful and can pose risks to donors, including infection and prolonged recovery times. This paper advocates for policy reform to facilitate the collection, storage, and utilization of umbilical cords. By addressing regulatory barriers and implementing standardized protocols, hospitals in the UAE can not only contribute to advancements in regenerative medicine but also solidify the nation’s position as a leader in this emerging field, ultimately improving patient outcomes and reducing the disease burden both locally and regionally. This is particularly relevant given the significant burden of cardiovascular diseases and type 2 diabetes mellitus (T2DM) in the UAE, where 17.3% of the population aged 20 to 79 is affected with T2DM. Cardiovascular diseases and T2DM are few of the many disorders that can benefit from MSC therapy. Utilizing umbilical cord biowaste for such diseases can further build the UAE’s status as a hub for medical tourism and accentuate it’s growing prominence in the field of regenerative medicine.

T cell and soluble co-inhibitory receptor expression in patients with visceral leishmaniasis are markers of treatment response and clinical outcome

Abstract Background Co-inhibitory receptors (immune checkpoints) regulate activated immune cells. Their expression on T cells can limit host defense. We hypothesized that chronic Leishmania donovani infection in patients with visceral leishmaniasis (VL) leads to expression of co-inhibitory receptors that could be markers of treatment response and clinical outcome. Method A prospective cohort of 21 subjects with VL (7 with HIV coinfection) and 10 controls was established to measure T cell expression of co-inhibitory receptors (PD-1, Tim-3, LAG-3, CTLA-4, and TIGIT) by flow cytometry in discarded remnants of diagnostic splenic or bone marrow aspirates and peripheral blood collected before and after treatment. Plasma levels of soluble co-inhibitory proteins (sPD-1, sTim-3, sLAG-3, and sCTLA-4), and selected cytokines were determined by immunoassay. Results Expression of co-inhibitory receptors in peripheral blood T cells generally reflected findings in spleen and bone marrow aspirates. PD-1 and Tim-3 were upregulated in CD4+ T cells in HIV-negative and HIV-positive subjects with VL compared to controls. CD8+ T cells from HIV-negative subjects with VL displayed a similar pattern. Plasma levels of sPD-1 and sTim-3 were also greater in VL patients than controls. CD8+ and CD4+ T cells co-expressing PD-1 and Tim-3 showed considerable decline with treatment. Mortality in HIV-negative VL patients was associated with increased CD8+ T cells co-expressing Tim-3 and PD-1, triple positive CD4+ and CD8+ T cells (PD-1+Tim-3+LAG-3+), and elevated sLAG3. Conclusion Tim-3 and PD-1 expression on CD4+ and CD8+ T cells, and increased plasma sLAG-3, were markers of treatment response and clinical outcome in patients with VL.

FLAER Revealed Normally Expected Non-PNH FLAER-Dim Immature Myeloid Cells (CD117+/CD34-) In Bone Marrow Aspirates and Could Be Utilized as a Marker of Hierarchical Hematopoiesis.

