T-cell large granular lymphocytic leukemia in Vietnam: Using microscope-to-screen videoconferencing to improve diagnosis.

OBJECTIVES: Leukemia diagnosis in Vietnam is limited by a lack of hematopathology training and expert consultation as well as the cost of high-magnification digitization of hematology slides. Screen-sharing software allows international collaboration with experienced hematopathologists for improved diagnostic accuracy. METHODS: A hematopathology education and consultation program was proposed for Vietnam hospitals. By appointment, pathologists in Vietnam with access to a microscope camera, imaging software, and high-speed internet were invited to review slides and data with a volunteer board-certified hematopathologist in the United States using secure videoconferencing software. A single hospital in southern Vietnam assigned a pathologist proficient in English to access this service. All consultations from this site with clinicopathologic information were logged. After a 2-year period of online consultation, case slides for selected diagnoses were reviewed under the microscope in Vietnam to assess concordance. RESULTS: In total, 135 consultations were logged, 53 of which were for blood and bone marrow. T-cell large granular lymphocytic leukemia (T-LGLL) was 1 of the most frequent bone marrow consultation-related diagnoses; all diagnoses of this entity were confirmed by in-person microscopy (100% concordance). A records search and physician surveys found no prior documented diagnoses of T-LGLL made in Vietnam before this education and consultation program. CONCLUSIONS: Our virtual consultation model has improved patient care in Vietnam by providing correct diagnoses to inform best practices in treatment. As a result of our program, the first Vietnam diagnoses of T-LGLL were made and may help expand on the literature in this area. This model could provide cost-effective, real-time consultation and education services for pathologists in underserved communities.

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.

Heinz body hemolysis following extended use phenazopyridine in a post-HCT patient with hemorrhagic cystitis: An old problem for a new generation.

Hemorrhagic cystitis is a common complication following the use of cyclophosphamide. Associated dysuria can be painful and there are few good options to relieve pain. Phenazopyridine has historically been utilized for dysuria and is available over the counter. However, it is associated with hematologic side effects with prolonged use. Here we present a case of a patient who developed Heinz body hemolysis following prolonged administration of phenazopyridine to treat cyclophosphamide-induced hemorrhagic cystitis following hematopoietic stem cell transplant.

Myeloid Sarcoma Expressing Keratins and Mimicking Carcinoma-Case Report and Literature Review.

Unusual presentations of otherwise common hematopoietic neoplasms are a well-recognized diagnostic challenge. Herein, we present a case study of a previously healthy 64 year old woman with myeloid sarcoma whose diagnosis was delayed by an unusual immunohistochemical staining pattern, including cytokeratin expression, by the neoplastic cells and by possible anchoring bias introduced by radiographic and flow cytometric immunophenotyping reports. This case study emphasizes the need to integrate clinical, radiographic, histologic, and immunophenotyping data for rapid and accurate tissue diagnoses while being wary of the lack of specificity for many common immunophenotypic markers.

Evaluation of Opportunities to Improve Hematopathology Diagnosis for Vietnam Pathologists.

OBJECTIVES: We evaluate the need for, feasibility of, and impediments to improving hematopathology diagnoses for cancer hospitals in Vietnam. METHODS: Two hematopathologists from the United States visited three major cancer treatment hospitals in Vietnam to workshop a sampling of difficult hematopathology cases. With Vietnamese pathologists, they toured histopathology, immunohistochemistry, and ancillary laboratory facilities. RESULTS: Automated tissue processors and slide staining equipment were documented for each of the three hospitals. Between seven and 11 hematopathology cases were reviewed for each hospital. Exact/complete diagnostic concordance was 50% or less for all three laboratories. The major impediments to accurate specific diagnoses were limitations of immunohistochemical stains, limited stains available in house, and, for one of the hospitals, difficulty with interpretation of the immunohistochemistry. CONCLUSIONS: Vietnamese pathologists would benefit from hematopathology training or opportunities to consult with hematopathologists in the United States. Expert hematopathology consultation services are currently unavailable within Vietnam, as postgraduate training for laboratory physicians consists of residency training in anatomic pathology only. Limitations in the quality of histopathology and immunohistochemistry could impose a barrier to success of efforts to improve hematopathology diagnosis. Implementation of a histopathology and immunohistochemistry quality improvement program might overcome this limitation.

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

OBJECTIVES: Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. METHODS: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. RESULTS: Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. CONCLUSIONS: Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care.

Unusual extramedullary hematopoietic neoplasms in lymph nodes.

