2016年版WHO淋巴肿瘤分类概述

2016年WHO淋巴肿瘤的修订版问世,内容较2008年版有些变化.文章结合过去8年内的一些临床、病理、遗传学和分子生物学的进展,阐明了一些非常早期的淋巴增生性病变的诊断和临床处理,修饰了一些淋巴瘤的诊断标准,深化了遗传学/分子生物学在多种淋巴瘤诊治中的意义.新的分类中也加入了少数临时的淋巴瘤类型.     

Distribution of lymphoma subtypes in Ukraine according to the WHO 2016 classification

The Ukrainian Lymphoma Registry (ULR) was established in 2019 with the aim of monitoring the quality of diagnosis, staging, and treatment of lymphoma in Ukraine. Between September 2019 and October 2021, 546 patients with newly diagnosed lymphoma were prospectively registered. All cases were diagnosed according to the 2016 updated WHO lymphoma classification. The male-to-female ratio (M/F) for the whole population was 0.7, with a median age of 46 years (range 18–95). The adoption of the 2016 WHO classification resulted in the identification of 36 different lymphoma subtypes, with 132 cases (24.2%) classified differently compared to the 2008 WHO classification. Only 12 cases (2.8%) were true new entities, including seven cases of high-grade B-cell lymphoma NOS, three of anaplastic large B-cell lymphoma, ALK-negative, 1 case of HHV8+ DLBCL NOS, and 1 of high-grade B-cell lymphoma with C-MYC and BCL2/BCL6 rearrangement. Moreover, 55 (61.1%) entities, including 37 defined by WHO 2008 and 18 defined by WHO 2016, were not represented at all. The analysis of cases registered in the ULR provides a comprehensive breakdown of the subtypes, stage distribution, and treatment of malignant lymphomas (ML) in Ukraine, supporting the usefulness of prospective data collection and timely reporting. We believe that this study is the first step toward a better understanding of the real-life outcomes of patients with ML.     

MR-spectroscopic imaging of glial tumors in the spotlight of the 2016 WHO classification

Journal of Neuro-Oncology - The purpose of this study is to map spatial metabolite differences across three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and...     

Who is WHO in myelodysplastic syndromes? Clinical implications of the WHO classification

Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic clonal stem cell diseases characterized by dysplastic morphologic features with a varying percentage of leukemic blasts and clinical bone marrow failure. The French-American-British (FAB) system served as the gold standard of MDS classification for more than two decades. The World Health Organization (WHO) classification, built on the backbone of the FAB classification, is an attempt to further improve the prognostic value of MDS classification as well as to establish its clinical utility as a tool to select different treatments. In this article we highlight the major differences between the FAB classification and the WHO MDS classification. We discuss in more detail the experience of using the new WHO classification since its publication and review the studies that have tried to validate the prognostic value of the new classification or apply it to predict clinical responses to various treatments.     

Surgical management of lower-grade glioma in the spotlight of the 2016 WHO classification system

Journal of Neuro-Oncology - According to the 2016 WHO classification lower-grade gliomas consist of three groups: IDH-mutated and 1p/19q co-deleted, IDH-mutated and IDH-wildtype tumors. The aim of...     

Prognostic significance of imaging contrast enhancement for WHO grade II gliomas

In this study, we investigated the prognostic value of MRI contrast enhancement (CE) at the time of histological diagnosis specifically in a selected population of WHO grade II gliomas. We reviewed 927 histologically proven WHO grade II gliomas for which contrast-enhanced MR images were available at the time of histological diagnosis. CE patterns were classified into three categories: "patchy and faint," "nodular-like," and "ring-like." CE progression over time was recorded before oncological treatment on successive MR images, when available. CE was present in 143 cases (15.9%), with 93 patchy and faint, 50 nodular-like, and no ring-like patterns. CE areas were time progressive before oncological treatment in 35 of the 56 available cases (62.5%). Regardless of its pattern, the presence of CE was not significantly associated with a worsened prognosis (p = 0.415) by univariate analysis. Only the nodular-like pattern of CE (p < 0.01) and the time-progressive CE (p < 0.001) in the available subgroup proved to be statistically associated with survival since first oncological treatment. The present results show the necessity, in cases of WHO grade II gliomas, to study CE at the time of histological diagnosis and, whenever possible, to follow its progression over time before oncological treatment. Nodular-like CE and time-progressive CE are associated with a worsened prognosis, both suggesting malignant transformation, even though histopathological examination cannot initially disclose signs of malignancy in those areas.     

