5/21/2018. Prostate Adenocarcinoma vs. Urothelial Carcinoma. Common Differential Diagnoses in Urological Pathology. Jonathan I.

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1 Common Differential Diagnoses in Urological Pathology Jonathan I. Epstein Prostate Adenocarcinoma vs. Urothelial Carcinoma 1

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3 NKX3.1 NKX3.1 3

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7 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. 7

8 Clear Cell Adenocarcinoma vs. Nephrogenic Adenoma Clear Cell Adenocarcinoma 8

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11 Nephrogenic Adenoma 11

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15 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 15

16 Polypoid Cystitis Reaction to injury Indwelling catheters, fistulae, abscesses, longstanding 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 16

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20 Nested Variant of Urothelial Cancer vs. Von Brunn Nests 20

21 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 Older male patients Clinical Features 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 21

22 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 22

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25 Von Brunn Nests 25

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27 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 27

28 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 28

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31 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. 31

32 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 32

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35 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 35

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37 Infiltrating Adenocarcinoma of the Bladder 37

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41 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. 41

42 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 42

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44 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. 44

45 Inverted Urothelial Papilloma 45

46 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 46

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50 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 50

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