Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
Head Neck Pathol. 2020 Jun;14(2):489-496. doi: 10.1007/s12105-019-01068-4. Epub 2019 Aug 31.
Papillary salivary gland neoplasms are rare tumors usually arising in the minor salivary glands of the oral cavity. Their classification has been historically confusing due to overlapping histologic features, but molecular analysis may clarify these entities. Sialadenoma papilliferum (SP) is a peculiar member of this group that demonstrates both an endophytic ductal and an exophytic squamous component. SP closely resembles syringocystadenoma papilliferum of the skin, a tumor which has recently been shown to harbor BRAF V600E or HRAS mutations. We sought to perform histologic and immunophenotypic analysis of a group of SP, along with BRAF and HRAS mutational analysis. We collected 13 SP cases from 7 females and 6 males ranging from 2 to 91 years (mean 62.8). Five exophytic ductal papillomas were also analyzed as controls. Histological analysis was performed along with immunohistochemistry for CK7, p63, and SOX10. BRAF VE1 immunohistochemistry was done in all tumors, and BRAF V600E and HRAS Sanger sequencing was successfully performed in all but two cases. Histologic analysis revealed that SP consisted not only of classic SP (9 of 13 cases) but also an oncocytic variant (4 of 13 cases) characterized by a glandular component that uniformly exhibited abundant granular cytoplasm and prominent nucleoli. By immunohistochemistry, all SP demonstrated luminal CK7 and basal p63 expression, but SOX10 was expressed only in conventional SP (9 of 9 cases). BRAF VE1 immunohistochemistry was positive in 9 of 9 conventional SP but 0 of 4 oncocytic SP; staining was present in both the exophytic and endophytic components. BRAF V600E mutational status was confirmed by Sanger sequencing in 11 cases (7 conventional and 4 oncocytic). The exophytic ductal papillomas were negative for BRAF mutations, and all tumors tested were negative for HRAS mutations. In summary, we demonstrated that SP consists of two variants: (1) conventional SP which is SOX10-positive and harbors BRAF V600E mutations similar to syringocystadenoma papilliferum of the skin; and (2) an oncocytic variant which is SOX10-negative and negative for BRAF mutations. We also demonstrated that both the endophytic glandular component and exophytic squamous components of conventional SP harbor BRAF V600E mutations and are therefore neoplastic.
涎腺乳头状肿瘤是一种罕见的肿瘤，通常发生在口腔的小涎腺中。由于其组织学特征重叠，其分类一直存在混淆，但分子分析可能会阐明这些实体。乳头状涎腺瘤（SP）是该组中一个特殊的成员，它具有内胚层导管和外胚层鳞状两种成分。SP 与皮肤的汗管囊腺瘤乳头状瘤非常相似，后者最近被证明携带 BRAF V600E 或 HRAS 突变。我们试图对一组 SP 进行组织学和免疫表型分析，并进行 BRAF 和 HRAS 突变分析。我们收集了 7 名女性和 6 名男性的 13 例 SP 病例，年龄从 2 岁到 91 岁不等（平均 62.8 岁）。还分析了 5 例外生导管状乳头瘤作为对照。进行了组织学分析，并进行了 CK7、p63 和 SOX10 的免疫组化分析。所有肿瘤均进行了 BRAF VE1 免疫组化检查，除 2 例外，所有肿瘤均成功进行了 BRAF V600E 和 HRAS Sanger 测序。组织学分析显示，SP 不仅由经典的 SP（13 例中的 9 例）组成，还由一个嗜酸细胞变体（13 例中的 4 例）组成，其特征是腺管成分均匀表现出丰富的颗粒状细胞质和明显的核仁。通过免疫组化，所有 SP 均显示出腔 CK7 和基底 p63 的表达，但仅在常规 SP（9 例中的 9 例）中表达 SOX10。BRAF VE1 免疫组化在 9 例常规 SP 中阳性，但在 4 例嗜酸细胞 SP 中为阴性；染色存在于外生性和内生性成分中。BRAF V600E 突变状态通过 Sanger 测序在 11 例（7 例常规和 4 例嗜酸细胞）中得到证实。外生性导管状乳头瘤无 BRAF 突变，所有检测的肿瘤均无 HRAS 突变。总之，我们证明 SP 由两种变体组成：（1）常规 SP，SOX10 阳性，携带与皮肤的汗管囊腺瘤乳头状瘤相似的 BRAF V600E 突变；（2）SOX10 阴性的嗜酸细胞变体，无 BRAF 突变。我们还证明，常规 SP 的内胚层腺管成分和外生性鳞状成分均携带 BRAF V600E 突变，因此是肿瘤性的。