Fluorescently labeled aerolysin (FLAER) is widely used for the identification of paroxysmal nocturnal hemoglobinuria (PNH) clones in peripheral blood (PB) samples. However, there are only a few reports on the differential fluorescent intensity of FLAER in normal bone marrow (BM) cell subpopulations. The purpose of this study was to evaluate FLAER expression during normal and pathological hematopoiesis, to map the critical existence of non-PNH FLAER-dim cells. A total of 54 BM aspirates were prospectively analyzed with FLAER-based flow cytometric (FC) protocols, during their routine work-up. These were obtained from patients with the following diagnoses: PNH (3), infections/reactive (5), myelodysplastic syndromes (MDS) (7), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) (4), chronic myelogenous leukemia (CML) (3), acute myelogenous leukemia (AML) at diagnosis (20), AML in measurable residual disease (MRD) assessment (7), and B-cell acute lymphoblastic leukemia (B-ALL) in MRD assessment (5). The applied protocols consisted of FLAER, HLA-DR, CD14, CD33, CD34, CD66b, CD38, CD117, CD64, CD45, and FLAER, CD66c, CD14, CD33, CD34, CD66b, CD123, CD16, CD64, and CD45, respectively. FLAER expression was assessed in CD34++/CD38- and CD34+/CD38+ stem cells, CD34-/CD117+/HLA-DR+/CD33+ myeloid precursors, and CD64+/CD14-/HLA-DR+ monocyte precursors but also in mature myeloid cells. All patients revealed an intermediate FLAER intensity in CD34++/CD38- stem cells, with a discrete FLAER-negative subpopulation observed only in maturing CD34+/CD38+ stem cells of patients with PNH. The lowest FLAER intensity was noticed in CD34-/CD117+/HLA-DR+/CD33+ myeloid precursors, not only in patients with PNH but also in PNH-negative BM aspirates. An ascending FLAER intensity was further observed during monocytic and granulocytic maturation, with a discrete FLAER-negative population in CD64+/CD14-/HLA-DR+ monocyte precursors and maturing neutrophils and monocytes of patients with PNH only. The maturation pattern of FLAER expression was further confirmed in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid (ATRA), where FLAER was concurrently upregulated with CD66b in a consecutive series of PB samples tested over a 20-day-period after diagnosis. The application of FLAER in PNH-positive and PNH-negative reactive or malignant BM aspirates identified normally expected non-PNH FLAER-dim CD34-/CD117+/HLA-DR+/CD33+ myeloid precursors in all samples. A specific FLAER-associated maturation pattern was observed, which is proposed for further study within MRD and diagnostic protocols.

Myeloprotective potential of leaves extract fractions of Cnidoscolus aconitifolius in myelo suppression

Chemotherapy has been associated with myelosuppression. Myeloprotection is the main remedy to myelosuppression. Nature has been endowed with natural molecules rich in therapeutic components and one of such nature is Cnidoscolus aconitifolius (CA) which has been reported to be rich in antioxidants. The aim of the study was to investigate myelo-protective potential of CA in myelo-suppressed animal model. Albino rats (n = 32) were divided into 8 groups of 4 rats each labelled A-H out of which 7 groups (B-H) were induced intraperitoneally for myelosuppression with cyclophosphamide (CP) and only 6 groups (C-H) were treated with CA extracts for four weeks. Group A served as normal control, groups B-H was induced for myelosuppression with cyclophosphamide. Group B served as myelo-suppressed control, groups C, D and E, received 100mg/kg body weight (bw) methanol fractions of CA while groups F, G and H received 200mg/kg body weight methanol fractions of CA. Two milliliters of blood were collected into ethylenediaminetetraacetic acid containers for total white blood cell count and absolute granulocyte count on days 3, 12 and 21 using mindray auto analyser BC-360. On day 30, bone marrow (BM) was harvested from one rat per group for BM examination and cellularity. Following administration of (CP), myelosuppression set in as observed in significant decreased (P &lt; 0.05) in total white blood cell (TWBC) count and absolute granulocyte count. Extract fractions of CA caused significant increase (P &lt; 0.05) in TWBC count and absolute granulocyte count in all the treated groups on days 12 and 21 compared with baseline. Bone marrow cellularity of all the treated groups revealed normal myeloid erythroid ratio indicating normal marrow cellularity. The findings in this study suggested myelo-protection by Cnidoscolus aconitifolius against cyclophosphamide induced myelosuppression.

Central nervous system crystal-storing histiocytosis: A case report and literature review.

Crystal-storing histiocytosis (CSH) is a rare form of histiocytosis with intralysosomal accumulations of immunoglobulins or paraproteins that aggregate as crystals. Central nervous system (CNS) involvement of CSH is uncommon but should be considered in cases of persistent parenchymal enhancement on neuroimaging. We describe one local case of CNS CSH and 10 additional cases identified by literature review. Among 11 CSH patients, lesions involved either the dura (2/11) or brain parenchyma (9/11). Two cases had leptomeningeal enhancement. One case had spinal cord involvement. Two cases were associated with marginal zone lymphoma; one case was associated with an immunoglobulin A-plasma cell dyscrasia. Eight of 11 cases had outcome data available: 7/8 cases had clinical and/or radiological improvement and 1/8 had radiological stability. Central nervous system involvement of CSH is rare. Potential cases should be comprehensively evaluated for lymphoma or myeloma with positron emission tomography/computed tomography (CT) of the body or alternatively, CT of the chest, abdomen, pelvis and nuclear bone scan, bone marrow biopsy, serum protein electrophoresis, and cerebrospinal fluid protein electrophoresis. Treatment is targeted toward the underlying malignancy.

