Kidney tumours

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.
  • May include 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).

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).

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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:

	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:

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:
  • Renal cell carcinoma with sarcomatoid differentiation.
  • Renal mucinous tubular and spindle cell carcinoma.
  • Wilms tumour.
• Benign:
  • Angiomyolipoma.
  • Cystic nephroma.

WHO classification

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

Renal cell tumours

Common:

• Clear cell renal cell carcinoma.
• Multilocular clear cell renal cell carcinoma.
• Papillary renal cell carcinoma.
• Papillary adenoma.
• Chromophobe renal cell carinoma.
• Oncocytoma.

Less common:

• Carcinoma of the collecting ducts of Bellini.
• Renal cell carcinoma, unclassified.
• Renal medullary carcinoma.
• Xp11 translocation carcinoma.
• Mucinous tubular and spindle cell carcinoma.
• Carcinoma associated with neuroblastoma.

Metanephric tumours

• Metanephric adenoma.
• Metanephric stromal tumour.
• Metanephric adenofibroma.

Nephroblastic tumours

• Nephrogenic rests.
• Nephroblastoma.

Mesenchymal tumours

Childhood:

• Clear cell sarcoma of the kidney.
• Rhabdoid tumour.
• Congenital mesoblastic nephroma

Adults:

• Unique to kidney:
  • Juxtaglomerular cell tumour.
  • Renomedullary interstitial cell tumour.

Other:

• Angiomyolipoma.
• Epithelioid angiomyolipoma.
• Leiomyosarcoma.
• Angiosarcoma.
• Pleomorphic undifferentiated sarcoma.
• Hemangiopericytoma.
• Solitary fibrous tumour.
• Osteosarcoma.
• Schwannoma.

Mixed mesenchymal and epithelial tumours

• Cystic nephroma.
• Mixed epithelial and stromal tumour.
• Synovial sarcoma.

Others

• Neuroendocrine tumours.
• Hematologic tumours.
• Germ cell tumours.
• Metastases.

Renal cell carcinoma

Overview

General

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

Origin

• Proximal renal tubule.

Clinical

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

Risk factors

• Smoking - most important.
• Chemical exposures (arsenic, asbestos, cadmium, organic solvents, pesticides, fungal toxins).
• Chronic renal failure.
  • Acquired cystic renal disease.
• Male>female (~2:1).
• Hereditary - familial syndromes (see Hereditary RCC).

Subtypes of RCC

RCC (renal cell carcinoma) comes in different subtypes:

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

IHC - is it RCC?

• RCC Ma (+), CD10 (+) -- specific for RCC

IHC - differentiation of types

• Clear cell RCC vs. papillary RCC:
  • CK7 (-ve CCRCC), AMACR (+ve in PRCC).
• Papillary RCC type 1 vs. papillary RCC type 2:
  • E-cadherin +ve in PRCC type 2.
  • EMA (MUC1) +ve in PRCC type 1.

• ChRCC vs. oncocytoma (ONC):
  • CK7 (ChRCC +ve membrane), CK20, CD15.
  • CK7 -- ChRCC 86% +ve vs. ONC 0% +ve.
  • CD15 -- ChRCC 11% +ve vs. ONC 57% +ve.
  • Hale's colloidal iron +ve in ChRCC, usually neg. in ONC.
  • PAX2 -- ChRCC (1/11) +ve vs. ONC (20/23) +ve.
  • Kidney-specific cadherin (Ksp-cadherin) -- ChRCC 97% +ve (distinctive membrane pattern) vs. ONC only 3% +ve.

• ChRCC & renal oncocytoma vs. others:
  • CD117 (ckit) +ve (100% membrane, ~75% cytoplasmic).
• Clear cell RCC vs. chromophobe RCC:
  • Hale's colloidal iron (+ve in ChRCC).
  • CK7 (cell membrane +ve in ChRCC).

