Table 1 Crucial clinical information that influences on how the pathologist should proper interpret microscopic findings

Demographics

Sex, age, symptoms, comorbidities

Malignancy is rare in young people; denuded biopsies are concerning for CIS particularly in the setting of hematuria; renal stones, recurrent infections, indwelling catheter, and obstruction are associated with benign mimickers of urothelial cancer;

Cystoscopy

Flat (velvety), papillary, ulceration, nodular, multiple, scar

Red velvety patches suggest CIS; pathologist may insist on deeper cuts to find papillae in an initially flat lesion; ulceration is associated with aggressive disease; Inverted papilloma and mesenchymal lesions have nodular morphology; multiple lesions should be placed in separate containers to receive each a diagnosis.

Chronology

new/ de novo tumor, recurrent lesion, re-TURB, second look, random biopsies/follow-up

Incompletely resected tumors may hide higher grade areas, which can impact final diagnosis and stage; exclusion of a prior urothelial malignancy is a criterion for PUNLMP; de novo CIS is a rare diagnosis weather CIS on follow-up may represent residual/recurrent disease.

Location

Precise location, particularly if bladder neck/ trigone, dome, anterior wall.

Important for follow-up (residual / recurrent) and for precise accession at cystectomy (particularly if previous complete TURB or neoadjuvant therapy); Squamous metaplasia in the female trigone is physiological; Urachal remnants and lesions are exclusive to the dome; Carcinoma in diverticula is never staged pT2; Muscularis propria have peculiar peri-orificial anatomy which may impact stage; anteriorly located tumors may be technically difficult to resect.

Procedure

Biopsy or TURB (partial or total resection)

Incompletely resected tumors may hide higher grade areas, which can impact final diagnosis and stage.

Previous therapies

TURB, intravesical therapy, systemic neoadjuvant therapy

Intravesical therapy is more intense in the surface (buried carcinoma phenomenon) and inflammation may produce reactive atypia; Radiation therapy can induce severe nuclear atypia, which is particularly important in flat lesions and within 12 months of last dose.