Journal of Clinical and Experimental Hematopathology : JCEH

Myelodysplastic syndromes (MDS) are myeloid neoplasms that are driven by genetic mutations. Generally, it is thought that a higher number of mutations is associated with worse prognosis. However, the impact of genetic mutations when they occur in the same functional class has not been well studied. Here we investigated the impact of multiple spliceosome mutations on prognosis in MDS patients, hypothesizing that multiple mutations in the same class are biologically redundant and would not affect prognosis. Departmental Next Generation Sequencing (NGS) database (>6000 cases) was queried and the data was analyzed to identify cases with spliceosome mutations (SF3B1, SRSF2, U2AF1, ZRSR2, U2AF1)...

Tumoral microRNAs, such as miR-125b and miR-155b, are important gene expression regulators with complex pathogenetic mechanisms. However, their role in DLBCL, especially when cell-of-origin classification is considered, are still to be elucidated. In a series of 139 DLBCL cases considering germinal center (GC) versus nonGC subtypes, we investigated miR-125b and miR-155b expression by in situ hibridization and their association with some immunophenotypic presentations, including MYC, BCL2 and TP53 expression, MYC, BCL2 and BCL6 translocation status, as well as clinicopathological features and outcomes...

Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017...

Follicular lymphoma (FL) is an indolent B-cell lymphoma with a germinal center (GC) B cell phenotype that typically harbors t(14;18)(q32;q21). t(14;18) juxtaposes IGH on 14q32 and BCL2 on 18q21, resulting in overexpression of the anti-apoptotic BCL2 protein. However, t(14;18) is also found in the peripheral blood or lymphoid nodes (LNs) of otherwise healthy individuals. Moreover, overt FL has several additional gene alterations involved in epigenetic modification, JAK/STAT signaling, immune modulation, and NF-κB signaling, indicating multi-step lymphomagenesis in FL...

Classic Hodgkin lymphoma (CHL) was first described in 1832 by Thomas Hodgkin, and is characterized by a small number of Hodgkin and Reed-Sternberg cells in a rich inflammatory background. However, even in this modern era, due to the histological and biological overlap with CHL and other B-cell malignancies, including mediastinal grey zone lymphoma and other lymphomas accompanied by "Hodgkinoid cells", their discrimination is challenging and sometimes impossible. The complexity and ambiguity of the boundaries of CHL and its related diseases make the definition of CHL unresolved...

Myeloid sarcoma (MS) is a condition characterized by a tumor mass of myeloid blasts in any site of the body other than the bone marrow, with or without acute myeloid leukemia. A 93-year-old man underwent laparoscopy-assisted distal gastrectomy with D1 lymphadenectomy for advanced gastric cancer. Other than metastatic foci of gastric cancer cells, some dissected lymph nodes showed destructive architecture with proliferation of small- to medium-sized atypical hematopoietic cells. Those cells were focally positive for naphthol AS-D chloroacetate esterase...

High-grade B-cell lymphoma with 11q aberrations (HGBL-11q) has been classified for the first time as a high-grade mature B-cell neoplasm according to the 5th edition of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. HGBL-11q is morphologically and immunohistochemically similar to Burkitt lymphoma (BL) or HGBL; it is characterized by gain in the 11q23.2-11q23.3 region and loss in the 11q24.1-qter region but it lacks MYC translocation. HGBL-11q is a rare tumor, and its exact frequency in Japan remains unclear...

A Japanese subgroup analysis from the Asian phase II study of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) was performed to evaluate the efficacy and safety outcomes of the Japanese population. In this Asian phase II study, darinaparsin was administered to 65 patients, including 37 Japanese patients. In the Japanese population, the histopathological type of PTCL was PTCL, not otherwise specified in 26 patients (70.3%), angioimmunoblastic T-cell lymphoma in 9 patients (24...

Scarce data are available regarding neoplastic PD-L1 (nPD-L1, clone SP142) expression in cutaneous T-cell lymphoma. We recently documented a possible association of increased nPD-L1 expression with tumor progression to secondary nodal involvement in two cases of CD30-positive primary cutaneous large T-cell lymphoma (PC-LTCL) (Pathol Int 2020;70:804). Notably, the nodal sites exhibited classic Hodgkin lymphoma (CHL) mimicry related to both morphology and tumor microenvironment (TME), i.e., abundant PD-L1-positive tumor-associated macrophages and low-level PD-1 expression on T-cells...

A 71-year-old Japanese man presented with severe thrombocytopenia. A whole-body CT at presentation showed small cervical, axillary, and para-aortic lymphadenopathy, leading to suspicion of immune thrombocytopenia due to lymphoma. Biopsy was difficult to perform because of severe thrombocytopenia. Thus, he received prednisolone (PSL) therapy and his platelet count gradually recovered. Two and a half years after PSL therapy initiation, his cervical lymphadenopathy slightly progressed without other clinical symptoms...

