UROTHELIAL CARCINOMA

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Should Tubulocystic-RCC be recognized as an entity at this time? 1. Yes 73% 2. No 3. Uncertain even with personal experience/ knowledge 4. Not enough personal experience/knowledge 5% 7% 14% 1 2 3 4
Challenges for Pathologists Diagnostic Marker Novel Tumor Entities Prognostic Marker Predictive Marker Correct Staging? Relevant Grading? Are there any?
Page 1 and 2:
Basel Seminars in Pathology Postgra
Page 3 and 4:
UPDATE ON PATHOLOGY STANDARDS FOR B
Page 5 and 6:
Molecular Pathways for Bladder Canc
Page 7:
HISTOLOGIC GRADE UROTHELIAL NEOPLAS
Page 10 and 11:
What’s New in the 2012 Consensus
Page 12 and 13:
Reporting of Bladder Cancer • Gui
Page 14 and 15:
• Seen with instrumentation with
Page 16 and 17:
Squamous Metaplasia • Should be r
Page 18 and 19:
GRADING OF UROTHELIAL LESIONS • F
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NORMAL
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Urothelial Dysplasia • Overall fe
Page 24 and 25:
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
Page 35 and 36:
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
Page 103 and 104:
Lymph node involvement: • Approx.
Page 105 and 106:
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
Page 149 and 150:
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
Page 171 and 172:
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
Page 233 and 234:
PSEUDOSARCOMATOUS MYOFIBROBLASTIC P
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Gross PMP • Exophyticpolypoid mas
Page 246 and 247:
ROLE OF IMMUNOHISTOCHEMISTRY IN THE
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PROVING UROTHELIAL DIFFERENTIATION
Page 250 and 251:
CA in the bladder, h.o of lung canc
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Paraganglioma Epith. LMS PEComa Mel
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p63
Page 257 and 258:
Plasmacytoid U Ca
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• Markers of urothelium and uroth
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S100P S100P GATA3 GATA3 A-F: S100P,
Page 263 and 264:
GATA 3 & S100 P: Diagnostic utility
Page 265 and 266:
PARAGANGLIOMA
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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
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Radiation-Reactive Radiation CIS
Page 298 and 299:
AUA GUIDELINE 2007 UPDATE: • Stan
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Typical pattern: • Arranged in gr
Page 302 and 303:
Muscularis mucosae or muscularis pr
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Am J Surg Pathol. 2009 ;33:91-8 SMO
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Smoothelin hyperplastic
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Smoothelin
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SMA - M. Mucosae
Page 313 and 314:
Smoothelin
Page 315 and 316:
CAUTERY: MINIMAL EFFECT ON IHC
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M. Mucosae vs. M. Propria in TURBT
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M. Mucosae vs. M. Propria in TURBT
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Smoothelin: Negative - Suggestive o
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Courtesy: Dr John Eble
Page 329 and 330:
METASTASIS TO THE BLADDER Prostate
Page 331 and 332:
?Urothelial Carcinoma vs. ?Prostati
Page 333 and 334:
Concurrent PCa & UCa
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PCa PCa NKX3.1 P501S PSMA
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100% 100% 90% 88% 88% 88% 80% 70% 6
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Clear cell Ca Neph. adenoma
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U Ca. with small tubules Nephrogeni
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Nephrogenic adenoma Clear cell aden
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CCCa Pax 2 S100A1 Ki67
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P Ca A Pax 2 S100A1 Ki67
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PMP / Pseudotumors
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SMA
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Sarcomatoid urothelial carcinoma
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Leiomyosarcoma
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Spindle cell lesions Benign (PMP) v
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SARC CA p63 CK 5/6 or HMCK p63
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Session plan Renal Pathology for th
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Tubules - Normal
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Interstitial inflammation - tubuloi
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Tubulointerstitial nephritis Classi
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CKD, previous tuberculosis, HCV pos
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AKI, ANCA positive, cortex - TIN, g
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Male 59 years. Acute rise in creati
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35 patients with IgG4-TIN: 27 (77%)
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Male 70 years AKI Diagnosis?
