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1.
Cancers (Basel) ; 16(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38927897

ABSTRACT

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.

2.
Exp Mol Pathol ; 137: 104908, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38824688

ABSTRACT

PURPOSE: The aim of this study was to clarify DNA methylation profiles determining the clinicopathological diversity of urothelial carcinomas. METHODS: Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation450 BeadChip in 46 paired samples of non-cancerous urothelium (N) and corresponding cancerous tissue (T), and 26 samples of normal control urothelium obtained from patients without urothelial carcinomas (C). For genes of interest, correlation between DNA methylation and mRNA expression was examined using the Cancer Genome Atlas database. In addition, the role of a selected target for cancer-relevant endpoints was further examined in urothelial carcinoma cell lines. RESULTS: The genes showing significant differences in DNA methylation levels between papillary carcinomas and more aggressive non-papillary (nodular) carcinomas were accumulated in signaling pathways participating in cell adhesion and cytoskeletal remodeling. Five hundred ninety-six methylation sites showed differences in DNA methylation levels between papillary and nodular carcinomas. Of those sites, that were located in CpG-islands around transcription start site, 5'-untranslated region or 1st exon, 16 genes exhibited inverse correlations between DNA methylation and mRNA expression levels. Among the latter, only the KLF11 gene showed papillary T sample-specific DNA hypermethylation in comparison to C and N samples. The DNA methylation levels of KLF11 were not significantly different between T samples and N samples or T samples and C samples for patients with papillo-nodular or nodular carcinomas. Knockdown experiments using the urothelial carcinoma cell lines HT1376 and 5637, which are considered models for papillary carcinoma, revealed that KLF11 participates in altering the adhesiveness of cells to laminin-coated dishes, although cell growth was not affected. CONCLUSION: These data indicate that DNA hypermethylation of KLF11 may participate in the generation of papillary urothelial carcinomas through induction of aberrant cancer cell adhesion to the basement membrane.


Subject(s)
Carcinoma, Papillary , Cell Adhesion , DNA Methylation , Urinary Bladder Neoplasms , Humans , DNA Methylation/genetics , Cell Adhesion/genetics , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Female , Cell Line, Tumor , Male , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urothelium/pathology , Urothelium/metabolism , Aged , Gene Expression Regulation, Neoplastic , Middle Aged , CpG Islands/genetics , Repressor Proteins/genetics
3.
Virchows Arch ; 484(3): 465-473, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38349387

ABSTRACT

Brentuximab vedotin (BV), CD30 specific antibody drug conjugate, has been used to treat anaplastic large cell lymphoma (ALCL) and classic Hodgkin lymphoma (CHL); it is also used in the treatment of other CD30-positive peripheral T-cell lymphomas. We aimed to investigate the incidence and clinicopathological characteristics of patients with ALCL or CHL with loss of or decrease in CD30 expression after BV-containing therapy. Twelve and nine patients with refractory/relapsed CHL and ALCL, respectively, were analyzed after receiving BV-containing therapy. In four ALCL patients (44%), CD30 expression was lost/decreased in re-biopsy materials, including one with complete loss and three with a reduction of less than 20%. All 12 CHL patients showed consistent CD30 expression levels after BV treatment. Compared with five ALCL patients with consistent CD30 expression, four ALCL patients with a loss of/decrease in CD30 expression received a higher cumulative dose of BV (P = 0.014) and revealed a lower intensity of CD30 expression in initial biopsy materials (P = 0.017). The subtypes of ALCL (ALK positive, ALK negative, and primary cutaneous) were not related to the loss of/decrease in CD30 expression. In conclusion, 44% of ALCL patients, regardless of histological subtypes, showed a loss of/decrease in CD30 expression after receiving BV-containing therapy, but this phenomenon was not observed in CHL patients. A higher cumulative dose of BV and a lower amount of CD30 antigen in tumor cells in the initial biopsy materials might be predictors of a loss of/decrease in CD30 expression in ALCL patients.