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We encountered a case of calreticulin mutation-positive essential thrombocythemia (ET) with TAFRO syndrome-like features, followed by a rapid fatal course. The patient had been on anagrelide therapy for approximately three years for management of ET; however, she suddenly stopped going for follow-up and discontinued the medicine for a year. She presented with fever and hypotension, suggestive of septic shock, and was transferred to our hospital...

CD5-positive diffuse large B cell lymphoma (CD5+ DLBCL) is a high-risk lymphoma type. Recently, the PEARL5 (a Phase II trial of DA-EPOCH and Rituximab with HD-MTX therapy for newly diagnosed DLBCL with CD5 expression) study demonstrated the efficacy of the DA-EPOCH-R (cyclophosphamide, etoposide, doxorubicin, vincristine, prednisone, and rituximab)/HD-MTX (high-dose methotrexate) regimen for CD5+ DLBCL. In this report, we revealed the impact of the DA-EPOCH-R/HD-MTX regimen on the clinical course of CD5+ DLBCL in the real-world...

Outcomes of patients with histologic transformation (HT) of follicular lymphoma (FL) have been believed to be poor. The most common histologic subtype of transformation from FL is diffuse large B-cell lymphoma (DLBCL), which accounts for 90% of the cases, and the remaining 10% of the cases include classic Hodgkin lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, B-acute lymphoblastic leukemia/lymphoma, histiocytic/dendritic cell sarcoma, and anaplastic large cell lymphoma-like lymphoma. Because the histologic criteria for the diagnosis of DLBCL transformed from FL are unclear, convenient histopathological criteria for HT are required...

In the 2016 update of the World Health Organization (WHO) classification of myeloid neoplasms, acute undifferentiated leukemia (AUL) was defined by a lack of lineage-specific markers. AUL has very poor prognosis and no established therapies due to its rarity. We report a case of a 31-year-old man with AUL who showed complete molecular response to an acute lymphoblastic leukemia (ALL)-based regimen and received allogeneic hematopoietic stem cell transplantation. The patient's blast cells were CD7-positive and localized to lymph nodes in the neck and to a large mediastinal mass; there was also rearrangement of the T-cell receptor delta locus...

Autoimmune pancytopenia is rarely seen with Hodgkin lymphoma, and only one pediatric case of pancytopenia after autologous hematopoietic stem cell transplantation (HSCT) has been reported. We herein report a case of autoimmune pancytopenia that developed after autologous HSCT for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). A 56-year-old Japanese woman underwent autologous HSCT for NLPHL. She developed autoimmune pancytopenia seven months after autologous HSCT. In this case, PSL was effective, and the blood cell counts normalized completely...

Cholesterol uptake via LDL receptor (LDLR) is increased in some malignant tumors, and incorporated LDL contribute to lipid droplet formation. Burkitt's lymphoma is known to have a large number of vacuoles in the cytoplasm, however, intracellular vacuoles are also seen in high-grade lymphomas such as adult T-cell leukemia/lymphoma, diffuse large B-cell lymphoma and primary central nervous system lymphoma. Recent studies have shown that esterified cholesterol is the main component of these vacuoles and the expression of cholesterol metabolism-related molecules such as LDLR, acetyl-CoA acetyltransferase 1 (ACAT1) which esterifies free cholesterol, and scavenger receptor class B type I (SR-BI) which effluxes free cholesterol, was significantly upregulated in lymphoma cells...

It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases)...

We describe two patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL). The first patient (case 1) was a woman in her late 70s who presented with a tumor in the left frontal lobe, whereas the second patient (case 2) was a man in his early 70s who presented with a left frontal lobe tumor associated with intratumoral hemorrhage. The histopathology of the tumor specimen disclosed the proliferation of large cells with centroblastic (case 1) or immunoblastic/plasmablastic (case 2) cytomorphology and an accumulation of the tumor cells within the perivascular space...

Richter's syndrome (RS) of the central nervous system (CNS) is known to have an extremely poor prognosis. Ibrutinib has been reported to have some activity in patients with RS, despite its poor prognosis. Although ibrutinib crosses the blood-brain barrier, its efficacy in RS patients with CNS involvement remains unknown. Here, we report a case of RS isolated in the CNS that was confirmed to be clonally related to chronic lymphocytic leukemia (CLL) by immunoglobulin heavy chain gene analysis. Although the median survival of patients with RS clonally related to CLL was significantly shorter than that of patients with RS clonally unrelated to CLL, the patient received ibrutinib monotherapy without experiencing any significant adverse events, and the disease remained stable with ibrutinib until 6 weeks later...

Bone marrow necrosis (BMN) occurs most frequently in hematological malignancies and sometimes in non-hematological disorders. Lymphoid diseases causing necrosis are regarded as high-grade disease. B-lymphoblastic leukemia/lymphoma is the most common malignant cause of BMN. Here, we present two patients with follicular lymphoma (FL) and MYC gene abnormalities who developed BMN. In one case of BMN, the necrosis disappeared in response to chemotherapy, and the patient survived with complete remission. In the other case, BMN remained even after chemotherapy, and effective chemotherapy could not be administered due to suppressed hematopoiesis, which led to the lymphoma worsening and the patient's death...