Possible Concomitant Aggressive NK Cell Leukemia and EBV-positive T-cell lymphoma; Using the online beta version of WHO-HAEM5 and videoconferencing software to make diagnoses accessible in an emerging economy.

BACKGROUND: Using the World Health Organization Classification 5th edition (beta version online; WHO-HAEM5bv) in emerging economies is key to global healthcare equity. Although there may be ongoing updates, hesitancy in accepting and reporting these diagnoses in publication conflicts with the WHO's commitment to global accessibility. Aggressive NK cell leukemia (ANKL) and systemic EBV-positive T-cell lymphoma of childhood (SEBVTCL) with CD4-positive immunophenotype are both rare entities, are most described in Asians and East Asians, are associated with prior systemic chronic active EBV disease (CAEBV), and presentation with Hemophagocytic Lymphohistiocytosis (HLH). Recognizing and diagnosing any one of these entities requires not only training and experience in hematopathology, but good cooperation between clinical physicians and all areas of the laboratory. We describe a 30-year-old woman who presented to a Vietnam hospital and was rapidly diagnosed with ANKL, SEBVTCL, and HLH using WHO-HAEM5bv essential criteria, aided by expert consultation from a United States (US) board certified hematopathologist in real-time using video conferencing software. METHODS: Zoom™ videoconferencing software; Immunohistochemistry; flow cytometric immunophenotyping; polymerase chain reaction (PCR), Next Generation Sequencing (NGS). RESULTS: At the time of hospital admission, automated complete blood count (CBC) with differential count showed slight anemia, slight lymphocytosis, and moderate thrombocytopenia. HIV serology was negative. Whole blood PCR for EBV was positive showing 98,000 copies/ml. A lymph node biopsy revealed histology and immunohistochemistry consistent with the online beta version WHO-HAEM5 classification of SEBVTCL arising in CAEBV. Blood and bone marrow studies performed for staging revealed no histologic or immunohistochemical evidence of T-cell lymphoma in the bone marrow core, however, atypical blood smear lymphocyte morphology and blood immunophenotyping by flow cytometry were consistent with WHO-HAEM5 classification of ANKL. NGS revealed no evidence of genetic variant(s) associated with HLH in Vietnam. All laboratory studies were performed at Blood Transfusion Hematology Hospital (BTHH) in Ho Chi Minh City Vietnam. CONCLUSION: Although Vietnam, an emerging economy, currently lacks the laboratory infrastructure to more rigorously confirm a rare synchronous presentation of two distinct EBV-driven T/NK cell neoplasms, these two concomitant diagnoses were made using only laboratory techniques available in Vietnam with the help of WHO-HAEM5bv and real-time video consultation by a US hematopathologist.

Diagnostic utility of bone marrow examination for the assessment of patients with fever of unknown origin: a 10-year single-centre experience.

Bone marrow (BM) examination is included in the diagnostic algorithm of fever of unknown origin (FUO), although its role is not clearly determined. The purpose of this study was to assess the role of BM studies in patients with FUO. We retrospectively reviewed 45 consecutive patients (25% human immunodeficiency virus-positive) with FUO who underwent a BM study in the University Hospital of Salamanca from 2000 to 2010. We analysed the diagnostic role of BM smears, multiparameter flow cytometry analysis, histology and microbiological cultures. Five patients (11%) were finally diagnosed by BM study (three had an infectious disease and two were found to have haematological malignancies), all of whom were immunocompetent patients. Histology was the most useful study (diagnosis was obtained in 4/5 patients), while BM cultures did not establish the final diagnosis in any patient. Flow cytometry established the diagnosis in one patient, although this patient was also diagnosed by histology. In conclusion, BM study is useful for establishing the aetiology of FUO. BM biopsy for histological examination should be always mandatory if a BM examination is performed.

Marrow assessment for hemophagocytic lymphohistiocytosis demonstrates poor correlation with disease probability.

OBJECTIVES: To evaluate the amount of hemophagocytosis in 64 marrow core biopsy specimens and aspirates from 58 patients with clinical suspicion for secondary hemophagocytic lymphohistiocytosis (HLH) or reported findings of hemophagocytosis. METHODS: A review of medical records assigned patients to a low-risk (45 patients) or high-risk (13 patients) HLH group, and association with histologic findings was examined using the Fisher exact test. RESULTS: The amount of hemophagocytosis in aspirate or the core biopsy specimen did not correlate with disease probability (P = .17 and P = .63, respectively). Of the clinical/laboratory criteria assessed, the most significant correlations with HLH were highly elevated ferritin (P = .01), cytopenias (P = .02), and fever (P = .009). CONCLUSIONS: Our findings indicated that marrow histologic findings alone do not reliably predict the probability of HLH, and an isolated finding of hemophagocytosis, even when present in a high amount, lacks specificity for HLH.

Assessment of clinical and laboratory presentations of familial hemophagocytic lymphohistiocytosis patients with homozygous W374X mutation.

Homozygous W374X mutation was identified in unrelated 13 patients (6M/7F) from consanguineous families, 62% of which had history of deceased sibling. Haplotype analysis provided evidence for the probable existence of a founder effect. Age at disease onset ranged from 1 day to 5.5 months (median 2 months). Hepatic dysfunction was observed in 69%, ascite 62%, hypertriglyceridemia 77%, each hyperferritinemia and hypofibrinogenemia 85%, CNS involvement 46% of patients while birth weights were in normal range. Those with very high ferritin (>20,000ng/ml) had extremely low fibrinogen levels. Two-thirds of patients receiving HLH protocol died within 20 days of therapy.