Kidney

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Kidney Urinary Tract Neoplasms

• Jaroslava Dušková
• Inst. Pathol. ,1st Med. Faculty,
• Charles Univ. Prague
• http//www1.lf1.cuni.cz/jdusk/

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Kidney Cancer

• 2 of the total human cancer burden, MF
  21, middle age
• preference for developed
  (industrialized) countries
• risk factors TOBACCO SMOKING,
  OBESITY

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Symptoms

• silent for a long time
• - discovered by chance
• hematuria, backache, abdominal mass,
  metastatic spread
• early hematogenic spread possible

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WHO classification of tumours of the kidney
(2004)
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WHO Histogenetic groups (
number of nosology units identified)

• Renal cell (12)
• Metanephric (3)
• Nephroblastic (3)
• Mesenchymal (18)
• Mixed mesenchymal and epithelial (3)
• Neuroendocrine (5)
• Hematopopietic and lymphoid (3)
• Germ cell (2)
• Metastatic (-)

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Epithelial Neoplasms of the Pelvis

• Benign - papillomas
• Malignant - carcinomas
• papillocarcinomas
• squamous cell

Urinary ways
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Kidney Tumours

• Benign
• Malignant

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Kidney Adenoma

• Definition
• Formerly - diam. 2-3 cm
• Recently only diam. less than 5mm without a
  clear cell component
• tubulopapillary architecture
• lack of atypiae mitoses

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Epithelial Kidney Tumours

• papillary tubulopapillary
• (lt5mm!)
• oncocytic (oncocytoma)
• metanephric

• benign
• ADENOMAS

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Oncocytoma

• Kidney cortex
• may be multicentric and bilateral
• Macro tan with a central stellate scar
• Micro - eosinophillic granular cytoplasm
  bizarre nuclei
• Elmi mitochondria filling up the cytoplasm
• Biological behaviour benign

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Kidney Tumours - mesenchymal

• Angiolipoleiomyoma mixed mesenchymal tumour

12
Metanephric Adenoma

• small dark cells
• acinar and glomeruloid formations
• calkospherites, calcifying
• non agressive

13
Benign Kidney Tumours Mimicking Carcinomas and
Sarcomas

• Metanephric adenoma - large cellular
• Oncocytoma - large with atypiae
• Angioleiomyolipoma - large with atypiae

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Epithelial Kidney Tumours

• Clear Conventional Cell
• Papillary (chromophillic)
• type 1
• type 2
• Chromophobe
• classical
• eosinophillic
• Sarcomatoid
• Cystic
• Collecting Duct

• malignant
• CARCINOMAS

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Clear Cell Ca (Grawitz tumour) (75)

• Solid / cystic
• Unilocullar or multilocular
• Micro - solid or tubulocystic
• clear cytoplasm (fat glycogen)
• Immunohistochemistry cytokeratins, vimentin,
  CD10, EMA, S-100
• Cytogenetics deletion of the short arm
  chromosome 3 (3p)
• Prognosis G, pT dependent
• Sarcomatoid variant is the most malignant

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Papillary (Chromophillic) Ca (10)

• In dialysed more frequent
• X-ray hypovascular
• Histology papillary/ tubulopapillary
• type 1 cubic cells
• type 2 - cylindric cells (worse prognosis)
• Genetics trisomy or tetrasomy 7 and 17
• in men often Y chromosome missing
  
• mutation of c-met oncogen
• Prognosis G, pT dependent
• slightly better than in conventional ca

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Chromophobe Carcinoma (5)

• Macro - brown color
• Mikro - solid, cytoplasms clear or
  eosinophillic, positive in Hales
  colloidal iron staining,
• raisin-like cell nuclei
• Elmi microvesicles in cytoplasm
• Genetics missing chromosomes -
• 1, 2, 10, 13, 6, 21, 17
• Prognosis G, pT dependent

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Collecting Duct Carcinoma

• Starts in the medulla
• Micro
• adenocarcinoma urothelial like
• hobnail cells
• papillary
• fibroplasia, mucin production
• Imuno cytokeratin 13, vimentin, lectin
• Prognosis unfavourable

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Nephroblastoma (Wilmstumour)

• syn. - embryonal adenosarcoma
• Children - preschool age
• Macro gray-white large retroperitoneal mass
  palpable through abdominal wall
• Micro undifferentiated renal blastema, tubular
  and glomeruloid formations may be present
• Prognosis curable (stage!)
• Follow up - nephroblastomatosis

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Role of the Pathologist in the Kidney Tumour
Diagnostics

• Typing
• Biological Behaviour
• Grading
• Staging

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Grading

• Nuclear Fuhrman et al. 1982
• Nuclear plus architecture
• Proliferation factors - PCNA, Ki 67, Bcl 2
• Morphometry
• DNA Analysis
• AgNOR
• Angiogenesis
• Cytometry Flow cytometry

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Staging

• Size
• Kidney capsule infiltration
• Angioinvasion
• Metastases in the lymph nodes
• Number of lymph nodes involved
• Metastases in the surrounding organs

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Nuclear Grading in Kidney Cancer (Fuhrman et al.
1982)

• Grade I small, uniform, round (10 ? )
• inaparent or missing nucleoli
• Grade II larger irregular (15 ?)
• nucleoli small
• Grade III large, irregular margins (20 ?)
  nucleoli large
• Grade IV large, bizarre, pleomorphic

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Factors with an Adverse Prognosis Influence in
Kidney Cancer

• Size diam. more than 12 cm
• Invasion to venes recidives
• Grading G III and G IV
• Staging most important
• Proliferation Index
• p53 Expression

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Kidney Cancer complications 1.

