Difference between revisions of "Kidney tumours"
Jump to navigation
Jump to search
m (→Stains) |
(wikify kidny) |
||
| Line 1: | Line 1: | ||
'''Kidney tumours''' - includes '''malignant kidney tumours''' and '''benign kidney tumours'''. Medical renal diseases are dealt with in the [[medical renal diseases]] article. | '''[[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. | Pediatric kidney tumours are dealt with in the ''[[pediatric kidney tumours]]'' article. | ||
Revision as of 04:55, 11 October 2011
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.[1]
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):
- Renal fascia (Gerota's fascia).
- Perinephric fat.
- Renal capsule.
- 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) |
WHO classification
- Based on 2004 iteration - as per WMSP, slightly modified.[5]
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
Nephroblastic tumours
- Nephrogenic rests.
- Nephroblastoma.
Mesenchymal tumours
Childhood:
Adults:
- Leiomyosarcoma.
- Angiosarcoma.
- Pleomorphic undifferentiated sarcoma.
- Solitary fibrous tumour.
- Others - see: soft tissue lesions.
Mixed mesenchymal and epithelial tumours
Others
- Neuroendocrine tumours.
- Hematologic tumours.
- Germ cell tumours.
- Metastases.
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
- Smoking - most important.[7]
- Chemical exposures (arsenic, asbestos, cadmium, organic solvents, pesticides, fungal toxins).[7]
- Chronic renal failure.
- Male>female (~2:1).
- Hereditary - familial syndromes (see Hereditary RCC).
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]
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:
- 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
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.
Hereditary renal cell carcinoma
The classics - which are all autosomal dominant:[9]
- Von Hippel-Lindau syndrome.
- VHL gene mutation.
- Clear cell RCC.
- Hereditary clear cell carcinoma.
- VHL gene mutation.
- Hereditary papillary carcinoma
- MET proto-oncogene mutation.
- PaRCC type 1.[24]
- Hereditary leiomyomatosis and renal cell cancer:[24]
- FH (fumarate hydratase) gene mutation.[25]
- PaRCC type 2.
- Benign leiomyomas skin/uterus.
- Uterine leiomyosarcoma.
- Birt–Hogg–Dubé syndrome:[24]
- FLCN (folliculin) gene mutation.[26]
- 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).[27]
Notes:
- A total of ten hereditary renal cancer syndromes have been described. In eight of the ten the gene is known.[28]
Grading RCC
General
Some subtypes are graded based on the Fuhrman system which considers:[29]
- 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.[30]
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.[31]
- 2 vs. 3: grade 3 has nucleoli @ 10x objective.
- 3 vs. 4: grade 4 has pleomorphism/hyperchromasia.
Clear cell renal cell carcinoma
- Often abbreviated CRCC.
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:[32]
- Solid or trabecular pattern.
- Polygonal cells.
- Clear cytoplasm.
- Central nucleus.
- Delicate branching vasculature.
- Often called "chicken wire-like" vasculature.
Notes:
- Cytoplasm may be eosinophilic.[33]
- This change is typically focal - other areas have a classic appearance.
- Chicken wire-like vasculature present - helps distinguish from other tumours.
- Hyaline bodies common.[34]
- Not common in papillary RCC.
Clear cell vs. adrenocortical carcinoma:
- ACC: EMA- (epithelial membrane antigen), cytokeratin mostly neg., inhibin+ (neg. in RCC).[35]
Images:
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.[36] Clear cell vs. chromophobe:
- Chromophobe: "translucent" (NOT quite clear), reticulated, Hale's colloidal iron stain+, CK7+ (cell membrane).
Multilocular cystic renal cell carcinoma
General
- No recurrences or metastasis in the literature.[37]
- This makes one wonder... is it really cancer.
- Case report rare.[38]
Gross
Features:[37]
- Cystic with thin septa.
- Well circumscribed.
Note:
- This tumour, radiologically, can often be separated from other cystic tumours.[39]
Microscopic
Features:[37]
- 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[40] into type 1 and type 2 -- see below.
