UROTHELIAL CARCINOMA

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How should we grade clear cell RCC? 1. Fuhrman 2. Nucleolar 78% 22% 0% 1 2 3
How should we grade papillary RCC? 1. Fuhrman 2. Nucleolar 3. Collapsed nucleolar 84% 9% 8% 0% 1 2 3 4
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Basel Seminars in Pathology Postgra
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UPDATE ON PATHOLOGY STANDARDS FOR B
Page 5 and 6:
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
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Courtesy: Dr John Eble
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METASTASIS TO THE BLADDER Prostate
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?Urothelial Carcinoma vs. ?Prostati
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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?
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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
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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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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
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 600 and 601: Should Tubulocystic-RCC be recogniz
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 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
Page 650: Differential Diagnosis of Renal Cel
Page 653: Renal Tumors with Eosinophilic Cyto
Page 658: Birt Hogg Dubé syndrome
Page 661 and 662: Are the hybrid tumors associated wi
Page 663 and 664: For distinguishing clear cell RCC f
Page 665 and 666: Clear Cell Renal Cancer VHL Deletio
Page 667 and 668: Early on in VHL disease, the vast m
Page 669 and 670: 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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