Difference between revisions of "Kidney tumours"

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====Anaplasia====
====Anaplasia====
Subclassified as:<ref name=Ref_WMSP282>{{Ref WMSP|282}}</ref>
#Focal anaplasia.
#Diffuse anaplasia.
Any of the following:
Any of the following:
#Atypical mitoses.
#Atypical mitoses.
#Hyperchromasia.
#Nuclear hyperchromasia.
#Nuclear size variation (of the tumour cells) > 3x.
#Nuclear size variation (of the tumour cells) > 3x.



Revision as of 18:48, 1 October 2011

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

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).[1]

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)

Renal cell carcinoma

Overview

General

  • Relatively common form of cancer.
  • Often abbreviated RCC.
  • AKA hypernephroma.[5]

Origin

  • Proximal renal tubule.

Clinical

  • Classically described as a triad:[6]
    • Hematuria (most common symptom).
    • Abdominal mass.
    • Flank pain.
  • Frequently picked-up on imaging (incidentaloma) ~ 1/3 of cases.

Risk factors

  • Smoking.
  • Some chemicals.
  • Hemodialysis.
  • Male>female (~2:1).
  • Hereditary - familial syndromes (see Hereditary RCC).

Subtypes of RCC

RCC (renal cell carcinoma) comes in different subtypes:[7]

  • 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.[8]
  • CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.[9]

IHC - is it RCC?

  • RCC Ma (+), CD10 (+) -- specific for RCC[10]

IHC - differentiation of types

  • Clear cell RCC vs. papillary RCC:
    • CK7 (-ve CCRCC), AMACR (+ve in PRCC).[11]
  • Papillary RCC type 1 vs. papillary RCC type 2:
    • E-cadherin +ve in PRCC type 2.[12]
    • EMA (MUC1) +ve in PRCC type 1.[12]
  • ChRCC vs. oncocytoma (ONC):
    • CK7 (ChRCC +ve membrane), CK20, CD15.[11]
    • CK7 -- ChRCC 86% +ve vs. ONC 0% +ve.[13]
    • CD15 -- ChRCC 11% +ve vs. ONC 57% +ve.[14]
    • Hale's colloidal iron +ve in ChRCC, usually neg. in ONC.[15]
    • PAX2 -- ChRCC (1/11) +ve vs. ONC (20/23) +ve.[16]
    • Kidney-specific cadherin (Ksp-cadherin) -- ChRCC 97% +ve (distinctive membrane pattern) vs. ONC only 3% +ve.[17]
  • ChRCC & renal oncocytoma vs. others:
    • CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic).[18]
  • Clear cell RCC vs. chromophobe RCC:
    • Hale's colloidal iron (+ve in ChRCC).[15]
    • CK7 (cell membrane +ve in ChRCC).

Notes:

  • One paper[19] describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
  • Another paper I came across:[20]
  • c-kit (CD117) not useful for differentiating ONC and ChRCC.[16]
  • E-cadherin not useful for differentiating ChRCC and ONC.[21]

Hereditary RCC

The classics - which are all autosomal dominant:[7]

  1. Von Hippel-Lindau syndrome (clear cell tumours).
  2. Hereditary clear cell carcinoma (VHL gene).
  3. Hereditary papillary carcinoma (MET proto-oncogene mutation).

Others:

  • Hereditary papillary carcinoma (TFE3 related translocations).[22]

Review paper:
Verine, J.; Pluvinage, A.; Bousquet, G.; Lehmann-Che, J.; de Bazelaire, C.; Soufir, N.; Mongiat-Artus, P. (Nov 2010). "Hereditary renal cancer syndromes: an update of a systematic review.". Eur Urol 58 (5): 701-10. doi:10.1016/j.eururo.2010.08.031. PMID 20817385.

Grading RCC

General

Some subtypes are graded based on the Fuhrman system which considers:[23]

  • 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.[24]

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.[25]
  • 2 vs. 3: grade 3 has nucleoli @ 10x objective.
  • 3 vs. 4: grade 4 has pleomorphism/hyperchromasia.

