Kidney tumours

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A kidney tumour (renal oncocytoma). (WC/Emmanuelm)

Kidney tumours - includes malignant kidney tumours (kidney cancer) 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

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

Layers (superficial to deep):

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

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Missed renal biopsy

KIDNEY (LESION), LEFT, CORE BIOPSY:
- RENAL PARENCHYMA.
- NEGATIVE FOR MASS LESION, SEE COMMENT.

COMMENT:
No mass lesion is apparent in the tissue sampled. A re-biopsy should be considered.

Renal parenchyma:
- Glomeruli: seven glomeruli sampled, no apparent glomerular pathology on the H&E sections.
- Interstitium: interstitial fibrosis is not identified.
- Tubules: no pathology is apparent.
- Vessels: mild atherosclerosis, no hyalinization of arterioles apparent.

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]

Morphologic feature 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/Nephron)
Oncocytoma (WC/Nephron)

Common DDx

Spindle cell tumours

Malignant spindle cell tumours of the kidney:

Benign spindle cell tumours of the kidney:

Renal tumours with eosinophilic cytoplasm

WHO classification of renal neoplasia

  • Based on 2004 iteration - as per WMSP, slightly modified.[5] Online, the classification can found here.

Renal cell tumours

Common:

Less common:

Metanephric tumours

Nephroblastic tumours

Mesenchymal tumours

Childhood:

Adults:

Other:

Mixed mesenchymal and epithelial tumours

Others

Vancouver modification of WHO classification

In 2012, several additions were made:[6]

"Emerging" entities are:

Renal cell carcinoma

Overview

General

  • Relatively common form of cancer.
  • Often abbreviated RCC.
  • AKA hypernephroma.[7]
  • RCC represents approx. 90% of malignancies in kidneys of adults.[8]

Origin

  • Proximal renal tubule.

Clinical

  • Classically described as a triad:[9]
    • 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:[10]

  • 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.[11]
  • CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.[12]
  • The exam answer (worst to best): clear cell RCC, papillary RCC, chromophobe RCC.

IHC - is it RCC?

  • RCC Ma (+), CD10 (+) -- specific for RCC[13]

IHC - differentiation of types

  • Clear cell RCC vs. papillary RCC:
    • CK7 (-ve CCRCC), AMACR (+ve in PRCC).[14]
  • Papillary RCC type 1 vs. papillary RCC type 2:
    • E-cadherin +ve in PRCC type 2.[15]
    • EMA (MUC1) +ve in PRCC type 1.[15]
  • ChRCC vs. oncocytoma (ONC):
    • CK7 (ChRCC +ve membrane), CK20, CD15.[14]
    • CK7 -- ChRCC 86% +ve vs. ONC 0% +ve.[16]
    • CD15 -- ChRCC 11% +ve vs. ONC 57% +ve.[17]
    • Hale's colloidal iron +ve in ChRCC, usually neg. in ONC.[18]
    • PAX2 -- ChRCC (1/11) +ve vs. ONC (20/23) +ve.[19]
    • Kidney-specific cadherin (Ksp-cadherin) -- ChRCC 97% +ve (distinctive membrane pattern) vs. ONC only 3% +ve.[20]
  • ChRCC & renal oncocytoma vs. others:
    • CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic).[21]
  • Clear cell RCC vs. chromophobe RCC:
    • Hale's colloidal iron (+ve in ChRCC).[18]
    • CK7 (cell membrane +ve in ChRCC).

Notes:

  • One paper[22] describes CD10, parvalbumin, AMACR, CK7 and S100A1 as being useful.
  • Another paper I came across:[23]
  • c-kit (CD117) not useful for differentiating ONC and ChRCC.[19]
  • E-cadherin not useful for differentiating ChRCC and ONC.[24]

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.

Renal cell carcinoma with sarcomatoid differentiation

  • AKA sarcomatoid renal cell carcinoma.

General

Features:[25]

  • Not recognized as a distinct entity in 2004 WHO classification.[26]
    • It is considered an indicator of progression.
    • Previously considered a distinct entity.[26][27]
  • Tend to present at higher stage.
  • Worse prognosis when adjusted for stage.
  • Fuhrman grade 4 by definition.

Microscopic

Features:[25]

  1. Renal cell carcinoma.
  2. Sarcomatoid component:

Notes:

Images:

Renal cell carcinoma with rhabdoid morphology

  • AKA renal cell carcinoma with rhabdoid change.

