Koji Nikkuni

Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV‐8‐negative multicentric Castleman disease

Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi‐organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus‐8 (HHV‐8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV‐8‐negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese‐born and two US‐born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23–72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed. Am. J. Hematol. 91:220–226, 2016.

Elevated serum interferon γ-induced protein 10 kDa is associated with TAFRO syndrome

Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder. It is characterized by inflammatory symptoms, and interleukin (IL)-6 contributes to the disease pathogenesis. Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD, although the etiology of HHV-8-negative MCD is idiopathic (iMCD). A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been reported as TAFRO-iMCD, however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established. We retrospectively compared levels of serum interferon γ-induced protein 10 kDa (IP-10), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-10, and other cytokines between 11 cases of TAFRO-iMCD, 6 cases of plasma cell type iMCD, and 21 healthy controls. During flare-ups, patients with TAFRO-iMCD had significantly higher serum IP-10 and tended to have lower PDGF-AA levels than the other 2 groups. In addition, serum IL-10, IL-23, and vascular endothelial growth factor-A were elevated in both TAFRO-iMCD and iMCD. Elevated serum IP-10 is associated with inflammatory diseases including infectious diseases. There was a strong correlation between high serum IP-10 and the presence of TAFRO-iMCD, suggesting that IP-10 might be involved in the pathogenesis of TAFRO-iMCD.

Clinical value of assessing the response to imatinib monitored by interphase FISH and RQ-PCR for BCR-ABL in peripheral blood for long-term survival of chronic phase CML patients: results of the Niigata CML-multi-institutional co-operative clinical study

This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.46 years. At 5 years, the overall survival (OS) rate and progression-free survival (PFS) rate were 94.4 and 92.0%, respectively. The estimated rate of the CCyRe and MMR were 81.7 and 67.1%, respectively. 106 patients achieving the CCyRe had significantly better OS and PFS than 27 patients without achieving the CCyRe. Patients with MMR had significantly better survival free from death, progression, imatinib withdrawal and a loss of the CCyRe, than patients whose response level remained in the CCyRe without achieving MMR until 18 months. Our observation suggests that the response level of the CCyRe on PB serve as a prognostic indicator, and achieving MMR provides stable long-term survival.

Extramedullary T lymphoid blast crisis representing an additional translocation, t(6;8)(q25;q22) in a patient with Philadelphia-positive chronic myelogenous leukemia after allogeneic bone marrow transplantation

A patient with extramedullary crisis from chronic myelogenous leukemia after allogeneic bone marrow transplantation is reported. A pathological neck lymph node observed after transplantation revealed pre-T lymphoblastic phenotype, and the fluorescence in situ hybridization (FISH) analysis showed recipient type sex chromosomes and bcr/abl fusion gene. The cells represented an additional translocation, t(6;8)(q25;q22). No rearrangements of the T-cell receptor (TCR) beta, gamma or delta chain genes were observed. The absence of TCR rearrangement indicated the clonogenic involvement of pluripotent hematopoietic stem cells by Philadelphia chromosome. Bone marrow specimens at that time showed donor type sex chromosomes and no bcr/abl-positive cells by FISH.

Anaplastic lymphoma kinase negative sarcomatoid variant of anaplastic large-cell lymphoma presenting as a malignant fibrous histiocytoma.

It has been reported that 25–60% of anaplastic large cell lymphomas (ALCL) carry the t(2;5)(p23;q35) translocation that results in the production of a novel chimeric protein anaplastic lymphoma kinase (ALK). Because ALK-positive ALCL has a more favorable prognosis than ALK-negative ALCL, recent investigations have suggested subclassification of ALCL according to ALK expression [1]. The sarcomatoid variant of ALCL is an extremely rare condition, which is easily misdiagnosed as high-grade sarcoma [2]. The ALK expression of sarcomatoid lymphoma has seldom been assessed. We report a case of sarcomatoid ALCL presented as malignant fibrous histiocytoma with evaluation of ALK expression. A 51-year-old man presented at another hospital with a 2-month history of an enlarging superficial mass in his left groin. The diagnosis based on biopsy results was high-grade sarcoma, probably a myxoid malignant fibrous histiocytoma. The patient was referred to our hospital. Physical examination revealed a soft, ulcerated, infected, immobile tumor which bled easily measuring 23 23 cm in the left groin (Fig. 1). Bacterial cultures of the tumor demonstrated more than ten types of Gram-positive and Gram-negative bacteria. Magnetic resonance imaging

O1-13-5Treatment with R-bendamustine followed by Y-90 ibritumomab tiuxetan for relapsed/refractory low-grade B-cell lymphoma

Satoshi Kaito, Yusuke Kanemasa, Yuki Sasaki, Toshihiro Okuya, Tsukasa Yamaguchi, Miho Tamura, Tatsu Shimoyama, Yashshi Omuro, Tunekazu Hishima, Yoshiharu Maeda Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, Department of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, Department of pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan