They Do Look Alike : in Biopsy Samples Gladell P. Paner, MD Departments of Pathology and Surgery (Urology) University of Chicago, IL USA Gladell.paner@uchospitals.edu
Benign in Needle Biopsy 1. Benign crowded glands 2. Atrophy simple, post atrophic hyperplasia, partial 3. Hyperplasia usual, atypical adenomatous (adenosis), clear cell cribriform, basal cell, sclerosing adenosis More important classification whether its CANCER or NOT! 4. Metaplasia nephrogenic, mucinous 5. Reactive atypia inflammatory, post-therapy, ischemic 6. Inflammation prostatitis, xanthoma, nonspecific granulomatous, malakoplakia 7. Artifacts crushed glands, rectal tissue 8. Histoanatomic structures - a. Prostatic (PSA+) - cribriform central zone gland, verumontanum mucosal gland b. Non-prostatic (PSA-) - Mesonephric remnants, Cowper s gland, seminal vesicles, ejaculatory duct, paraganglion Srigley J. Mod Pathol. 2004;17:328. Trpkov K. Mod Pathol. 2018;31:S22. 2
Benign in Needle Biopsy Important to know what exactly the benign mimic - MIMICS 3
Which Cancer Patterns Are Mimicked? 1. Gleason architecture Majority (well-formed gland) Hyperplasia (cribriform), xanthoma, paraganglion (fused) Inflammation (infiltrative, solid) Am J Surg Pathol 2016;40:244 2. Carcinoma variants atrophic (atrophy), pseudohyplastic and microcystic (hyperplasia), foamy gland (xanthoma), pleomorphic giant cell (seminal vesicle/ejaculatory duct), mucinous (metaplasia), signet ring cell (inflammation) 4
Well-formed glands (GP 3) cancers what to look for? Architecture Cytoplasm Nuclei Lumina Racemase + Basal cells - PSA + 5
What makes us pause to commit to a diagnosis? MOST morphologic features are NOT SPECIFIC needs a combination for our TRESHOLD Cancer Benign Crystalloids Mucin 6
What makes us pause to commit to a diagnosis? MOST morphologic features are NOT SPECIFIC needs a combination for our TRESHOLD Cancer Benign Nerve invasion 7
Features Considered Specific for Cancer (vs. Atypical glands) Circumferential NI Glomerulation Mucinous fibroplasia Extraprostatic 8
Benign Crowded Glands PIN4: Some racemase staining & patchy basal cells + Atypical architecture 9
Diffuse Atrophy Atrophic Cancer Focal Basophilic, angulated Nuclear atypia, luminal features 10
Atrophy Atrophic Cancer HMWK + (prominent basal cells) PIN4: racemase+,basal cells- 11
Postatrophic Hyperplasia (Lobular Atrophy) Atrophic duct/acini + proliferating acinar glands DX: Similar approach with simple atrophy 12
Partial Atrophy One of the most problematic Irregular or undulating, cuboidal, pale/clear 13
Partial Atrophy Cancer -/+ nucleoli, w/ complete atrophy HMWK: patchy basal cells PIN4: Racemase+, Basal cells- 14
Adenosis (Atypical Adenomatous Hyperplasia) Small glands, crystalloids, concretions Gleason pattern 1 or 2 Racemase -/weak+, basal cells patchy + 15
Adenosis (Atypical Adenomatous Hyperplasia) Usually in TURP TZ, circumscription Biopsy abrupt transition HMWK; patchy basal cells Inconspicuous nucleoli 16
Hyperplastic Pattern in Cancers Benign hyperplastic gland PIN4: racemase+, b. cells- Basal nuclei, luminal content, adjacent to usual cancer Pseudohyperplastic carcinoma Microcystic carcinoma (WHO 2016) 17
Basal Cell Hyperplasia Proliferative glands Multilayered Cancer PIN4: racemase+, bc- Multilayered, lacks atypia 18
Basal Cell Hyperplasia (Cribriform) Basal cell carcinoma Adenoid cystic-like BC hyperplasia Invasive, desmoplasia Ki-67: High (>20%) 19
Cribriform Club Central zone gland Clear cell cribriform hyperplasia Basal cell (adenoid cystic-like) hyperplasia Benign Cribriform HG PIN Atypical cribriform lesion Intermediate Intraductal carcinoma Cribriform Gleason pattern 4 carcinoma Cribriform ductal adenocarcinoma Basal cell/adenoid cystic carcinoma Cancer 20
Clear Cell Cribriform Hyperplasia Cribriform Gleason pattern 4 Lacks atypia, with basal cells IDC-P PIN4: racemase+, bc+ Florid growth 21
Nephrogenic Adenoma (Metaplasia) Intraprostatic proliferation Urethra, biphasic: papillary + glands Thick BM, cuboidal, flat, hobnail cells Infiltrative 22
Nephrogenic Adenoma (Metaplasia) PIN4: Racemase overexpression 23
Nephrogenic Adenoma (Metaplasia) PIN4: Racemase+, HMWK+ Florid growth: Fused pattern Pax8 + Fused pattern 24
Mesonephric Remnant Hyperplasia Periprostatic/bladder neck Tubules + colloid-like material Florid, fusion Lobular Infiltrativ e PSA- 25
Verumontanum Mucosal Glands Hyperplasia Urethra, ED, small glands, concretions Basal cells readily discernable PIN4: HMWK+ 26
Cowper s gland (Bulbourethral gland) Lobular Foamy Gland Carcinoma Mucinous Skeletal muscles 27
Mucinous Metaplasia Mucinous Carcinoma 28
Seminal Vesicle/Ejaculatory Duct Pleomorphism + pigments Pleomorphic giant cell carcinoma (2016 WHO) PSA/PSAP-, Pax8+ 29
Paraganglia Extraprostatic, nested, pale to amphophilic, neuroendocrine cells Vascularity 30
Xanthoma Hypernephromatoid carcinoma Foamy gland carcinoma Radiation-treated cancer CD68+ 31
Non-Specific Chronic Granulomatous Inflammation Small cell carcinoma Polymorphous cell infiltrates Synaptophysin + 32
Chronic Inflammation Individual cell (GP5) carcinoma Hormonally treated carcinoma 33
Benign Mimics in the Era of Active Surveillance To what extent should we work-up possible GP3 mimics? 1. Patient falls under criteria for AS - 3+3, <3 cores +, <50% involvement, ct2a, PSA <10 ng/ml despite having atypical focus of mimic vs. cancer. 2. Follow-up biopsy showing no apparent increase in volume and grade, including the atypical focus of mimic vs. cancer. 34
Thank you! 35