261例急性髓系白血病的WHO分型

目的对急性髓系白血病(AML)患者的WHO分型系统进行评价。方法对按FAB标准确诊并进行了染色体核型分析和/或AML特异相关融合基因检测的259例AML和21例RAEB蛳t患者,重新分类计数其血片和骨髓片,按WHO标准回顾性进行分型诊断,并进行了按WHO标准分型诊断后各亚型之间的诱导化疗疗效比较。结果21例RAEB蛳t患者中2例按WHO标准重新诊断为AML。AML伴(t8;21)/AML1蛳ETO与按国内AML标准确诊的M2b、AML伴t(15;17)/PML蛳RARα与M3/M3v、AML伴inv(16)(p13q22)或t(16;16)(p13;q22)/CBFB蛳MYH11与M4Eo的吻合率为100%。21例(11.2%)的患者重新归入AML伴有多系发育异常。AML伴t(8;21)/AML1蛳ETO和AML伴inv(16)(p13q22)或t(16;16)(p13;q22)/CBFB蛳MYH11患者的诱导化疗CR率显著高于不另做分类的AML患者(P<0.05)。有多系增生异常患者的诱导化疗CR率明显低于无多系增生异常患者(P<0.05)。结论AML的WHO分型各亚型的一致性及与临床疗效相关性较FAB分型更好。     

2016年版WHO淋巴瘤分类新进展及其应用

淋巴瘤分类从早期到2016年版世界卫生组织（WHO）分类经历了一系列变化。2016年版WHO淋巴瘤分类旨在提供最新的淋巴瘤诊断类型、更准确的诊断标准以及生物学与临床的相关性,从而推动淋巴瘤领域的基础研究,促进未来的治疗进展,为患者提供更好的服务。     

Reclassification of 400 consecutive glioma cases based on the revised 2016WHO classification

In this study, we reclassified 400 consecutive glioma cases including pediatric cases, using the revised 2016 WHO classification with samples collected from the Kyushu University Brain Tumor Bank. The IDH1/2, H3F3A, key genetic markers in the 2016 classification, were analyzed using high-resolution melting, with DNA extracted from frozen tissues. The 1p/19q codeletions were evaluated using a microsatellite-based loss of heterozygosity analysis, with 18 markers, to detect loss of the entire chromosome arm. In the integrated diagnosis, 29 oligodendroglioma cases and 28 anaplastic oligodendroglioma cases were diagnosed as “IDH-mutant and 1p/19q-codeleted,” while 2 oligodendroglioma cases and 5 anaplastic oligodendroglioma cases were diagnosed as not otherwise specified (NOS). These “NOS” cases were either IDH-mutants or 1p/19q-codeleted, although characteristic oligodendroglial features were evident histologically. Better overall survival of patients with oligodendroglioma correlated with the molecular characteristic of “IDH-mutant and 1p/19q-codeleted,” rather than the WHO grade. Eleven “glioblastoma, IDH-wild-type” cases were classified as “1p/19q-codeleted”, however, chromosome 10 loss was also detected in 10 out of 11 cases. The 2016 WHO criteria for glioma classification leads to better diagnosis of patients. However, there are technical pitfalls and problems to be solved in the molecular analysis of routine diagnostics.     

Clinical significance of vasculogenic mimicry in human gliomas

Vasculogenic mimicry (VM) is known as non-endothelial tumor cell-lined microvascular channels in aggressive tumors. We have previously found the presence of VM in high-grade gliomas. In this study, we aimed to identify VM patterns in gliomas and to explore their clinical significance. Tumor samples as well as their detailed clinical/prognostic data were collected from 101 patients. Vasculogenic mimicry in the glioma samples was determined by dual staining for endothelial marker CD34 and periodic acid–Schiff (PAS). Tumor samples were also immunohistochemically stained for Ki-67, VEGF, COX-2 and MMP-9. The association between VM and the clinical characteristics of the patients were analyzed. A Kaplan–Meier survival analysis and log-rank tests were performed to compare survival times of the patients. Vasculogenic mimicry was present in 13 out of 101 samples. The higher grade gliomas had a higher incidence of VM than that of lower grade gliomas (P = 0.006). Vasculogenic mimicry channels were associated with the expression of COX-2 and MMP-9 (P < 0.05). While there was no association between the existence of VM and the sex, age and preoperative epilepsy of the patients, or expression of Ki-67 and VEGF. However, patients with VM-positive gliomas survived a shorter period of time than those with VM negative gliomas (P = 0.027). Interestingly, in high-grade gliomas, the level of microvascular density was lower in VM positive tumors than those VM negative tumors (P = 0.039). Our results suggest that VM channels in gliomas correlate with increasing malignancy and higher aggressiveness, and may provide a complementation to the tumor’s blood supply, especially in less vascularized regions, which may aid in the identification of glioma patients with a poorer prognosis.     