Notes:

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

RCC vs. Urothelial cell carcinoma

Main article: Urothelium

• 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:

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

Microscopic

Features:

1. Renal cell carcinoma.
2. Sarcomatoid component:
   • Fibrosarcoma - most common.
   • Undifferentiated - common.
   • Rhabdomyosarcoma - very rare.

Note:

• In essence, any kidney tumour with spindle cells or rhabdoid cells should make one think of this.

Images:

• Sarcomatoid change in RCC (webpathology.com).
• Sarcomatoid changes in CCRCC (ascopubs.org).
• Sarcomatoid changes in RCC (scielo.br).

Hereditary renal cell carcinoma

The classics - which are all autosomal dominant:

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.
4. Hereditary leiomyomatosis and renal cell cancer:
   • FH (fumarate hydratase) gene mutation.
   • PaRCC type 2.
   • Benign leiomyomas skin/uterus.
   • Uterine leiomyosarcoma.
5. Birt–Hogg–Dubé syndrome:
   • FLCN (folliculin) gene mutation.
   • 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).

Notes:

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

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.

Renal cell carcinoma grading

• AKA Fuhrman grade.

General

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

• 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.
• Anything with spindle cells or rhabdoid cells should make one think grade 4, as it is likely a renal cell carcinoma with sarcomatoid differentiation.

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.
  • Spindle cells or rhabdoid cells also make something grade 4 (see renal cell carcinoma with sarcomatoid differentiation).

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.
• 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

• Abbreviated CRCC or CCRCC.

General

• Most common subtype of RCC.
• May be associated with Von Hippel-Lindau syndrome.

Gross

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

Microscopic

Features:

• Solid or trabecular pattern.
• Polygonal cells.
• Clear cytoplasm.
• Central nucleus.
• Delicate branching vasculature.
  • Often called "chicken wire-like" vasculature.
• +/-Rhabdoid cells:
  • Eccentric nucleus.
  • Abundant eosinophilic cytoplasma.

Notes:

• Cytoplasm may be eosinophilic.
  • This change is typically focal - other areas have a classic appearance.
  • Chicken wire-like vasculature present - helps distinguish from other tumours.
• Hyaline bodies common.
  • Not common in papillary RCC.
• Clear cytoplasm - due to lipid content.

DDx:

• Chromophobe renal cell carcinoma.
• Clear cell papillary renal cell carcinoma.
• Xp11.2 translocation carcinoma.
• Adrenocortical carcinoma (ACC)
  • EMA -ve, CKs mostly -ve, inhibin +ve (neg. in RCC).
• Alveolar soft part sarcoma.
• Adrenal gland, normal.

Images

• 

  CRCC - intermed. mag. (WC/Nephron)

• 

  CRCC - high mag. (WC/Nephron)

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. Clear cell vs. chromophobe:

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

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KIDNEY, LEFT, NEPHRECTOMY:
- CLEAR CELL RENAL CELL CARCINOMA, pT1a, MARGINS NEGATIVE FOR MALIGNANCY.
- PLEASE SEE TUMOUR SUMMARY.

Note:

• The surgeon wants the diagnosis and margin status; thus, these are included in the diagnosis line with the tumour stage.

Micro

The sections show a tumour with a chicken wire-like vasculature composed of clear cells with basally stratified nuclei. Hemosiderin-laden macrophages are present. Necrosis is present. Abundant hyaline globules are present.

There is no perinuclear clearing. The cytoplasm is not whispy. Collections of macrophages are not identified within the stroma of the tumour. Papillae are not evident.

Rare, small nucleoli are visible with the 10x objective. The tumour nuclei are approximately 15 micrometers.

Multilocular cystic renal cell carcinoma

General

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

Gross

Features:

• Cystic with thin septa.
• Well circumscribed.

Note:

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

Microscopic

Features:

• 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 into type 1 and type 2 -- see microscopic.
  • Type 1 and Type 2 are different on a cytogenetic and molecular basis.

