Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California At Los Angeles, Los Angeles, CA, USA.
Head Neck Pathol. 2020 Dec;14(4):869-875. doi: 10.1007/s12105-020-01128-0. Epub 2020 Jan 27.
Intraductal carcinoma (IDC) is the current designation for a salivary gland neoplasm previously referred to as "low-grade salivary duct carcinoma" and "low-grade cribriform cystadenocarcinoma," among others. IDC is conceptually believed to be similar to ductal carcinoma in-situ of the breast. Although IDC is one entity in the current WHO Classification of Head and Neck Tumors, recent studies have suggested that at least three subtypes exist: a low-grade, intercalated duct-like variant with frequent RET rearrangements; a high-grade apocrine variant with complex, salivary duct carcinoma-like genetics; and a mixed variant. We sought to characterize an unusual form of low-grade, purely apocrine IDC. Three cases of apocrine-type IDC with low-grade histology were retrieved from the authors' consultation files. Immunohistochemistry for androgen receptor, GCDFP-15, S100, smooth muscle actin, and p40 was performed. A custom, targeted next generation sequencing (NGS) panel including 1425 cancer-related genes was also done on all cases. All three cases developed in the parotid glands of men, aged 51, 63, and 73 years (mean, 62 years). All cases consisted of large, rounded macrocysts surrounded by smaller nests which were lined by cells with abundant granular eosinophilic cytoplasm and large round nuclei with prominent nucleoli. Pleomorphism was mild, the mitotic rate was low, and necrosis was absent. No cases had any invasive foci or areas of intercalated duct-like morphology. By immunohistochemistry, all cases were diffusely positive for androgen receptor and GCDFP-15, surrounded entirely by an intact layer of small myoepithelial cells positive for S100, smooth muscle actin, and p40. Targeted NGS results were obtained from two cases: both harbored HRAS mutations and copy number losses in TP53, while one case each harbored mutations in PIK3CA, SPEN, and ATM. Fusions were absent in both cases. All three patients were treated by surgery alone, and are currently free of disease (follow up 12-190 months). This study confirms the existence of a low-grade, purely apocrine form of IDC. In its pure form, i.e., without an intercalated duct-type component, low-grade apocrine IDC is genetically similar to high-grade salivary duct carcinoma, with frequent HRAS and PI3K pathway mutations. Despite its molecular similarities to the aggressive salivary duct carcinoma, low-grade apocrine IDC appears to behave in a very indolent manner, supporting is classification as a non-invasive neoplasm, and underscoring the need to distinguish these tumors from each other.
导管内癌（IDC）是一种唾液腺肿瘤的现用名称，此前曾被称为“低级别唾液导管癌”和“低级别筛状囊腺癌”等。ID C 在概念上被认为与乳腺的导管原位癌相似。虽然 IDC 是目前世界卫生组织头颈部肿瘤分类中的一个实体，但最近的研究表明，至少存在三种亚型：一种是具有频繁 RET 重排的低级别、中间导管样变体；一种是具有复杂唾液导管癌样遗传学的高级别大汗腺变体；还有一种是混合变体。我们试图描述一种不常见的低级别、纯大汗腺 IDC 形式。从作者的咨询档案中检索到 3 例具有低级别组织学的大汗腺型 IDC。对雄激素受体、GCDFP-15、S100、平滑肌肌动蛋白和 p40 进行免疫组织化学染色。还对所有病例进行了包括 1425 个癌症相关基因的定制靶向下一代测序（NGS）面板检测。所有 3 例均发生于男性的腮腺，年龄分别为 51、63 和 73 岁（平均 62 岁）。所有病例均由大的圆形大囊泡组成，周围环绕着较小的巢，这些巢由具有丰富颗粒状嗜酸性细胞质和大圆形核、核仁明显的细胞排列而成。多形性轻微，有丝分裂率低，无坏死。没有病例有任何浸润灶或中间导管样形态区域。免疫组织化学染色显示，所有病例均弥漫性表达雄激素受体和 GCDFP-15，完全被一层由 S100、平滑肌肌动蛋白和 p40 阳性的小肌上皮细胞环绕。从 2 例中获得了靶向 NGS 结果：均存在 HRAS 突变和 TP53 的拷贝数缺失，而各有 1 例存在 PIK3CA、SPEN 和 ATM 的突变。在这两种情况下都不存在融合。所有 3 例患者均仅接受手术治疗，目前均无疾病（随访 12-190 个月）。本研究证实了存在低级别、纯大汗腺形式的 IDC。在其纯形式中，即没有中间导管样成分，低级别大汗腺癌在遗传上与高级别唾液导管癌相似，常有 HRAS 和 PI3K 通路突变。尽管与侵袭性唾液导管癌具有分子相似性，但低级别大汗腺癌似乎表现出非常惰性的方式，支持其被归类为非浸润性肿瘤，并强调需要将这些肿瘤彼此区分开来。