Clinical relevance of 1p and 19q deletion for patients with WHO grade 2 and 3 gliomas

PURPOSE: To assess the frequency of chromosomes 1p and 19q deletions in gliomas and to correlate 1p deletion with prognosis in patients with grade 2 and grade 3 gliomas independently of histologic subtype. METHODS: We retrospectively evaluated 208 patients with WHO grade 2 and 3 gliomas who had 1p/19q molecular studies performed between 2000 and 2004. DNA was extracted from tumor tissue and germline material and evaluated by PCR using microsatellite markers for each chromosome. RESULTS: There were 113 men and 95 women with a median age at diagnosis of 40. Thirty-eight patients had a low-grade astrocytoma (A2), 58 low-grade oligodendroglioma (O2), 31 low-grade oligoastrocytoma (OA2), 21 anaplastic astrocytoma (A3), 37 anaplastic oligodendroglioma (O3), and 23 had an anaplastic oligoastrocytoma (OA3). Chromosome 1p analysis was performed in all patients and showed deletions in 105 patients (76% of O2, 42% of OA2, 21% of A2, 89% of O3, 17% of AO3, and 14% of A3). Chromosome 19q studies were performed in 118 patients and showed deletions in 46 (56% of O2, 45% of OA2, 27% of A2, 76% of O3, 11% of OA3 and 0% of A3). On multivariate analyses, chromosome 1p was a prognostic factor for prolonged PFS (HR = 1.75, P = 0.03) and OS (HR = 3.59, P = 0.02) in grade 2 gliomas but not for grade 3 (HR = 0.81, P = 0.7 for PFS; HR = 1.31, P = 0.7 for OS). CONCLUSION: Chromosome 1p deletion is a significant positive prognostic marker in diffuse, grade 2 gliomas regardless of histologic subtype.     

Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas.

BACKGROUND: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade II gliomas treated with surgery alone using imaging and clinical criteria. PATIENTS AND METHODS: Thirty patients with histologically verified WHO grade II gliomas (17 astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). RESULTS: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, 11 SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%). CONCLUSIONS: Temozolomide has single-agent activity in patients with WHO grade II cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities.     

Characterization of primary glioma cell lines derived from the patients according to 2016 CNS tumour WHO classification and comparison with their parental tumours

Journal of Neuro-Oncology - Gliomas represent about 80% of primary brain tumours and about 30% of malignant ones, which today don’t have a resolution therapy because of their variability. A...     

Clinicopathological features and prognostic factors of Japanese patients with "peripheral T-cell lymphoma, unspecified" diagnosed according to the WHO classification

Clinicopathological features of 36 patients, male: 58.3%; median: 68 years, with “peripheral T-cell lymphoma, unspecified” diagnosed by the WHO criteria were reviewed. Majority (69.4%) had stage IV disease with frequent involvements into bone marrow, spleen, liver, and skin. According to the IPI, 72.2% were categorized as high or high-intermediate risk group. CR and PR were achieved in 12 and 10 out of 31 patients treated by CHOP-based chemotherapy, respectively. One- and two-year overall survivals were 60.6 and 25.0%, respectively. Performance status, serum LDH, and B symptom were significant prognostic factors. Survival of CD4−/CD8+ cases, corresponding to cytotoxic T-cell lymphoma, was significantly worse than that of CD4+/CD8−.     

The incidence and significance of thromboembolic complications in patients with high-grade gliomas

Coagulation system abnormalities in patients with malignancy ranges from asymptomatic laboratory abnormalities to overt clinical manifestations. To determine the incidence and significance of clinically manifest thromboembolic phenomena in patients with high-grade gliomas, the records were analyzed of 77 patients that presented between January 1985 and June 1988. Fifteen patients (19%) had clinically manifest deep venous thrombosis and/or pulmonary emboli during the course of their disease. All these patients were ambulatory before and at the time of diagnosis of the event. The thromboembolic episodes occurred at the time of initial management of the primary tumor while there was documented clinical improvement in the functional status of the patient or at the time of progression of the disease. One patient died as a result of a pulmonary embolism; in two others, an embolism was a significant contributor to the patient's death. Anticoagulation resulted in complications in two of eight patients treated. Thromboembolic events occur with high frequency in patients with high-grade gliomas and contribute to the high morbidity and mortality seen in these patients. The optimum approach to screening and the treatment of these events has not been determined.     

Observation after surgery for low grade glioma: long-term outcome in the light of the 2016 WHO classification

Journal of Neuro-Oncology - The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase promoter non-methylated glioblastoma to experimental...