汗孔癌是一种向汗管上部分化的恶性汗腺肿瘤，可能是由先前存在的良性汗孔瘤转变而来。 2019 年，Sekine 等人。证明大多数孔瘤和孔癌中存在 YAP1::MAML2 和 YAP1::NUTM1 融合。最近，我们的小组在良性孔瘤的一个子集中发现了 PAK2 融合。在此，我们报告了一系列 12 例含有 PAK1/2/3 融合的毛孔癌病例。其中 5 名患者为男性，中位年龄为 79 岁（范围：59-95 岁）。肿瘤位于躯干（n = 7）、大腿（n = 3）、颈部（n = 1）或腹股沟区域（n = 1）。四名患者出现远处转移。镜下观察，7例有良性孔瘤成分和恶性浸润部分。所有肿瘤均观察到导管形成，而漏斗状/角囊肿和细胞质空泡化的细胞分别在七个和六个肿瘤中检测到。在三种情况下，侵袭成分包括细长细胞的增殖，其中一些形成假血管空间，而另一些则具有主要的实性或小梁生长模式。 CEA 和 EMA 的免疫组织化学染色证实了导管的存在。在三个样本中检测到局灶性雄激素受体表达。全RNA测序证明LAMTOR1::PAK1 (n = 2)、ZDHHC5::PAK1 (n = 2)、DLG1::PAK2、CTDSP1::PAK1、CTNND1::PAK1、SSR1::PAK3、CTNNA1::PAK2、RNF13 ::PAK2、ROBO1::PAK2 和 CD47::PAK2。 6 例病例中存在 HRAS 激活突变（G13V，n = 3，G13R，n = 1，Q61L，n = 2）。我们的研究表明，PAK1/2/3 融合是缺乏 YAP1 的毛孔癌子集的致癌驱动因素重新排列。© 2024 作者。组织病理学由约翰·威利出版

Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.