Difference between revisions of "Kidney tumours"

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DDx:  
DDx:  
*[[Malacoplakia]].  
*[[Malakoplakia]].  
**Basophilic inclusions -- inside or outside of macrophages - often size of RBC or larger ([[Michaelis-Gutmann bodies]]).
**Basophilic inclusions -- inside or outside of macrophages - often size of RBC or larger ([[Michaelis-Gutmann bodies]]).
*RCC - esp. PaRCC (as this has foamy macrophages).
*RCC - esp. PaRCC (as this has foamy macrophages).

Revision as of 15:10, 23 June 2010

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 of medical disease (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]

Renal cell carcinoma

General

  • Relatively common form of cancer.
  • Often abbreviated RCC.

Origin

  • Proximal renal tubule.

Clinical

  • Classically described as a triad:[2]
    • 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

RCC (renal cell carcinoma) comes in different subtypes:[3]

  • 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.[4]
  • CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.[5]

IHC - is it RCC?

  • RCC Ma (+), CD10 (+) -- specific for RCC[6]

IHC - differentiation of types

  • clear cell RCC vs. papillary RCC
    • CK7 (-ve CCRCC), AMACR (+ve in PRCC)[7]
  • papillary RCC type 1 vs. papillary RCC type 2
    • E-cadherin +ve in PRCC type 2[8]
    • EMA (MUC1) +ve in PRCC type 1[8]
  • ChRCC vs. oncocytoma (ONC)
    • CK7 (ChRCC +ve membrane), CK20, CD15[7]
    • CK7 -- ChRCC 86% +ve vs. ONC 0% +ve[9]
    • CD15 -- ChRCC 11% +ve vs. ONC 57% +ve[10]
    • Hale's colloidal iron +ve in ChRCC, usually neg. in ONC[11]
  • ChRCC & renal oncocytoma vs. others
    • CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic)[12]
  • clear cell RCC vs. chromophobe RCC
    • Hale's colloidal iron (+ve in ChRCC)[11]
    • CK7 (cell membrane +ve in ChRCC)

Notes:

  • One paper[13] describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
  • Another paper I came across:[14]
  • ckit (CD117) not useful for differentiating ONC and ChRCC.

Tabular comparison

Selected common tumours of the kidney:[15][16]

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 low-high 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
wispy eosinophilic
cytoplasm
eosinophilic, granular cytoplasm

Notes:

  • Cell shape: all have epithelioid morphology.

Hereditary RCC

The classics - which are all autosomal dominant:[3]

  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).[17]

Grading

General

Some subtypes are graded based on the Fuhrman system which considers:[18]

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

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.[19]

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 @ 5x objective.[20]
  • 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:[21]

  • Clear cells.
  • Solid or trabecular pattern.
  • Delicate branching vasculature.
  • Hyaline bodies common.[22]
    • Not common in papillary RCC.

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.[23]

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).[24]

Papillary RCC

General

  • Often subclassified[25] into type 1 and type 2 -- see below.
  • May be abbreviated PRCC.

Epidemiology

  • Associated with dialysis associated cystic disease.[26]

Microsopy

Features:[27]

  • Cuboidal or low columnar cell in papillae.
  • Interstitial foam cells in vascular cores - key feature.[28]
    • Most sensitive and specific feature of PRCC.[29]
  • 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.[30]

Histological subtyping:[25]

  • 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:[25]

  • AMACR +ve.[31]
  • 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:[32]

  • Classic.
  • Eosinophilic variant.

Gross

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

Microscopy

Classic Histo.[33][32], 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.

Eosinophilic variant:[32]

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

Notes:

  • May have psammoma bodies.

Image: Oncocytic chromophobe RCC (wikimedia.org).

