Case 7 - NGYN

History:
55 year old male with a history of
bladder cancer
voided urine -5ml of clear yellow fluid

Dr. Stelow
 Case 7

Dr. Stelow
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 55‐year‐old man with a 
history of bladder cancer
Voided Urine ‐ 5ml of clear yellow fluid
Cytologic Features
Atypical single cells / loose clusters. Small amount of
delicate somewhat frothy cytoplasm.. Eccentric,
enlarged nuclei with smooth contours. Fine
chromatin with rare granules and small / indistinct
nucleoli. Clean background!!
 Single Cells / Loose clusters
Normal urothelial or squamous cells
Other cells of the tract, including prostate, 
seminal vesicle and renal
Reactive cells
Neoplastic cells
Well…..  The nuclei are a bit 
larger than I like to see with 
normal urothelial cells and 
the N/C ratios look to be a 
bit more than I’m 
accustomed to seeing with 
normal urothelial cells 
 Single Cells / Loose Clusters
Normal urothelial or squamous cells.
Other cells of the tract, including prostate, 
seminal vesicle and renal.
Reactive cells
Neoplastic cells
Well…..  The cells really aren’t 
large enough, or strange enough 
to be from the prostate or 
seminal vesicle… no pigment 
either… background doesn’t look 
like the patient should be 
shedding renal tubular cells
 Single Cells
Normal urothelial or squamous cells.
Other cells of the tract, including prostate, 
seminal vesicle and renal.
Reactive cells
Neoplastic cells
 Reactive Cells
Acute and Chronic Cystitis, NOS
Specific Infections
Virus (Herpes, Adenovirus, CMV, Polyoma…)
Other Cystitis (Interstitial, hemorrhagic…)
Metaplasia (Cystitis cystica / glandularis)
Endometriosis, etc
Chemotherapeutic / Radiation effect

Background is awfully clean…
 Reactive Cells
Acute and Chronic Cystitis, NOS
Specific Infections
Virus (Herpes, Adenovirus, CMV, Polyoma…)
Other Cystitis (Interstitial, hemorrhagic…)
Metaplasia (Cystitis cystica / glandularis)
Endometriosis, etc
Chemotherapeutic / Radiation effect
I see nothing I can call viral 
cytopathic effect…
Decoy
 Reactive Cells
Acute and Chronic Cystitis, NOS
Specific Infections
Virus (Herpes, Adenovirus, CMV, Polyoma…)
Other Cystitis (Interstitial, hemorrhagic…)
Metaplasia (Cystitis cystica / glandularis)
Endometriosis, etc
Chemotherapeutic / Radiation effect
The cells really aren’t columnar or 
vacuolated…
 Reactive Cells
Acute and Chronic Cystitis, NOS
Specific Infections
Virus (Herpes, Adenovirus, CMV, Polyoma…)
Other Cystitis (Interstitial, hemorrhagic…)
Metaplasia (Cystitis cystica / glandularis)
Endometriosis, etc
Chemotherapeutic  / Radiation effect
The cells really aren’t vacuolated and 
… the background is awfully clean…
 Chemotherapeutic / Radiation 
Effect
BCG
Mitomycin C / Thiotepa / Intravesicular
therapy
Cyclophosphamide / Systemic therapy
Radiation
Well… changes secondary to therapy are 
probably the most common cause of false 
positive diagnoses … but…there are no 
granulomas and giant cells… no 
background necrotic debris… no 
degeneration… no nuclear or cytoplasmic
vacuolization
 Neoplasm
Bladder / Urethra / Ureter – Urothelial
Bladder / Urethra / Ureter – Other
Renal
Prostate
 Neoplasm
Bladder / Urethra / Ureter – Urothelial
Bladder / Urethra / Ureter – Other
Renal
Prostate
Bladder / Urethra / Ureter ‐ Other
Squamous cell carcinoma / Adenocarcinoma / 
Spindle cell carcinoma
Mesenchymal tumor
Hematolymphoid tumor
Benign Tumor: Nephrogenic Adenoma
Metastasis
Bladder / Urethra / Ureter ‐ Other
Squamous cell carcinoma / Adenocarcinoma / 
Spindle cell carcinoma
Mesenchymal tumor
Hematopoeitic tumor
Benign Tumor: Nephrogenic Adenoma
Metastasis
 Nephrogenic Adenoma
Reactive / neoplastic lesions (inflammation, 
treatment, trauma, transplant patients)
Implants of renal tubular cells – Pax‐2
Can be papillary or flat
Papillary, tubular, and cystic structures lines 
by a single layer of cuboidal cells with round 
nuclei and fine chromatin
 Nephrogenic Adenoma
Cytology
Loosely cohesive papillary clusters
Amphophilic cytoplasm with vacuoles, 
typically indenting the nucleus, occasional 
signet ring cells
Slightly increased N/C ratio
Round to oval nuclei with fine chromatin and 
small nucleoli
Background usually inflammatory
Often interpreted as atypical
 Bladder / Urethra / Ureter ‐
Urothelial
Urothelial carcinoma – low vs high grade
Variants – squamous and glandular, 
architectural variants, lymphoepithelioma, 
plasmacytoid, other
 Plasmacytoid Variant
High‐grade urothelial carcinoma
Present at high stage and have poor outcome
Infiltrating rather bland, plasmacytoid single 
cells
 Plasmacytoid Variant
Cytology
Low cellular, single cells and loose clusters
Moderate amphophilic cytoplasm
Increased, but not that increased N/C ratio
Oval, eccentric nuclei
Inconspicuous nucleoli
Well…..  You do what 
you want with it but I 
can’t call it cancer
 Real World
Atypical Urothelial Cells, present single and in 
small clusters, suspicious for recurrent 
malignancy – See Note