Subject(s)
Hodgkin Disease , Immunoconjugates , Lymphoma, Large-Cell, Anaplastic , Humans , Brentuximab Vedotin/therapeutic use , Lymphoma, Large-Cell, Anaplastic/pathology , Immunoconjugates/adverse effects , Ki-1 Antigen , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Receptor Protein-Tyrosine Kinases
4.
J Clin Exp Hematop ; 63(3): 181-186, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37518270

ABSTRACT

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.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Neoplasm Recurrence, Local , Male , Female , Humans , Aged , Adult , Neoplasm Recurrence, Local/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , B-Lymphocytes/pathology , Germinal Center/metabolism , Germinal Center/pathology , Biopsy, Needle , Prognosis
5.
IJU Case Rep ; 6(3): 161-164, 2023 May.
Article in English | MEDLINE | ID: mdl-37144078

ABSTRACT

Introduction: Renal cell carcinoma with TFEB amplification is rare and reportedly aggressive. We herein report a case of renal cell carcinoma with TFEB translocation and amplification in which long-term control was achieved by multimodal therapy including a vascular endothelial growth factor -receptor inhibitor. Case presentation: A 70-year-old man was referred to our institution for the treatment of renal cell carcinoma with multinodal metastases. Open nephrectomy and lymph node dissection were performed. Immunohistochemistry for transcription factor EB was positive, and fluorescent in situ hybridization revealed TFEB rearrangement and amplification. The diagnosis was TFEB-translocated and -amplified renal cell carcinoma. VEGFA amplification was also demonstrated by fluorescent in situ hybridization. The residual and recurrent tumors were treated and controlled for 52 months by vascular endothelial growth factor-receptor target therapy, radiation therapy, and additional surgery. Conclusion: A good long-term response to anti-vascular endothelial growth factor drug therapy may be due to VEGFA amplification and subsequent vascular endothelial growth factor overexpression.

6.
J Clin Exp Hematop ; 63(1): 12-18, 2023.
Article in English | MEDLINE | ID: mdl-36990772

ABSTRACT

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. One of the proposed criteria of HT from our institute is the presence of diffuse architecture with a proportion of large lymphoma cells of ≥20%, and for challenging cases, Ki-67 index ≥50% is used as a reference. Patients with HT to non-DLBCL have poorer outcomes than those with HT to DLBCL; thus, rapid and accurate histologic diagnosis is desired. In this review, we discussed the recent literatures describing the histopathologic variety and proposal of definition of HT.


Subject(s)
Lymphoma, Follicular , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Large-Cell, Anaplastic , Plasmablastic Lymphoma , Humans , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/pathology , Pathologists , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Cell Transformation, Neoplastic/pathology
7.
Hum Pathol ; 135: 84-92, 2023 05.
Article in English | MEDLINE | ID: mdl-36702355

ABSTRACT

BCL2 positivity by immunohistochemistry is helpful for the diagnosis of follicular lymphoma (FL); however, a minority of FL cases are BCL2-negative, and the diagnosis is thus challenging. We retrospectively analyzed the incidence, morphology, immunophenotype, and genetic status of BCL21+ (weakly/focally positive by clone 124), BCL20 (negative), and BCL2controversial FLs compared with BCL22+ (strongly positive) FLs to clarify diagnostic clues. In 1068 FL cases, 103 (10%) with BCL21+ (37 cases, 4%), BCL20 (61 cases, 6%), or BCL2controversial (5 cases, 0.5%) were included in the final analysis. BCL21+ and BCL20 FLs tended to have limited stage disease, nodal disease, and grades 3A/3B histology and showed a higher complete response rate than BCL22+ FLs. Among 103 BCL20, BCL21+, or BCL2controversial FL cases, 34 (33%) had a diffuse area composed of CD20-positive small-to medium-sized lymphoid cells, a feature of low-grade B-cell lymphoma. Interfollicular dense CD20-positive cells and interfollicular clusters of CD10-positive cells were observed in 59% and 37% of cases, respectively. In remaining 13/40 cases (33%), BCL2 was converted to BCL22+ by other clones E17/SP66. CD23 and MUM1 were positive in 10/40 (25%) and 1/40 (3%) cases, respectively. IGH/BCL2 fusion and clonality were detected in 6/37 (16%) and 31/34 (91%) cases, respectively. In conclusion, morphological examination of the distribution of CD20-and/or CD10-positive cells and the presence of diffuse area could be used to diagnose FL in most cases. The majority of the remaining FL cases could be diagnosed using other BCL2 clones and clonality analyses.