IHC

  • CK7 +ve cell membrane.[32]

DDx:

  • May appear similar to oncotyoma -- particularily the eosinophilic variant.
    • IHC: CK7: chromophobe = cell membrane CK7+; oncoctyoma = patchy cytoplasmic +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

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.[34]

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

Histology

  • Eosinophilic cytoplasm key feature.
  • Cells arranged in nests.
  • Slightly enlarged nuclei, but no significant pleomorphism (size variation).
  • Nuclei uniform and round.[34]

Notes:

  • May look like eosinophilic variant of chromophobe RCC -- this is the main DDx.
    • May need IHC to differentiate (CK7: oncocytoma = cytoplasm +ve, chromophobe = cell membrane +ve).

Images:

Angiomyolipoma

General

  • Mostly benign mesenchymal tumour.
  • Presentations: flank pain, hematuria, incidentaloma.[35]
  • AMLs occur may be elsewhere in the body, e.g. liver,[36] but are most common in the kidney.

Epidemiology

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

Microscopy

  • Muscle.
  • Adipose tissue - not always present.[37]
  • Blood vessels.

Cytologic features[37]

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

IHC

  • Melanocytic markers +ve[38] (e.g. HMB-45 +ve).
  • Epithelial markers -ve.[38]
  • SMA +ve.
  • CD117 +/-.

Additional paper: [37]

Notes:

  • There is a suggestion that an epithelioid variant is more worisome,[39] but this is not the case in all studies.[40]

Ki-67 can be used to help distinguish btw 'em -- epithelioid variant Ki-67 +ve.[41]

Xanthogranulomatous pyelonephritis

General

  • May mimic RCC (esp. radiologically).
  • Usually lower pole ???
  • Associated with:
    • Diabetes mellitus,
    • History of UTI,[42]
    • Nephrolithiasis,
    • GU obstruction.[43]
  • Occasionally an indication of nephrectomy.[42][43]
  • Most common organism (in the context of nephrectomy specimens) - Proteus mirabilis.[43]

Microscopy

  • 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.

Microscopy

  • Spindle cells.

Metanephric adenoma

General

  • Benign.

Micro

Features:

  • Small uniform cells with:
    • Fine chromatin.
    • No apparent nucleolus.
    • A relatively smooth nuclear membrane.

DDx:

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

Images:

Cystic nephroma

General

  • AKA renal epithelial stromal tumour (REST) and mixed epithelial stromal tumour (MEST).
  • Rare - approx. 1.5% of renal neoplasms.[44]
  • Benign.
  • Prevalence: males > females.

Microscopic

Features:

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

Imagea:

IHC

Features:[44]

  • ER +ve.
  • PR +ve.
  • CD10 +ve.

DDx

  • Tubulocystic carcinoma.

Mucinous spindle cell carcinoma

Microscopy

  • Mucin - may be scant.
  • Spindle cells.


Collecting duct carcinoma

Epidemiology

  • Rare.

Microscopy

Features:[45]

  • 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 ??? [46]

See also

References

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  4. Capitanio, U.; Cloutier, V.; Zini, L.; Isbarn, H.; Jeldres, C.; Shariat, SF.; Perrotte, P.; Antebi, E. et al. (Jun 2009). "A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population-based study.". BJU Int 103 (11): 1496-500. doi:10.1111/j.1464-410X.2008.08259.x. PMID 19076149.
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  6. Zhou M, Roma A, Magi-Galluzzi C (June 2005). "The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms". Clin. Lab. Med. 25 (2): 247?7. doi:10.1016/j.cll.2005.01.004. PMID 15848735.
  7. 7.0 7.1 Zhou M, Roma A, Magi-Galluzzi C (June 2005). "The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms". Clin. Lab. Med. 25 (2): 247?7. doi:10.1016/j.cll.2005.01.004. PMID 15848735.
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  9. Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG (August 2007). "Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis". Arch. Pathol. Lab. Med. 131 (8): 1290?. PMID 17683191. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=1290.
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  44. 44.0 44.1 PMID 17454754. Cite error: Invalid <ref> tag; name "pmid17454754" defined multiple times with different content
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