UROTHELIAL CARCINOMA

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Am J Surg Pathol. 2009 ;33:91-8 SMOOTHELIN - Contractile protein - Fully differentiated muscle cells - Hyperplastic muscularis mucosae (-) to weak - Diffuse and stongpositivity specific for muscularis propria Validated by Miyamoto et. al. Am J Surg Pathol. 2010 - Emphasize overlap in staining pattern and caution in interpretation
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Basel Seminars in Pathology Postgra
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UPDATE ON PATHOLOGY STANDARDS FOR B
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Molecular Pathways for Bladder Canc
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HISTOLOGIC GRADE UROTHELIAL NEOPLAS
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What’s New in the 2012 Consensus
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Reporting of Bladder Cancer • Gui
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• Seen with instrumentation with
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Squamous Metaplasia • Should be r
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GRADING OF UROTHELIAL LESIONS • F
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NORMAL
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Urothelial Dysplasia • Overall fe
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Urothelial Dysplasia • The diagno
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ATYPIA OF UNKNOWN SIGNIFICANCE (WHO
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Grading of Urothelial Carcinoma •
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Papilloma
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PUNLMP
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LOW GRADE
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HIGHGRADE
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P A P I L O M A L M P L O W G R A D
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Courtesy R. Montironi, Italy Exophy
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Inverted High Grade without invasio
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Inverted Papilloma
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Inverted PUNLMP
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Inverted LG
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Inverted HG
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Inverted HG, Non Inv
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WHO (2004) /ISUP : Prognostic Signi
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Contributions of WHO (2004) /ISUP
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Handling grade heterogeneity in bla
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Grading Papillary Urothelial Neopla
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Papillary Hyperplasia with Cytologi
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Dysplasia with early papillary feat
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Grading Invasive Cancer • Practic
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• 2 types of muscle - awareness i
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Muscularis Mucosae Muscle • Hyper
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M. mucosae muscle patterns Typical
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M. mucosae muscle pattern Hypertrop
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Muscularis Propria • Several term
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Muscle Involved by UCa, Indetermina
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Assessment of pT2 vs. pT3 - cystect
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Microinvasive Urothelial Carcinoma
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Substratification or Substaging of
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Extensive invasion
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Retraction a mimic of vascular-lymp
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Vascular Lymphatic Invasion (LVI)
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2013 International Society of Urolo
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Lymph node involvement: • Approx.
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THE BEST BLADDER CANCER PATHOLOGY S
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PSEUDONEOPLASTIC MIMICS OF BLADDER
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EMPHYSEMATOUS & BULLOUS CYSTITIS
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AMYLOIDOSIS
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MALAKOPLAKIA
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NORMAL PARAGANGLIONIC TISSUE
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CIS
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REACTIVE ATYPIA History of stones,
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CIS REACTIVE ATYPIA
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RADIATION ATYPIA
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INTRAVESICAL THERAPY
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Polyoma Virus Infection • Usually
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Papillary tumor Micropapillary U Ca
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Low magnification distinction Broad
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Cystoscopic & microscopic mimic Pap
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Papillary Polypoid cystitis
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ALL THAT IS PAPILLARY BLADDER IS NO
