Difference between revisions of "Kidney tumours"

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'''Kidney tumours''' - includes '''malignant kidney tumours''' and '''benign kidney tumours'''.  Medical renal diseases are dealt with in the [[medical renal diseases]] article.
'''[[Kidney]] tumours''' - includes '''malignant kidney tumours''' and '''benign kidney tumours'''.  Medical renal diseases are dealt with in the [[medical renal diseases]] article.


Pediatric kidney tumours are dealt with in the ''[[pediatric kidney tumours]]'' article.
Pediatric kidney tumours are dealt with in the ''[[pediatric kidney tumours]]'' article.

Revision as of 04:55, 11 October 2011

Kidney tumours - includes malignant kidney tumours and benign kidney tumours. Medical renal diseases are dealt with in the medical renal diseases article.

Pediatric kidney tumours are dealt with in the pediatric kidney tumours article.

Renal specimens

  • Renal biopsy - usually for renal onocytoma vs. renal cell carcinoma (RCC) or medical diseases - see medical kidney.
  • Partial nephrectomy.
  • Nephrectomy.
  • Nephroureterectomy (includes ureter) - done for urothelial cell carcinoma (UCC) of the renal pelvis and ureteric UCC.
  • Radical nephrectomy - includes Gerota's fascia.

In excisions done for tumours, a comment should be made about kidney distant from the tumour. People with less renal mass, i.e. less kidney, are predisposed to focal segmental glomerulosclerosis (FSGS).

Anatomy

The anatomy is important for properly staging renal neoplasms.

Layers (superficial to deep):

  1. Renal fascia (Gerota's fascia).
  2. Perinephric fat.
  3. Renal capsule.
  4. Renal parenchyma (cortex).

Tabular comparison (selected tumours)

Selected common tumours of the kidney:[2][3]

Clear cell RCC Papillary RCC
type 1
Papillary RCC
type 2
Chromophobe RCC
classic variant
Chromophobe RCC
eosinophilic variant
Oncocytoma
Gross Golden yellow, solid friable friable light brown light brown mahogany/brown, +/-central scar
Architecture nests, sheets papillary, simple papillary,
pseudostratified
nests, sheets nests, sheets nests, sheets
Nuclear atypia low-high
typically medium-high
low-medium medium-high low-high, "raisinoid"
nuc. membrane
low-high, "raisinoid"
nuc. membrane
low-medium, round nuclei
Cytoplasm clear eosinophilic eosinophilic cobwebs/clear eosinophilic/cobwebs eosinophilic/
granular & abundant
Other delicate vessels,
necrosis common
histiocytes
in fibrovascular cores, >0.5 cm
histiocytes
in fibrovascular cores, >0.5 cm
perinuclear clearing, thick vessels perinuclear clearing, thick vessels in loose fibrous/hyaline stroma
IHC CK7-, EMA+ AMACR+, EMA+, CK7+ AMACR+, E-cadherin+, CK7- CD117+, CK7+ (membrane) CD117+, CK7+ (membrane) Vimentin-, EMA+
Main DDx chromophobe
classic variant
PaRCC type 2, mets PaRCC type 1, mets clear cell RCC oncocytoma chromophobe
eosinophilic variant
Key features clear cells, vascular papillae, histiocytes
simple epithelium
papillae, histiocytes,
stratified
perinuc. clearing,
wispy cytoplasm
perinuc. clearing,
wispy eosinophilic
cytoplasm
eosinophilic, granular cytoplasm
Image(s) CCRCC (WC) PaRCC - intermed. (WC), PaRCC - high (WC) ChRCC (WC) Oncocytoma (WC)

Notes:

  • Cell shape: all have epithelioid morphology.

