Fig. 1: Radiographic and molecular characterization of treatment-emergent squamous cell carcinoma.

a Clinical course of the patient. ADT: Androgen deprivation therapy, mCRPC: metastatic castration resistant prostate cancer, FDG: Fluorodeoxyglucose, PSMA: Prostate specific membrane antigen, ICI: Immune checkpoint inhibitor, SBRT: Stereotactic body radiation therapy. b Comparative PSMA-PET and FDG-PET imaging (I) PSMA-PET scan with low uptake in the same two hilar lymph nodes. (II) FDG-PET scan with high metabolic activity in two left hilar lymph nodes. (III) PSMA-PET scan with avid uptake at the same T10 metastasis. (IV) FDG-PET scan with avid uptake at the T10 metastasis. c Histologic and immunohistochemical findings of mediastinal lymph nodes biopsies (I) Hematoxylin and eosin (H&E) stain showing squamous morphology. (II) Positive staining for p40. (III) Negative staining for NKX3-1. (IV) Weak staining for ERG. (V) H&E stain highlighting focal tumor clusters without squamous differentiation, (VI) which show NKX3-1 positivity. (VII) H&E stain of radical prostatectomy specimen (with treatment effect): Residual intraductal (left; with surrounding basal cells) and invasive (middle/right; without basal cells) carcinoma was present (b represents a higher magnification of boxed area in a). The tumor cells had pale cytoplasm and small round nuclei with prominent nucleoli. c Focally, in less than 5% of the tumor, squamous differentiation (sqd) was seen in the intraductal carcinoma; squamous differentiation was not seen in the invasive component. d Genomic profiling of the patient’s primary tumor from the radical prostatectomy specimen and a metastatic lesion from an enlarged mediastinal lymph node with low PSMA expression on PSMA PET scan (tumor purity 30% and 50%, respectively).