UROTHELIAL CARCINOMA

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Polybromo-1 (BAF180) in ccRCC ~40% ccRCC mutated in PBRM1! I. Varela et al., Nature: 469, 2011. Nucleosome/Histone/Chromatin Remodeling Complexes K.W. Trotter and T.K. Archer, Nucl Recept Signal, 6:e004, 2008
Loss of PBRM1 expression is correlated with tumor stage, grade and survival Rafal Pawłowski et al., Int J Cancer, 2012
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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
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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
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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
Page 685 and 686: „Translocation“ Type of Renal C
Page 687: 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
Page 699: Edmunds W: Trans.Path.Soc.London 43
Page 702 and 703: 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
Page 712: 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
Page 733 and 734: Xu X. et al.L Cell 148, 886-895, 20
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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