CD3+/CD57+ T-cell large granular lymphocyte leukemia (T-LGLL) is an indolent neoplasm, exhibiting mostly CD8+, less frequently CD4+ phenotypes, and T-LGLL consisting of 2 populations with CD8+ and CD4+ phenotypes is markedly rare. An 87-year-old female was admitted under a diagnosis of immune thrombocytopenia (ITP) with a platelet count of 5.0×109/L and increased number of LGL with unknown etiology. Her neutrophil count also decreased to 0.27×109/L and she was positive for antineutrophil antibody. The WBC count was 2.7×109/L with 34.7% LGL and flow cytometry (FCM) analysis revealed 16% CD3+/CD4+/CD8dim/CD57+ and 20.9% CD3+/CD8+/CD57+ populations. These populations also expressed granzyme B and perforin. Circulating mononuclear cells were found to be clonal by PCR analysis of T-cell receptor ß-chain gene. Serum immunofixation and bone marrow FCM analyses demonstrated 2 clonal B-cells producing IgG-λ and IgA-λ. Deep amplicon sequencing of STAT3 and STAT5B genes revealed a STAT3 R302G mutation with an allele burden of 2.6%. The thrombocytopenia and neutropenia were successfully treated by prednisolone and romiplostim with negative conversion of antineutrophil antibody. This is the first reported case of T-LGLL with dual components of CD4+/CD8dim and CD4-/CD8+ populations in terms of multiple comorbidities related to the respective CD8+ and CD4+ T-LGLLs.
B-Lymphocytes , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Leukemia, Large Granular Lymphocytic , Lymphocytosis , Mutation, Missense , Neoplasm Proteins , Neutropenia , Purpura, Thrombocytopenic, Idiopathic , STAT3 Transcription Factor , Aged, 80 and over , Amino Acid Substitution , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Female , Humans , Immunoglobulin lambda-Chains/genetics , Immunoglobulin lambda-Chains/metabolism , Leukemia, Large Granular Lymphocytic/genetics , Leukemia, Large Granular Lymphocytic/metabolism , Leukemia, Large Granular Lymphocytic/pathology , Lymphocytosis/genetics , Lymphocytosis/metabolism , Lymphocytosis/pathology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neutropenia/genetics , Neutropenia/metabolism , Neutropenia/pathology , Purpura, Thrombocytopenic, Idiopathic/genetics , Purpura, Thrombocytopenic, Idiopathic/metabolism , Purpura, Thrombocytopenic, Idiopathic/pathology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism
Acquired amegakaryocytic thrombocytopenia (AATP) is a rare disease characterized by thrombocytopenia and the disappearance of marrow megakaryocytes. A 43-year-old man was admitted because of thrombocytopenia of 1.0×109/L. Bone marrow aspirate demonstrated normal hematopoiesis lacking megakaryocytes, and AATP was diagnosed. The serum concentration of thrombopoietin (TPO) was high (7.72 fmol/mL). Prednisolone (PSL) at 60 mg/day was started and the platelet count recovered to 1,335×109/L; however, excessive megakaryocytopoiesis and subsequent decline in platelet count were noted 14 days later. At the peak platelet count, the TPO remained at 3.79 fmol/mL and returned to a normal level of 0.40 fmol/mL during the period of normal platelet count after PSL tapering. The marked thrombocytosis in response to prednisolone may have been caused by the high TPO after the resolution of suppressed megakaryopoiesis. Marked rebound thrombocytosis beyond 1,000×109/L after successful PSL treatment for AATP has not been previously reported.
Bone Marrow Cells , Megakaryocytes , Myelopoiesis/drug effects , Prednisolone/adverse effects , Thrombocytopenia , Thrombocytosis , Adult , Autoantigens/blood , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Humans , Iodide Peroxidase/blood , Iron-Binding Proteins/blood , Male , Megakaryocytes/metabolism , Megakaryocytes/pathology , Platelet Count , Prednisolone/administration & dosage , Thrombocytopenia/blood , Thrombocytopenia/drug therapy , Thrombocytopenia/pathology , Thrombocytosis/blood , Thrombocytosis/chemically induced , Thrombocytosis/pathology
A diagnosis of acute monocytic leukemia (AML-M5) based on α-naphthyl butyrate esterase (α-NB) staining has some problems, because AML-M5 leukemic cells often show weak or faint positivity on α-NB staining. In these situations, some cases of AML-M5 tend to be misdiagnosed as AML-M0. Therefore, we evaluated the significance of weak or faint α-NB staining in AML-M5 diagnosed by flow cytometry (FCM). Nineteen AML cases in which leukemic cells were negative for naphthol AS-D chloroacetate esterase staining were studied. For FCM, we defined leukemic cells as having a monocytic nature when more than 10% of the leukemic cells were positive for at least one of the following antigens: CD4, CD11c, CD14, and CD64. The monocytic nature determined by FCM was consistent with positive or weak positivity on α-NB staining. Five of 6 cases in which leukemic cells exhibited faint positivity for α-NB staining could be diagnosed as AML-M5 by FCM, while negative α-NB staining was consistent with a diagnosis of AML-M0. These results suggest that AML-M5 should be taken into consideration even when leukemic cells are faintly positive for α-NB staining.
