浦野 誠

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are salivary gland tumors with biphasic differentiation, composed of luminal ductal cells and abluminal basal cells with a high nuclear-to-cytoplasmic ratio. While BCA is a relatively common benign tumor, BCAC is a rare malignancy, and its genetic context and relationship with BCA remain unclear. We investigated 93 BCA and 36 BCAC cases to further characterize these two tumor entities from histological and molecular perspectives. BCA/BCAC proliferated in a mixture of tubular, trabecular, solid, cribriform, and membranous patterns. A jigsaw puzzle pattern, peripheral palisading, S100-positive stroma, cystic change, and sclerosis were observed in approximately 50% of the cases. BCAC demonstrated the following malignant features: infiltration to surrounding tissue, tumor necrosis, and increased mitotic activity (81%, 22%, and 22%, respectively). The nuclear expression of β-catenin was frequently observed in both BCA and BCAC (89% and 60%), and CTNNB1 hotspot mutations were detected in 46% and 48% of BCA and BCAC cases, respectively. Tubular patterns of growth, jigsaw puzzle patterns, peripheral palisading, S100-positive stroma, and cystic changes were more common in β-catenin-positive BCA/BCAC than in β-catenin-negative BCA/BCAC. Among the β-catenin-negative BCA/BCAC cases, one case each harbored PLAG1 and MYB rearrangements. We concluded that β-catenin-positive BCA and BCAC share common histologic and molecular features, and BCAC is considered a malignant counterpart of BCA. β-Catenin-negative BCA/BCAC might include morphological mimickers, which can be genetically classified into other tumor types, including pleomorphic adenoma and adenoid cystic carcinoma.

OBJECTIVES: Recent advances in systemic therapy for salivary duct carcinoma (SDC) have been driven by the development of HER2- and androgen receptor (AR)-targeted therapies. Trastuzumab deruxtecan has proven effective not only in HER2-positive but also HER2-low breast and gastro-esophageal cancers. However, the significance of HER2-low expression in SDC remains unknown. This study aimed to investigate the clinicopathologic characteristics, prognostic implications, and impact on efficacy to AR-targeted therapy in HER2-low SDC. MATERIALS AND METHODS: This was a multi-center, observational study. HER2 status was reclassified as follows: HER2-positive (IHC3+ or 2+/ISH+ ), HER2-low (IHC1+ or 2+/ISH-), and HER2-zero (IHC0). The subjects were compared in three groups: total population, curative treatment cohort, and AR-targeted therapy cohort. RESULTS: The total population consisted of 526 patients, of whom, 271 (52 %), 184 (35 %), and 71 (13 %) had HER2-positive, -low, and -zero tumors, respectively. Sex, M category, histological origin, Ki67, and p53 expression differed significantly between the HER2-low and HER2-positive cases. No differences in relapse-free or overall survival were observed for HER2 status in the curative treatment cohort; however, in the AR-targeted therapy cohort, the HER2-low group had significantly better response rates (41.6 % vs. 18.9 %, Odds ratio = 0.30, P = 0.012) and longer median progression-free survival (6.9 vs. 4.2 months, Hazard ratio = 1.61, P = 0.029) than those of the HER2-positive group. CONCLUSION: HER2-low showed different clinicopathologic features from HER2-positive cases, with no prognostic differences observed in patients who underwent curative treatment. Still, HER2-low may be associated with the efficacy of AR-targeted therapy.