Unusual Presentation of Myeloid Sarcoma as Thigh Mass

IntroductionMyeloid sarcoma (MS) is a tumor containing myeloid blasts, with or without maturation, involving any anatomical site other than the bone marrow. It can occur de novo or following a hematological malignancy. CaseWe report a 6-year-old female who presented with fever and a rapidly enlarging left thigh mass. The initial provisional diagnosis considered was tubercular hip arthritis with an abscess, but imaging investigations suggested neoplastic swelling. A biopsy of the mass showed a malignant small-round cell tumor. Bone marrow aspiration revealed the diagnosis of acute myeloid leukemia without the presence of blasts in the peripheral smear. ConclusionMS is a rare malignancy. The diagnosis is often delayed due to a lack of clinical suspicion and the absence of blasts in peripheral blood. This report aims to enhance the awareness of pediatric nurse practitioners that MS should also be considered as a differential for an extremity mass.

A novel pathogenic variant in ALAS2 gene in young Indian male with X-linked sideroblastic anemia: a case report

BackgroundCongenital sideroblastic anemias are heterogenous disorders with variable phenotypic expression. The most common form is X-linked and is caused by pathogenic variants of the 5-aminolevulinate synthase 2 (ALAS2) enzyme of heme biosynthesis.Case presentationA 19 year old Indian young male presented with severe microcytic anemia. Bone marrow examination revealed ring sideroblasts. Using second generation sequencing, a novel pathogenic variant (Arg204Leu) was found in exon 5 of the ALAS2 gene, establishing the diagnosis of X-linked sideroblastic anemia. On treatment with oral pyridoxine supplement the patient’s hemoglobin level returned to normal.ConclusionsMore than 100 pathogenic variants in the ALAS2 gene have been reported to date. The Arg204Leu variant in our case adds to the XLSA pathogenic variant data base. The associated anemia is fully responsive to pyridoxine supplementation.

Diagnosis of myelodysplastic syndromes: the classic and the novel.

The Myelodysplastic syndromes (MDS) are a heterogenous group of clonal bone marrow (BM) stem cell myeloid neoplasms, characterized by bone marrow (BM) dysplasia, macrocytic anemia or cytopenia with a tendency for leukemic transformation. The suspicion of MDS is raised by a typical but not specific clinical picture and routine labs, but the gold standard for MDS diagnosis is still BM examination with the presence of uni-or multi-lineage dysplasia and blast percentage, together with exclusion of other reasons. Cytogenetics is also a part of the diagnostic process. Flow cytometry and genetics are helpful but are not always mandatory for MDS diagnosis. This review summarizes the current steps in the diagnostic approach for a patient suspected of having MDS. We also describe new concepts that use non-invasive diagnostic technologies, especially digital methods as well as peripheral blood genetics. The hope is that one day these will mature, be introduced into clinical practice, and perhaps in many cases even replace the invasive BM biopsy.

Modelling post-chemotherapy stem cell dynamics in the bone marrow niche of AML patients

Acute myeloid leukemia (AML) is a stem cell-driven malignancy of the blood forming (hematopoietic) system. Despite of high dose chemotherapy with toxic side effects, many patients eventually relapse. The “7+3 regimen”, which consists of 7 days of cytarabine in combination with daunorubicin during the first 3 days, is a widely used therapy protocol. Since peripheral blood cells are easily accessible to longitudinal sampling, significant research efforts have been undertaken to characterize and reduce adverse effects on circulating blood cells. However, much less is known about the impact of the 7+3 regimen on human hematopoietic stem cells and their physiological micro-environments, the so-called stem cell niches. One reason for this is the technical inability to observe human stem cells in vivo and the discomfort related to bone marrow biopsies. To better understand the treatment effects on human stem cells, we consider a mechanistic mathematical model of the stem cell niche before, during and after chemotherapy. The model accounts for different maturation stages of leukemic and hematopoietic cells and considers key processes such as cell proliferation, self-renewal, differentiation and therapy-induced cell death. In the model, hematopoietic (HSCs) and leukemic stem cells (LSCs) compete for a joint niche and respond to both systemic and niche-derived signals. We relate the model to clinical trial data from literature which longitudinally quantifies the counts of hematopoietic stem like (CD34+CD38-ALDH+) cells at diagnosis and after therapy. The proposed model can capture the clinically observed interindividual heterogeneity and reproduce the non-monotonous dynamics of the hematopoietic stem like cells observed in relapsing patients. Our model allows to simulate different scenarios proposed in literature such as therapy-related impairment of the stem cell niche or niche-mediated resistance. Model simulations suggest that during the post-therapy phase a more than 10-fold increase of hematopoietic stem-like cell proliferation rates is required to recapitulate the measured cell dynamics in patients achieving complete remission. We fit the model to data of 7 individual patients and simulate variations of the treatment protocol. These simulations are in line with the clinical finding that G-CSF priming can improve the treatment outcome. Furthermore, our model suggests that a decline of HSC counts during remission might serve as an indication for salvage therapy in patients lacking MRD (minimal residual disease) markers.