Clear cell carcinoma

Gross

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

Microscopic

Features:[26]

  • Clear cells.
  • Solid or trabecular pattern.
  • Delicate branching vasculature.

IHC

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

Note: Hale's colloidal iron does not stain iron... it stains hemosiderin.[28] Clear cell vs. chromophobe:

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

Clear cell vs. adrenocortical carcinoma:

  • ACC: EMA- (epithelial membrane antigen), cytokeratin mostly neg., inhibin+ (neg. in RCC).[29]

Papillary RCC

General

  • Often subclassified[30] into type 1 and type 2 -- see below.
  • May be abbreviated PRCC.

Epidemiology

  • Associated with dialysis associated cystic disease.[31]

Microsopy

Features:[32]

  • Cuboidal or low columnar cell in papillae.
  • Interstitial foam cells in vascular cores - key feature.[33]
    • Most sensitive and specific feature of PRCC.[34]
  • Highly vascular.

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

Size criterion:

  • Papillary lesions must be >0.5 cm to be called carcinoma; smaller lesions (<=0.5 cm) are called papillary adenomas.[35]

Histological subtyping:[30]

  • 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:[30]

  • AMACR +ve.[36]
  • HMWCK (34betaE12) +ve.
  • Panker (AE1/AE3) +ve.
  • CK7 +ve ~90% of type 1, 20% of type 2.

More reading:

Clear cell vs. papillary

  • Papillary: +histiocytes, +intracellular hemosiderin, CK7+.

Chromophobe RCC

General

  • Sometimes abbreviated ChRCC.

There are two subtypes:[37]

  • Classic.
  • Eosinophilic variant.

Gross

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

Microscopic

Features - classic type:[38][37], 3 P's mnemonic:

  • 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.

Features - eosinophilic variant:[37]

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

Notes:

  1. May have psammoma bodies.
  2. May appear similar to oncotyoma -- particularily the eosinophilic variant.

Image: Oncocytic chromophobe RCC (WC).

IHC

  • CK7 +ve cell membrane.[37]

DDx:

  • May appear similar to oncotyoma -- particularily the eosinophilic variant.
    • IHC may be useful to differentiate (CK7: oncocytoma = cytoplasm +ve, chromophobe = cell membrane +ve).
  • Classic ChRCC may be challenging to differentiate from clear cell RCC.
    • Perinuclear clearing is not seen in clear cell RCC.
    • ChRCC has wisps in the cytoplasm

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.

Benign & mimics

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.[39]

Image: Renal oncocytoma with central scar (wikipedia.org).

Histology

Features:

  • Eosinophilic cytoplasm - slightly granular key feature.
  • Cells arranged in nests.
  • Nuclei uniform and round.[39]
    • Slightly enlarged nuclei, but no significant pleomorphism (size variation) - important.

Notes:

  • May look like eosinophilic variant of chromophobe RCC -- this is the main DDx.
    • A comparison based on histomorphology: Tabular comparison between ChRCC & oncocytoma.
      • No perinuclear clearing -- this is seen in ChRCC.
    • IHC may be useful to differentiate (CK7: oncocytoma = cytoplasm +ve, chromophobe = cell membrane +ve).

Images:

Angiomyolipoma

General

  • Mostly benign mesenchymal tumour.
  • Presentations: flank pain, hematuria, incidentaloma.[40]
  • AMLs occur may be elsewhere in the body, e.g. liver,[41] 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

  • Muscle.
  • Adipose tissue - not always present.[42]
  • Blood vessels.

Cytologic features[42]

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

IHC

  • Melanocytic markers +ve[43] (e.g. HMB-45 +ve).
  • Epithelial markers -ve.[43]
  • SMA +ve.
  • CD117 +/-.

Additional paper: [42]

Notes:

  • There is a suggestion that an epithelioid variant is more worisome,[44] but this is not the case in all studies.[45]

Ki-67 can be used to help distinguish btw 'em -- epithelioid variant Ki-67 +ve.[46]

Xanthogranulomatous pyelonephritis

General

  • May mimic RCC (esp. radiologically).
  • Usually lower pole ???
  • Associated with:
    • Diabetes mellitus,
    • History of UTI,[47]
    • Nephrolithiasis,
    • GU obstruction.[48]
  • Occasionally an indication of nephrectomy.[47][48]
  • Most common organism (in the context of nephrectomy specimens) - Proteus mirabilis.[48]

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.

