Journal of Clinical and Experimental Hematopathology最新文献

Here we describe our experience with a rare case of methotrexate (MTX)-associated lymphoproliferative disorder (LPD) initially diagnosed as follicular lymphoma (FL) and then in relapse as classic Hodgkin lymphoma (CHL). A 66-year-old man was admitted to the hospital with fever and abdominal and lower back pain after a transient remission of MTX-associated FL (MTX-FL) following MTX withdrawal. Computed tomography (CT) showed para-aortic lymphadenopathy, which was compatible with one of the previous FL lesions. We considered a relapse of FL and started bendamustine and rituximab. Although his initial symptoms and para-aortic lymphadenopathy regressed after the first course, he began to have dorsal pain, and multiple osteolytic lesions were detected on CT. We biopsied a Th4 vertebra osteolytic lesion, and the results indicated MTX-associated CHL (MTX-CHL). We successfully treated advanced MTX-CHL with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD). This case suggests the importance of repeat biopsy of a new lesion arising after resolution of previously affected sites in MTX-LPD and the effectiveness of A+AVD in treating advanced MTX-CHL.

Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by the abundant infiltration of tumor microenvironment (TME) cells. The activity of TME cells reportedly plays an important role in the biology of FL. TME cells that reside within neoplastic follicles, such as T-follicular helper cells and follicular dendritic cells, have been shown to aid in FL development and progression through interactions with malignant B cells, whereas regulatory T cells have unexpectedly shown an apparently favorable prognostic impact in FL. Unfortunately, the understanding of the FL TME, particularly regarding minor cell subsets, has been hampered by unknown cell heterogeneity. As with other solid and hematologic cancers, novel single-cell analysis technologies have recently been applied to FL research and have uncovered previously unrecognized heterogeneities, not only in malignant B cells but also in TME cells. These reports have greatly increased the resolution of our understanding of the FL TME and, at the same time, raised questions about newly identified TME cells. This review provides an overview of the unique aspects of FL TME cells with a clinical viewpoint and highlights recent discoveries from single-cell analysis, while also suggesting potential future directions.

Thrombocytopenia is a frequent complication in chronic lymphocytic leukemia (CLL). Differentiating autoimmune thrombocytopenia from thrombocytopenia due to bone marrow infiltration is necessary for appropriate treatment, but sometimes difficult. Here we report a 60-year-old male patient with CLL who had achieved complete response after treatment with fludarabine, cyclophosphamide, and rituximab two years prior to presentation. He was admitted with severe thrombocytopenia that was unresponsive to intravenous immunoglobulin. Imaging studies revealed systemic enlarged lymph nodes and bone marrow aspiration was hypercellular with > 95% lymphocytes and scant megakaryocytes. Acalabrutinib 200 mg/day was administered for the treatment of CLL exacerbation. A gradual decrease in CLL cells and recovery of megakaryocytes in bone marrow were observed, but platelet counts remained low. Systemic administration of prednisolone 0.5 mg/kg, in addition to acalabrutinib, was started, considering the contribution of autoimmune thrombocytopenia; platelet recovery was rapid and sustained for more than a year. Even if bone marrow examination suggested thrombocytopenia due to direct leukemic infiltration, it is difficult to exclude the possibility of concomitant immunogenic thrombocytopenia. We conclude that for CLL patients with severe thrombocytopenia, repeating bone marrow examination and concurrent immunosuppressive therapies and treatment of the underlying CLL may be beneficial.

Follicular lymphoma is one of the most frequent lymphomas. Histologically, it is characterized by a follicular (nodular) growth pattern of centrocytes and centroblasts; mixed with variable immune microenvironment cells. Clinically, it is characterized by diffuse lymphadenopathy, bone marrow involvement, and splenomegaly. It is biologically and clinically heterogeneous. In most patients it is indolent, but others have a more aggressive evolution with relapses; and transformation to diffuse large B-cell lymphoma. Tumorigenesis includes an asymptomatic preclinical phase in which premalignant B-lymphocytes with the t(14;18) chromosomal translocation acquire additional genetic alterations in the germinal centers, and clonal evolution occurs, although not all the cells progress to the tumor stage. This manuscript reviews the pathobiology and clinicopathological characteristics of follicular lymphoma. It includes a description of the physiology of the germinal center, the genetic alterations of BCL2 and BCL6, the mutational profile, the immune checkpoint, precision medicine, and highlights in the lymphoma classification. In addition, a comment and review on artificial intelligence and machine (deep) learning are made.