Hereditary renal cell carcinoma

The classics - which are all autosomal dominant:[10]

  1. Von Hippel-Lindau syndrome.
    • VHL gene mutation.
    • Clear cell RCC.
  2. Hereditary clear cell renal cell carcinoma.
    • VHL gene mutation.
  3. Hereditary papillary renal cell carcinoma.
    • MET proto-oncogene mutation.
    • PaRCC type 1.[31]
  4. Hereditary leiomyomatosis and renal cell cancer:[31]
  5. Birt–Hogg–Dubé syndrome:[31]
    • FLCN (folliculin) gene mutation.[33]
    • 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).[34]

Notes:

  • A total of ten hereditary renal cancer syndromes have been described. In eight of the ten the gene is known.[35]

Molecular

Recurrent molecular changes in RCC:

  • Clear cell RCC:
    • Loss of 3p - contains the VHL gene.
  • Papillary RCC:
    • Sporadic:
      • Trisomy 7, 16, 17.
      • Loss of Y.
    • Familial:
      • Trisomy 7 - contains MET gene.[36]

Renal cell carcinoma grading

General

There are two systems:

  • Fuhrman grading:
    • Older and more complicated.
    • Based on nuclear size and shape, chromatin pattern and nucleolar size.[37]
    • More complicated.
  • ISUP grading:[38]
    • Newer and less complicated.
    • Mostly based on nucleolar size and to a much lesser degree on size and morphology
    • Developed based on Fuhrman grading.

ISUP grading

Criteria:[38]

  • Grade 1 - nucleoli absent/very small at 400x. §
  • Grade 2 - nucleoli seen with 400x, but not at 100x. §§
  • Grade 3 - nucleoli seen at 100x, i.e. with the 10x objective.
  • Grade 4 - extreme nuclear pleomorphism (esp. nuclear enlargement) or sarcomatoid differentiation (spindle cells[28] or rhabdoid cells).

Cavets:[38]

  • Higher grade component trumps lower grade component.
    • No agreed upon minimum quantity of high grade component for upgrading.
      • 37% use 1 field of view with the x10 objective. †
      • 41% use 1 field of view with the x40 objective. ‡
  • Grading system not used for chromophobe RCC.
    • The experience with the Fuhrman grading system showed it is not prognostic for chromophobe RCC.[39]

Notes:

  • † Suffers from IPFitis.
  • ‡ Suffers from HPFitis.
  • § Some describe Grade 1 nuclei as lymphocyte-like.[citation needed]
  • §§ Some suggest the following relationship between grading/nucleoli:[citation needed]
    • Grade 1 = nucleoli seen at 400x.
    • Grade 2 = nucleoli seen at 200x.
    • Grade 3 = nucleoli seen at 100x.

Clear cell renal cell carcinoma

Multilocular cystic renal cell carcinoma

Papillary renal cell carcinoma

Chromophobe renal cell carcinoma

Clear cell papillary renal cell carcinoma

Unclassified renal cell carcinoma

  • Abbreviated URCC.

Renal translocation carcinomas

Renal tumour with Xp11.2 translocation

Renal tumour with t(6;11) translocation

  • AKA t(6;11) renal cell carcinoma.

Benign tumours

Papillary adenoma of the kidney

  • AKA renal papillary adenoma.

Renal oncocytoma

Angiomyolipoma

  • Abbreviated AML.

Mimics

Xanthogranulomatous pyelonephritis

  • Abbreviated XGP.

Malakoplakia

Rare stuffs

Juxtaglomerular cell tumour

  • AKA juxtaglomerular tumour, reninoma.[40]

Renomedullary interstitial cell tumour

Metanephric adenoma

  • Should not be confused mesonephric adenoma, another term for nephrogenic adenoma.
    • Memory device: metanephric adenoma is a tumour.

Renal epithelial and stromal tumour

Abbreviated REST.

The lumping term for both:[42]

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

Mixed epithelial and stromal tumour

  • Abbreviated MEST.

Cystic nephroma

Renal mucinous tubular and spindle cell carcinoma

  • AKA renal mucinous tubular spindle cell carcinoma.
  • AKA mucinous tubular and spindle cell carcinoma of the kidney.[43]

Collecting duct carcinoma

Renal medullary carcinoma

Tubulocystic carcinoma of the kidney

Acquired cystic disease-associated renal cell carcinoma

Kidney metastasis

  • AKA renal metastasis, metastatic kidney disease.

Pediatric

The most common is nephroblastoma (Wilms tumour).

Others include:

See also

References

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