Epidemiology

• Associated with acquired renal cystic disease.
• May be familial.

Microscopic

Features:

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

Size criterion:

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

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

DDx:

• Clear cell RCC.
  • Papillary: +histiocytes, +intracellular hemosiderin, CK7+.
• Clear cell papillary renal cell carcinoma.
• Metanephric adenoma - esp. solid PRCC type 1.
• Collecting duct carcinoma - esp. PRCC type 2.
• Renal papillary adenoma.

Images

• 

  PaRCC - intermed. mag. (WC/Nephron)

• 

  PaRCC - high mag. (WC/Nephron)

Histological subtyping

Subtypes:

• 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.

Others:

• Oncocytic - oncocytic cytoplasm.
  • Extremely rare ~ largest series is 12 cases.

IHC

Features:

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

More reading:

• e-immunohistochemistry.info

Molecular

Features:

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

Note:

• Not used for diagnosis.

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KIDNEY, RIGHT, NEPHRECTOMY:
- PAPILLARY RENAL CELL CARCINOMA, ONCOCYTIC -- SEE COMMENT;
- FUHRMANN GRADE 2;
- SURGICAL MARGINS NEGATIVE;
- PLEASE SEE TUMOUR SUMMARY.

COMMENT:
The oncocytic variant of papillary renal cell carcinoma (RCC) is uncommon and not widely
recognized as a subtype of papillary RCC.  The prognostic significance of the oncocytic 
cytoplasm is uncertain.[1]  The histomorphology in this case is compatible with a type 1 
papillary RCC.

1. Ann Diagn Pathol. 2006 Jun;10(3):133-9.

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.

There are two subtypes:

• Classic.
• Eosinophilic variant.

Gross

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

Image:

• Chromophobe RCC (flickr.com).

Microscopic

Classic

Features - classic type (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.

Notes:

• May have psammoma bodies.
• May be described as "plant-like"; plant cells have (thick) cell walls.
• The perinuclear clearing is often somewhat patchy, i.e. it is usually not present in very tumour cell.

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:

• 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

• 

  Oncocytic chromophobe RCC. (WC/Nephron)

www:

• Chromophobe RCC - several images (upmc.edu).

Stains

• Hale's colloidal iron +ve (blue granular cytoplasmic).

Images:

• ChRCC Hale's colloidal iron - several images (nature.com).
• ChRCC Hale's colloidal iron (ultrapath.org).
• ChRCC Hale's colloidal iron (diagnosticpathology.org).

IHC

• CK7 +ve cell membrane.
• CD117 +ve.
• Vimentin -ve.

Molecular

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

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KIDNEY, RIGHT UPPER POLE, PARTIAL NEPHRECTOMY:
- CHROMOPHOBE RENAL CELL CARCINOMA.

COMMENT:
The sections show a mix of clear cells with wispy cytoplasm, and cells with eosinophilic
cytoplasm and perinuclear halos. There are no true papillae. 

Stains and immunostains:
Positive: CK7, CAM5.2, EMA, pankeratin, CD117, colloidal iron.
Negative: AMACR, CD10, CD68, RCC, vimentin.

Clear cell papillary renal cell carcinoma

• AKA clear cell tubulopapillary renal cell carcinoma.
• Abbreviation CCPRCC.

General

• New entity not in the WHO classification.

Microscopic

Features:

• Features of both:
  1. Clear cell RCC.
  2. Papillary RCC.
     • Often do not have true papillae.
• Apical nuclei - key feature.
  • In most glandular structures the nuclei are usu. basally located, i.e. in the cytoplasm adjacent to the basement membrane.

DDx:

• Papillary renal cell carcinoma.
• Clear cell renal cell carcinoma
• Xp11.2 translocation carcinoma.

Images

• 

  CCPRCC - high mag. (WC/Nephron)

• 

  CCPRCC - very high mag. (WC/Nephron)

www:

• Clear cell papillary RCC - several images (upmc.edu).
• CCPRCC (flickr.com).

