Inverted urothelial papilloma in a cat.

A 12-year-old neutered female cat was referred with clinical signs referable to lower urinary tract disease. Clinical examination revealed a tense, painful urinary bladder, and proximal urethral thickening. Endoscopic studies showed a pedunculated mass with polypoid projections. Multiple full-thickness mucosal biopsies were obtained, and the mass was almost completely excised. The neoplasm was confined to the mucosa and consisted of epithelial cells arranged in anastomosing trabeculae and nests, growing downward into the lamina propria. Neoplastic cells showed minimal atypia and low mitotic activity. Histological findings were consistent with inverted urothelial papilloma. Feline papillomavirus DNA was not amplified from biopsies. One year later, the cat had no urological signs, and urinary bladder was normal at ultrasound. To the authors' knowledge, this is the first report of a case of inverted urothelial papilloma in a cat and is a differential diagnosis for low-grade urothelial carcinoma and other lesions with inverted growth pattern.

Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder.

Inverted urothelial papilloma (IUP) and urothelial papilloma (UP) are rare urothelial neoplasms that typically follow a benign clinical course. Oncogenic mutations in FGFR3, HRAS, and the TERT promoter have been reported in these entities but no comprehensive molecular analysis has been performed. We sought to characterize the genomic landscape of IUP and UP using whole-exome and targeted next-generation sequencing. In IUP, 10 of 11 tumors harbored oncogenic hotspot mutations in HRAS and the remaining tumor had an oncogenic KRAS mutation. None of the IUP tumors harbored TERT promoter or FGFR3 mutations. In UP, 8 of 11 tumors had oncogenic KRAS mutations and two had oncogenic HRAS mutations. One UP tumor had oncogenic mutations in FGFR3, PIK3CA, and the TERT promoter, and arose in a patient with recurrent non-invasive papillary urothelial carcinomas. In contrast to urothelial carcinoma, the APOBEC mutational signature was not present in any IUP and UP tumors, and oncogenic alterations in chromatin remodeling genes were uncommon in both IUP and UP. The current study suggests that IUP and UP are driven primarily by RAS pathway activation and lack the more common genomic features of urothelial cancers. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Distinct mutational landscape of inverted urothelial papilloma.

A recent study has identified gene mutations involving the MAPK/ERK pathway, particularly the HRAS gene, in all inverted urothelial papillomas (IUPs), in the absence of pathway mutations in TERT promoter, FGFR3, and TP53/RB1genes. Neither recurrence nor progression was observed in IUPs. These data support several longstanding hypotheses: (1) IUPs are benign and do not recur or progress; (2) they harbor mutations that are different from those of urothelial carcinoma; and (3) they arise through different molecular mechanisms than low- or high-grade urothelial carcinoma. As the most critical differential diagnosis in this context is inverted-type urothelial carcinoma, more comprehensive studies are needed to compare and contrast these entities. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Inverted urothelial papilloma: A case report.

Inverted urothelial papilloma (IUP) is an unusual tumor that typically presents as a non-invasive, endophytic urothelial neoplasm. Though fairly well described in the bladder, IUP of the upper urinary tract is fairly rare, with only 68 cases documented in English language literature. Our patient presented with an IUP of the distal left ureter and was treated with a distal ureterectomy and reimplant of the ureter with a psoas hitch.

Proteomic-Based Machine Learning Analysis Reveals PYGB as a Novel Immunohistochemical Biomarker to Distinguish Inverted Urothelial Papilloma From Low-Grade Papillary Urothelial Carcinoma With Inverted Growth.

Background: The molecular biology of inverted urothelial papilloma (IUP) as a precursor disease of urothelial carcinoma is poorly understood. Furthermore, the overlapping histology between IUP and papillary urothelial carcinoma (PUC) with inverted growth is a diagnostic pitfall leading to frequent misdiagnoses. Methods: To identify the oncologic significance of IUP and discover a novel biomarker for its diagnosis, we employed mass spectrometry-based proteomic analysis of IUP, PUC, and normal urothelium (NU). Machine learning analysis shortlisted candidate proteins, while subsequent immunohistochemical validation was performed in an independent sample cohort. Results: From the overall proteomic landscape, we found divergent 'NU-like' (low-risk) and 'PUC-like' (high-risk) signatures in IUP. The latter were characterized by altered metabolism, biosynthesis, and cell-cell interaction functions, indicating oncologic significance. Further machine learning-based analysis revealed SERPINH1, PKP2, and PYGB as potential diagnostic biomarkers discriminating IUP from PUC. The immunohistochemical validation confirmed PYGB as a specific biomarker to distinguish between IUP and PUC with inverted growth. Conclusion: In conclusion, we suggest PYGB as a promising immunohistochemical marker for IUP diagnosis in routine practice.

Inverted urothelial papilloma: A rare pathology in young girl. A case report and literature review.

Bladder cancer is relatively common in the general population but is considered a rare entity in children. Rhabdomyosarcoma is the most frequently encountered bladder tumor in children. Inverted papilloma of the urinary bladder is a rare presentation in adults and is considered extremely rare in the pediatric age group. We report a case of inverted urothelial papilloma (IUP) in the bladder in an 8-year-old girl who presented with painless gross hematuria. Radiological investigations, cystoscopy, and histological examination revealed the rare pathology of IUP of the bladder and a resection was performed. No recurrence was encountered after 3 years of follow-up.

Inverted urothelial papilloma of the upper urinary tract: description of two cases with systematic literature review.

BACKGROUND: Inverted urothelial papilloma (IUP) of the upper urinary tract is an uncommon benign tumour that occasionally presents as a polypoid mass causing urinary obstruction. Histologically, IUP is characterised by a proliferating urothelium arranged in cords and trabeculae, in continuity with overlying intact epithelium, and extending into the lamina propria in a non-invasive, endophytic manner. Cytological atypia is minimal or absent. Top differential diagnoses include urothelial carcinoma with inverted growth pattern and florid ureteritis cystica. Although urothelial carcinomas of the upper urinary tract with prominent inverted growth pattern commonly harbour microsatellite instability, the role of the mutator phenotype pathway in IUP development is still unclear. The aim of this study was to describe two additional cases of IUP of the upper urinary tract, along with an extensive literature review. CASE PRESENTATION: We observed two polypoid tumours originating in the renal pelvis and the distal ureter, respectively. Both patients, a 76-year-old woman and a 56-year-old man, underwent surgery because of the increased likelihood of malignancy. Histology was consistent with IUP and patients are alive and asymptomatic after long-term follow-up (6 years for the renal pelvis lesion and 5 years for the ureter lesion). The tumours retained the expression of the mismatch-repair protein MLH1, MSH2, and PMS2 whereas loss of MSH6 was found in both cases. CONCLUSIONS: When completely resected, IUP does not require rigorous surveillance protocols, such as those for urothelial carcinoma and exophytic urothelial papilloma. It is therefore important for the surgical pathologist to be aware of this rare entity in order to ensure correct patient management.