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Bladder Biopsy Interpretation, 2nd
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TIGHTLY CLUSTERED UROTHELIUM
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TIGHTLY CLUSTERED UROTHELIUM
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U Ca. with small tubules Nephrogeni
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NEPHROGENIC ADENOMA - THE BIG MIMIC
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NEPHROGENIC ADENOMA
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NEPHROGENIC ADENOMA
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NEPHROGENIC ADENOMA Clues to benign
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FLORID REACTIVE PROLIFERATIONS norm
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POST-RADIATION PSEUDOCARCINOMATOUS
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LORID CYSTTTIS GLANDULARIS ITH MUCI
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MULLERIANOSIS • Endometriosis, en
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PSEUDOSARCOMATOUS MYOFIBROBLASTIC P
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Gross PMP • Exophyticpolypoid mas
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ROLE OF IMMUNOHISTOCHEMISTRY IN THE
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PROVING UROTHELIAL DIFFERENTIATION
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CA in the bladder, h.o of lung canc
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Paraganglioma Epith. LMS PEComa Mel
Page 255 and 256: p63
Page 257 and 258: Plasmacytoid U Ca
Page 259 and 260: • Markers of urothelium and uroth
Page 261 and 262: S100P S100P GATA3 GATA3 A-F: S100P,
Page 263 and 264: GATA 3 & S100 P: Diagnostic utility
Page 265 and 266: PARAGANGLIOMA
Page 267: Identification of Succinate Dehydro
Page 270 and 271: CIS REACTIVE
Page 272 and 273: NORMAL
Page 274 and 275: CK-20
Page 276 and 277: REACTIVE UROTHELIUM
Page 278 and 279: CK-20
Page 280 and 281: Reactive CD44
Page 282 and 283: CA-INSITU
Page 284 and 285: CK-20
Page 286 and 287: CIS CK20
Page 288 and 289: CK20 (+) CD44(-)
Page 290 and 291: p53
Page 292 and 293: CD44
Page 294 and 295: Reactive CIS
Page 296 and 297: Radiation-Reactive Radiation CIS
Page 298 and 299: AUA GUIDELINE 2007 UPDATE: • Stan
Page 300 and 301: Typical pattern: • Arranged in gr
Page 302 and 303: Muscularis mucosae or muscularis pr
Page 306 and 307: SMA hyperplastic
Page 308 and 309: SMA
Page 310 and 311: Hypertrophic muscularis mucosae
Page 312 and 313: Smoothelin - M. Mucosae
Page 314 and 315: SMOOTHELIN IN DESMOPLASIA: NEGATIVE
Page 316: TYPES OF MUSCULARIS PROPRIA INVASIO
Page 319: Smoothelin SPLAYING/FRACTURING OF M
Page 322 and 323: SMA
Page 324 and 325: METASTATIC ADENOCARCINOMA TO THE BL
Page 328 and 329: CK 7 CK20 CDX2 B-CATENIN
Page 330 and 331: New Prostate Lineage Associated Mar
Page 332 and 333: ?Urothelial Carcinoma vs. ?Prostati
Page 334 and 335: UCa GATA3 CK5/6 S100P
Page 336: Prostatic adenocarcinoma ERG IHC Ur
Page 341 and 342: AMACR
Page 343 and 344: Clear cell Ca Neph. adenoma
Page 345 and 346: U Ca. with small tubules Nephrogeni
Page 347 and 348: NA Pax 2 S100A1 Ki67
Page 349 and 350: U Ca Pax 2 S100A1 Ki67
Page 351 and 352: Spindle cell lesions of bladder •
Page 353 and 354: PSFMT/ PMP Immunohistochemistry •
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Keratin-AE1/AE3 Desmin
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AE1/AE3
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SMA
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PMP ALK 1 KERATIN AE1/3 SMA
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Tubulointerstitial lesions Ian Robe
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Tubules - Normal
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Tubules - Atrophy Distribution give
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Interstitial inflammation - tubuloi
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Tubulointerstitial nephritis The na
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AKI, ANCA positive, cortex - TIN, g
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Beware TIN + red cell casts In rena
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Male 59 years. Acute rise in creati
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IgG4-related TIN
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Male 70 years AKI Rigors, breathles
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Male, 57 years. Acute renal failure
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Ascending infection (pyelonephritis
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Ascending infection (pyelonephritis
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PVN can be seen in native kidneys L
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Tubulointerstitial infiltrates in t
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Female, 57 years. Acute renal failu
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Haemoglobin Myoglobin Diagnosis?
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Diagnosis?
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Light chain tubulopathy Typically a
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Light chain tubulopathy kappa lambd
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Acute tubular injury in the post mo
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Acute tubular injury in the post mo
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Tacrolimus toxicity Diagnosis?
