探讨泪腺腺样囊性癌高级别转化(LACC-HGT)的临床病理学特征。

回顾性分析首都医科大学附属北京同仁医院病理科2011年1月至2019年12月间确诊的8例LACC-HGT病例。其中，男性4例(4只眼)，女性4例(4只眼)；年龄19~65岁，中位年龄44.5岁。记录所有患者的性别、年龄、首发症状、肿瘤大小及骨质破坏情况；观察组织病理学特点；利用免疫组织化学EnVision法标记P63、腺泡来源标志物转录因子SRY相关蛋白10(SOX10)、细胞角蛋白7(CK7)、分化簇117(CD117)、Ki-67、原癌基因MYB、人表皮生长因子受体-2(Her-2)及雄激素受体(AR)等的表达情况。

8例LACC-HGT患者中，临床表现为眼球突出者5例，占62.5%(5/8)；眼睑肿胀者1例，占12.5%(1/8)；眼球突出伴眼睑肿胀者2例，占25%(2/8)。肿瘤大小2~5 cm，平均(3.50±0.92)cm。骨质破坏者6例，占75%(6/8)。2例随访数据不全，其余6例随访期间均出现转移，转移部位包括腮腺、肺、脑、骨及区域淋巴结等，其中4例死亡。患者存活时间3~54个月，中位生存时间26个月。8例肿物均为实性，肿物最大直径2~5 cm，平均3.5 cm。肿物切面灰白、实性且质地中等，与周围组织边界不清。8例LACC-HGT病例中均可见经典ACC区域。其中，低级别的筛状型结构者2例，占25%(2/8)；实性型结构者3例，占37.5%(3/8)；筛状与实性混合型且实性成分>30%者3例，占37.5%(3/8)。高级别转化(HGT)区域占肿瘤镜下总面积的比例为60%~90%，肿瘤细胞排列呈实性未分化癌或低分化腺癌形态，片状；实性片巢常大于一个低倍镜视野。细胞异型性明显，胞核显著增大，核仁及核分裂象易见(平均38.75个/10高倍镜视野)。病理组织学显示神经浸润者8例，占100%(8/8)；脉管侵犯者5例，占62.5%(5/8)；间质促纤维结缔组织反应者7例，占87.5%(7/8)；坏死者6例，占75%(6/8)，其中4例伴钙化。免疫组织化学染色显示在经典腺样囊性癌(ACC)区域，P63在管周、筛周及筛孔周的肌上皮细胞核表达，在实性巢中可呈斑驳状表达；CK7和CD117在管腔面腺上皮以及筛状结构中向导管分化的细胞表达，而在实性巢中表达较弥漫；MYB蛋白在肌上皮和腺上皮中均呈胞核表达；在HGT区域，P63阳性肿瘤细胞明显减少，部分区域完全消失，而CK7和CD117在肿瘤中呈胞膜弥漫强阳性表达，提示腺泡来源的标志物SOX10呈胞核阳性表达，MYB蛋白亦呈核阳性表达。Ki-67增殖指数在HGT区域约为40%~70%(平均52.5%)，在经典ACC区域约为10%~30%(平均15%)。Her-2和AR在ACC及HGT区域均呈阴性表达。

LACC-HGT组织病理学特征显著，生物学行为差，病理医师应根据组织病理学及免疫组织化学特点做出正确诊断，以指导临床治疗及预后评估。

To investigate the clinico-pathological characteristics of lacrimal adenoid cystic carcinoma with high-grade transformation (LACC-HGT).

The clinical and pathological data of 8 cases of LACC-HGT were retrospectively analyzed. Among of them, there were 4 males (4 eyes) and 4 females (4 eyes); aged from 19 to 65 years old with a median age of 44.5 years old. Gender, age, first symptoms, tumor size and bone destruction of all patients were recorded, and histopathological characteristics were observed. Immunohistochemical study for P63, SOX10 (SRY-related HMG box 10 protein), cytokeratin 7 (CK7), cluster of differentiation 117 (CD117), Ki-67, MYB, human epidermal growth factor receptor 2 (Her-2) and androgen receptor (AR) was carried out.

Among of these cases, 5 cases had exophthalmos, accounting for 62.5% (5/8); 1 case had swollen eyelids, accounting for 12.5% (1/8); 2 cases had exophthalmos with swollen eyelids, accounting for 25% (2/8). The tumor size was 2 to 5 cm with an average of (3.50±0.92) cm. 6 cases had bone destruction, accounting for 75% (6/8). Follow-up data of 2 cases were incomplete. 4 cases died of the remaining 6 cases with complete follow-up data all who had metastasis, and the metastatic sites included parotid gland, lung, brain, bone and regional lymph nodes. The survival time of the dead patients was 3 to 54 months, with a median survival time of 26 months. 8 cases of masses were all solid, with a maximum diameter of 2 to 5 cm and an average of 3.5 cm. The cut surface of the tumor was gray, solid and medium in texture, and the boundary with the surrounding tissue was not clear. The classic adenoid cystic carcinoma (ACC) area was shown in all 8 cases, of which showed low-grade cribriform structures (2 cases), accounting for 25% (2/8), solid structures (3 cases), accounting for 37.5% (3/8). 3 cases had cribriform and solid mixed structures and solid content>30%, accounting for 37.5% (3/8). The high-grade transformation (HGT) area accounted for 60% to 90% of the total tumor areas. LACC-HGT presented either as solid undifferentiated carcinoma or poorly differentiated adenocarcinoma. Histological examination showed obvious cell atypia, significantly enlarged nucleus, and prominent nucleoli and active mitosis (average 38.75/10 high power field). Nerve invasion (8 cases) and vascular invasion (5 cases) were observed, accounting for 100% (8/8) and 62.5% (5/8), respectively. Desmoplastic reaction (7 cases) and necrosis (6 cases) were found, accounting for 87.5% (7/8) and 75% (6/8), respectively. 4 cases with necrosis were accompanied by calcification. Immunohistochemical staining showed that in ACC region, P63 was expressed in the nucleus of myoepithelial cells in the peritubular and pericribriform areas, and shown in a mottled pattern in the solid nests. CK7 and CD117 were expressed in the luminal facial glands in tubular or cribriform areas, and more diffusely expressed in solid nests. MYB protein was expressed in nuclei of both myoepithelial and glandular epithelium. In HGT areas, P63-positive tumor cells were decreased, even disappeared completely in some areas, and CK7 and CD117 were diffusely and strongly positively expressed. The acinar-derived marker SOX10 was positively expressed in the nucleus, as well as MYB protein. The Ki-67 proliferation index was about 40% to 70% (average 52.5%) in the HGT region, and about 10% to 30% (average 15%) in the classic ACC region. Her-2 and AR were negatively expressed in ACC and HGT regions.

LACC-HGT was showd distinctive histopathological features and poor biological behaviors. Accurate diagnosis should be confirmed based on histopathological and immunohistochemical characteristics, which is significant to guide clinical treatment and prognostic evaluation.