- May be abbreviated PRCC.
Epidemiology
- Associated with acquired renal cystic disease.[41]
- May be familial.
Microsopic
Features:[32]
- Cuboidal or low columnar cell in papillae.
- Interstitial foam cells in vascular cores - key feature.[42]
- Most sensitive and specific feature of PRCC.[43]
- Highly vascular.
Size criterion:
- Papillary lesions must be >0.5 cm to be called carcinoma; smaller lesions (<=0.5 cm) are called papillary adenomas.[44]
Mnemonic HIP: highly vascular, interstitial foam cells, papillae.
DDx:
- Clear cell RCC.
- Papillary: +histiocytes, +intracellular hemosiderin, CK7+.
- Metanephric adenoma - esp. solid PRCC type 1.
Histological subtyping
Subtypes:[40]
- 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:[40]
- AMACR +ve.[45]
- HMWCK (34betaE12) +ve.
- Panker (AE1/AE3) +ve.
- CK7 +ve ~90% of type 1, 20% of type 2.
More reading:
Molecular
Features:[9]
- Sporadic: trisomies 7, 16, 17.
- Familial: trisomy 7.
- Chromosome 7 = location of MET gene.
Note:
- Not used for diagnosis.[46]
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.[30]
There are two subtypes:[47]
- Classic.
- Eosinophilic variant.
Gross
- Tan, light-brown.
- Solitary.
- Well-circumscribed.
Microscopic
Classic
Features - classic type (3 P's mnemonic):[48][47]
- 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.
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:[47]
- Eosinophilic (finely granular) cytoplasm.
- Perinuclear clearing - key feature.
- Periphery of cell distinct.
- Smaller cells than classic subtype.
Notes:
- May have psammoma bodies.
DDx:
- 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.
- Clear cell RCC, eosinophilic variant.
- Perinuclear clearing is not seen in clear cell RCC.
- ChRCC has wisps in the cytoplasm.
Image:
Stains
- Hale's colloidal iron +ve (blue granular cytoplasmic).
Images:
- ChRCC Hale's colloidal iron (ultrapath.org).[49]
- ChRCC Hale's colloidal iron (diagnosticpathology.org).
IHC
- CK7 +ve cell membrane.[47]
- CD117 +ve.
- Vimentin -ve.
Molecular
- Extensive aneusomy (monosomy?):[37]
- Loss of chromosomes: 1, 2, 6, 10, 13, 17, 21.
Clear cell papillary renal cell carcinoma
General
- New entity not in the WHO classification.
Microscopic
Features:[50]
- Features of both:
- Clear cell RCC.
- Papillary RCC.
- Often do not have true papillae.
DDx:
IHC
Features:[50]
- CK7 +ve.
- Usu. -ve in CRCC.
- CD10 -ve.
- Usu. +ve in RCC.
- TFE3 -ve.
- By definition +ve in Xp11.2 translocation carcinoma.
- AMACR -ve.
- Usu. +ve in PaRCC.
Others:[50]
- HIF-1alpha +ve.
- GLUT-1 +ve.
Renal translocation carcinomas
Renal tumour with Xp11.2 translocation
General
- Defined by the presence of a fusion gene form 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.[51]
Microscopic
Features:[52]
- Large cells.
- Clear or eosinophilic cytoplasm.
- Papillae or nests.
- Psammoma bodies - common.[53]
- 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.
IHC
- TFE3 +ve (nucleus) - key feature.[52]
- CD10 +ve.
- Vimentin +ve.
Others:
- HMB-45 & Melan A -ve.
- Positive in epithelioid angiomyolipoma.
Molecular
- Translocation involving TFE3, e.g. t(X;1)(p11.2;q21).[52]
Renal tumour with t(6;11) translocation
General
- Not common.
- Lymph node metastases are common.
- Essentially a pediatric tumour - case report of an adult.[54]
Microscopic
Features:
- Hyaline material between nests.