IHC

Features:

• CK7 +ve.
  • Usually -ve in clear cell RCC.
• CD10 -ve.
  • Usually +ve in clear cell RCC.
  • Positive in Xp11.2 translocation carcinoma.
• TFE3 -ve.
  • By definition +ve in Xp11.2 translocation carcinoma.
• AMACR -ve.
  • Usu. +ve in Papillary RCC.
• Smooth muscle actin +ve (focal).

Others:

• HIF-1alpha +ve.
• GLUT-1 +ve.

How to remember: The two key stains are opposite of what the name implies.

• Clear cell RCC: CK7 negative. In this tumour it is the opposite - CK7 is positive.
• Papillary RCC: AMACR positive. In this tumour it is the opposite - AMACR is negative.

Unclassified renal cell carcinoma

• Abbreviated URCC.

General

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

Microscopic

Features:

• Malignant tumour that is one of the following:
  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).

DDx:

• Clear cell renal cell carcinoma.
• Collecting duct carcinoma.
• Undifferentiated carcinoma.
• Metastatic carcinoma.

Renal translocation carcinomas

Renal tumour with Xp11.2 translocation

General

• Defined by the presence of a fusion gene formed 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.

Microscopic

Features:

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

Notes:

• Looks clear cell RCC or papillary RCC or a hybrid between the two.
• May resemble alveolar soft part sarcoma.

DDx:

• Clear cell RCC.
• Papillary RCC.
• Epithelioid angiomyolipoma.
• Clear cell papillary renal cell carcinoma.

Images

• 

  Xp11.2 translocation RCC - intermed. mag. (WC/Nephron)

• 

  Xp11.2 translocation RCC - high mag. (WC/Nephron)

www:

• Translocation carcinoma (flickr.com).

IHC

• TFE3 +ve (nucleus) - key feature.
• CD10 +ve.
• Vimentin +ve.
• CK7 -ve.
  • Positive in ~20% of cases.

Others:

• HMB-45 & Melan A -ve.
  • Positive in epithelioid angiomyolipoma.

Molecular

• Translocation involving TFE3, e.g. t(X;1)(p11.2;q21).

Renal tumour with t(6;11) translocation

General

• Not common.
• Lymph node metastases are common.
• Essentially a pediatric tumour - case report of an adult.

Microscopic

Features:

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

Molecular

• t(6;11)(p21;q12) Alpha/TFEB.

Benign tumours

Papillary adenoma of the kidney

• AKA renal papillary adenoma.

General

• Benign.
• Considered a precursor for papillary renal cell carcinoma (PaRCC).
  • Stains like PaRCC.
  • Found with an increased frequency within the content of PaRCC.

Microscopic

Features:

1. Histomorphology of papillary renal cell carcinoma.
2. Must be <=0.5 cm.
   • Diagnostic size cutoff - larger lesions are papillary renal cell carcinoma.

DDx:

• Papillary renal cell carcinoma.
• Metanephric adenoma.

Images:

• Renal papillary adenoma (nih.gov).

IHC

• AMACR +ve.

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.

Image

• 

  Renal oncocytoma with central scar. (WP)

Microscopic

Features:

• Eosinophilic cytoplasm - slightly granular key feature.
• Cells arranged in nests.
• Nuclei uniform and round.
  • 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.
    • Oncocytoma typically has: no perinuclear clearing, no raisinoid nuclei, no binucleation.

DDx:

• Chromophobe renal cell carcinoma, eosinophilic variant.
• Clear cell renal cell carcinoma, eosinophilic variant.

Images

• 

  Oncocytoma - high mag. (WC/Nephron)

• 

  Oncocytoma - intermed. mag. (WC/Nephron)

• 

  Oncocytoma - low mag. (WC/Nephron)

Stains

• Hale's colloidal iron -ve
  • ChRCC +ve (blue granular cytoplasmic).