Challenges in the diagnostics of mantle cell lymphoma in an elderly comorbid patient

We present a case of a rare lymphoproliferative disease diagnosed while differentiating between the causes of exudative-constrictive pericarditis. An 83-year old man was hospitalized with shortness of breath, edema and newly diagnosed atrial fibrillation (AF). Initially, the signs and symptoms were interpreted as manifestations of heart failure due to old myocardial infarction, arterial hypertension and AF. However, no significant systolic or diastolic dysfunction of the left ventricle and valve disease were identified and natriuretic peptide level was normal. Despite treatment, dyspnea and edema persisted, and pleural effusion (requiring drainage) and pericardial effusion increased. Repeated echocardiography showed signs of exudative-constrictive pericarditis. We consequently excluded the infectious (tuberculosis) and non-infectious (electrolyte disorders, hypothyroidism, solid tumors) etiologies of effusion. Taking into account the long-standing mediastinal lymphadenopathy (the patient had been previously examined, but the cause not identified), anemia, episodes of low-grade fever, weight loss, and polyneuropathy, a lymphoproliferative disease was suspected. Serum protein electrophoresis identified an M spike in the gamma globulin region. Immunophenotyping of peripheral blood lymphocytes and immunohistochemical examination of bone marrow confirmed the diagnosis of mantle cell lymphoma. The patient was referred for specialized treatment. At 5 months of the follow-up, the therapy was successful, the patient was stable with no cardiac complaints, no edema, and no new AF episodes. The case demonstrates the need to strictly follow differential diagnostic algorithms to identify the causes of nonspecific symptoms beyond one medical specialty.

Autopsy diagnosis of diffuse intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC), a severe liver cancer, makes up to 20% of all hepatic malignancies and is difficult to diagnose early due to its often asymptomatic nature. This case report documents a rare presentation of ICC with multiple diffuse nodules not previously recorded in medical literature. A 65-year-old man with no significant medical history presented with back pain, anorexia, and significant weight loss. Elevated tumor markers and enlarged lymph nodes were observed, though imaging did not reveal a primary liver mass. Diagnostic efforts, including computed tomography and positron emission tomography scans and biopsies of lymph nodes and bone marrow, suggested adenocarcinoma of unknown primary origin. A definitive diagnosis was only made post-mortem, revealing multiple diffuse nodules in the liver identified as ICC, marking a rare presentation without a primary mass. This case highlights the diagnostic challenges posed by atypical ICC manifestations, where typical imaging does not indicate a primary mass, delaying diagnosis and treatment. The findings emphasize the importance of considering ICC in differential diagnoses in cases of unknown primary adenocarcinoma with liver involvement. The discovery of ICC with diffusely infiltrative nodules underscores the necessity for comprehensive diagnostic evaluations in patients presenting with nonspecific systemic symptoms and abnormal liver findings.

