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. 2024 Oct;85(4):566-578.
doi: 10.1111/his.15214. Epub 2024 May 24.

Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases

Thibault Kervarrec  1   2   3 , Danna Westphal  4   5 , Daniel Pissaloux  6   7 , Mélanie Legrand  1 , Franck Tirode  6   7 , Anne Neuhart  6   7 , Francoise Drouot  3   8 , Jürgen C Becker  9   10   11 , Nicolas Macagno  3   12 , Alice Seris  3   13 , Thomas Jouary  3   13 , Fanny Beltzung  14 , Marie-Laure Jullie  3   14 , Paul W Harms  15   16 , Bernard Cribier  17 , Samia Mourah  18 , Fanélie Jouenne  18 , Gaelle Fromont  1 , Baptiste Louveau  18 , Maxence Mancini  18 , Dmitry V Kazakov  19 , Arnaud de la Fouchardière  3   4   5 , Maxime Battistella  3   20
Affiliations

Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases

Thibault Kervarrec et al. Histopathology. 2024 Oct.

Abstract

Aims: 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.

Methods and results: 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.

Conclusion: Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.

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References

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