Cole Grayson G, Levin Matt, Ferber David, Roark Spencer C, Sadow Peter M, Lubin Daniel, Guilmette Julie, Pettus Jason R, Fisch Adam S, Sajed Dipti P, Zakka Fouad R, Lingen Mark W, Cipriani Nicole A
Department of Pathology, University Hospitals, Cleveland, OH, USA.
Cell IDx, Inc. (A Division of Leica Biosystems), San Diego, CA, USA.
Head Neck Pathol. 2025 Sep 12;19(1):109. doi: 10.1007/s12105-025-01841-8.
Salivary duct carcinoma (SDC) is the most common malignancy to arise in a pleomorphic adenoma (PA). Intracapsular or non-invasive carcinoma ex PA (CXPA) is defined by the presence of malignant-appearing tumor cells within the PA that do not violate the tumor border. Knowledge regarding the possible morphologic spectrum and prognosis of intratumoral CXPA is scarce. This study aims to evaluate the morphologic, immunohistochemical, and clinical features of PAs with apocrine / salivary-duct-like intratumoral atypia.
Surgical pathology databases were queried for in situ or intracapsular/intratumoral SDC ex PAs and PAs with atypical epithelial cells (AEC). Exclusion criteria included recurrent lesions, invasion, positive margins, atypia only in myoepithelial cells, or other morphologic variants. Chromogenic multiplex (androgen receptor (AR) and HER2) and monoplex (p40) assays were performed on all available cases, as well as on a control group of non-atypical benign PAs and overtly invasive SDCs. Clinical outcomes were recorded.
96 cases were identified: 23 AEC, 6 apocrine metaplasia, 41 benign PA, 8 SDC ex PA. All AEC, apocrine metaplasia, and benign cases were treated with surgery alone, with 3 AEC cases also receiving a neck dissection. No case recurred. Five of 8 SDC ex PA recurred; 3 died of disease. AR and HER2 were respectively expressed in 96% and 22-48% of AEC; 83% and 0% of apocrine metaplasia; 51% and 0% of benign PA; and 86-100% and 38-57% of SDC ex PA. Patients had increasing average age from benign (~ 50 years) to atypical/in situ (60 years) to invasive carcinoma (~ 70 years).
The presence of epithelial atypia within a PA (ranging from isolated AR expression to apocrine metaplasia to overtly dysplastic/malignant epithelial cells) does not portend recurrence or metastasis if the atypia is confined within the borders of the adenoma and negative margins are achieved. Therefore, use of the term "in situ/intracapsular/intratumoral salivary duct carcinoma ex pleomorphic adenoma" is discouraged in light of good prognosis and potential for overtreatment by clinical teams. Nomenclature such as pleomorphic adenoma with epithelial "atypia" or "dysplasia" is recommended, followed by a comment regarding the morphologic features and likely indolent behavior.
涎腺导管癌（SDC）是多形性腺瘤（PA）中最常见的恶性肿瘤。包膜内或非侵袭性多形性腺瘤内癌（CXPA）的定义为多形性腺瘤内出现具有恶性特征的肿瘤细胞，但未侵犯肿瘤边界。关于肿瘤内CXPA可能的形态学谱和预后的知识尚少。本研究旨在评估具有大汗腺/涎腺导管样肿瘤内异型性的多形性腺瘤的形态学、免疫组化和临床特征。
查询手术病理数据库，以获取原位或包膜内/肿瘤内多形性腺瘤来源的SDC以及具有非典型上皮细胞（AEC）的多形性腺瘤。排除标准包括复发病变、侵袭、切缘阳性、仅肌上皮细胞出现异型性或其他形态学变异。对所有可用病例以及非典型良性多形性腺瘤和明显侵袭性SDC的对照组进行显色多重（雄激素受体（AR）和HER2）和单重（p40）检测。记录临床结果。
共识别出96例：23例AEC、6例大汗腺化生、41例良性多形性腺瘤、8例多形性腺瘤来源的SDC。所有AEC、大汗腺化生和良性病例均仅接受手术治疗，3例AEC病例还接受了颈部清扫。无病例复发。8例多形性腺瘤来源的SDC中有5例复发；3例死于疾病。AR和HER2分别在96%的AEC、83%的大汗腺化生、51%的良性多形性腺瘤以及86 - 100%的多形性腺瘤来源的SDC中表达；HER2分别在22 - 48%的AEC、0%的大汗腺化生、0%的良性多形性腺瘤以及38 - 57%的多形性腺瘤来源的SDC中表达。患者的平均年龄从良性（约50岁）到非典型/原位（60岁）再到侵袭性癌（约70岁）逐渐增加。
如果多形性腺瘤内的上皮异型性局限于腺瘤边界内且切缘阴性，则其出现（从孤立的AR表达到大汗腺化生再到明显发育异常/恶性上皮细胞）并不预示复发或转移。因此，鉴于预后良好且临床团队可能过度治疗，不建议使用“原位/包膜内/肿瘤内多形性腺瘤来源的涎腺导管癌”这一术语。建议使用诸如具有上皮“异型性”或“发育异常”的多形性腺瘤等命名，随后对形态学特征和可能的惰性行为进行说明。