Diagnostic and therapeutic challenges in rapidly progressing cardiac amyloidosis: a literature review based on case report

IntroductionCardiac amyloidosis is a rarely reported and potentially fatal variant of the systemic disease. Its early diagnosis could potentially lead to significantly improved clinical outcomes.Case presentationA 56-year-old female presented with dyspnea and palpitations. Her physical exam and non-invasive evaluation with cardiac magnetic resonance imaging (CMRI) revealed restrictive cardiomyopathy, and the bone marrow biopsy results showed systemic amyloidosis.DiscussionThe diagnosis of cardiac amyloidosis is not always straightforward, and delay can cause the progression of the disease and an increased risk of morbidity and mortality. Electrocardiograms, echocardiograms, cardiac magnetic resonance imaging, and histopathologic evaluation are the main methods for diagnosing cardiac amyloidosis. The treatment consists of controlling heart failure symptoms and disease-modifying interventions, including medical and surgical therapeutic methods.Clinical learning point (conclusion)Cardiac involvement is the main cause of death in systemic amyloidosis. Early suspicion, diagnosis, and treatment are crucial in improving patients’ survival. CMRI can play an essential role in the diagnosis of cardiac Amyloidosis. A graphical abstract is provided for visual summary.Graphical

Case Report on Griscelli Syndrome with Hemophagocytic Lymphohistiocytosis

Objective: This case report was written with the intention of educating pediatric caregivers regarding the early detection and management of Griscelli Syndrome type 2 (GS2), thereby preventing fatal consequences, and to draw light on the necessity for premarital genetic counselling and education in public. Case Report: A two months and 7 days old male baby presented with tachycardia, fever, abdominal distension, cough, loose stools, and vomiting. Head to toe examination showed hypo-pigmented hair with silvery grey eyebrows and eyelashes. Bone marrow aspiration showed increased histiocytes exhibiting haemophagocytosis. Suspecting Griscelli Syndrome, genetic test was done which indicated RAB27A gene mutations, thereby confirming the GS2 diagnosis. The child was treated with 2 litres of oxygen with nasal prong, meropenem, fluconazole, dexamethasone and packed red blood cell transfusion. In view of worsening sepsis baby was given with vancomycin, tigecycline and cyclosporine and later intubated. Conclusion: Consanguineous marriages are common in India and are one of the major reason for autosomal recessive disorders like GS2 in newborns. This highlights the need of both premarital genetic counseling and education among public. Keywords: Hypopigmented hair, haemophagocytosis, abdominal distension, RAB27A mutation

Leukocytosis and thrombocytosis after splenectomy: expected finding, infection, or something else: a case report

BackgroundLeukocytosis and thrombocytosis often follow splenectomy in blunt trauma patients, complicating the postoperative identification of infection. While the platelet count to white blood cell ratio provides diagnostic assistance to discern between expected laboratory alterations and infection, diagnoses such as leukemia are often overlooked.Case presentationA 53-year-old Hispanic male presented with abdominal pain, nausea, tachycardia, and focal peritonitis 4 days after being assaulted and struck multiple times in the abdomen. Initial white blood cell count was 38.4 × 109/L, platelet count was 691 × 109/L, and lipase was 55 U/L. Computed tomography abdomen/pelvis demonstrated a hematoma encasing the distal pancreas and abutting the stomach and colon. Emergent laparotomy revealed a nearly transected pancreas and devascularized colon, necessitating a distal pancreatectomy, splenectomy, and colonic resection with primary anastomosis. Postoperatively, he had a persistently elevated leukocytosis, thrombocytosis, segmented neutrophils, eosinophilia, and basophilia (peak at 70, 2293, 64, 1.1, and 1.2 × 109/L, respectively). Despite sepsis workup, including repeat computed tomography, no source was identified. Hematology/oncology was consulted for concern for hematologic etiology, with genetic testing and bone marrow biopsy performed. The diagnosis of breakpoint cluster–Abelson gene-positive chronic myeloid leukemia was made based on genetic tests, including polymerase chain reaction and fluorescence in situ hybridization analysis, which confirmed the presence of the Philadelphia chromosome. Bone marrow biopsy suggested a chronic phase. The patient was treated with hydroxyurea and transitioned to imatinib.ConclusionsThrombocytosis following splenectomy is a common complication and a plate count to white blood cell count ratio < 20 indicates infectious etiology. A significantly elevated white blood cell count (> 50 × 109/L) and thrombocytosis (> 2000 × 109/L) may suggest something more ominous, including chronic myeloid leukemia , particularly when elevated granulocyte counts are present. Chronic myeloid leukemia workup includes peripheral smear, bone marrow aspiration, and determination of Philadelphia chromosome. Post-splenectomy vaccines are still indicated within 14 days; however, the timing of immunization with cancer treatment must be considered. Tyrosine kinase inhibitors are the first-line therapy and benefits of pretreatment with hydroxyurea for cytoreduction remain under investigation. Additionally, tyrosine kinase inhibitors have been associated with gastrointestinal perforation and impaired wound healing, necessitating heightened attention in patients with a new bowel anastomosis.

