Journal of Clinical and Experimental Hematopathology最新文献

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy composed of immature cells that exhibit plasmacytoid dendritic cell (pDC) differentiation. The diagnosis of BPDCN is often challenging due to its rarity and morphologic and phenotypic overlap with other hematologic malignancies, such as acute myeloid leukemia (AML). The emergence of tagraxofusp, a CD123-directed cytotoxin, and other novel therapies has underscored the importance of accurately diagnosing BPDCN. This review initially outlined the clinical and histopathological features of BPDCN, including patients with immunoblastoid morphology. Various proposed diagnostic criteria based on flow cytometry and immunohistochemistry findings were presented, highlighting critical points of caution in the diagnostic process. Strategies for detecting minimal residual disease or microinvasion in BPDCN, a significant clinical issue, were also discussed. Additionally, we reviewed the recurrent 8q24 (MYC) and MYB rearrangements observed in BPDCN, which can aid in diagnosis. Furthermore, we explored mature plasmacytoid dendritic cell proliferation (MPDCP) associated with myeloid neoplasm, which is characterized by a clonal proliferation of pDCs in cases with a defined myeloid neoplasm and may also serve as a potential differential diagnosis for BPDCN. Lastly, we discussed pDC-AML, characterized by pDC proliferation in AML cases, which can also be part of MPDCP and is often associated with frequent RUNX1 mutations. Overall, this review provides insights into BPDCN diagnosis and highlights the current challenges in its detection and differential diagnosis.

Intravascular lymphoma (IVL) is a rare subtype of lymphoma, mostly of B-cell origin. A few cases of IVL have been reported as having NK/T cell origins (IVNKTL). These cases are known to be fatal, especially when systemic symptoms are present. We report the case of a patient of IVNKTL who was refractory to initial treatment and received autologous hematopoietic stem cell transplantation (auto-HSCT). She has maintained complete remission (CR) for over eight years. Our case might support the evidence of auto-HSCT for the treatment of IVNKTL with chemosensitivity.

Severe atopic dermatitis (AD) is known to be associated with a risk of lymphoma. We herein report a case of ALK-negative anaplastic large cell lymphoma (ALK-ALCL) complicated by severe AD during treatment with baricitinib, which is an oral, selective, and reversible Janus Kinase (JAK) 1 and 2 inhibitor used in the treatment of AD. Next-generation sequencing (NGS) demonstrated the TP53 p.G266E mutation, suggesting that this was the trigger of the disease and the cause of its refractory course. The JAK/signal transducer and activator of transcription (STAT) pathway is often activated in tumor cells of ALCLs, suggesting that it is a therapeutic target. The causal connection between baricitinib and lymphomagenesis remains unknown; however, this patient developed ALK-ALCL with TP53 mutations during baricitinib treatment.

Little is known about real-world treatment practices for chronic lymphocytic leukemia (CLL) in Japan. We aimed to assess the time to discontinuation/dose reduction of Bruton tyrosine kinase inhibitors (BTKis) in patients with CLL in a real-world clinical setting in Japan. This was a retrospective observational database study using data from the Medical Data Vision database (from 1 May 2016 to 30 September 2021). Among the 483 patients with CLL who were treated with BTKis, 182 (37.7%) started treatment with a reduced dose of BTKi (lower than the standard dose), 302 (62.5%) experienced at least one dose reduction during the study period, and 123 (25.5%) discontinued BTKi treatment early (for any reason) during the study period. The median time to BTKi discontinuation was 52.3 weeks in 286 patients who started treatment with a standard dose and 57.1 weeks in 182 patients who started treatment with a reduced dose. The use of prophylaxis with anti-infectives was similar during treatment with BTKis and non-BTKis. There was no major difference in the incidence rate of cardiovascular-related adverse events during treatment with BTKis and non-BTKis. This study provides valuable information for future research on the treatment of CLL patients in Japan.

One-third of the patients with diffuse large B-cell lymphoma (DLBCL) experience relapse despite receiving standard R-CHOP chemotherapy. We aimed to elucidate the clinical course and prognosis in older patients with relapsed or refractory (R/R) DLBCL in a single-center experience in Japan. We conducted a retrospective survey of 52 older patients with R/R DLBCL (aged >65 years at diagnosis; 54% men) who received R-CHOP chemotherapy, to assess their clinical course and prognosis. The median progression-free survival was 8.5 months. Seventeen patients had central nervous system (CNS) relapse, with 11 receiving high-dose methotrexate or whole-brain irradiation. Briefly, 30 patients underwent salvage chemotherapy, whereas 11 received palliative care only. Overall survival (OS) from initial treatment and progression were 20.8 and 7.8 months, respectively. Patients with disease progression within 12 months from initial treatment had a significantly poorer OS than those with disease progression over 12 months, while CNS relapse did not affect OS. Among the 41 reported deaths, 40 were due to lymphoma. As the prognosis in older patients with R/R DLBCL is poor even after salvage chemotherapy, improved initial treatment strategies to reduce the risk of progression and more effective and feasible treatments after progression are warranted.