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Drug-associated tubular injury Mech
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The End
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Session plan Renal Pathology for th
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Tumour nephrectomy specimens Common
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Glomerular lesions - sclerosis Scle
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Diabetic nephropathy Earliest chang
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Diabetic nephropathy: Linear GBM po
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Diabetic nephropathy: Nodular scler
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Amyloidosis
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Amyloidosis
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Amyloidosis Beware! Congo red may b
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Immunotactoid Fibrillary GN
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Light chain deposition disease
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Light chain deposition disease
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Idiopathic FSGS Known cause of podo
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Focal segmental glomerulosclerosis
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Glomerular tip lesion A manifestati
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Glomerular lesions: proliferation M
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IgA nephropathy Commonest glomerulo
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Mesangial deposits have a character
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Classification of IgA nephropathy O
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MPGN, type I • Haematuria, protei
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C3 glomerulopathy = Isolated C3 dep
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Haematuria (90%), nephrotic syndrom
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Dense deposit disease
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Crescentic glomerulonephritis patte
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Arteritis (approx. 20%) Renal vascu
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Anti-GBM disease • Autoantibodies
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Anti-GBM disease Linear IgG in glom
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Male 46 years. Suffered from diabet
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Male 46 years. Suffered from diabet
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The End
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What to do? • Download Kidney Qui
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What to do? • Participants will s
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PathoPic A
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PathoPic C
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What is your main diagnosis? 1. chr
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What is your main diagnosis? 1. art
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What is your main diagnosis? 1. mal
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Solutions (I.S. Roberts)
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B PathoPic Dg: crescentic glomerulo
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D PathoPic Dg: no significant patho
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Dg: amyloidosis F
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Patterns of scarring Granular subca
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Patterns of scarring Granular subca
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Deep pitted cortical scars: Pattern
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Patterns of scarring Deep pitted co
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Patterns of scarring Segmental tran
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Malignant hypertension A cause of a
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Set 2
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PathoPic H
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PathoPic L
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What is your main diagnosis? 1. col
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What is your main diagnosis? 1. nec
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What is your main diagnosis? 1. Ran
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Descripition Involvement of cortex
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Description enlargement of the kidn
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Differential diagnosis Acute uric a
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Differences between megalocytic IN
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Comments to papillary necrosis
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Prevalence of Lesions of the Renal
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Pathogenetic types of papillary nec
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Types of papillary necrosis: Extend
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Phenacetin kidney Keep in mind: bla
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Phenacetin kidney Note bone formati
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Phenacetin kidney Capillary scleros
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Yellow papillary necrosis Think of
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Histological examples of papillary
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Typical examples of papillary necro
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Typical examples of papillary necro
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Common Challenges in Kidney Cancer
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ISUP Consensus Conference Vancouver
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Image-guided biopsy. Shah et al.: H
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Can we confidently diagnose renal o
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„Translocation“ Type of Renal C
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Xp11 Translocation Carcinoma in Adu
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Clear cell-papillary RCC, sporadic
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Should CCPRCC/CCTPRCC be Recognized
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Do you think CCPRCC/CCTPRCC and RAT
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DIFFERENTIAL DIAGNOSIS OF EOSINOPHI
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What percent of a tumor needs to be
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Assess prognosis in epithelioid AML
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Mixed Epithelial and Stromal Tumor
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Are Cystic Nephroma and Mixed Epith
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Do you consider CN and MEST variati
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Tubulocystic RCC
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Challenges for Pathologists Diagnos
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Sporadic Renal Cell Carcinoma Moch
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Definition Adenoma • Tumours with
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Survival (%) Type and Prognosis of
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How do you subtype papillary renal
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Hereditary Leiomyomatosis and RCC S
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Should HLRCC be Recognized as a Dis
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Grading of Chromophobe RCC Amin MA,
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How should we grade papillary RCC?
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Unlike the Skywalker family, once t
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Survival (%) Prognostic Relevance o
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If a Tumor Shows Sarcomatoid Morpho
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Tumor Staging Bonsib SM. Renal lymp
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For staging purposes, do you consid
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Should the component of necrosis be
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Challenges for Pathologists Diagnos
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A proposed marker-based strategy de
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VHL and tumor development Frew and
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Randomised studies in the first lin
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J Urology 180, pp. 860-866, 2008
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Frequenz VHL Mutation in clear cell
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Thank you
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Potential of Needle Biopsy • Diag
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Hereditary Renal Cancer Syndromes
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How should HOCT be recognized? 1. S
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Novel renal tumor types with clear
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Renal Tumors with Clear Cytoplasm A
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CA IX and Tumor Development Mutatio
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Montani et al.: Am J Surg Path, May
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Is loss of VHL sufficient to cause
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Inside the primary cilium Receptors
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a b c d e f Montani et al.: Am J Su
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Additional mutation in VHL-/- cells
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Is it Acceptable for MC-RCC to have
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Renal Cyst in ADPKD Ki-67
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Novel renal tumor types with clear
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TFE3-Proteine-Expression
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• 14/28 pts: Stage 4 • 11/13 pt
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Translocation Carcinomas (MiTF/TFE
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When should TFE3 and TFEB analysis
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Clear cell-papillary RCC, sporadic
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Differential Diagnosis of Cystic Re
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Are Cystic Nephroma and Mixed Epith
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smaller cysts with phyllodes glands
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Immunohistochemistry MTSC (%) Papil
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Which IHC marker do you think is th
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PAX2 expression pattern in 16 spora
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PAX2 expression and overall surviva
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Tumors with Spindle Cell Morphology
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Small Blue Round Cell Tumors of Kid
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CD-99
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CD 99 Ewing-Sarcoma/PNET
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Synaptophysin
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The future has arrived 82
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VHL and Deep Sequencing • several
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Loss of PBRM1 expression is correla
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Cell Surface Capturing Proteomics:
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Conclusions •Renal mass biopsy -
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