Hung S. Luu

Myeloid and lymphoid neoplasm with abnormalities of FGFR1 presenting with trilineage blasts and RUNX1 rearrangement: a case report and review of literature.

OBJECTIVES Myeloid and lymphoid neoplasms with abnormalities of fibroblast growth factor receptor 1 gene (FGFR1) are a rare and aggressive disease group that harbors translocations of FGFR1 with at least 14 recognized partner genes. We report a case of a patient with a novel t(17;21)(p13;q22) with RUNX1 rearrangement and trilineage blasts. METHODS A 29-year-old man with relapsed T-lymphoblastic lymphoma in the cervical nodes showed a myeloproliferative neoplasm in his bone marrow with three separate populations of immunophenotypically aberrant myeloid, T-lymphoid, and B-lymphoid blasts by flow cytometry. Cytogenetic and fluorescent in situ hybridization studies showed unique dual translocations of t(8;13)(p11.2;q12) and t(17;21)(p13;q22) with RUNX1 rearrangement. RESULTS The patient was initiated on a mitoxantrone, etoposide, and cytarabine chemotherapy regimen and died of complications of disease 1 month later. CONCLUSIONS To our knowledge, this is the first reported case of a myeloid and lymphoid neoplasm with abnormalities of FGFR1 with t(17;21)(p13;q22) and trilineage blasts.

Applying the Principles of Lean Production to Gastrointestinal Biopsy Handling: From the Factory Floor to the Anatomic Pathology Laboratory

OBJECTIVES To implement Lean principles to accommodate expanding volumes of gastrointestinal biopsies and to improve laboratory processes overall. DESIGN Our continuous improvement (kaizen) project analyzed the current state for gastrointestinal biopsy handling using value-stream mapping for specimens obtained at a 487-bed tertiary care pediatric hospital in Dallas, Texas. We identified non-value-added time within the workflow process, from receipt of the specimen in the histology laboratory to the delivery of slides and paperwork to the pathologist. To eliminate non-value-added steps, we implemented the changes depicted in a revised-state value-stream map. RESULTS Current-state value-stream mapping identified a total specimen processing time of 507 minutes, of which 358 minutes were non-value-added. This translated to a process cycle efficiency of 29%. Implementation of a revised-state value stream resulted in a total process time reduction to 238 minutes, of which 89 minutes were non-value-added, and an improved process cycle efficiency of 63%. CONCLUSIONS Lean production principles of continuous improvement and waste elimination can be successfully implemented within the clinical laboratory.

Detection of Intracellular Parasites by Use of the CellaVision DM96 Analyzer during Routine Screening of Peripheral Blood Smears

ABSTRACT Conventional microscopy is the gold standard for malaria diagnosis. The CellaVision DM96 is a digital hematology analyzer that utilizes neural networks to locate, digitize, and preclassify leukocytes and characterize red blood cell morphology. This study compared the detection rates of Plasmodium and Babesia species on peripheral blood smears utilizing the CellaVision DM96 with the rates for a routine red blood cell morphology scan. A total of 281 slides were analyzed, consisting of 130 slides positive for Plasmodium or Babesia species and 151 negative controls. Slides were blinded, randomized, and analyzed by CellaVision and microscopy for red cell morphology scans. The technologists were blinded to prior identification results. The parasite detection rate was 73% (95/130) for CellaVision and 81% (105/130) for microscopy for positive samples. The interobserver agreement between CellaVision and microscopy was fair, as Cohens kappa coefficient equaled 0.36. Pathologist review of CellaVision images identified an additional 15 slides with parasites, bringing the total number of detectable positive slides to 110 of 130 (85%). Plasmodium ovale had the lowest rate of detection at 56% (5 of 9); Plasmodium malariae and Babesia spp. had the highest rate of detection at 100% (3/3 and 6/6, respectively). The detection rate by CellaVision was 100% (23/23) when the parasitemia was ≥2.5%. The detection rate for <0.1% parasitemia was 63% (15/24). Technologists appropriately classified all negative specimens. The percentage of positive specimens detectable by CellaVision (73%) approaches results for microscopy on routine scan of peripheral blood smears for red blood cell morphology.

Mature neutrophils with Auer rods following treatment with all-trans retinoic acid for acute promyelocytic leukemia.

![Figure][1] A 37-year-old woman initially presented with pancytopenia and found to have leukopenia (2.1 × 103/μL) with 13% atypical promyelocytes, anemia (hemoglobin of 6.8 g/dL), and thrombocytopenia (41 000 per μL). The atypical promyelocytes were medium to large in size with frequent

Automated cell counts on CSF samples: A multicenter performance evaluation of the GloCyte system

Automated cell counters have replaced manual enumeration of cells in blood and most body fluids. However, due to the unreliability of automated methods at very low cell counts, most laboratories continue to perform labor‐intensive manual counts on many or all cerebrospinal fluid (CSF) samples. This multicenter clinical trial investigated if the GloCyte System (Advanced Instruments, Norwood, MA), a recently FDA‐approved automated cell counter, which concentrates and enumerates red blood cells (RBCs) and total nucleated cells (TNCs), is sufficiently accurate and precise at very low cell counts to replace all manual CSF counts.

Mucosa-associated lymphoid tissue (MALT) lymphoma presenting as subglottic stenosis: single-agent treatment using rituximab.

Inspiratory stridor due to subglottic stenosis is a well-known entity, with the vast majority of adult cases due to intubation, external trauma, and less commonly idiopathic progressive subglottic stenosis (IPSS) and systemic rheumatic diseases. With very few exceptions, the widening of airway caliber requires surgical intervention. We present a case with this relatively common presentation but caused by an exceedingly rare disease entity, a laryngeal MALT lymphoma treated successfully with single-agent chemotherapy.

