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.

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

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).

Sign out

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:

WHO classification

  • 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

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]
  • The exam answer (worst to best): clear cell RCC, papillary RCC, chromophobe RCC.

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.

Renal cell carcinoma with sarcomatoid differentiation

  • AKA sarcomatoid renal cell carcinoma.

General

Features:[24]

  • Not recognized as a distinct entity in 2004 WHO classification.[25]
    • It is considered an indicator of progression.
    • Previously considered a distinct entity.[25][26]
  • Tend to present at higher stage.
  • Worse prognosis when adjusted for stage.
  • Fuhrman grade 4 by definition.

Microscopic

Features:[24]

  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:[9]

  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.[30]
  4. Hereditary leiomyomatosis and renal cell cancer:[30]
  5. Birt–Hogg–Dubé syndrome:[30]
    • FLCN (folliculin) gene mutation.[32]
    • 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).[33]

Notes:

  • A total of ten hereditary renal cancer syndromes have been described. In eight of the ten the gene is known.[34]

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.[35]

Renal cell carcinoma grading

  • AKA Fuhrman grade.

General

Some RCC subtypes are graded based on the Fuhrman system which considers:[36]

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

Notes:

Criteria & grades

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.[38]
  • 2 vs. 3: grade 3 has nucleoli @ 10x objective.
  • 3 vs. 4: grade 4 has pleomorphism/hyperchromasia (or spindle cells or rhabdoid cells).

Clear cell renal cell carcinoma

Multilocular cystic renal cell carcinoma

General

  • No recurrences or metastasis in the literature.[39]
    • This makes one wonder... is it really cancer.
  • Case report rare.[40]

Gross

Features:[39]

  • Cystic with thin septa.
  • Well circumscribed.

Note:

  • This tumour, radiologically, can often be separated from other cystic tumours.[41]

Microscopic

Features:[39]

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

DDx:

IHC

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

Papillary renal cell carcinoma

Chromophobe renal cell carcinoma

Clear cell papillary renal cell carcinoma

Unclassified renal cell carcinoma

  • Abbreviated URCC.

General

  • Uncommon.
  • A WHO classification diagnosis of exclusion.
  • Worse prognosis than clear cell renal cell carcinoma.[42]
  • High variation in the prevalence (when comparing institutions); this suggests a lack of uniformity in the diagnosis of this subtype.[42]

Microscopic

Features:

  • Malignant tumour that is one of the following:[43][44]
    1. A combination of other RCC histologic types (~35% of cases of URCC).
    2. Has a "non-identifiable" pattern/unrecognizable cell type (~60% of cases of URCC).
    3. Pure sarcomatoid RCC without an identifiable (epithelioid) RCC subtype (~5% of cases of URCC).[44]

DDx:

Renal translocation carcinomas

Renal tumour with Xp11.2 translocation

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.[46]

Benign tumours

Papillary adenoma of the kidney

  • AKA renal papillary adenoma.

General

Microscopic

Features:

  1. Histomorphology of papillary renal cell carcinoma.
  2. Must be <=0.5 cm.[48][49]

DDx:

Images:

IHC

Renal oncocytoma

Angiomyolipoma

  • Abbreviated AML.

Mimics

Xanthogranulomatous pyelonephritis

  • Abbreviated XGP.

Malakoplakia

Rare stuffs

Juxtaglomerular cell tumour

  • AKA juxtaglomerular tumour, reninoma.[50]

General

  • Rare.
  • Etiology: increased renin.

Clinical:[50]

  • Hypertension.
  • Increased aldosterone.
    • Causes hypokalemia.
  • Increased plasma renin.

Microscopic

Features:[51]

  • Polygonal cells.
  • Abundant granular, eosinophilic cytoplasm.[52]
  • Perinuclear halo.

DDx:

Image:

Stains

Cytoplasmic granules.[52]

  • PAS +ve.
  • PASD +ve.

IHC

Features:[51]

  • Actin +ve.
  • Cytokeratin -ve.
  • HMB-45 -ve.

EM

Features:

  • Vesicles - contain renin.[53]

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:[55]

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

Mixed epithelial and stromal tumour

  • Abbreviated MEST.

General

  • Rare - approx. 1.5% of renal neoplasms.[56]
  • Benign.
  • Prevalence: males > females.

Note:

  • Turbiner et al.[55] 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:[56]

  • 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.
  • AKA mucinous tubular and spindle cell carcinoma of the kidney.[57]

Collecting duct carcinoma

Renal medullary carcinoma

Tubulocystic carcinoma of the kidney

Acquired cystic disease-associated renal cell carcinoma

Pediatric

The most common is nephroblastoma (Wilms tumour).

Others include:

See also

References

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