Subject(s)
Lymphoma, B-Cell , Lymphoma, Follicular , Humans , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/genetics , Lymphoma, Follicular/pathology , Retrospective Studies , Lymphoma, B-Cell/pathology , Proto-Oncogene Proteins c-bcl-2/genetics , Translocation, Genetic
9.
JGH Open ; 6(4): 257-262, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35475204

ABSTRACT

Background and Aim: This study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features. Methods: We retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed. Results: A total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B-cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa-associated lymphoid tissue (MALT) lymphoma (9%), peripheral T-cell lymphoma-NOS (2%), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine. Conclusions: Colorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types.

10.
Hum Pathol ; 124: 14-23, 2022 06.
Article in English | MEDLINE | ID: mdl-35307403

ABSTRACT

Histopathological diagnoses are challenging for rare CD3-and CD20-negative extramedullary leukemias/lymphomas. We report 118 cases of CD3- CD20-extramedullary leukemias/lymphomas (2.4% of 4977 cases). CD45 was positive in 68% of cases. Forty-nine (41%) cases were anaplastic large cell lymphomas. Thirty-five (30%) cases were large B-cell lymphomas/plasmablastic lymphomas positive for at least one of the following markers: CD79a, PAX5, CD19, CD138, and MUM1. Nine (8%) cases were peripheral T/NK-cell lymphomas, where at least CD43, CD45RO, or cytotoxic molecules were positive; 4, 3, and 2 cases were extranodal NK/T-cell lymphoma, nasal type, peripheral T-cell lymphoma-not otherwise specified, and adult T-cell leukemia/lymphoma, respectively. The remaining 25 (21%) cases included 11, 8, and 6 cases of myeloid sarcoma, blastic plasmacytoid dendritic cell neoplasm, and B- or NK-cell lymphoblastic leukemia/lymphoma, respectively. For large B-cell lymphoma/plasmablastic lymphoma diagnosis, MUM1 (92%) was the most sensitive marker, followed by CD79a (63%), PAX5 (52%), CD138 (42%), and CD19 (36%). EBER 1 and HHV8 were positive in 32% and 0% of the cases. For peripheral T/NK-cell lymphomas other than ALCL, CD45RO and CD43 were positive in nine cases; however, cytotoxic molecules (TIA1, 86%; granzyme B, 71%) were the most sensitive markers. In conclusion, most cases of the 118 (2.4%) CD3- CD20- extramedullary leukemia/lymphoma were represented by anaplastic large cell lymphomas (41%). The second most frequent group of neoplasia, large B-cell lymphoma/plasmablastic lymphoma (30%), characterized a special diagnostic challenge when B-cell markers were not expressed, requiring immunohistochemistry for multiple B-cell markers and molecular analysis in some cases.


Subject(s)
Leukemia , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Large-Cell, Anaplastic , Lymphoma, T-Cell, Peripheral , Plasmablastic Lymphoma , Adult , Antigens, CD19 , Humans , Immunohistochemistry , Lymphoma, T-Cell, Peripheral/pathology , Plasmablastic Lymphoma/diagnosis
11.
Cancer Med ; 11(10): 2106-2116, 2022 05.
Article in English | MEDLINE | ID: mdl-35129305

ABSTRACT

Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low-tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow-up from the first progression was 79.8 months (range, 2.1-227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4-30.2), and 76.5% (95% CI, 68.0-84.1) of the patients subsequently underwent the second-line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6-94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4-38.8) (HR, 2.13; 95% CI, 1.48-3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first-line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7-NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0-25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes.


Subject(s)
Lymphoma, Follicular , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cohort Studies , Humans , Incidence , Lymphoma, Follicular/drug therapy , Rituximab/therapeutic use , Watchful Waiting
12.
Ann Hematol ; 101(4): 799-810, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35032188

ABSTRACT

The prognosis of patients with aggressive adult T cell leukemia-lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints.


Subject(s)
B7-H1 Antigen , CTLA-4 Antigen/metabolism , Leukemia-Lymphoma, Adult T-Cell , Programmed Cell Death 1 Receptor/metabolism , Adult , Humans , Leukemia-Lymphoma, Adult T-Cell/metabolism , Prognosis , Programmed Cell Death 1 Receptor/analysis , Retrospective Studies
13.
Int J Clin Oncol ; 26(12): 2275-2281, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34468885

