Pilomatrix-like high grade carcinomas involving urinary bladder: a novel divergent differentiation in urothelial carcinoma

Abstract The full morphologic spectrum of divergent differentiations in urothelial carcinoma is still unknown. Herein, we describe two cases of pilomatrix-like high grade carcinomas (PiMLC) involving bladder. Case #1 was a 55-year-old male with a bladder tumor with basaloid nests, geographic necrosis, and shadow cells. The tumor cells were positive for LEF1, β-catenin (nuclear/cytoplasmic staining), CK5/6, CD10, BerEP4, p63 (focal-to-patchy) and AMACR (patchy), and negative for CK7, GATA3, CDX2, INSM1, chromogranin, synaptophysin, p40, CK20, calponin, CD117, S100, smooth muscle actin, p16 and high-risk HPV in-situ hybridization. PD-L1 and Her2 were negative. Trop-2 immunostain showed modest expression (H-score: 75). There were rare microscopic foci of surface disease with a similar basaloid appearance that were also positive for LEF1 and negative for GATA3. Genomic profiling of the tumor revealed an  APC mutation, suggesting β-catenin/Wnt pathway dysregulation. Additionally, mutations in TERT ,  CDKN2A , and  TP53 were present. The patient was transitioned to hospice shortly after initiating chemotherapy. Case #2 was a 78-year-old male with a large bladder mass with basaloid nests and abundant shadow cells. Conventional UC was focally present. The tumor cells were positive for p63, β-catenin (nuclear/cytoplasmic staining), CK14 (focal), and CK20 (focal), and negative for GATA3, Uroplakin, NUT, and Her2. Genomic profiling of the tumor revealed a  CTNNB1 mutation, suggesting β-catenin/Wnt pathway dysregulation. Additionally, mutations in RB1 ,  KMT2A , and  TP53 were present. Overall, these two cases describe PiMLC of urinary bladder with evidence supporting novel pilomatrix-like divergent differentiation from urothelial carcinoma.