Tabular comparison of oncocytoma and chromophobe RCC

Histomorphologic features useful to distinguish chromophobe RCC (eosinophilic variant) and oncocytoma:[4]

ChRCC (eosinophilic
variant)
Renal oncocytoma
Nuclear morphology "raisinoid"/wrinkled appearance round with small nucleolus,
usu. little size variation
Multinucleation common - binucleation uncommon
Chromatin coarse fine
Architecture solid, crowded nests spaced nests /
archipelago-like, solid
Cytoplasm perinuclear halo, may be focal no perinuclear halo
Degenerative foci
(focal atypia & pleomorphism)
absent present in ~20% of cases
Image ChRCC (WC) Oncocytoma (WC)

WHO classification

  • Based on 2004 iteration - as per WMSP, slightly modified.[5]

Renal cell tumours

Common:

Less common:

Metanephric tumours

Nephroblastic tumours

Mesenchymal tumours

Childhood:

Adults:

Mixed mesenchymal and epithelial tumours

Others

Renal cell carcinoma

Overview

General

  • Relatively common form of cancer.
  • Often abbreviated RCC.
  • AKA hypernephroma.[6]
  • RCC represents approx. 90% of malignancies in kidneys of adults.[7]

Origin

  • Proximal renal tubule.

Clinical

  • Classically described as a triad:[8]
    • Hematuria (most common symptom).
    • Abdominal mass.
    • Flank pain.
  • Frequently picked-up on imaging (incidentaloma) ~ 1/3 of cases.

Risk factors

Subtypes of RCC

RCC (renal cell carcinoma) comes in different subtypes:[9]

  • Clear cell carcinoma (70-80% of RCC) -- abbrev. CCRCC,
  • Papillary renal cell carcinoma (10-15% of RCC) -- abbrev. PRCC,
  • Chromophobe renal carcinoma (5% of RCC) -- abbrev. ChRCC,
  • Collecting duct (Bellini duct) carcinoma (1% of RCC).

Notes:

  • Subtype is an independent predictor of mortality - but adds very little to multivariate models with staging information.[10]
  • CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.[11]

IHC - is it RCC?

  • RCC Ma (+), CD10 (+) -- specific for RCC[12]

IHC - differentiation of types

  • Clear cell RCC vs. papillary RCC:
    • CK7 (-ve CCRCC), AMACR (+ve in PRCC).[13]
  • Papillary RCC type 1 vs. papillary RCC type 2:
    • E-cadherin +ve in PRCC type 2.[14]
    • EMA (MUC1) +ve in PRCC type 1.[14]
  • ChRCC vs. oncocytoma (ONC):
    • CK7 (ChRCC +ve membrane), CK20, CD15.[13]
    • CK7 -- ChRCC 86% +ve vs. ONC 0% +ve.[15]
    • CD15 -- ChRCC 11% +ve vs. ONC 57% +ve.[16]
    • Hale's colloidal iron +ve in ChRCC, usually neg. in ONC.[17]
    • PAX2 -- ChRCC (1/11) +ve vs. ONC (20/23) +ve.[18]
    • Kidney-specific cadherin (Ksp-cadherin) -- ChRCC 97% +ve (distinctive membrane pattern) vs. ONC only 3% +ve.[19]
  • ChRCC & renal oncocytoma vs. others:
    • CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic).[20]
  • Clear cell RCC vs. chromophobe RCC:
    • Hale's colloidal iron (+ve in ChRCC).[17]
    • CK7 (cell membrane +ve in ChRCC).

Notes:

  • One paper[21] describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
  • Another paper I came across:[22]
  • c-kit (CD117) not useful for differentiating ONC and ChRCC.[18]
  • E-cadherin not useful for differentiating ChRCC and ONC.[23]

RCC vs. Urothelial cell carcinoma

  • Clinically/radiologically, it may not be possible to differentiate renal pelvis UCC and RCC if the tumour is large.
  • Pathologically, this is not very difficult.
  • On gross specimens, it is almost always obvious what one is dealing with:
    • UCC = nephroureterectomy.
    • RCC = partial nephrectomy, nephrectomy or radical nephrectomy.

Hereditary renal cell carcinoma

The classics - which are all autosomal dominant:[9]

  1. Von Hippel-Lindau syndrome.
    • VHL gene mutation.
    • Clear cell RCC.
  2. Hereditary clear cell carcinoma.
    • VHL gene mutation.
  3. Hereditary papillary carcinoma
    • MET proto-oncogene mutation.
    • PaRCC type 1.[24]
  4. Hereditary leiomyomatosis and renal cell cancer:[24]
    • FH (fumarate hydratase) gene mutation.[25]
    • PaRCC type 2.
    • Benign leiomyomas skin/uterus.
    • Uterine leiomyosarcoma.
  5. Birt–Hogg–Dubé syndrome:[24]
    • FLCN (folliculin) gene mutation.[26]
    • Skin lesions (fibrofolliculoma, trichodiscoma, acrochordon).
    • ChRCC most common, other types seen (e.g. oncocytoma).
    • Variable penetrance (autosomal dominant).

