UROTHELIAL CARCINOMA

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Muscularis Propria • Several terms are currently being used to describe both MP (deep muscle, muscle proper or detrusor muscle) and MM (superficial muscle). These terms are not recommended and use of standardized nomenclature of “MP muscle bundles” is recommended • It is important to document the presence or absence of MP in a biopsy irrespective of involvement • Some institutions recommend not mentioning the presence or absence of MP in low grade tumors and require documentation in high grade tumors only
Muscularis Propria • In cystectomy specimens, a more objective and reproducible anatomical or extent of disease criterion is needed between pT2a and pT2b subcategories • Substaging of pT2 disease and recognition of pT3 disease is not tenable in TURBT specimens
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
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HISTOLOGIC GRADE UROTHELIAL NEOPLAS
Page 10 and 11:
What’s New in the 2012 Consensus
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Reporting of Bladder Cancer • Gui
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• 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
Page 22 and 23:
Urothelial Dysplasia • Overall fe
Page 24 and 25:
Urothelial Dysplasia • The diagno
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ATYPIA OF UNKNOWN SIGNIFICANCE (WHO
Page 31 and 32: Grading of Urothelial Carcinoma •
Page 33 and 34: Papilloma
Page 35 and 36: PUNLMP
Page 37 and 38: LOW GRADE
Page 39 and 40: HIGHGRADE
Page 41 and 42: P A P I L O M A L M P L O W G R A D
Page 43 and 44: Courtesy R. Montironi, Italy Exophy
Page 45 and 46: Inverted High Grade without invasio
Page 47 and 48: Inverted Papilloma
Page 49 and 50: Inverted PUNLMP
Page 51 and 52: Inverted LG
Page 53 and 54: Inverted HG
Page 55 and 56: Inverted HG, Non Inv
Page 57 and 58: WHO (2004) /ISUP : Prognostic Signi
Page 59 and 60: Contributions of WHO (2004) /ISUP
Page 61 and 62: Handling grade heterogeneity in bla
Page 63 and 64: Grading Papillary Urothelial Neopla
Page 65: Papillary Hyperplasia with Cytologi
Page 68 and 69: Dysplasia with early papillary feat
Page 70 and 71: Grading Invasive Cancer • Practic
Page 74 and 75: • 2 types of muscle - awareness i
Page 76 and 77: Muscularis Mucosae Muscle • Hyper
Page 78 and 79: M. mucosae muscle patterns Typical
Page 80 and 81: M. mucosae muscle pattern Hypertrop
Page 84 and 85: Muscle Involved by UCa, Indetermina
Page 88 and 89: Assessment of pT2 vs. pT3 - cystect
Page 91 and 92: Microinvasive Urothelial Carcinoma
Page 93 and 94: Substratification or Substaging of
Page 95 and 96: Extensive invasion
Page 97 and 98: Retraction a mimic of vascular-lymp
Page 99 and 100: Vascular Lymphatic Invasion (LVI)
Page 101 and 102: 2013 International Society of Urolo
Page 103 and 104: Lymph node involvement: • Approx.
Page 105 and 106: THE BEST BLADDER CANCER PATHOLOGY S
Page 107 and 108: PSEUDONEOPLASTIC MIMICS OF BLADDER
Page 109 and 110: EMPHYSEMATOUS & BULLOUS CYSTITIS
Page 113 and 114: AMYLOIDOSIS
Page 115 and 116: MALAKOPLAKIA
Page 117: NORMAL PARAGANGLIONIC TISSUE
Page 123 and 124: CIS
Page 125: REACTIVE ATYPIA History of stones,
Page 130: CIS REACTIVE ATYPIA
Page 134 and 135:
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
Page 298 and 299:
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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Page 518 and 519:
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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
Page 598 and 599:
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
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
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Chemokine receptor CXCR4 downregula
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Agents such as sunitinib act throug
Page 646 and 647:
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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UROTHELIAL CARCINOMA

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