Most of salivary gland neoplasms (benign and malignant) are characterized by recurrent gene fusions. Pleomorphic adenoma (PA), the most frequent salivary gland tumor, is driven by chromosomal rearrangements involving PLAG1 mapped to 8q12 and HMGA2 mapped to 12q13-15 in most cases. Multiple fusion partners have been identified including CTNNB1, FGFR1, LIFR, CHCHD7 and TCEA for PLAG1 fusions and NFIB, WIF1 and FHIT for HMGA2 fusions. To date, no data exist on the morphology of the few reported HMGA2-WIF1-rearranged PAs. We present 28 major salivary gland adenomas displaying distinctive trabecular and canalicular morphology associated with recurrent genotype. Patients were 15 females and 13 males aged 43 to 87 (median: 65). All tumors originated from the parotid. Their size range was 1 to 4 cm (mean: 2.3). Histologically, all tumors showed elongated or columnar cells arranged into bilayered to multilayered communicating and branching strands and trabeculae in a manner similar to canalicular adenoma of minor salivary glands or trabecular myoepithelioma with variable solid confluent intercalated duct-like areas. Fifteen tumors were exclusively canalicular/trabecular while 13 had intermingled or well-demarcated conventional (chondromyxoid) PA component comprising 5 to >50% of the tumor. The monomorphic areas expressed uniformly CK7 (28/28), vimentin (21/21), S100 (24/24), SOX10 (16/17) and variably p63 (8/21) and mammaglobin (6/16) but were negative with p40 (0/24), smooth muscle actin (0/24) and MUC4 (0/16). Targeted RNA sequencing revealed HMGA2 fusions in 14/16 (87%) assessable cases. Fusion partner was WIF1 (12), RPSAP52 (1) and HELB (1). Separate testing of the 2 components in 1 hybrid tumor showed same HMGA2/WIF1 fusion. HMGA2 immunohistochemistry was homogeneously positive in all cases including the 2 fusion-negative cases. A control cohort of 12 genuine canalicular adenomas revealed no HMGA2 fusions (0/4) and lacked HMGA2 immunoreactivity (0/12). This study highlights a distinctive variant in the spectrum of PA characterized by prominent trabecular and canalicular adenoma-like morphology. Our data confirm that canalicular adenomas in major salivary glands (either monomorphic or part of hybrid tumors) are distinct from canalicular adenoma of minor salivary glands. Their uniform genotype irrespective of presence or absence of a conventional PA component argues for classifying those tumors lacking a conventional PA component as “monomorphic variants of PA” rather than canalicular/basal cell adenomas, intercalated duct adenoma, trabecular myoepithelioma or true hybrid tumors.

大多数唾液腺肿瘤（良性和恶性）都以复发性基因融合为特征。多形性腺瘤 (PA) 是最常见的唾液腺肿瘤，在大多数情况下是由染色体重排驱动的，涉及映射到 8q12 的PLAG1和映射到 12q13-15 的HMGA2 。已鉴定出多个融合伴侣，包括用于PLAG1融合的CTNNB1、FGFR1、LIFR、CHCHD7和TCEA ，以及用于HMGA2融合的NFIB、WIF1和FHIT。迄今为止，尚无有关少数报道的HMGA2-WIF1重排 PA形态的数据。我们提出了 28 个主要唾液腺腺瘤，显示出与复发基因型相关的独特小梁和小管形态。患者包括 15 名女性和 13 名男性，年龄在 43 岁至 87 岁之间（中位数：65 岁）。所有肿瘤均起源于腮腺。它们的大小范围为 1 至 4 厘米（平均值：2.3）。组织学上，所有肿瘤均显示细长或柱状细胞排列成双层至多层的交通和分支链和小梁，其方式类似于小唾液腺小管腺瘤或小梁肌上皮瘤，具有可变的固体汇合嵌入导管样区域。15 个肿瘤完全是小管/小梁肿瘤，而 13 个肿瘤具有混合或界限清楚的常规（软骨粘液样）PA 成分，占肿瘤的 5% 至 >50%。单态区域一致表达 CK7 (28/28)、波形蛋白 (21/21)、S100 (24/24)、SOX10 (16/17) 以及不同程度的 p63 (8/21) 和乳房珠蛋白 (6/16)，但呈阴性与 p40 (0/24)、平滑肌肌动蛋白 (0/24) 和 MUC4 (0/16)。靶向 RNA 测序显示14/16 (87%) 可评估病例中存在HMGA2融合。融合伙伴是WIF1 (12)、RPSAP52 (1) 和HELB (1)。对 1 个混合肿瘤中的 2 个成分进行单独测试显示出相同的HMGA2/WIF1融合。所有病例的 HMGA2 免疫组织化学均呈阳性，包括 2 例融合阴性病例。12 个真正的小管腺瘤的对照队列显示没有HMGA2融合 (0/4) 且缺乏 HMGA2 免疫反应性 (0/12)。这项研究强调了 PA 谱中的一个独特变异，其特征是突出的小梁和小管腺瘤样形态。我们的数据证实，大唾液腺小管腺瘤（单形性或混合肿瘤的一部分）与小唾液腺小管腺瘤不同。无论是否存在传统 PA 成分，其统一的基因型都支持将那些缺乏传统 PA 成分的肿瘤分类为“PA 的单形变体”，而不是小管/基底细胞腺瘤、闰管腺瘤、小梁肌上皮瘤或真正的混合肿瘤。