NOTE:  We do not have the patient’s original 
specimen for review and, furthermore, it is 
unclear from the inadequate history what 
disease he actually had… Thanks, a lot, David!
 Reactive Atypical CIS

Pattern
Cellularity Variable Scant High
Single Cells Rare Scattered Numerous
Arrangement Pap and loose Loose Loose
Cell Size Up / Uniform Up / Uniform Up / Pleomorphic
Cytoplasm Vacuolated Clear / Homog Clear / Homog
NCR Preserved Increased Very Increased
Nuclear
Position Central Eccentric Eccentric
Enlargement Slight Slight Moderate
Anisonucleosis Absent Slight Mod / Marked
Shape Oval Oval / Round Variable
Shape Variation Absent Slight Mod / Marked
Contours Smooth Nothched Pleomorphic
Hyperchromasia Absent Mild Mod / Marked
Chromatin Fine Granular Coarse
Nucleolus Large Absent / Small Variable / Large
 What does atypical mean?
It means there’s somewhere between a
20-50% chance that the patient has a
malignancy, depending on your own
threshold for the diagnosis and the pretest
probability of the particular patient.
Do ancillary testing if you so wish.
 Out on a Limb
Recurrent Urothelial Carcinoma, Plasmacytoid
Variant
 NGYN Case 7
Audience Vote

1) Benign urothelium, treatment effect

2) Urothelial carcinoma
3) Nephrogenic adenoma
4) Cystitis glandularis
5) Renal cell carcinoma
 Panelists’ Signout

Atypical urothelial cells

Malignant cells present
– favor high grade TCC
Recurrent urothelial carcinoma
Atypical single cells, suspicious for
malignancy
 Panelists’ “Best Diagnosis”

1) Urothelial carcinoma ? Plasmacytoid

variant
2) Urothelial carcinoma ? Ileal conduit
3) Urothelial carcinoma, high grade
4) Benign urothelial cells ? Chemotherapy
effect
Original Signout & Management

Malignant tumor cells present

– consistent with TCC
Cystoscopy
Bladder biopsy
 Final Diagnosis

Nephrogenic Adenoma
What Did I Learn – Case 7

Not atypical enough for HG TCC

Too atypical for LG TCC
Presenting as predominantly single cells
Very smooth chromatin
Vacuolization not seen but there are hints
Think about nephrogenic adenoma
 Case 8 - NGYN

History:
34 year old male with history of prior
right renal mass, now with left renal
mass, enlarged retroperitoneal lymph
nodes radiologically

Dr. Auger