Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. © 2022 The Pathological Society of Great Britain and Ireland.

Recent advances in nanocarrier-loaded gels: Which drug delivery technologies against which diseases?

The combination of pharmaceutical technologies can be a wise choice for developing innovative therapeutic strategies. The association of nanocarriers and gels provides new therapeutic possibilities due to the combined properties of the two technologies. Gels support the nanocarriers, localize their administration to the target tissue, and sustain their release. In addition to the properties afforded by the gel, nanocarriers can provide additional drug sustained release or different pharmacokinetic and biodistribution profiles than those from nanocarriers administered by the conventional route to improve the drug therapeutic index. This review focuses on recent (over the last ten years) in vivo data showing the advances and advantages of using nanocarrier-loaded gels. Liposomes, micelles, liquid and solid lipid nanocapsules, polymeric nanoparticles, dendrimers, and fullerenes are all nanotechnologies which have been recently assessed for medical applications, such as cancer therapy, the treatment of cutaneous and infectious diseases, anesthesia, the administration of antidepressants, and the treatment of unexpected diseases, such as alopecia.