Others:

  • Hereditary papillary carcinoma (TFE3 related translocations).[27]

Notes:

  • A total of ten hereditary renal cancer syndromes have been described. In eight of the ten the gene is known.[28]

Grading RCC

General

Some subtypes are graded based on the Fuhrman system which considers:[29]

  • Nuclear pleomorphism (size, shape).
  • Chromatin pattern.
  • Nucleoli prominence.

Notes:

  • The system was validated for clear cell RCC.
  • Fuhrman nuclear grade is not prognostic in chromophobe RCC and should not be used in that context.[30]

Criteria & grades

  • Grade 1: no nucleoli, near 'normal' appearance.
  • Grade 2: finely granular chromatin (key feature), no nuclei visible with 10x objective lens.
  • Grade 3: nucleoli seen easily (key feature).
  • Grade 4: prominent pleomorphism (key feature), hyperchromasia, macronucleoli.

Note: Most tumours are grade 2 & 3.

Fuhrman grading in short

  • 1 vs. 2: grade 2 has granular chromatin, grade 2 has nucleoli visible @ 20x objective.[31]
  • 2 vs. 3: grade 3 has nucleoli @ 10x objective.
  • 3 vs. 4: grade 4 has pleomorphism/hyperchromasia.

Clear cell renal cell carcinoma

  • Often abbreviated CRCC.

General

Gross

  • Gold/yellow.
  • +/-Haemorrhage (common).
  • +/-Necrosis (common in large tumours).
  • +/-Calcification.
  • +/-Cysts.

Microscopic

Features:[32]

  • Solid or trabecular pattern.
  • Polygonal cells.
  • Clear cytoplasm.
  • Central nucleus.
  • Delicate branching vasculature.
    • Often called "chicken wire-like" vasculature.

Notes:

  • Cytoplasm may be eosinophilic.[33]
    • This change is typically focal - other areas have a classic appearance.
    • Chicken wire-like vasculature present - helps distinguish from other tumours.
  • Hyaline bodies common.[34]
    • Not common in papillary RCC.

Clear cell vs. adrenocortical carcinoma:

  • ACC: EMA- (epithelial membrane antigen), cytokeratin mostly neg., inhibin+ (neg. in RCC).[35]

Images:

IHC

  • CK7 -ve.
  • CK20 -ve.
  • Hale's colloidal iron -ve.
    • +ve in chromophobe RCC.

Note: Hale's colloidal iron does not stain iron... it stains hemosiderin.[36] Clear cell vs. chromophobe:

  • Chromophobe: "translucent" (NOT quite clear), reticulated, Hale's colloidal iron stain+, CK7+ (cell membrane).

Multilocular cystic renal cell carcinoma

General

  • No recurrences or metastasis in the literature.[37]
    • This makes one wonder... is it really cancer.
  • Case report rare.[38]

Gross

Features:[37]

  • Cystic with thin septa.
  • Well circumscribed.

Note:

  • This tumour, radiologically, can often be separated from other cystic tumours.[39]

Microscopic

Features:[37]

  • Polygonal cells within the septa.
  • Clear cytoplasm.
  • +/-Calcification (common).

DDx:

  • Cystic renal disease with macrophages in the septa.
  • Cystic clear cell renal cell carcinoma.

IHC

  • EMA +ve.
  • Keratins +ve.
  • CD68 -ve.

Papillary renal cell carcinoma

  • Abbreviated PRCC, PaRCC and papillary RCC.

General

  • Often subclassified[40] into type 1 and type 2 -- see below.
  • May be abbreviated PRCC.

Epidemiology

Microsopic

Features:[32]

  • Cuboidal or low columnar cell in papillae.
  • Interstitial foam cells in vascular cores - key feature.[42]
    • Most sensitive and specific feature of PRCC.[43]
  • Highly vascular.