Myeloid, plasma cell, and lymphoblastic neoplasms are expected findings in bone marrow but are much less commonly diagnosed as primary processes in lymph nodes. The objective of this review is to aid pathologists in recognizing common hematopoietic neoplasms in the unusual setting of initial presentation in lymph nodes. Review of historical background and evolution of testing strategies is presented to improve understanding of the need for accurate diagnosis and classification using current nomenclature. The review is based on peer-reviewed literature and the personal experience of the authors. The University of Minnesota Medical Center, Fairview provides lymph node diagnostic consultation services for its busy oncology and therapeutic hematopoietic cell transplant divisions serving patients from around the globe. Although readily recognizable when they present in bone marrow, myeloid leukemia in the form of myeloid sarcoma, plasmacytoma, and lymphoblastic lymphoma can create diagnostic and classification challenges when they present as primary lymph node pathologies. Use of all diagnostic tools may be necessary to ensure accurate and reproducible diagnoses.

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges.

Double- and triple-hit lymphomas (DHL/THL) are aggressive B-cell neoplasms characterized by translocation of MYC with concurrent BCL2 and/or BCL6 translocation. In this retrospective study from one institution, we report clinicopathologic features of 13 cases (9 DHL/4 THL). The median age was 59 years (range 30-74) and patients included eight females and five males. Presentation included enlarging lymphadenopathy/masses (11 patients) and abnormal peripheral blood findings (2 patients). Features which raised the differential of an immature neoplasm included terminal deoxynucleotidyl transferase positivity (four cases, two THL/two DHL); dim CD45 expression (seven cases), lack of CD20 (two cases), or lack of surface immunoglobulin light chain (three cases) by flow cytometry; and blastoid morphology (two cases). We conclude that expression of TdT in a B-cell lymphoma with mature features or expression of surface light chain in a case otherwise suggestive of B-lymphoblastic leukemia/lymphoma should prompt an expedited evaluation for DHL/THL.

Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia.

Early after umbilical cord blood transplantation, patients show marked differences in bone marrow (BM) hematogone percentages. Little is known about whether these differences are clinically relevant. We hypothesized that early recovery of hematogones may be associated with improved transplantation outcomes. BM aspirates were assessed from 88 patients with acute myeloid leukemia by two independent reviewers at day 21 and 100 after umbilical cord blood transplantation. Interobserver variability for BM hematogone percentages at these time points showed correlation coefficients of 0.83 and 0.98, respectively (P ≤ .01 for both). A high percentage of hematogones at day 21 was associated with less acute graft-versus-host disease grade 3 to 4 (P = .01). At day 100, a high percentage of BM hematogones was associated with improved overall survival (P = .02) and lower treatment-related mortality (P ≤ .01). This study shows that BM hematogone percentages may be useful prognostic indicators in patients with acute myeloid leukemia after umbilical cord blood transplantation and should be routinely reported in BM differential counts.

Treatment of a CNS relapse while on therapy for Burkitt lymphoma.

The treatment of Burkitt lymphoma (BL) has come a long way in regards to survival, with the majority of even the advanced stage patients being cured. The prognosis for relapsed BL remains dismal, despite attempts to further intensify therapy. We report on a patient with advanced stage BL who relapsed in the CNS while on therapy. The patient was successfully treated with an intensified regimen based on a concentration times time (C x T) CNS-directed model. Our experience shows both the feasibility and efficacy of such an approach in a patient with an otherwise very poor prognosis.

Cutaneous pseudolymphoma: an unusual presentation of a scalp mass.

The term cutaneous pseudolymphoma (CPL), an accumulation of lymphocytes in response to a foreign antigen or unknown stimuli lacks specificity, and has been used when neither cause nor mechanism for the lymphocytic proliferation has been identified. Cases of childhood CPL are rare and require extensive investigation because of their potential for malignant transformation. We report a case of a child with a scalp mass diagnosed as CPL.

Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients.

BACKGROUND AND OBJECTIVES: Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy. DESIGN AND METHODS: Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005. RESULTS: Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made. INTERPRETATION AND CONCLUSIONS: We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.

First report of donor cell-derived acute leukemia as a complication of umbilical cord blood transplantation.

Donor cell leukemia is a rare complication after allogeneic hematopoietic stem cell transplantation. A 12-month-old boy underwent unrelated donor umbilical cord blood transplant (UCBT) for refractory Langerhan's cell histiocytosis. Forty months after transplantation, he developed acute myeloid leukemia. Cytogenetic and molecular analysis confirmed donor cell origin. The Cord Blood Bank (CBB) contacted the donor's family and established that the child, now 7 years old, was healthy. This represents the first reported case of donor cell leukemia following UCBT. This case illustrates that donor cell leukemia is a rare but real event after UCBT as with other stem cell sources and highlights the need for CBBs to maintain linkage data between donors and recipients.