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Hantavirus nephropathy
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Male, 57 years. Acute renal failure
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Ascending infection (pyelonephritis
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Tubulointerstitial infiltrates in t
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Tubulointerstitial infiltrates in t
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Things in tubules Casts, crystals,
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Acute phosphate nephropathy First c
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Diagnosis?
Page 404 and 405:
Acute tubular injury Ischaemia, dru
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Light chain tubulopathy
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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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Drug-associated tubular injury Drug
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Gentamicin toxicity Diagnosis?
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Drug-associated tubular injury Mech
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Glomerular lesions Ian Roberts Oxfo
Page 420 and 421:
Tumour nephrectomy specimens Things
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Glomeruli- Normal
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Nodular glomerulosclerosis Diabetic
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Diabetic nephropathy: thickened bas
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Diabetic nephropathy: Diffuse mesan
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Diabetic nephropathy: Insudative le
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Amyloidosis Congo red
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Amyloidosis
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Amyloidosis
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Immunotactoid Fibrillary GN 0.06% o
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Light chain deposition disease
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Focal segmental glomerulosclerosis
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Page 446 and 447:
Page 448 and 449:
Glomerular lesions: proliferation M
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Glomerular lesions: proliferation E
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The diagnosis of IgA nephropathy is
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The histology of IgA nephropathy is
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Mesangiocapillary GN = Membranoprol
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Mesangiocapillary GN, type I C3
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C3 glomerulopathy MPGN and C3 glome
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Dense deposit disease
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Glomerular lesions: necrosis Ruptur
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Renal vasculitis May be isolated re
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Renal vasculitis European vasculiti
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Anti-GBM disease Autoantibodies to
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Remember: multiple pathologies are
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Male 46 years. Suffered from diabet
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Diagnoses: Diabetic nephropathy Oxa
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Interactive Kidney Quiz Ian S. Robe
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Test vote How did you learn about t
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Set 1
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PathoPic B
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PathoPic D
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What is your main diagnosis? 1. chr
Page 492 and 493:
What is your main diagnosis? 1. amy
Page 494 and 495:
What is your main diagnosis? 1. no
Page 496 and 497:
A PathoPic Dg: arteriolosclerosis,
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Dg: diabetic kidney C PathoPic
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Dg: malignant nephrosclerosis E
Page 502 and 503:
RCPath “Minimum” dataset for tu
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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
Page 514 and 515:
Malignant hypertension A cause of a
Page 516 and 517:
Page 518 and 519:
Page 520 and 521:
Malignant vs benign vascular diseas
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PathoPic G
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PathoPic I
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What is your main diagnosis? 1. gou
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What is your main diagnosis? 1. met
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What is your main diagnosis? 1. ren
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Solutions (M.J. Mihatsch)
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Descripition Involvement of cortex
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Description Whitish discoloration a
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Description Massive enlargement of
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Description Brownish discoloration
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Papillary necrosis Pg: i.e. vascula
Page 546 and 547:
Papillary necrosis Pg: i.e. vascula
Page 548 and 549:
Types of papillary necrosis: Extend
Page 550 and 551: Black papillary necrosis Think of p
Page 552 and 553: Phenacetin kidney Compete necrosis
Page 554 and 555: Phenacetin kidney Note massive base
Page 556 and 557: Phenacetin kidney Note: Massive lip
Page 558 and 559: Typical examples of papillary necro
Page 560 and 561: White papillary necrosis Think of v
Page 562 and 563: Red papillary necrosis Think of vas
Page 564 and 565: I hope you will never overlook papi
Page 566 and 567: Challenges for Pathologists Renal M
Page 568: Do the morphotypes of RCC have prog
Page 571 and 572: Potential of Needle Biopsy • Diag
Page 573 and 574: Novel renal tumor types with clear
Page 575 and 576: Am J Surg Path 28, 2004 41 Carcinom
Page 578 and 579: Should Acquired Cystic Disease- RCC
Page 580 and 581: Clear cell papillary RCC has: 1. PO
Page 582 and 583: Which name should be used for 1. Cl
Page 585 and 586: 1. Yes 2. No Should Thyroid-Like Fo
Page 587 and 588: If focal (
Page 589 and 590: Denote AMLs with epithelioid morpho
Page 591: Differential Diagnosis of Cystic Re
Page 594 and 595: smaller cysts with phyllodes glands
Page 596 and 597: Are Cystic Nephroma and Mixed Epith
Page 598 and 599: If you consider CN and MEST variati
Page 602 and 603: Prognosis • Type • Stage • Gr
Page 604: Papillary renal cell carcinoma Type
Page 608 and 609: Differential Diagnosis: metanephric
Page 610 and 611: The distinction between type 1 vers
Page 612 and 613: Should Oncocytic Papillary-RCC be r
Page 614: Leiomyomas of the Skin
Page 618 and 619: Fuhrman Grading in RCC Hong SK, BJU
Page 620 and 621: How should we grade clear cell RCC?