Size criterion:

  • Papillary lesions must be >0.5 cm to be called carcinoma; smaller lesions (<=0.5 cm) are called papillary adenomas.[44]

Mnemonic HIP: highly vascular, interstitial foam cells, papillae.

DDx:

  • Clear cell RCC.
    • Papillary: +histiocytes, +intracellular hemosiderin, CK7+.
  • Metanephric adenoma - esp. solid PRCC type 1.

Histological subtyping

Subtypes:[40]

  • Type 1 - single layer of cells on basement membrane.
    • usually low grade nuclear features, i.e. low Fuhrman grade.
  • Type 2 - pseudostratification of cells.
    • Usually high grade nuclear features, i.e. high Fuhrman grade.

IHC

Features:[40]

  • AMACR +ve.[45]
  • HMWCK (34betaE12) +ve.
  • Panker (AE1/AE3) +ve.
  • CK7 +ve ~90% of type 1, 20% of type 2.

More reading:

Molecular

Features:[9]

  • Sporadic: trisomies 7, 16, 17.
  • Familial: trisomy 7.
    • Chromosome 7 = location of MET gene.

Note:

  • Not used for diagnosis.[46]

Chromophobe renal cell carcinoma

  • Abbreviated ChRCC.

General

  • Least common of the common types of RCC.
  • Fuhrman grading for this entity is controversial, as it does not appear to have any predictive value.[30]

There are two subtypes:[47]

  • Classic.
  • Eosinophilic variant.

Gross

  • Tan, light-brown.
  • Solitary.
  • Well-circumscribed.

Microscopic

Classic

Features - classic type (3 P's mnemonic):[48][47]

  • Pale cytoplasm, with wisps of eosinophilic material; the cells are not completely clear, they have "cobwebs".
  • Perinuclear clearing, i.e. a pale halo surrounds the nucleus - key feature.
  • Periphery of cell distinct, i.e. cell membrane is easy to discern.

Notes:

DDx:

  • Clear cell RCC (classic).
    • Perinuclear clearing is not seen in clear cell RCC.
    • ChRCC has wisps in the cytoplasm.

Eosinophilic variant

Features - eosinophilic variant:[47]

  • Eosinophilic (finely granular) cytoplasm.
  • Perinuclear clearing - key feature.
  • Periphery of cell distinct.
  • Smaller cells than classic subtype.

Notes:

  1. May have psammoma bodies.

DDx:

  1. Oncocytoma - particularly the eosinophilic variant.
    • IHC may be useful to differentiate (CK7: oncocytoma = cytoplasm +ve, chromophobe = cell membrane +ve).
    • A comparison based on histomorphology: Tabular comparison between ChRCC & oncocytoma.
      • Oncocytoma typically has: no perinuclear clearing, no raisinoid nuclei, no binucleation.
  2. Clear cell RCC, eosinophilic variant.
    • Perinuclear clearing is not seen in clear cell RCC.
    • ChRCC has wisps in the cytoplasm.

Image:

Stains

Images:

IHC

  • CK7 +ve cell membrane.[47]
  • CD117 +ve.
  • Vimentin -ve.

Molecular

  • Extensive aneusomy (monosomy?):[37]
    • Loss of chromosomes: 1, 2, 6, 10, 13, 17, 21.

Clear cell papillary renal cell carcinoma

  • AKA clear cell tubulopapillary renal cell carcinoma.[50]

General

  • New entity not in the WHO classification.

Microscopic

Features:[50]

  • Features of both:
    1. Clear cell RCC.
    2. Papillary RCC.
      • Often do not have true papillae.

DDx:

IHC

Features:[50]

Others:[50]

  • HIF-1alpha +ve.
  • GLUT-1 +ve.

Renal translocation carcinomas

Renal tumour with Xp11.2 translocation

General

  • Defined by the presence of a fusion gene form with TFE3 @ Xp11.2.
  • TFE3 is the gene involved in the translocation seen in alveolar soft part sarcoma (ASPS).
  • Poor prognosis ~ 50% present at stage IV, majority of lymph node metastases.
  • ~1/3 of childhood RCC.[51]

Microscopic

Features:[52]

  • Large cells.
  • Clear or eosinophilic cytoplasm.
  • Papillae or nests.
  • Psammoma bodies - common.[53]
    • Calcification is considered the classic histomorphologic feature.
  • Hyaline bodies - common.

