Urinary bladder

Pathobasic

Pathology Lukas Bubendorf

• Biopsy

• TUR-B

• Resection

• Cytology

– Voided urine, washings

Methods

• Benign lesions

• Neoplastic lesions

Flat

Papillary

Solid

Agenda

Benign lesions

• Nonspecific Cystitis

• Granulomatous (after BCG)

• Eosinophilic cystitis

• Interstitial cystitis

• Polypoid cystitis

• Others…..

Interstitial cystitis

• Unknown etiology

• Middle-aged and older

women

• Nonspecific histology

• Early non-ulcer type

• Classic ulcer type (Hunner)

• Typical histology:

– Hemorrhagic foci

– Mast cells (debatable)

– Ulceration

– Granulation tissue

• Clinical symptoms

• Exclude infection

Polypoid cystitis

• Up to ¼ misdiagnosed

as low-grade UC

• F>M

• Unspecific

• Polypoid, edema,

erythema, non-

branched, broad-based

fronds

• Reactive urothelium

• Low-power!

Von Brunn Nests

• Invaginated nests of of

cytologically benign

urothelial cells

• May be pronounced in

the UUT (ureter)

• Common (-90%)

Differential diagnosis

• Nested UC

• Inverted papilloma

• Paraganglioma

Flat lesions

• Urothelial carcinoma in situ (CIS)

• Reactive urothelial atypia

• Urothelial atypia of unknown

significance

• Urothelial dysplasia

Urinary cytology

High-grade urothelial carcinoma Denuding cystitis

CIS

Schematic representation of CIS

Epstein et al, Biopsy Interpretation, 2016

CIS with early papillary formation

Papillary urothelial neoplasms

• Papilloma

• Inverted papilloma

• PUNLMP

• Papillary UC low-grade

• Papillary UC high-grade

Papillary urothelial proliferation uncertain

malignant potential (UPUMP) (Papillary and flat urothelial hyperplasia)

Urothelial papilloma

• Uncommon

• Younger adults

• Often small

• Recur rarely

<10%

• Normal urothelium

• Vacuolization

Inverted urothelial papilloma

• Benign, rare

• Mostly solitary

• Smooth surface

• Trabecular, glandular

• Palisaded basal cells

• Central spaces with colloid-like m.

Healthy

urothelium pT1

pTa

CIS

pT2-4

-9p/q

p53 mut.

FGFR3 mut

p53 mut. Additional

mutations

Chromosomal

instability

Progression of urothelial carcinoma: genetic model

Hedegaard J et al, Cancer Cell 2016

Molecular pathogenesis of urothelial carcinoma

Hedegaard J et al, Cancer Cell 2016 NMIBC

Cancer Cell 2014;25:152

micropapillary mucinous

plasmacytoid Clear cell

The many faces of divergent differentiation in urothelial carcinoma

Humphrey

Eur Urol

2016

Linder BJ, J Urol 2013

Histological variants – the Mayo experience

(33% of entire cohort)

Nested variant of UC

• Deceptively bland

• Disorderly proliferation crowded small

nests beneath the urotheliom

• Little or no nuclear atypia

• +/- tubules, microcysts

• Myxoid stroma

• Large nested: muscle invasion

• DD: von Brunn nests, inverted low-

grade lesions

Nested variant of UC

Large nested variant of UC

High-grade Low-grade

G1 G2 G3

WHO

2016

WHO

1973

Example: pTa G2 (high-grade)

Training the grading of papillary UC

http://www.isupweb.org