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犬淋巴瘤:分类类型、疾病分期、肿瘤亚型、有丝分裂率和治疗与生存的关系。

Canine lymphomas: association of classification type, disease stage, tumor subtype, mitotic rate, and treatment with survival.

机构信息

VDx Pathology, 5622 Cowell Blvd, Davis, CA 95618, USA.

出版信息

Vet Pathol. 2013 Sep;50(5):738-48. doi: 10.1177/0300985813478210. Epub 2013 Feb 26.

DOI:10.1177/0300985813478210
PMID:23444036
Abstract

Canine lymphoma is the neoplasm most often treated by chemotherapy, yet there are few data to correlate response to therapy with its different subtypes. This study is based on biopsy specimens from 992 dogs for which lymphoma was the clinical diagnosis. All cases were phenotyped by immunohistochemistry for CD3 and CD79alpha. Cases with histiocytic proliferation were evaluated immunohistochemically for CD18. Clonality was verified in 12 cases by polymerase chain reaction (PCR). Survival (event time) data and complete survival information (cause of death or time to last follow-up) were available on 456 dogs. Additional covariate information when available included size, age, sex, phenotype, stage and grade of lymphoma, mitotic index, and treatment protocol. Because of the many subtypes of B- and T-cell lymphoma, the cases were grouped into 7 diagnostic categories: (1) benign hyperplasia; (2) low-grade B-cell; (3) high-grade B- and T-cell; (4) low-grade T-cell; (5) centroblastic large B-cell of all mitotic grades (subdivided by clinical stage); (6) immunoblastic large B-cell of all mitotic grades, and (7) high-grade peripheral T-cell. Grouping was determined by histological grade (based on mitotic rate/400× field, with low-grade 0-5, intermediate 6-10, and high-grade >10) and stage for survival function estimation. No association with survival was found for size (based on breed of dog) or sex. All diagnostic categories of indolent or low-grade type had low mitotic rates, whereas those with clinically high grades had high mitotic rates. The diagnostic category with the most cases was centroblastic large B-cell lymphoma. Compared with dogs in this largest represented group of lymphomas, dogs with high-grade lymphomas had significantly higher mortality rates, and dogs with low-grade T-cell lymphomas had significantly lower mortality rates. Treatments for high-, intermediate-, and low-grade lymphomas were divided into 4 groups: absence of treatment, chemotherapy with or without hydroxydaunorubicin, and only prednisone. Dogs with low-grade T-cell (T-zone) lymphomas had the longest median survival (622 days), whereas the shortest median survival was in dogs with T-cell high-grade (peripheral T-cell) subtype (162 days). The dogs with centroblastic large B-cell lymphomas had a median survival of 127 days with low stage, 221 days with intermediate stage, and 215 days with advanced stage. Dogs with T-zone lymphoma were probably diagnosed in later stages of disease because of the lack of signs associated with progression. As with human lymphomas, a histological diagnosis with immunophenotyping is a minimal requirement for diagnosis of a specific subtype.

摘要

犬淋巴瘤是最常通过化疗治疗的肿瘤,但目前很少有数据将对治疗的反应与不同的亚型相关联。本研究基于 992 只犬的活检标本,这些犬的临床诊断为淋巴瘤。所有病例均通过免疫组化对 CD3 和 CD79alpha 进行表型分析。对有组织细胞增生的病例进行 CD18 的免疫组化评估。在 12 例病例中通过聚合酶链反应 (PCR) 验证了克隆性。在 456 只犬中获得了生存 (事件时间) 数据和完整的生存信息 (死亡原因或最后一次随访时间)。当有其他协变量信息时,包括大小、年龄、性别、表型、淋巴瘤的分期和分级、有丝分裂指数和治疗方案。由于 B 细胞和 T 细胞淋巴瘤的许多亚型,将病例分为 7 个诊断类别:(1)良性增生;(2)低级别 B 细胞;(3)高级别 B 细胞和 T 细胞;(4)低级别 T 细胞;(5)所有有丝分裂级别的中胚层性大 B 细胞 (按临床分期细分);(6)所有有丝分裂级别的免疫母细胞性大 B 细胞,和 (7)高级别外周 T 细胞。分组是根据组织学分级 (基于有丝分裂率/400×视野,低级别为 0-5,中级为 6-10,高级为>10) 和生存功能估计的分期确定的。大小 (基于犬种) 或性别与生存无关。所有惰性或低级别类型的诊断类别均具有低有丝分裂率,而具有临床高分级的诊断类别具有高有丝分裂率。病例最多的诊断类别是中胚层性大 B 细胞淋巴瘤。与最大的淋巴瘤代表性群体中的犬相比,高级别淋巴瘤的犬死亡率明显更高,而低级别 T 细胞淋巴瘤的犬死亡率明显更低。高级别、中级别和低级别淋巴瘤的治疗分为 4 组:无治疗、有或没有羟基柔红霉素的化疗以及仅用泼尼松。低级别 T 细胞 (T 区) 淋巴瘤的中位生存时间最长 (622 天),而 T 细胞高级别 (外周 T 细胞) 亚型的中位生存时间最短 (162 天)。中胚层性大 B 细胞淋巴瘤的犬在低分期时的中位生存时间为 127 天,中分期为 221 天,晚期为 215 天。T 区淋巴瘤的犬可能在疾病的晚期被诊断出来,因为缺乏与进展相关的迹象。与人类淋巴瘤一样,组织学诊断和免疫表型分析是诊断特定亚型的最低要求。

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