Notes:

DDx:

  • Clear cell RCC.
  • Papillary RCC.
  • Epithelioid angiomyolipoma.

IHC

  • TFE3 +ve (nucleus) - key feature.[52]
  • CD10 +ve.
  • Vimentin +ve.

Others:

Molecular

Renal tumour with t(6;11) translocation

General

Microscopic

Features:

  • Hyaline material between nests.
  • Large cells with clear to eosinophilic cytoplasm.

Molecular

  • t(6;11)(p21;q12) Alpha/TFEB.[55]

Benign tumours

Papillary adenoma

General

  • Benign.

Microscopic

Features:

  1. Histomorphology of papillary renal cell carcinoma.
  2. Must be <=0.5 cm.[44]
    • Larger lesions are papillary renal cell carcinoma.

Renal oncocytoma

General

  • Can be difficult to distinguish radiologically from RCC (chromophobe subtype).
    • ... and pathologists occasionally struggle like the radiologists.
  • Benign tumour - the reason it is excised is... one cannot be certain it isn't a RCC.

Gross

  • Brown, mahogany brown.
  • 1/3 have a characteristic central scar.[56]

Image:

Microscopic

Features:

  • Eosinophilic cytoplasm - slightly granular key feature.
  • Cells arranged in nests.
  • Nuclei uniform and round.[56]
    • Slightly enlarged nuclei, but no significant pleomorphism (size variation) - important.

Notes:

  • May look like eosinophilic variant of chromophobe RCC -- this is the main DDx.

Images:

IHC

  • CK7 +ve (cytoplasm).
    • Chromophobe renal cell carcinoma = cell membrane +ve.
  • CD117 -ve. (???)

Angiomyolipoma

  • Abbreviated AML.

General

  • Benign mesenchymal tumour.
  • Presentations: flank pain, hematuria, incidentaloma.[57]
    • Tumours >4 cm considered a risk for bleeding.[58]
  • AMLs occur may be elsewhere in the body, e.g. liver,[59] but are most common in the kidney.
  • In the PEComa group of tumours.

Epidemiology

  • May be associated with tuberous sclerosis -- 70% have an AML.
    • When compared to sporadic cases:
      • More often bilateral.
      • Usually bigger.

Microscopic

Features:

  • Smooth muscle.
  • Adipose tissue - not always present[60] - key feature.
  • Abundant blood vessels.

Notes:

  • There is a suggestion that an epithelioid variant is more worisome.[61]
    • This is not confirmed by all studies.[62]

DDx:

Cytologic

Features[60]

  • Nuclei - round/ovoid.
  • Chromatin - bland.

IHC

  • Melanocytic markers +ve[63] (e.g. HMB-45 +ve).
  • Epithelial markers -ve.[63]
  • SMA +ve.
  • CD117 +/-.
  • Ki-67:[64]
    • Epithelioid variant of AML +ve.
    • Conventional AML -ve.

Mimics

Xanthogranulomatous pyelonephritis

General

  • May mimic RCC (esp. radiologically).
  • Usually lower pole ???
  • Associated with:
    • Diabetes mellitus,
    • History of UTI,[65]
    • Nephrolithiasis,
    • GU obstruction.[66]
  • Occasionally an indication of nephrectomy.[65][66]
  • Most common organism (in the context of nephrectomy specimens) - Proteus mirabilis.[66]

Microscopic

  • Abundant macrophages.
  • +/-Giant cells.

Image:

IHC

  • CD68 +ve.
  • RCC markers (CD10, RCC) all negative.

DDx:

  • Malakoplakia.
  • RCC - esp. PaRCC (as this has foamy macrophages).
  • Granulomatous disease.

Malakoplakia

Rare stuffs

Medullary fibroma

General

  • Rare.

Epidemiology

  • Benign.

Gross

  • Small, white well circumscribed nodule in medulla.

Microscopic

  • Spindle cells.

