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Common Differential

Diagnoses in

Urological Pathology

Jonathan I. Epstein

Prostate Adenocarcinoma vs.

Urothelial Carcinoma

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NKX3.1

NKX3.1

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Proposed ISUP Recommendations

• Option to use PSA as a first test to identify Pca. and GATA3 to

identify UC.

• If GATA3 not available, then HMWCK and p63.

• If the tumor shows strong PSA positivity and negative for HMWCK

and p63, the findings are diagnostic of Pca.

• If the tumor is negative for PSA and diffusely strongly positive for

p63 and HMWCK, the findings are diagnostic of UC.

Proposed ISUP Recommendations

• If the tumor is equivocal/weak/negative for PSA and negative/focal

for p63 and HMWCK, then need to do p501S, NKX3.1 and GATA3.

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Clear Cell Adenocarcinoma vs.

Nephrogenic Adenoma

Clear Cell Adenocarcinoma

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Nephrogenic Adenoma

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Ki67 in Clear Cell Adenocarcinoma

Ki67 in NA

Nephrogenic Adenoma vs. Clear Cell

Adenocarcinoma

Nephrogenic Adenoma

• Usually < 1cm. Can be large.

• 20% multifocal

• M:F 2:1

• Prior injury

• Solid – rare, focal

• No mitoses

• No clear cells

• PAX8 positive

Clear Cell Adenocarcinoma

• Typically large

• Unifocal

• Rare in men

• No prior injury

• Solid areas common

• Mitotic figures common

• Typically clear cells

• PAX8 positive

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Polypoid Cystitis

• Reaction to injury

• Indwelling catheters, fistulae, abscesses, long-

standing urinary obstruction

• Often recognized as inflammatory by urologist at

cystoscopy

• Spectrum: bullous, polypoid, papillary

Mimic of Urothelial Carcinoma

• Can have isolated papillary fronds rarely branching papillae

• Base of the papillary stalks typically both broad and narrow yet uncommonly can be only narrow

• Urothelium diffusely and focally thickened in some cases

• Reactive urothelial atypia often present

• Rare mitotic figures not uncommon

• Fibrosis (not edema) within polypoid stalks in some cases

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Nested Variant of Urothelial Cancer vs.

Von Brunn Nests

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Nested Variant

Urothelial Carcinoma

• Murphy WM, Deana DG. The nested variant of

transitional cell carcinoma: a neoplasm resembling

proliferation of Brunn’s nests. Mod Pathol

1992;5:240-3

Clinical Features

• Older male patients

• To date, nested variant of urothelial carcinoma has

been reported in only 4 women

• Typically present with hematuria

Location

• Anywhere in the bladder

• Only two cases of nested variant of urothelial

carcinoma in the ureter

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Histology – Difficult to Diagnose as Cancer

• Cytologically, may show very uniform, bland cells

with only focal moderate atypia

• Nucleoli may be prominent and mitoses may be seen,

but are usually not numerous

• Lymphatic invasion uncommon

• Overlying urothelium may be normal in appearance

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Von Brunn Nests

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Prognosis (Mayo Clinic 2013)

• Clinical course generally aggressive

• 69% pT3-pT4 & 19% LN+

• 10 year cancer specific survival 41%

• Same prognosis vs. usual urothelial carcinoma stage for stage

• Nested variant of urothelial carcinoma is critical to

recognize given its aggressive biology despite its

deceptively bland cytology

• The diagnosis is based on the H&E appearance

• In cases of diagnostic uncertainty or a superficial

biopsy, convey your uncertainty to the urologist and

request additional tissue sampling

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Radiation Change

Radiation Change in the Prostate

• RT affect in Benign Prostate - Differential Diagnosis

from Prostate Cancer

• RT results – Affect on Prognosis

– Positive for cancer (w/o treatment affect)

– Negative for cancer

– Positive for cancer (with treatment affect)

• More atypia in cases treated with IRT (seeds) than XRT

• No change in epithelial atypia over time in men treated with IRT. With XRT, less epithelial atypia in cases biopsies >48 months after treatment

• RT atypia may persist for a long time: Prominent RT atypia detected 72 months after IRT

• Some cases clinicians not aware of remote h/o of RT or do not relay this on to pathologists. Pathologists must be able to recognize RT atypia w/o relying on the clinician to provide this history

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Radiation Biopsy Results: Cancer with

Treatment Affect

Histologically cancer is seen, yet shows treatment effect

with degenerative features. Cancer is present, yet is it

viable?

Prognosis: Similar to cases with no cancer.

Do not grade radiated cancer with treatment effect.

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Radiation Biopsy Results: Positive

Histologically, ordinary prostate cancer is seen, which

resembles non-radiated cancer.

If biopsy is done >12 months following radiation,

indicates progression of cancer. Can assign a Gleason

grade.

Cystitis Glandularis (Intestinal Type)

Colonic Metaplasia

Features Mimicking Adenocarcinoma

• Mucinous extravasation

• Rare involvement of muscle

Distinguishing Features from Adenocarcinoma

• Lack of cytologic atypia

• Lack of necrosis

• Lack of signet cells

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Endocervicosis

Endocervicosis

• Typically in women in their 30s and 40s

• Symptoms of pelvic pain, frequency, dysuria, hematuria,

dyspareunia, dysmenorrhea

• Most common in bladder. Also seen in uterine cervix, vagina

• Mass (up to 5 cm) seen in posterior bladder wall with

occasional extravesical involvement

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Infiltrating Adenocarcinoma

of the Bladder

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Radiotherapy of the Bladder:

Pseudocarcinomatous Hyperplasia

Less familiar to pathologists is radiation-induced

pseudocarcinomatous hyperplasia.

The first series to report this mimicker of invasive

urothelial carcinoma was by Baker and Young in

2000 (2). Four cases were described, with follow-up

available in one patient, which was benign.

• 70 cases: 60 males/10 females

• Mean age 67 (33-85)

• 76.5% prior pelvic RT

• Developed on average 4.5 years (9 mos.-13 yrs). after

prior RT

• 2 systemic chemo, 3 indwelling catheter, 2 intravesical

chemo, 1 prior RP, 4 severe peripheral vascular disease,

1 AV malformation in the bladder, 1 sickle cell trait, 2

(2.9%) no identifiable contributing factor.

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Follow-up

• Three of 40 patients with follow-up (mean 27 months)

had subsequently found to have UC

• 1 – prior positive cytology and FISH

• 1 – prior high grade papillary UC

• 1 – unknown history

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Histology: Resemblance to Cancer

• Architectural pattern mimicking cancer:

44% with >50% involvement of LP

• Most cases (61%) had prominent nucleoli

• All had mild to moderate pleomorphism

• 28% with mitotic figures (1-8/10HPF)

Histologic Clues to Benign Nature

• Edema (94%), vascular congestion (78%), hemosiderin (56%)

• Nests do not extend irregularly down into the lamina propria or muscularis propria as is seen with the urothelial carcinoma.

• Ulceration (39%) and thickened vessels (72%), which are clues to the prior irradiation.

• Most importantly fibrin deposits with in many cases the urothelial nests encircling the fibrin.

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Inverted Urothelial Papilloma

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• Most commonly seen at trigone, yet may be anywhere

urothelium present.

• Usually solitary (3% multiple).

• Polypoid or sessile with smooth surface

• Wide size range

• Not related to increased risk of subsequent urothelial

carcinoma

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Comparison to Urothelial Carcinoma

• Lacks cytological atypia

• Mitotic activity limited to basal cell layer

• Lacks inflammation and reactive stroma

• Squamous metaplasia lacks keratin formation

• Lacks muscularis propria invasion