Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Head Neck Pathol. 2022 Dec;16(4):1063-1072. doi: 10.1007/s12105-022-01464-3. Epub 2022 Jul 6.
Salivary duct carcinoma with rhabdoid features (SDC-RF) is a recently-described salivary gland tumor that bears striking histologic similarity to lobular carcinoma of the breast. While this tumor has an apocrine phenotype that supports classification as a variant of SDC, it infrequently arises in association with conventional SDC. Furthermore, discohesive architecture can be seen in non-apocrine salivary carcinomas, raising the possibility that discohesive growth should define a separate entity. In this study, we aimed to perform comprehensive molecular profiling of SDC-RF to better understand its pathogenesis and classification.
We documented the clinicopathologic features of 9 cases of SDC-RF and performed immunostains including AR, GCDFP, and e-cadherin on all cases. We also performed targeted next generation sequencing (NGS) panels on 7 cases that had sufficient tissue available.
The SDC-RF represented 8 men and 1 woman with a median age of 67 years (range 63-83 years) and included 6 parotid, 2 buccal, and 1 submandibular primary. All tumors were uniformly composed of discohesive cells with abundant eosinophilic cytoplasm; signet-ring cell features were seen in 2 cases. All tumors were also positive for AR (100%) and GCDFP (100%), and 7 tumors (78%) displayed lost or abnormal e-cadherin. NGS highlighted concomitant PIK3CA and HRAS mutations in 4 tumors, with additional cases harboring TP53, PTEN, and AKT1 mutations. Furthermore, CDH1 alterations were seen in 6 cases, including a novel CDH1::CORO7 fusion. Among 5 patients with follow-up available, 3 (60%) developed local recurrence and widespread distant metastasis and died of disease at a median 20 months (range 10-48 months).
Overall, our findings confirm frequent CDH1 mutations and e-cadherin inactivation in SDC-RF, similar to discohesive tumors from other sites. We also highlight an apocrine molecular profile similar to conventional SDC. However, occasional AKT1 mutation and signet-ring features suggest SDC-RF may also be related to mucinous adenocarcinoma. As more salivary tumors with discohesive growth are identified, it may become clearer whether SDC-RF should remain in the SDC family or be recognized as a separate entity.
具有横纹肌样特征的唾液腺癌（SDC-RF）是一种最近描述的唾液腺肿瘤，其组织学特征与乳腺小叶癌具有显著的相似性。虽然这种肿瘤具有支持分类为 SDC 变体的分泌性表型，但它很少与常规 SDC 相关。此外，非分泌性唾液腺癌中也可见到离散的结构，这提示离散性生长应该定义为一个独立的实体。在这项研究中，我们旨在对 SDC-RF 进行全面的分子谱分析，以更好地了解其发病机制和分类。
我们记录了 9 例 SDC-RF 的临床病理特征，并对所有病例进行了包括 AR、GCDFP 和 E-cadherin 在内的免疫组化染色。我们还对 7 例有足够组织的病例进行了靶向下一代测序（NGS）面板分析。
SDC-RF 代表了 8 名男性和 1 名女性，中位年龄为 67 岁（范围 63-83 岁），包括 6 例腮腺、2 例颊部和 1 例下颌下原发肿瘤。所有肿瘤均由均匀离散的细胞组成，细胞胞浆丰富嗜酸性；2 例可见印戒细胞特征。所有肿瘤均为 AR（100%）和 GCDFP（100%）阳性，7 例肿瘤（78%）显示 E-cadherin 缺失或异常。NGS 突出了 4 例肿瘤中同时存在 PIK3CA 和 HRAS 突变，此外还有病例存在 TP53、PTEN 和 AKT1 突变。此外，6 例存在 CDH1 改变，包括一种新的 CDH1::CORO7 融合。在 5 例有随访资料的患者中，3 例（60%）发生局部复发和广泛远处转移，中位随访 20 个月（范围 10-48 个月）后死于疾病。
总的来说，我们的研究结果证实了 SDC-RF 中经常发生 CDH1 突变和 E-cadherin 失活，与其他部位的离散性肿瘤相似。我们还强调了与常规 SDC 相似的分泌性分子谱。然而，偶尔的 AKT1 突变和印戒细胞特征提示 SDC-RF 可能也与黏液性腺癌有关。随着更多具有离散性生长的唾液腺肿瘤被识别，是否 SDC-RF 应保留在 SDC 家族中或被视为一个独立的实体可能会变得更加清晰。