Metanephric adenoma

General

  • Benign.
  • Afflicts adults and occasionally children.
  • May be associated with polycythemia.[67]

Microscopic

Features:[68]

  • Small uniform cells with:
    • Fine chromatin.
    • No apparent nucleolus.
    • A relatively smooth nuclear membrane.
  • Variable architecture - may be sheets or ductal.

DDx:

  • Epithelioid nephroblastoma (Wilms tumour) - these typically have:
    • Irregular nuclear membrane.
    • Nucleoli.
    • Mitoses (rare in metanephric adenoma).
  • Papillary RCC.[68]

Images:

IHC

  • WT-1 +ve.
  • CD57 +ve.
  • CK7 -ve.

Renal epithelial and stromal tumour

The lumping term for both:[69]

  1. Mixed epithelial and stromal tumour.
  2. Cystic nephroma.

Mixed epithelial and stromal tumour

  • Abbreviated MEST.

General

  • Rare - approx. 1.5% of renal neoplasms.[70]
  • Benign.
  • Prevalence: males > females.

Note:

  • Turbiner et al.[69] have suggested that cystic nephroma and mixed epithelial and stromal tumour (MEST) are one tumour.
    • The lumping term renal epithelial and stromal tumour, abbreviated REST.

Microscopic

Features:

  • Cysts lined by simple epithelium with hobnailing - key feature.
  • Stroma has an ovarian look:
    • Blue (basophilic).
    • Spindle cells.

Notes:

  • Parenchymal elements (e.g. glomueruli, tubules) are not found in the septa between the cysts.

Images:

IHC

Features:[70]

  • ER +ve.
  • PR +ve.
  • CD10 +ve.

DDx

  • Tubulocystic carcinoma.

Cystic nephroma

General

Gross

  • Bubble wrap-like appearance.

Image:

Microscopic

Features:

  • Cysts lined by simple epithelium with hobnailing - key feature.
  • Stroma has an ovarian look:
    • Blue (basophilic).
    • Spindle cells.

Notes:

  • Parenchymal elements (e.g. glomueruli, tubules) are not found in the septa between the cysts.

Images:

IHC

Features:

  • ER +ve.
  • PR +ve.
  • CD10 +ve.

Renal mucinous tubular and spindle cell carcinoma

  • AKA renal mucinous tubular spindle cell carcinoma.

General

  • Rare.[3]
  • Accepted by WHO in 2004 as a separate entity.[71]
  • Relatively good prognosis.

Microscopic

Features:[72]

  • Mucin - may be scant.
  • Spindle cells.

DDx:

  • Sarcomatoid papillary RCC. (???) [73]

IHC

Features:[74]

  • CD10 -ve.
  • AE1/AE3 +ve.
  • AMACR +ve.
  • CK7 +ve.

Collecting duct carcinoma

General

  • Rare.
  • Poor prognosis.
  • Usu. central location.

Microscopic

Features:[75]

  • Tubular structures with tapered ends.
    • May be described as tubulopapillary.
  • Hobnail pattern - cell width smaller at basement membrane than free surface.[76]
  • High grade nuclear features (nuclear pleomorphism).
  • High mitotic rate.

Notes:

  • Benign urothelium must present to excluded urothelial carcinoma.
  • Desmoplastic stroma may be prominent.

DDx:

IHC

Features:[3]

  • CD117 +ve.
  • E-cadherin +ve.
  • CD10 -ve.
  • AMACR -ve.

Renal medullary carcinoma

General

  • Rare.
  • Usually young adults.
  • Associated with sickle cell trait (heterozygotes for the sickle cell allele).[77]
  • Aggressive/poor prognosis.[78]

Aside:

  • Kidney disease assoc. with sickle cell disorders:[77]
    1. Papillary necrosis.
    2. Nephrotic syndrome.
    3. Renal infarction.
    4. Pyelonephritis.

Gross

Features:[78]

  • Well circumscribed.
  • Renal medulla.

Microscopic

Features:[77][78]

  • Variable architecture:
  • Desmoplastic stroma - prominent.
  • Inflammation:
    • Lymphocytes.
    • Neutrophils - margination in vessels.

DDx:

Image:

IHC

  • SMARCB1 (INI1) -ve.[79]

Pediatric

The most common is nephroblastoma (Wilms tumour).

Others include:

See also

References

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