UROTHELIAL CARCINOMA

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Tubulointerstitial nephritis Classification by cause: Drug-associated PPIs, antibiotics, NSAIDS + many others Associated with systemic autoimmune disease SLE, Sjogrens, TINU Infections bacterial, viral Sarcoidosis Localised inflammation around tumours in nephrectomy specimens is not tubulointerstitial nephritis.
Tubulointerstitial nephritis The nature of the infiltrate differs according to cause – but not specific. Clinical history is essential
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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
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p63
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Plasmacytoid U Ca
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• Markers of urothelium and uroth
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S100P S100P GATA3 GATA3 A-F: S100P,
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GATA 3 & S100 P: Diagnostic utility
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PARAGANGLIOMA
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Identification of Succinate Dehydro
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CIS REACTIVE
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NORMAL
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CK-20
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REACTIVE UROTHELIUM
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CK-20
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Reactive CD44
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CA-INSITU
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CK-20
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CIS CK20
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CK20 (+) CD44(-)
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p53
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CD44
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Reactive CIS
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Radiation-Reactive Radiation CIS
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AUA GUIDELINE 2007 UPDATE: • Stan
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Typical pattern: • Arranged in gr
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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
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Smoothelin
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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
Page 325: 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
Page 335 and 336: PCa PCa NKX3.1 P501S PSMA
Page 338: 100% 100% 90% 88% 88% 88% 80% 70% 6
Page 342 and 343: Clear cell Ca Neph. adenoma
Page 344 and 345: U Ca. with small tubules Nephrogeni
Page 346 and 347: Nephrogenic adenoma Clear cell aden
Page 348 and 349: CCCa Pax 2 S100A1 Ki67
Page 350 and 351: P Ca A Pax 2 S100A1 Ki67
Page 352 and 353: PMP / Pseudotumors
Page 354 and 355: SMA
Page 356: Sarcomatoid urothelial carcinoma
Page 361: Leiomyosarcoma
Page 365 and 366: Spindle cell lesions Benign (PMP) v
Page 367: SARC CA p63 CK 5/6 or HMCK p63
Page 370 and 371: Session plan Renal Pathology for th
Page 372 and 373: Tubules - Normal
Page 374 and 375: Interstitial inflammation - tubuloi
Page 378 and 379: CKD, previous tuberculosis, HCV pos
Page 380 and 381: AKI, ANCA positive, cortex - TIN, g
Page 382 and 383: Male 59 years. Acute rise in creati
Page 384 and 385: 35 patients with IgG4-TIN: 27 (77%)
Page 386 and 387: Male 70 years AKI Diagnosis?
Page 388 and 389: Hantavirus nephropathy
Page 390 and 391: Male, 57 years. Acute renal failure
Page 392 and 393: Ascending infection (pyelonephritis
Page 394 and 395: Tubulointerstitial infiltrates in t
Page 396 and 397: Tubulointerstitial infiltrates in t
Page 398 and 399: Things in tubules Casts, crystals,
Page 400 and 401: Acute phosphate nephropathy First c
Page 402 and 403: Diagnosis?
Page 404 and 405: Acute tubular injury Ischaemia, dru
Page 406 and 407: Light chain tubulopathy
Page 408 and 409: Acute tubular injury in the post mo
Page 410 and 411: Acute tubular injury in the post mo
Page 412 and 413: Drug-associated tubular injury Drug
Page 414 and 415: Gentamicin toxicity Diagnosis?
Page 416 and 417: Drug-associated tubular injury Mech
Page 418 and 419: Glomerular lesions Ian Roberts Oxfo
Page 420 and 421: Tumour nephrectomy specimens Things
Page 422 and 423: Glomeruli- Normal
Page 424 and 425: 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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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
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What is your main diagnosis? 1. amy
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What is your main diagnosis? 1. no
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A PathoPic Dg: arteriolosclerosis,
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Dg: diabetic kidney C PathoPic
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Dg: malignant nephrosclerosis E
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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
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Malignant hypertension A cause of a
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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
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Papillary necrosis Pg: i.e. vascula
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Types of papillary necrosis: Extend
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Black papillary necrosis Think of p
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Phenacetin kidney Compete necrosis
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Phenacetin kidney Note massive base
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Phenacetin kidney Note: Massive lip
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Typical examples of papillary necro
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White papillary necrosis Think of v
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Red papillary necrosis Think of vas
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I hope you will never overlook papi
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Challenges for Pathologists Renal M
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Do the morphotypes of RCC have prog
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Potential of Needle Biopsy • Diag
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Novel renal tumor types with clear
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Am J Surg Path 28, 2004 41 Carcinom
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Should Acquired Cystic Disease- RCC
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Clear cell papillary RCC has: 1. PO
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Which name should be used for 1. Cl
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1. Yes 2. No Should Thyroid-Like Fo
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If focal (
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Denote AMLs with epithelioid morpho
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Differential Diagnosis of Cystic Re
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smaller cysts with phyllodes glands
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Are Cystic Nephroma and Mixed Epith
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If you consider CN and MEST variati
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Should Tubulocystic-RCC be recogniz
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Prognosis • Type • Stage • Gr
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Papillary renal cell carcinoma Type
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Differential Diagnosis: metanephric
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The distinction between type 1 vers
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Should Oncocytic Papillary-RCC be r
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Leiomyomas of the Skin
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Fuhrman Grading in RCC Hong SK, BJU
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How should we grade clear cell RCC?
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How should we grade chromophobe RCC
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For Sarcomatoid Tumors Do You Repor
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Do You Consider a Tumor Area Sarcom
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Tumor Staging
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When invasion of the renal sinus is
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Should the presence or absence of t
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Should any assessment of amount (pe
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ISUP Consensus Conference Vancouver
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Molecular Pathways and Targeted The
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Chemokine receptor CXCR4 downregula
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Agents such as sunitinib act throug
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VHL-Mutation ↔ Gene expression Ba
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Driver and Passenger VHL Mutations
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Differential Diagnosis of Renal Cel
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Renal Tumors with Eosinophilic Cyto
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Birt Hogg Dubé syndrome
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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
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A Ksp-Cre - pos - pos - pos Vhlh fl
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pVHL localizes to primary cilia in
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a c b d Montani et al.: Am J Surg P
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Multilocular cystic renal cell carc
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What terminology for a multicystic
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In the setting of acquired cystic d
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„Translocation“ Type of Renal C
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„Translocation“ Type of Renal C
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t(X;1)
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Should t(6;11) RCC be Recognized as
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When a translocation carcinoma is s
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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
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Renal Tumors with Papillary Archite
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In the absence of classical histolo
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Clin Cancer Res 2009;15:3297-3304 -
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A, Western blot analysis of HK-2 ce
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Tumors with Spindle Cell Morphology
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Which marker do you use most freque
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Primary Renal Synovial Sarcoma Immu
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SYT-SSX Fusion from translocation t
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Renal carcinoid from a horseshoe ki
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DD „Small round blue“ cell tumo
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Xu X. et al.L Cell 148, 886-895, 20
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Polybromo-1 (BAF180) in ccRCC ~40%
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wt versus VHL-/- cells VHL-loss der
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VHL and a Serum Screening Test for
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