White Blood Cell and Peripheral Blast Counts in Leukemia Patients with Non-Graying WBC-Diff Scattergram

Graying scattergram of White Blood Cell differential (WBC-diff) is often accompanied by blasts in the blood and/or leukocytosis in leukemia patients. Therefore, monitoring White Blood Cell (WBC) and peripheral blast count is crucial for patient management. In contrast, patients with non-graying WBC-diff scattergrams may have varying WBC counts and peripheral blasts. This study aimed to establish the cut-off values of WBC and peripheral blast counts that could predict a non-graying scattergram in leukemia patients. A retrospective descriptive study with a cross-sectional design analyzed secondary data from 21 leukemia patients. The acute and chronic leukemia diagnosis were based on bone marrow aspirates, which simultaneously showed a graying WBC-diff scattergram on Complete Blood Count (CBC). Receiver Operating Characteristic (ROC) curve analysis was conducted when the patient’s CBC displayed a non-graying scattergram. The cut-off value for WBC count was 16,380 x 109/L with an Area Under Curve (AUC) of 0.932, a sensitivity of 85.7%, p = 0.001, and the cut-off for peripheral blast count was 35.5% with an AUC of 0.872, the sensitivity of 76.2%, p=0.001. The results suggest that a non-graying scattergram of the WDF channel in leukemia is more likely associated with WBC counts below 16,380 x 109/L and peripheral blast counts below 35.5%, which have excellent and good predictive value.

A girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report.

Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.

Hemophagocytic Lymphohistiocytosis as an Unusual Presentation in a Patient with Human Immunodeficiency Virus-associated Bone Marrow Classic Hodgkin Lymphoma: A Case Report with Literature Review

Abstract Introduction/Objective Compared to the general population, people living with human immunodeficiency virus (HIV) have a higher incidence of lymphoproliferative disorders including classic Hodgkin lymphoma (CHL). Hemophagocytic lymphohistiocytosis (HLH) triggers in HIV patients include HIV itself and HIV-associated malignancies or infections, all of which can have many overlapping symptoms, causing diagnostic challenges and delays in initiating treatments. Methods/Case Report A 56-year-old HIV-positive man presented with septic shock-like symptoms, pancytopenia, hyperferritinemia, transaminitis, elevated IL2-receptor alpha and hepatomegaly. Mild retroperitoneal lymphadenopathy found on imaging yielded non-diagnostic biopsies. A bone marrow (BM) biopsy showed no malignancy or disseminated infections and a rare hemophagocyte. Treatment for HIV-triggered HLH lead to a marked clinical improvement. Three months later he presented with worsening symptoms, negative cultures, and an EBV+ CHL on a BM biopsy. Mild increase in lymphadenopathy and multiple liver/spleen hypodensities found on imaging could not be biopsied due to rapidly deteriorating patient’s condition and death. Results (if a Case Study enter NA) NA Conclusion Per studies, HLH is more frequent in the HIV-associated lymphomas compared to the non-HIV- associated ones, usually presenting as a sepsis-like syndrome in these patients. Probability of HLH development was particularly high with BM involvement and CHL. From 2010, seven cases of HIV-associated CHL presenting with HLH were found in the literature with these findings: (n=8, including ours) sex- all males; average age- 45 years (range 28- 64); average HIV viral loads- 83,369 copies/mL (range: undetectable-&amp;gt;300,000); average absolute CD4 count- 98 cells/microliter (range: 8-314); interval from HIV diagnosis- new to 26 years; anti-retroviral treatment- 6; symptoms- fever (all), other symptoms were variable; HLH-2004 protocol criteria- all; biopsy-proven hemophagocytes- 3; EBV+ CHL- all (6 were diagnosed on BM biopsies); outcomes- remission (2), response to treatment (4), death (2). CHL- triggered HLH in HIV patients is a complex diagnostic entity. A high index of suspicion and thorough investigations including early BM biopsies can ensure better outcomes.