Acinic cell carcinoma (AciCC) is traditionally considered as a low-grade salivary gland carcinoma. However, a subset demonstrates high-grade features with a higher mortality rate and distant metastasis. In this large retrospective study of 117 cases, we aimed to establish a histologic grading scheme for AciCC. Adverse independent prognostic factors identified on the multivariate analysis included older age, tumor necrosis, nuclear anaplasia, lymphovascular invasion, absence of tumor-associated lymphoid stroma, and high American Joint Committee on Cancer (AJCC) pT and pN stages. A 3-tiered grading scheme using 4 pathologic parameters (mitotic index, necrosis, tumor border, and fibrosis at the frankly invasive front) was subsequently applied. Compared with low/intermediate-grade, high-grade AciCC defined as a mitotic index ≥5/10 HPFs and/or necrosis was an independently adverse prognostic factor. The 5-year overall survival was 50% in high-grade AciCCs, and 100% in low-grade or intermediate-grade AciCCs. Compared with low-grade or intermediate-grade AciCC, high-grade tumors were associated with older age, larger tumor size, focal rather than diffuse zymogen granules, solid architecture, infiltrative tumor border, fibrosis at the frankly invasive front, lymphovascular invasion, perineural invasion, positive margin, high pT, and pN stages. NR4A3 was a highly sensitive and specific immunohistochemical stain for diagnosing AciCC with a sensitivity and specificity of 96% and 93%, respectively. In conclusion, although we proposed a 2-tiered grading system for AciCC with high-grade tumors defined by a mitotic count ≥5/10 HPFs and/or necrosis, more studies are needed to assess the prognostic value of intermediate grade. NR4A3 immunohistochemical stain is a useful diagnostic marker for AciCC.

腺泡细胞癌（AciCC）传统上被认为是低级别唾液腺癌。然而，一个子集表现出具有较高死亡率和远处转移的高级特征。在这项对 117 例病例进行的大型回顾性研究中，我们旨在建立 AciCC 的组织学分级方案。多变量分析确定的不良独立预后因素包括年龄较大、肿瘤坏死、核退行性变、淋巴血管侵犯、肿瘤相关淋巴基质缺失以及美国癌症联合委员会 (AJCC) pT 和 pN 分期较高。随后应用了使用 4 个病理参数（有丝分裂指数、坏死、肿瘤边界和明显侵袭性前沿的纤维化）的 3 级分级方案。与低/中级别相比，高级别 AciCC 定义为有丝分裂指数≥5/10 HPF 和/或坏死是独立的不良预后因素。高级别 AciCC 的 5 年总生存率为 50%，低级别或中级别 AciCC 的 5 年总生存率为 100%。与低级别或中级别 AciCC 相比，高级别肿瘤与年龄较大、肿瘤尺寸较大、局灶性而非弥漫性酶原颗粒、实体结构、浸润性肿瘤边界、明显浸润性前沿的纤维化、淋巴血管侵犯、神经周围相关。侵袭、阳性切缘、高 pT 和 pN 阶段。NR4A3 是一种高度敏感和特异性的免疫组织化学染色剂，用于诊断 AciCC，敏感性和特异性分别为 96% 和 93%。总之，尽管我们提出了 AciCC 的 2 级分级系统，其中高级别肿瘤由有丝分裂计数≥5/10 HPF 和/或坏死定义，但仍需要更多研究来评估中级肿瘤的预后价值。NR4A3 免疫组织化学染色是 AciCC 的有用诊断标记物。