Recurrent PAK2 rearrangements in poroma with folliculo‐sebaceous differentiation

Abstract

Aims Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine et al. demonstrated recurrent YAP1::MAML2 and YAP1::NUTM1 fusion in poroma and porocarcinoma. Follicular, sebaceous and/or apocrine differentiation has been reported in rare cases of poroma and whether these tumours constitute a variant of poroma or represent a distinctive tumour is a matter to debate. Herein we describe the clinical, immunophenotypic, and molecular features of 13 cases of poroma with folliculo‐sebaceous differentiation. Methods and results Most of the tumours were located on the head and neck region (n = 7), and on the thigh (n = 3). All presented were adults with a slight male predilection. The median tumour size was 10 mm (range: 4–25). Microscopically, lesions displayed features of poroma with nodules of monotonous basophilic cells associated with a second population of larger eosinophilic cells. In all cases, ducts and scattered sebocytes were identified. Infundibular cysts were present in 10 cases. In two cases high mitotic activity was noted, and in three cases cytologic atypia and areas of necrosis were identified. Whole transcriptome RNA sequencing demonstrated in‐frame fusion transcripts involving RNF13::PAK2 (n = 4), EPHB3::PAK2 (n = 2), DLG1::PAK2 (n = 2), LRIG1::PAK2 (n = 1), ATP1B3::PAK2 (n = 1), TM9SF4::PAK2 (n = 1), and CTNNA1::PAK2 (n = 1). Moreover, fluorescence in situ hybridisation (FISH) analysis revealed PAK2 rearrangement in an additional case. No YAP1::MAML2 or YAP1::NUTM1 fusion was detected. Conclusion Recurrent fusions involving the PAK2 gene in all analysed poroma with folliculo‐sebaceous differentiation in this study confirms that this neoplasm represents a separate tumour entity distinct from YAP1::MAML2 or YAP1::NUTM1 rearranged poromas.

Aggressive EWSR1::POU2AF3(COLCA2) spindle/round cell sarcoma of the sinonasal tract

“…It was first discovered in 2023 by Agaimy et al, 1 and up to now, 19 well-documented cases have been published. 3,4 This tumour best fits in the group of undifferentiated small round/spindle cell tumours with EWSR1 fusions. COLCA1 and COLCA2 (colorectal cancer associated 1 and 2) are both mapped to chromosomal region 11q23.1, and are both human genes that were discovered in 2014 as genetic loci associated with increased colorectal cancer risk.…”

“…1 These tumours exhibit a significant preference for the head and neck region (13 out of 19 cases), notably within the sinonasal area (9 out of 19 cases), although they can also occur in alternative sites, such as soft tissue and bone. 3,4 The use of targeted RNA sequencing facilitates the diagnostic process.…”

Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: An update

“…Regardless of this hypothesis, it is likely that PAK2 rearrangement is a critical oncogenic driver of apocrine poroma with folliculo-sebaceous differentiation, a close but distinct entity to eccrine poroma. 89 As tumours driven by YAP1::MAML2, YAP1:: NUTM1 and PAK2 fusions are associated with close but distinct morphologies, these tumours may also be associated with various risks of transformation. 14 Indeed, due to the frequent association of porocarcinoma with a benign poroma component, it is widely accepted that a progression from poroma to porocarcinoma can occur.…”