UROTHELIAL CARCINOMA

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Drug-associated tubular injury Drugs that cause direct tubular epithelial injury: Antibiotics Immunosuppressive drugs (CNI, sirolimus) Antiviral agents Chemotherapeutic agents (cisplatin, methotrexate, others) Herbal medications (aristolochic acid) Radiological contrast media Anaesthetic agents
Tacrolimus toxicity Diagnosis?
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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
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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
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 376 and 377: Tubulointerstitial nephritis Classi
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 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
Page 426 and 427: Diabetic nephropathy: thickened bas
Page 428 and 429: Diabetic nephropathy: Diffuse mesan
Page 430 and 431: Diabetic nephropathy: Insudative le
Page 432 and 433: Amyloidosis Congo red
Page 434 and 435: Amyloidosis
Page 436 and 437: Amyloidosis
Page 438 and 439: Immunotactoid Fibrillary GN 0.06% o
Page 440 and 441: Light chain deposition disease
Page 442 and 443: Focal segmental glomerulosclerosis
Page 448 and 449: Glomerular lesions: proliferation M
Page 450 and 451: Glomerular lesions: proliferation E
Page 452 and 453: The diagnosis of IgA nephropathy is
Page 454 and 455: The histology of IgA nephropathy is
Page 456 and 457: Mesangiocapillary GN = Membranoprol
Page 458 and 459: Mesangiocapillary GN, type I C3
Page 460 and 461: C3 glomerulopathy MPGN and C3 glome
Page 462 and 463:
Dense deposit disease
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Glomerular lesions: necrosis Ruptur
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Renal vasculitis May be isolated re
Page 468 and 469:
Renal vasculitis European vasculiti
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Anti-GBM disease Autoantibodies to
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Remember: multiple pathologies are
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Male 46 years. Suffered from diabet
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Diagnoses: Diabetic nephropathy Oxa
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Interactive Kidney Quiz Ian S. Robe
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Test vote How did you learn about t
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Set 1
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PathoPic B
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PathoPic D
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What is your main diagnosis? 1. chr
Page 492 and 493:
What is your main diagnosis? 1. amy
Page 494 and 495:
What is your main diagnosis? 1. no
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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
Page 510 and 511:
Patterns of scarring Deep pitted co
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Patterns of scarring Segmental tran
Page 514 and 515:
Malignant hypertension A cause of a
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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
Page 582 and 583:
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
Page 614:
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?
Page 622:
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
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
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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
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Early on in VHL disease, the vast m
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Distinct tumor suppressor mechanism
Page 671 and 672:
A Ksp-Cre - pos - pos - pos Vhlh fl
Page 673 and 674:
pVHL localizes to primary cilia in
Page 675 and 676:
a c b d Montani et al.: Am J Surg P
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Multilocular cystic renal cell carc
Page 679 and 680:
What terminology for a multicystic
Page 681 and 682:
In the setting of acquired cystic d
Page 683 and 684:
„Translocation“ Type of Renal C
Page 685 and 686:
„Translocation“ Type of Renal C
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
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Are Cystic Nephroma and Mixed Epith
Page 704 and 705:
Renal Tumors with Papillary Archite
Page 706 and 707:
In the absence of classical histolo
Page 708 and 709:
Clin Cancer Res 2009;15:3297-3304 -
Page 710 and 711:
A, Western blot analysis of HK-2 ce
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 736 and 737:
Polybromo-1 (BAF180) in ccRCC ~40%
Page 738 and 739:
wt versus VHL-/- cells VHL-loss der
Page 740 and 741:
VHL and a Serum Screening Test for
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