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease unrelated to the Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8) infection. Presently, iMCD is classified into iMCD-IPL (idiopathic plasmacytic lymphadenopathy), iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis/renal insufficiency, and organomegaly), and iMCD-NOS (not otherwise specified). The most common treatment for iMCD is using IL-6 inhibitors; however, some patients resist IL-6 inhibitors, especially for iMCD-TAFRO/NOS. Nevertheless, since serum IL-6 levels are not significantly different between the iMCD-IPL and iMCD-TAFRO/NOS cases, cytokines other than IL-6 may be responsible for the differences in pathogenesis. Herein, we performed a transcriptome analysis of cytokine storm-related genes and examined the differences between iMCD-IPL and iMCD-TAFRO/NOS. The results demonstrated that counts per million of STAT2, IL1R1, IL1RAP, IL33, TAFAIP1, and VEGFA (P < 0.001); STAT3, JAK2, MAPK8, IL17RA, IL18, TAFAIP2, TAFAIP3, PDGFA, VEGFC, CXCL10, CCL4, and CXCL13 (P < 0.01); and STAT1, STAT6, JAK1, MAPK1, MAPK3, MAPK6, MAPK7, MAPK9, MAPK10, MAPK11, MAPK12, MAPK14, NFKB1, NFKBIA, NFKBIB, NFKBIZ, MTOR, IL10RB, IL12RB2, IL18BP, TAFAIP6, TNFAIP8L1, TNFAIP8L3, CSF2RBP1, PDGFB, PDGFC, and CXCL9 (P < 0.05) were significantly increased in iMCD-TAFRO/NOS. Particularly, upregulated IL33 expression was demonstrated for the first time in iMCD-TAFRO/NOS. Thus, inflammatory signaling, such as JAK-STAT and MAPK, may be enhanced in iMCD-TAFRO/NOS and may be a cytokine storm.

Juvenile xanthogranuloma (JXG) is a rare benign non-Langerhans cell histiocytosis that usually occurs in cutaneous lesions on the head, neck, or upper trunk of neonates and young children. Intramuscular JXG, which invades muscle tissue, accounts for only 0.6% of all JXGs and mostly occurs in the skeletal muscles of the extremities or trunk. A 5-month-old girl was referred to our hospital. At the age of 3 months, she presented with a slow-growing lump on her left thigh. Magnetic resonance imaging (MRI) showed a 22 × 19 × 18 mm oval mass in her left thigh. First, needle biopsy results suggested deep JXG or myeloid sarcoma. Therefore, marginal resection was performed. Intraoperatively, the tumor adhered to the left tensor fasciae latae muscle and was resected together. Histopathological examination revealed a diffuse monotonous sheet-like proliferation of mononuclear histiocyte-like cells with pale, eosinophilic, foamy cytoplasm with a background of muscle and fatty tissue. Minimal mitotic figures and no nuclear atypia or multinucleated giant cells were observed. Immunohistochemical analysis was positive for CD68 (KP-1) and CD163; weakly positive for lysozyme; and negative for CD1a, S100, myeloperoxidase, and CD34. No blast proliferation was observed in the bone marrow. The patient was diagnosed with deep JXG and scheduled for periodic physical examination and MRI. Despite positive margins, the patient fared well without local recurrence 48 months after tumor removal. Understanding the unique pathology of deep JXG and detailed histological evaluation are important for decision-making.

Primary thyroid lymphoma is a rare type of cancer. Most cases involve large B-cell lymphomas (LBCLs), which largely show good prognoses. However, the reasons for this have not been understood. To identify the factors influencing the favorable clinical outcomes of thyroid LBCLs, clinicopathological and genetic analyses of 21 cases of thyroid LBCLs were performed, including immunohistochemistry, fluorescence in situ hybridization (FISH), and analysis for MYD88 mutations based on the World Health Organization Classification of Tumors, 5th Edition. The median age of the patients was 70 years (range, 54-80 years). Fifteen patients (71%) had limited-stage disease. The 5-year overall survival rate was 83% (95% confidence interval: 56%-94%). No instances of central nervous system (CNS) recurrence was observed. The series included 15 cases with diffuse LBCL not otherwise specified (DLBCLnos) and 6 cases with transformation of indolent BCLs (T-IBCLs). Immunohistochemistry subdivided DLBCLs into 12 germinal center B-cell (GCB) and 9 non-GCB subtypes. FISH analysis revealed split signals of MYC in 2/17 cases, MALT1 in 0/15 cases, and BCL6 in 3/15 cases. No MYD88 mutations were detected in any of the cases (0/21). The factors contributing to the favorable clinical course in thyroid LBCLs were a higher proportion of GCB phenotypes and the lack of MYD88 mutations in DLBCLnos and T-IBCLs. Even MYC-R cases showed better prognosis. Further studies involving a large series of LBCLs in extranodal organs are needed to expand on the findings of this study.