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive disease that is often diagnosed at an advanced stage. There is no standard treatment for metastatic ACC; EDP-M (etoposide, doxorubicin, and cisplatin plus mitotane) is one treatment option. A randomized controlled trial (FIRM-ACT) evaluating the efficacy of EDP-M showed progression-free survival (PFS) was 5.0 months, overall survival (OS) was 14.8 months, the response rate was 19%, and adrenal insufficiency occurred in 3.4% of patients. However, the efficacy and safety of this regimen in Asia are not fully reported. METHODS: We retrospectively analyzed 43 patients diagnosed with metastatic ACC at the National Cancer Center Hospital between 1997 and 2020. We evaluated PFS, OS, and response in 17 patients who received EDP-M as first-line therapy. RESULTS: The median age at treatment initiation was 45 years (range 18-74). Eight patients (47%) had autonomous hormone production, including six patients with hypercortisolism. The best response of partial response and stable disease was seen in two (12%) and ten (59%) patients, respectively. The median PFS was 6.2 months [95% confidence interval (CI): 4.3-10.0]. The median OS was 15.4 months (95% CI 11.6-not reached). Three patients received only one cycle due to adverse effects associated with hypercortisolism. Grade 3/4 adverse events associated with adrenal insufficiency occurred in three (17%) cases, resulting in EDP-M discontinuation. CONCLUSIONS: The EDP-M regimen had similar PFS to that observed in FIRM-ACT. Adrenal insufficiency was more frequent in the current study, but this could be managed with supportive endocrinological care such as cortisol replacement.


Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Adolescent , Adrenal Cortex Neoplasms/drug therapy , Adrenocortical Carcinoma/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/adverse effects , Doxorubicin/adverse effects , Etoposide/adverse effects , Humans , Middle Aged , Mitotane/adverse effects , Retrospective Studies , Treatment Outcome , Young Adult
14.
Pathol Int ; 71(10): 674-681, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34339560

ABSTRACT

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki-67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B-cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki-67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression-free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki-67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes.


Subject(s)
Cell Transformation, Neoplastic , Ki-67 Antigen/metabolism , Lymphoma, Follicular/pathology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Adult , Aged , Aged, 80 and over , Clinical Decision Rules , Female , Humans , Lymphoma, Follicular/metabolism , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Prognosis , Survival Analysis
15.
Hematol Oncol ; 39(5): 650-657, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34431557

ABSTRACT

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.


Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Lymphoma, Follicular/mortality , Transplantation Conditioning/mortality , Adult , Aged , Female , Follow-Up Studies , Humans , Lymphoma, Follicular/pathology , Lymphoma, Follicular/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Transplantation, Autologous , Transplantation, Homologous
16.
Acta Haematol ; 144(6): 641-648, 2021.
Article in English | MEDLINE | ID: mdl-34139685

ABSTRACT

INTRODUCTION: Excisional biopsy (EB) is considered the gold standard for lymphoma diagnosis. Although recent advances in interventional radiology enable sampling with core-needle biopsy (CNB), only few studies evaluated the utility of CNB compared to that of EB. METHODS: We analyzed patients with lymphoma who had a diagnostic biopsy at the National Cancer Center Hospital during 2002-2017. We investigated the clinical and pathological characteristics of CNB in 2017. RESULTS: The proportion of CNB utility in total biopsy procedures had increased from 11 to 48% during the 15 years. In 2017, CNB was opted more frequently than EB for a biopsy of superficial, abdominal, or anterior mediastinal lesions. Only one out of 72 patients who had CNB required re-biopsy with EB because of insufficiency. The incidence of complications was comparable between CNB and EB: 2 (4%) cases of minor bleeding with CNB and 1 (8%) case of minor bleeding with EB. The median time from the first visit to biopsy was significantly shorter with CNB (5.5 days) than with EB (15 days). CONCLUSION: There is an increasing trend in the utility of CNB. CNB is a less invasive method with shorter time to biopsy and can be considered an alternative to EB.