IHC

• CK7 -ve/+ve (cytoplasmic) .
  • Chromophobe renal cell carcinoma = cell membrane +ve.

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PORTION OF KIDNEY, RIGHT, PARTIAL NEPHRECTOMY:
- ONCOCYTOMA.

Micro

The sections show a tumour with cells arranged in nests. The tumour cells have abundant eosinophilic cytoplasm. The tumour cell nuclei are round and have round nucleoli. No perinuclear halos are apparent. Binucleation is not apparent. No zonal necrosis is identified. Focally, tumour nests are spaced reminiscent of an archipelago. Mitoses are not apparent. The tumour is moderately circumscribed.

The thin rim of renal parenchyma has no apparent pathology on the H&E stained sections.

Angiomyolipoma

• Abbreviated AML.

General

• Benign mesenchymal tumour.
• Presentations: flank pain, hematuria, incidentaloma.
  • Tumours >4 cm considered a risk for bleeding.
• AMLs occur may be elsewhere in the body, e.g. liver, 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.
• There is a suggestion that an epithelioid variant is more worisome.
  • This is not confirmed by all studies.

Microscopic

Features:

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

Epithelioid angiomyolipoma

Features:

• Carcinoma-like morphology.
• +/-Spindle cells.
• "High grade" nuclei.
  • Pleomorphic nuclei.

DDx:

• Clear cell renal cell carcinoma eosinophilic variant - esp. if epithelioid.

Images:

• Epithelioid AML (birjournals.org).
• Epithelioid AML (rsna.org).

Cytologic

Features

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

IHC

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

• Ki-67:
  • Epithelioid variant of AML +ve.
  • Conventional AML -ve.

Mimics

Xanthogranulomatous pyelonephritis

General

• May mimic RCC - espically radiologically.
• Usually lower pole.^{[citation needed]}
• Associated with:
  • Diabetes mellitus.
  • History of UTI.
  • Nephrolithiasis.
  • GU obstruction.
• Occasionally an indication of nephrectomy.
• Most common organism (in the context of nephrectomy specimens) - Proteus mirabilis.

Microscopic

• Abundant macrophages.
• +/-Giant cells.

DDx:

• Malakoplakia.
  • Basophilic inclusions -- inside or outside of macrophages - often size of RBC or larger (Michaelis-Gutmann bodies).
• RCC - especially PRCC (as this has foamy macrophages).
• Granulomatous disease.
• Chronic pyelonephritis.
• Interstitial nephritis.

Image

• 

  Xanthogranulomatous pyelonephritis - CD68 stain. (WC/Nephron)

Stains

• PAS-D -ve.
  • Done to look for malakoplakia.

IHC

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

Malakoplakia

Main article: Malakoplakia

Rare stuffs

Juxtaglomerular cell tumour

• AKA juxtaglomerular tumour, reninoma.

General

• Rare.
• Etiology: increased renin.

Clinical:

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

Microscopic

Features:

• Polygonal cells.
• Abundant granular, eosinophilic cytoplasm.
• Perinuclear halo.

DDx:

• Chromophobe renal cell carcinoma, eosinophilic variant.

Image:

• Reninoma (nature.com).

Stains

Cytoplasmic granules.

• PAS +ve.
• PASD +ve.

IHC

Features:

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

EM

Features:

• Vesicles - contain renin.

Renomedullary interstitial cell tumour

• AKA medullary fibroma.

General

• Benign.
• Common autopsy finding - one review says 26-41% of individuals at autopsy.
  • The commonality is somewhat in dispute.

Gross

• Small, white well-circumscribed nodule in medulla.
  • Typically less than 3 mm.

Image:

• Renal medullary fibroma (utah.edu).

Microscopic

Features:

• Small polygonal/stellate cells.
• Abundant loose/myxoid stroma.
• +/-Entrapped renal tubules.