Page 622: How should we grade chromophobe RCC
Page 625 and 626: For Sarcomatoid Tumors Do You Repor
Page 627 and 628: Do You Consider a Tumor Area Sarcom
Page 629 and 630: Tumor Staging
Page 631 and 632: When invasion of the renal sinus is
Page 633 and 634: Should the presence or absence of t
Page 635 and 636: Should any assessment of amount (pe
Page 637 and 638: ISUP Consensus Conference Vancouver
Page 639 and 640: Molecular Pathways and Targeted The
Page 641: Chemokine receptor CXCR4 downregula
Page 644 and 645: Agents such as sunitinib act throug
Page 646 and 647: VHL-Mutation ↔ Gene expression Ba
Page 648 and 649: Driver and Passenger VHL Mutations
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Differential Diagnosis of Renal Cel
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Renal Tumors with Eosinophilic Cyto
Page 658:
Birt Hogg Dubé syndrome
Page 661 and 662:
Are the hybrid tumors associated wi
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For distinguishing clear cell RCC f
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Clear Cell Renal Cancer VHL Deletio
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Early on in VHL disease, the vast m
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Distinct tumor suppressor mechanism
Page 671 and 672:
A Ksp-Cre - pos - pos - pos Vhlh fl
Page 673 and 674:
pVHL localizes to primary cilia in
Page 675 and 676:
a c b d Montani et al.: Am J Surg P
Page 677 and 678:
Multilocular cystic renal cell carc
Page 679 and 680:
What terminology for a multicystic
Page 681 and 682:
In the setting of acquired cystic d
Page 683 and 684:
„Translocation“ Type of Renal C
Page 685 and 686:
„Translocation“ Type of Renal C
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t(X;1)
Page 690 and 691:
Should t(6;11) RCC be Recognized as
Page 693 and 694:
When a translocation carcinoma is s
Page 696:
Leiomyomatous Renal Cell Carcinoma
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Edmunds W: Trans.Path.Soc.London 43
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Are Cystic Nephroma and Mixed Epith
Page 704 and 705:
Renal Tumors with Papillary Archite
Page 706 and 707:
In the absence of classical histolo
Page 708 and 709:
Clin Cancer Res 2009;15:3297-3304 -
Page 710 and 711:
A, Western blot analysis of HK-2 ce
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Tumors with Spindle Cell Morphology
Page 716 and 717:
Which marker do you use most freque
Page 719 and 720:
Primary Renal Synovial Sarcoma Immu
Page 721:
SYT-SSX Fusion from translocation t
Page 726:
Renal carcinoid from a horseshoe ki
Page 729:
DD „Small round blue“ cell tumo
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Xu X. et al.L Cell 148, 886-895, 20
Page 736 and 737:
Polybromo-1 (BAF180) in ccRCC ~40%
Page 738 and 739:
wt versus VHL-/- cells VHL-loss der
Page 740 and 741:
VHL and a Serum Screening Test for
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UROTHELIAL CARCINOMA

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