Subject(s)
Biopsy, Large-Core Needle , Biopsy/methods , Lymphoma/diagnosis , Adult , Aged , Aged, 80 and over , Biopsy/adverse effects , Biopsy, Large-Core Needle/adverse effects , Female , Hemorrhage/etiology , Humans , In Situ Hybridization, Fluorescence , Lymphadenopathy/pathology , Lymphoma/pathology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Retrospective Studies
17.
Hum Pathol ; 111: 84-91, 2021 05.
Article in English | MEDLINE | ID: mdl-33727166

ABSTRACT

We encountered two cases of CD5- blastoid variant mantle cell lymphoma (MCL), prompting us to investigate the proportion of CD5 negativity in MCL and assess the diagnosis of aggressive MCL variants. Among 117 patients diagnosed with MCL, CD5 negativity was observed in 13% (13/104) of cases with classical MCL and 15% (2/13) of cases with blastoid/pleomorphic variant MCL. Of the aggressive MCL variant cases, tumor cells exhibited intermediate nuclear size and required differential diagnosis between blastoid variant and classical MCL in six patients, and classical MCL cells were found in the background of aggressive variant tumors or in other sites in six patients. Of 1534 patients with diffuse large B-cell lymphoma (DLBCL), CD5 positivity was observed in 8% (121/1534) of cases. Immunohistochemical staining for cyclin D1 performed for these cases revealed one cyclin D1-positive and IGH/CCND1 fusion-positive case (0.9%, 1/114), namely pleomorphic variant MCL. Of the remaining 1413 patients initially diagnosed with CD5- DLBCL, the diagnoses of two patients (0.1%) were amended to CD5- blastoid variant MCL in the relapse phase based on morphology, cyclin D1 immunostaining, and fluorescence in situ hybridization. The incidence of CD5 negativity was similar between classical MCL and two aggressive variants. Accurate diagnosis of MCL variants was enabled by identifying a classical MCL component and/or CD5 positivity; however, we misdiagnosed two cases of CD5- blastoid variant MCL. A small number of MCL variants may be included in CD5- DLBCL cases. The diagnosis of CD5- aggressive variant MCL remains challenging but crucial because of its therapeutic significance.


Subject(s)
Biomarkers, Tumor/analysis , Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , CD5 Antigens/metabolism , Diagnosis, Differential , Female , Humans , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged
18.
Eur J Haematol ; 106(2): 213-220, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33098704

ABSTRACT

OBJECTIVES: This study aimed to evaluate the outcomes of local radiotherapy (LRT) in patients with histologic transformation (HT) following rituximab-containing chemotherapy. METHODS: We retrospectively analysed 92 patients with biopsy-confirmed HT undergoing rituximab-containing chemotherapy at our institution between 2003 and 2015. RESULTS: Of the 36 patients with limited-stage disease at diagnosis of HT, 29 (78%) received LRT. The estimated 5-year progression-free survival (PFS) rate was significantly better in patients who underwent LRT than in those who did not (93% and 42%, respectively; P < 0.05). Multivariate analyses employing age, sex, performance status, LRT and treatment response demonstrated that LRT was an independent prognostic factor for PFS (hazard ratio [HR]: 11.8; 95% confidence interval [CI]: 1.28-108.1; P < 0.05). Of the 32 patients who underwent LRT for HT lesion treatment, 31 (97%) did not show disease progression within radiation fields; among them, 27 patients (84%) survived without disease progression during the follow-up period. One patient developed hypothyroidism due to LRT; the others had no acute or late-onset complications of LRT. CONCLUSIONS: Our data support the recommendation of LRT for HT lesion treatment following rituximab-containing chemotherapy in select patients with localised HT, as a rational treatment approach with potentially limited toxicity.


Subject(s)
Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/therapy , Radiotherapy, Adjuvant , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Combined Modality Therapy , Humans , Lymphoma, B-Cell/mortality , Middle Aged , Neoplasm Grading , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Prognosis , Radiotherapy, Adjuvant/methods , Retrospective Studies , Rituximab/administration & dosage , Treatment Outcome
19.
Clin Case Rep ; 8(12): 3594-3595, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33363994

ABSTRACT

Most patients with IgA deficiency are asymptomatic, but duodenal nodular lymphoid hyperplasia is one symptom known to be associated with common variable immunodeficiency (CVID), including selective IgA deficiency and agammaglobulinemia.

20.
Cancer Med ; 9(23): 8864-8874, 2020 12.
Article in English | MEDLINE | ID: mdl-33022120

ABSTRACT

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy-proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2-4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy.


Subject(s)
Cell Transformation, Neoplastic , Decision Support Techniques , Lymphoma, Follicular/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Biopsy , Female , Health Status Indicators , Hemoglobins/analysis , Humans , L-Lactate Dehydrogenase/blood , Lymph Nodes/pathology , Lymphoma, Follicular/blood , Lymphoma, Follicular/pathology , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Reproducibility of Results , Retrospective Studies , Tokyo
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