Images

• 

  Renal medullary fibroma - low mag. (WC/Nephron)

• 

  Renal medullary fibroma - intermed. mag. (WC/Nephron)

• 

  Renal medullary fibroma - very high mag. (WC/Nephron)

www:

• Renomedullary interstitial cell tumour - low mag. (webpathology.com).
• Renomedullary interstitial cell tumour - high mag. (webpathology.com).

Metanephric adenoma

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

General

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

Microscopic

Features:

• 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.

Images

• 

  Metanephric adenoma (WC/Nephron)

• 

  Metanephric adenoma - cropped (WC/Nephron)

• 

  Metanephric adenoma - PaRCC-like - intermed. mag. (WC/Nephron)

• 

  Metanephric adenoma - PaRCC-like - very high mag. (WC/Nephron)

www:

• Metanephric adenoma (nature.com).

IHC

• WT-1 +ve.
• CD57 +ve.
• CK7 +ve. (???)
• PAX2 +ve.
• MUC1 +ve.
  • Marks distal renal tubule.

Renal epithelial and stromal tumour

Abbreviated REST.

The lumping term for both:

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

Mixed epithelial and stromal tumour

• Abbreviated MEST.

General

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

Note:

• Turbiner et al. 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

• 

  Cystic nephroma - low mag. (WC/Nephron)

• 

  Cystic nephroma - intermed. mag. (WC/Nephron)

IHC

Features:

• ER +ve.
• PR +ve.
• CD10 +ve.

DDx

• Tubulocystic carcinoma.

Cystic nephroma

General

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

Gross

• Bubble wrap-like appearance.

Image

• 

  Bubble wrap. (WC)

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

• 

  Cystic nephroma - low mag. (WC/Nephron)

• 

  Cystic nephroma - intermed. mag. (WC/Nephron)

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.

General

• Rare.
• Accepted by WHO in 2004 as a separate entity.
• Relatively good prognosis.

Microscopic

Features:

• Mucin - may be scant.
• Spindle cells.

DDx:

• Sarcomatoid papillary renal cell carcinoma.

Images:

• RMTSCC (ouhsc.edu).

IHC

Features:

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

Collecting duct carcinoma

• AKA Bellini duct carcinoma, AKA carcinoma of the collecting ducts of Bellini.

General

• Rare.
• Poor prognosis.
• Usu. central location.
• Typically young adults.

Microscopic

Features:

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

Notes:

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

DDx:

• Papillary renal cell carcinoma - type 2.
• Urothelial carcinoma with glandular differentiation.
• Metastatic adenocarcinoma.
• Renal medullary carcinoma - typically younger, sickle cell trait.

Images

www:

• CDC (webpathology.com).
• CDC - showing hobnail pattern (webpathology.com).
• CDC (rsna.org).

IHC

Features:

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

UCC:

• CK20 +ve

Renal medullary carcinoma

General

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

Aside:

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

Gross

Features:

• Well circumscribed.
• Renal medulla.

Microscopic

Features:

• Variable architecture:
  • Reticular - classic.
  • Adenoid cystic carcinoma-like appearance:
    • Cystic spaces.
  • Yolk sac-like.
  • Tubular.
• Desmoplastic stroma - prominent.
• Inflammation:
  • Lymphocytes.
  • Neutrophils - margination in vessels.

DDx:

• Yolk sac tumour.
• Collecting duct carcinoma.

Image:

• RMC (nature.com).

IHC

• SMARCB1 (INI1) -ve.

Acquired cystic disease-associated renal cell carcinoma

Main article: Acquired cystic disease-associated renal cell carcinoma

Pediatric

Main article: Pediatric kidney tumours

The most common is nephroblastoma (Wilms tumour).

Others include:

• Metanephric stromal tumour.
• Metanephric adenofibroma
• Metanephric adenoma.
• Clear cell sarcoma of the kidney.

See also

• Urinary bladder.
• Medical kidney.
• Malakoplakia - yellow lesion on gross; may mimic RCC.

External links

• Renal tumours with eosinophilic cytoplasm (uscap.org).