Closing the Brief Case: Disseminated Histoplasma capsulatum in a Patient with Newly Diagnosed HIV Infection/AIDS

CASE A69-year-old male with no known significant past medical history presented with 2 months of shortness of breath, dry cough, subjective fevers, and an unintentional 20-pound weight loss. Review of symptoms was also notable for constant, diffuse headaches and nausea without vomiting or abdominal pain. In 1986, the patient moved from El Salvador to Texas, where he worked in construction until the time of presentation. While in El Salvador, the patient noted multiple female sexual partners, although he was now monogamous with one female partner. On physical examination, he was afebrile and saturating 100% on room air. He was frail and appeared chronically ill. His lungs were clear upon auscultation bilaterally. Lab results were most notable for pancytopenia, with a white blood cell count of 3.82 109/liter (4.22 109 to 10.33 109/liter), hemoglobin of 8.1 g/dl (13.2 to 16.9 g/dl), and a platelet count of 31 109/liter (160 109 to 383 109/liter), as well as hyponatremia, with a sodium concentration of 124 mmol/liter (135 to 145 mmol/liter) and an elevated ferritin level of 57,180 ng/dl (30 to 400 ng/ml). Although not previously known to have human immunodeficiency virus (HIV), the patient’s 4th-generation HIV screening test for HIV type 1 (HIV-1) and HIV-2 antibodies and p24 antigen was positive. He was subsequently found to have a CD4 count of 29 cells/ l (365 to 1,437 cells/ l) and an HIV load of 720,440 copies/ml. A chest X ray was unremarkable, but a computerized tomography (CT) scan of the chest showed numerous tiny nodules measuring up to 5 mm in size. The dry cough and pancytopenia in concert with nodules upon CT chest exam in the setting of AIDS was concerning for disseminated histoplasmosis, and thus a bone marrow biopsy specimen with fungal culture was obtained. Microscopic examination of Giemsa-stained bone marrow aspirate smears revealed numerous oval intracellular yeast cells (2 to 4 m) in macrophages (Fig. 1A), consistent with the suspected diagnosis of disseminated Histoplasma capsulatum infection. The patient’s urine Histoplasma antigen test returned a level of 20 ng/ml. After 8 days, both his fungal blood culture and fungal bone marrow culture grew H. capsulatum. He was treated with liposomal amphotericin B for 2 weeks, followed by itraconazole indefinitely. Antiretroviral agents were held upon discharge, and he moved to another state with plans to follow up with an outside provider.

Characterization of the HBB: c.*233G > C Variant: No Evidence of a β-Thalassemic Phenotype

Abstract β-Thalassemia (β-thal) results from homozygous or compound heterozygous inheritance of β-globin alleles that yield decreased or absent synthesis of the β chain. Disease is frequently severe, requiring lifelong transfusion therapy. Heterozygosity for a β-thal allele results in an asymptomatic carrier state with mild but characteristic hematological findings. More than 200 β-globin alleles have been demonstrated to produce β-thal. For populations with a high prevalence of β-thal, screening for carrier status, genetic counseling and prenatal diagnosis are important components of efforts to both reduce disease incidence and provide early diagnosis and treatment. It is therefore important to define and characterize potential β-thal alleles. We sought to further characterize the previously reported β-thal allele, HBB: c.*233G > C. This variant is provisionally included in the HbVar database based on a study of Palestinians in the Gaza Strip with β-thal disease or carrier status (known or suspected) where 4.2% of subjects were found to have HBB: c.*233G > C. In our patient population, we detected the HBB: c.*233G > C variant in 17.3% of individuals (17 heterozygotes, one homozygote) undergoing β hemoglobin (Hb) gene sequencing at our laboratory over a 25-month period. Hematological parameters were analyzed to determine if these individuals demonstrated findings consistent with inheritance of a β-thal allele. Individuals with the HBB: c.*233G > C variant did not demonstrate any abnormalities in hematological parameters characteristic of β-thal carrier state (17 heterozygotes) or clinical evidence of disease (homozygote). Our data demonstrate no evidence for pathogenicity of the HBB: c.*233G > C variant but rather demonstrate that this variant is a common benign polymorphism.

Haematogone hyperplasia in copper deficiency

Copper deficiency is likely an underrecognized cause of anemia and neutropenia and may masquerade as a myelodysplastic syndrome (MDS). We report 2 cases of copper deficiency in which the diagnosis was suggested based on the characteristic morphologic findings, such as cytoplasmic vacuolization of erythroid and myeloid precursors and iron-containing plasma cells. It is interesting that both patients had hematogone hyperplasia. This phenomenon, largely absent in MDS, may aid in distinguishing nonclonal causes of cytopenias, such as copper deficiency, from MDS. It is of crucial importance to identify treatable causes of cytopenias when MDS is suspected. We recommend copper level assessment in patients suspected of having low-grade MDS, especially patients with neuropathy and normal results of cytogenetic studies.

Novel r(2)(p25q31) cytogenetic abnormality in a pediatric patient with acute leukemia of ambiguous lineage

We describe a case of acute leukemia of ambiguous lineage with a novel cytogenetic abnormality. A 1-year-old boy presented with abnormal complete blood count findings, and was found to have blasts and mild dysgranulopoiesis. The blasts showed immunophenotypic evidence of myeloid and T-lineage differentiation. Subsequent cytogenetic analysis showed r(2)(p25q31) as the sole stem line cytogenetic defect with clonal evolution. While cytogenetic abnormalities can have a critical role in the classification and prognostication of acute lymphoblastic and acute myeloid leukemia, the significance of cytogenetic abnormalities in acute leukemia of ambiguous lineage remains unclear. This finding has not been reported previously to the best of our knowledge.