Kojima Kazuhiro, Chambers James K, Nakashima Ko, Goto-Koshino Yuko, Uchida Kazuyuki
The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Japan Small Animal Medical Center, Tokorozawa, Saitama, Japan.
Vet Pathol. 2022 Mar;59(2):227-235. doi: 10.1177/03009858211057220. Epub 2021 Nov 18.
Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called "intraepithelial lymphocytosis") in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IELCE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8 in CD3 IELs was significantly lower in IELCE than in CE without intraepithelial lymphocytosis (IELCE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8 IEL among IELCE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3 cells, Ki67 immunopositivity was highest in ITCL, intermediate in IELCE, and lower in IELCE. A clonal TCR gene rearrangement was detected in 1/19 IELCE cases (5%), 15/54 IELCE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8GRB) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IELCE suggest that canine ITCL originates from these IELs, similar to human EATL.
人肠病相关T细胞淋巴瘤（EATL）被认为起源于上皮内淋巴细胞（IEL）；然而，犬肠道T细胞淋巴瘤（ITCL）的起源仍不清楚。使用经内镜收集的慢性肠病（CE；73例）和无透壁肿瘤性肿块病变的ITCL（64例）的犬十二指肠黏膜病变样本进行了组织学、免疫组织化学和克隆性检查。组织病理学检查显示，54/73例CE病例（74%）出现淋巴细胞上皮内积聚（称为“上皮内淋巴细胞增多症”），63/64例ITCL病例（98%）出现肿瘤淋巴细胞向上皮细胞浸润。免疫组织化学方面，伴有上皮内淋巴细胞增多症的CE中的IEL（IELCE）对CD3呈弥漫性免疫阳性，对CD5、CD8、CD20和颗粒酶B（GRB）呈散在免疫阳性。IELCE中CD3⁺ IELs中CD8的百分比显著低于无上皮内淋巴细胞增多症的CE（IELCE）。双重标记免疫组织化学显示，IELCE中CD8⁺ IELs中GRB表达的百分比很高。在64例ITCL病例中，64例（100%）CD3免疫阳性，22例（34%）CD5免疫阳性，8例（13%）CD8免疫阳性，12例（19%）CD20免疫阳性，13例（20%）CD30免疫阳性，49例（77%）GRB免疫阳性。在CD3⁺细胞中，Ki67免疫阳性在ITCL中最高，在IELCE中居中，在IELCE中较低。在1/19例IELCE病例（5%）、15/54例IELCE（28%）和38/58例ITCL（66%）中检测到克隆性TCR基因重排。这些结果表明，犬ITCL的免疫表型（CD8⁺GRB⁺）与CE中增多的IELs相似。IELCE中T细胞的高增殖活性和克隆性表明，犬ITCL起源于这些IELs，类似于人EATL。