We report two cases of diffuse large B-cell lymphoma (DLBCL) with composite germinal center B-cell (GCB) and non-GCB types. Case 1 was a 72-year-old woman with inguinal lymph node swelling. Two morphologically different lesions were concurrently observed in needle biopsy specimens. One lesion was DLBCL with centroblastic morphology and a GCB phenotype (CD10⁺, BCL6⁺, and MUM1^-), according to the Hans algorithm. The other lesion was DLBCL with anaplastic morphology and a non-GCB phenotype (CD10^-, BCL6⁺, and MUM1⁺). Considering cellular atypia, the GCB-type DLBCL likely progressed to non-GCB-type DLBCL. Case 2 was a 34-year-old man who underwent ileocecal resection, with four lesions observed in the ileum. All four lesions indicated centroblastic morphology. Three lesions showed a GCB phenotype (CD10⁺, BCL6⁺, and MUM1⁺), while the other showed a non-GCB phenotype (CD10^-, BCL6⁺, and MUM1⁺). These tumors were clonally related. BCL2 expression and MYC rearrangement were not related to changes in the cell of origin (COO) in either case. In conclusion, changes in the COO in DLBCL may not be uncommon. Therefore, investigation of the COO in other sites or at relapse may be needed if new drugs with different indications for each COO are developed.

We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS). At a median follow-up time of 69 months (range, 2-169 months), the 5-year progression-free survival (PFS) rates were 82.5% (95%CI, 46.1-95.3%) in the UFS, and 57.8% (95%CI, 38.1-73.2%) in the relapsed or refractory (R/R) patients (n=34), respectively. The 5-year PFS rates were 62.3% (95%CI, 34.0-81.3%) in primary resistant (n=13) or early relapsing (within 1 year from the initial diagnosis) patients (n=4), and 53.3% (95%CI, 25.9-74.6%) in those relapsing >1 year after the initial diagnosis (n=17), with no statistically significant difference (p=0.498). In R/R patients, multivariate analysis showed that the remission status before HDC/ASCT was an independent poor prognostic factor for progression-free survival (hazard ratio [HR], 17.0; 95%CI, 3.35-86.6; p=0.000630) and high-risk category in the international prognostic index for OS (HR, 9.39; 95%CI, 1.71-51.6; p=0.0100). The incidence of non-relapse mortality by 5 years, and 10 years were 12.2%, and 15.2%, respectively. Eleven patients (23.9%) developed second malignancies, which was the most frequent late complication after HDC/ASCT, with 5-year, and 10-year cumulative incidence of 16.9%, 22.5%, respectively. In conclusion, HDC/ASCT is effective for chemo-sensitive R/R DLBCL regardless of the timing and lines of therapy. However, careful observation is required, considering the long-term complications such as secondary malignancies.

We conducted this study with the objective of elucidating the mechanism of development of fibrosis in hematologic neoplasms and develop treatments for these patients. Among the suggested mechanisms of development of fibrosis is cases of hematologic neoplasms is the production of TGF-beta1 (transforming growth factor-beta-1) and TNF-alpha1 (tumor necrotizing factor-alpha-1) by the tumor cells, both of which are fibrosis-stimulating cytokines that act on fibroblasts to promote fibrosis. However, there are few reports based on human clinical pathology studies. We conducted an immunohistochemical study on paraffin-embedded formalin-fixed specimens obtained from 104 patients with various pathologic conditions (acute leukemia, malignant lymphoma, inflammation, cancer, etc.). The association of tissue fibrosis with positive immunohistochemistry for TGF- beta1 and/or TNF-alpha1, TGF-beta1 was found to be strongly associated with tissue fibrosis, and in cases with positive immunohistochemistry for TGF-beta1, the odds ratio for fibrosis was 12.8, which was significantly high. Combined positivity for TGF-beta1 and TNF-alpha1 was also associated with a significant odds ratio for fibrosis of 3.4, suggesting that TGF-beta1 expression is an important prerequisite. TGF-beta1 has been suggested as playing a relatively important role in tissue fibrosis. Future clinical application of these cytokines for both diagnosis and treatment is expected.