• metastatic spread generalisation
• manifestation via solitary bloodborne
  metastasis possible (pathological fracture,
  struma neoplastica)
• hematuria anemia

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Kidney Cancer complications 2.

• hormon production erythropoietin
  polyglobulia
• Wood L, Swanepoel C, du Toit A, Jacobs
  P.Clinically silent renal tumour producing
  erythropoietin. S Afr Med J. 2003
  Feb93(2)128-9.
• Shaheen M, Hilgarth KA, Hawes D, Badve S, Antony
  AC.  A Mexican man with "too much blood".
• Lancet. 2003 Sep 6362(9386)806.
• insulin, glukagon, renin, HPL like substances

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• Urothelial Tumours

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Urothelial Cancer

• approx. 3 of total human cancer burden
• increasing incidence
• industrialized countries
• risk factors TOBACCO SMOKING aniline dye
  industry
• phenacetin
• schistosomiasis

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Symptoms

• hematuria
• (obstruction)
• (metastases)

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Terminology

• the term
• UROTHELIAL
• be used rather than transitional...

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Normal urothelium

• multilayered
• variable number of layers
• empty bladder 4 - 6
• full bladder 2 - 3

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Variations of Urothelium slight reactive
changes

• von Brunns nests
• mucinous metaplasia
• squamous metaplasia
• (nonkeratinising, vagina type)

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Metaplasia

• Def change of one differentiated structure into
  another one
• (e.g. urothelium squamous epithelium)

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Metaplasia

• Significance
• dif. dg. problem
• with atypia
• precancerosis

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The WHO/ISUP Consensus Classification of
Urothelial Neoplasmsof the Urinary Bladder

• Epstein JI, Amin MB,Reuter VR, Mostofi FK,
• the Bladder Consensus Conference Committee
• Am.J. Surg.
  Pathol.,22,1998,1435-8

WHO 2004
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The WHO/ISUP Consensus Classification

1. Hyperplasia
2. Flat lesions with atypia
3. Papillary neoplasms
4. Invasive neoplasms

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The WHO/ISUP Consensus Classification

• I. Hyperplasia
• Flat
• Papillary

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Hyperplasia

• Def regular increase in number of uroth. layers
  (min. gt7, mostly gt10)
• slight increase in cell nuclei size,
• preserved architecture

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Hyperplasia

• Significance precancerosis
• 70 of patients with urothelial ca
  identical mutations

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The WHO/ISUP Consensus Classification

1. Hyperplasia
2. Flat lesions with atypia
3. Papillary neoplasms
4. Invasive neoplasms

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• II. Flat lesions with atypia
• Reactive (inflammatory) atypia
• Atypia of unknown significance
• Dysplasia (LG IUN)
• CIS (HG IUN)

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Dysplasia

• DEF
• disturbance of normal urothelium architecture
  cytology

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Dysplasia

• LG IUN low grade intraurothelial
  neoplasia
• HG IUN/ CIS high grade intraurothelial
  neoplasia

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The WHO/ISUP Consensus Classification

1. Hyperplasia
2. Flat lesions with atypia
3. Papillary neoplasms
4. Invasive neoplasms

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• III. Papillary neoplasms
• Papilloma
• Inverted papilloma
• Papillary Urothelial Neoplasm of Low Malignant
  Potential PUNLMP
• Papillary carcinoma, low grade
• Papillary carcinoma, high grade

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Papilloma WHO 1973 G0

• Def circumscribed solitary papillary lesion
  covered with cytologically and architecturally
  normal urothelium.

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Papillary neoplasm of low malignant
potential

• Def.
• well stratified urothelium bering features of
  slight dysplasia and increased number of layers

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The WHO/ISUP Consensus Classification

1. Hyperplasia
2. Flat lesions with atypia
3. Papillary neoplasms
4. Invasive neoplasms

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• Invasive neoplasms
• lamina propria invasion (pT1a,b)
• muscularis propria (detrusor muscle)
  invasion (pT2a,b)
• perivesical tissue macro/micro (pT3a,b)
• surrounding organs/ abdominal wall
  (pT4a,b)

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Less Common Types of Urinary Bladder Cancer

• microcystic carcinoma
• with  pseudosarcomatose stroma
• with bone or chondroid stromal metaplasia
• spinocellular
• adenocarcinoma
• undifferenciated ca
• with trophoblastic differentiation
• neuroendocrine

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Non-Epithelial Bladder Tumours - Mesenchymal

• leiomyomas and leiomyosarcomas rhabdomyosarcoma
  botryoides
• rhabdoid
• fibrohistiocytic
• vascular (capilllary, cavernous and angiovenous
  hemangiomas and hemangiosarcomas)
• malignant lymphomas

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Non-Epithelial Bladder Tumours - Neuroectodermal

• neurofibromas in Recklinghausens disease
• melanoma
• paraganglioma
• composite pigmented paraganglioma-ganglioneuroma

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Urinary Bladder Pseudotumors

• inflammatory
• malakoplakia
• amyloid deposits
• pseudosarcoma

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Cystectomy Biopsy Report

• MICRO
• type, grade (G) and stage (pT) of the tumor
• further urothelial abnormities
• lymphatic and blood vessel invasion
• presence / absence of the tumor in the
  resection margins and neighbouring organs
• further abnormities of the neighbouring
  organs

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Urinary Blader Cancer - complications

• local recidives
• progression
• metastases