Micro

Features:

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

DDx:

  • Wilm tumour (nephroblastoma) - these typically have:
    • Irregular nuclear membrane.
    • Nucleoli.
    • Mitoses.

Images:

Renal epithelial stromal tumour

  • Abbreviated REST.
  • AKA cystic nephroma, AKA mixed epithelial stromal tumour (MEST)[49] - some believe these are separate entities.

General

  • Rare - approx. 1.5% of renal neoplasms.[50]
  • Benign.
  • Prevalence: males > females.

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:[50]

  • ER +ve.
  • PR +ve.
  • CD10 +ve.

DDx

  • Tubulocystic carcinoma.

Renal mucinous tubular and spindle cell carcinoma

General

  • Rare.[3]
  • Accepted by WHO in 2004 as a separate entity.[51]

Microscopic

Features:[52]

  • Mucin - may be scant.
  • Spindle cells.

DDx:

  • Sarcomatoid papillary RCC. (???) [53]

IHC

Features:[54]

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

Collecting duct carcinoma

Epidemiology

  • Rare.

Microscopic

Features:[55]

  • Tubular structures with tapered ends.
  • High grade nuclear features (nuclear pleomorphism).
  • High mitotic rate.
  • Hobnail pattern - cell width smaller at basement membrane than free surface ??? [56]

Renal medullary carcinoma

General

  • Rare.
  • Associated with sickle cell trait (heterozygotes for the sickle cell allele).[57]
  • Aggressive/poor prognosis.[58]

Gross

Features:[58]

  • Well circumscribed.
  • Medulla.

Microscopic

Features:[57][58]

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

Kidney disease assoc. with sickle cell disorders:[57]

  • Papillary necrosis.
  • Nephrotic syndrome.
  • Renal infarction.
  • Pyelonephritis.

Image:

Pediatric

Wilms tumour

  • AKA nephroblastoma, AKA Wilms' tumour.

General

Gross

  • Lobulated tan mass.

Image: Wilms tumour (med.utah.edu).

Microscopic

Features - classically three components (blastema, immature stroma, tubules):[63]

  1. Malignant small round blue cells ("blastema"):
    • Size = ~ 2x RBC diameter.
    • Nuclear pleomorphism (variation of size, shape and staining).
      • Irregular nuclear membrane - important.
    • Scant/difficult to discern cytoplasm - basophilic (light blue).
    • Mitoses - common.
  2. Stroma ("immature stroma"):
    • Spindle cells:
      • Elliptical nuclear membrane.
      • Abundant loose cytoplasm.
  3. Tubular structures ("tubules"):
    • Usually clustered.
    • Vaguely resemble a glomerulus.
    • Usu. have a central (clear/white) space surrounded by a rim of intensely eosinophilic cytoplasm.
    • Nuclei of tubular structures often elongated and palisaded.

Other findings:

  • Commonly seen in association with nephrogenic rests.
    • Cluster of cells small (blue) cells; lack nuclear atypia seen in Wilms tumour.[64]
  • +/-Heterologous elements (skeletal muscle, smooth muscle adipose tissue, cartilage).[65]
    • Heterologous = doesn't normally belong there.[66]

DDx:

  • Metanephric adenoma.
  • Nephrogenic nests.
  • Other small round cell tumours.
  • Synovial sarcoma - esp. in adults.

Notes:

  • Palisade = fence made of stakes driven into the ground.[67]
  • Approximately 30-40% Wilms tumour cases have nephrogenic rests.[68]
  • The three phases are also called blastemal, epithelial and stromal.[65]

Images:

Anaplasia

Subclassified as:[65]

  1. Focal anaplasia.
  2. Diffuse anaplasia.

Any of the following:

  1. Atypical mitoses.
  2. Nuclear hyperchromasia.
  3. Nuclear size variation (of the tumour cells) > 3x.

IHC

  • WT-1 +ve.

See also

References

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