- Large cells with clear to eosinophilic cytoplasm.
Molecular
- t(6;11)(p21;q12) Alpha/TFEB.[55]
Benign tumours
Papillary adenoma
General
- Benign.
Microscopic
Features:
- Histomorphology of papillary renal cell carcinoma.
- Must be <=0.5 cm.[44]
- Larger lesions are papillary renal cell carcinoma.
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.[56]
Image:
Microscopic
Features:
- Eosinophilic cytoplasm - slightly granular key feature.
- Cells arranged in nests.
- Nuclei uniform and round.[56]
- 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.
- A comparison based on histomorphology: Tabular comparison between ChRCC & oncocytoma.
Images:
IHC
- CK7 +ve (cytoplasm).
- Chromophobe renal cell carcinoma = cell membrane +ve.
- CD117 -ve. (???)
Angiomyolipoma
- Abbreviated AML.
General
- Benign mesenchymal tumour.
- Presentations: flank pain, hematuria, incidentaloma.[57]
- Tumours >4 cm considered a risk for bleeding.[58]
- AMLs occur may be elsewhere in the body, e.g. liver,[59] 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.
- When compared to sporadic cases:
Microscopic
Features:
- Smooth muscle.
- Adipose tissue - not always present[60] - key feature.
- Abundant blood vessels.
Notes:
- There is a suggestion that an epithelioid variant is more worisome.[61]
- This is not confirmed by all studies.[62]
DDx:
- Clear cell renal cell carcinoma eosinophilic variant - esp. if epithelioid.
Cytologic
Features[60]
- Nuclei - round/ovoid.
- Chromatin - bland.
IHC
- Ki-67:[64]
- Epithelioid variant of AML +ve.
- Conventional AML -ve.
Mimics
Xanthogranulomatous pyelonephritis
General
- May mimic RCC (esp. radiologically).
- Usually lower pole ???
- Associated with:
- Occasionally an indication of nephrectomy.[65][66]
- Most common organism (in the context of nephrectomy specimens) - Proteus mirabilis.[66]
Microscopic
- Abundant macrophages.
- +/-Giant cells.
Image:
IHC
- CD68 +ve.
- RCC markers (CD10, RCC) all negative.
DDx:
- Malakoplakia.
- Basophilic inclusions -- inside or outside of macrophages - often size of RBC or larger (Michaelis-Gutmann bodies).
- RCC - esp. PaRCC (as this has foamy macrophages).
- Granulomatous disease.
Malakoplakia
Main article: Malakoplakia
Rare stuffs
Medullary fibroma
General
- Rare.
Epidemiology
- Benign.
Gross
- Small, white well circumscribed nodule in medulla.
Microscopic
- Spindle cells.
Metanephric adenoma
General
- Benign.
- Afflicts adults and occasionally children.
- May be associated with polycythemia.[67]
Microscopic
Features:[68]
- 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.[68]
Images:
IHC
- WT-1 +ve.
- CD57 +ve.
- CK7 -ve.
Renal epithelial and stromal tumour
The lumping term for both:[69]
Mixed epithelial and stromal tumour
- Abbreviated MEST.
General
- Rare - approx. 1.5% of renal neoplasms.[70]
- Benign.
- Prevalence: males > females.
Note:
- Turbiner et al.[69] 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:[70]
- ER +ve.
- PR +ve.
- CD10 +ve.
DDx
- Tubulocystic carcinoma.
Cystic nephroma
General
- Turbiner et al.[69] 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:
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.
General
Microscopic
Features:[72]
- Mucin - may be scant.
- Spindle cells.
DDx:
- Sarcomatoid papillary RCC. (???) [73]
IHC
Features:[74]
- CD10 -ve.
- AE1/AE3 +ve.
- AMACR +ve.
- CK7 +ve.
Collecting duct carcinoma
General
- Rare.
- Poor prognosis.
- Usu. central location.
Microscopic
Features:[75]
- Tubular structures with tapered ends.
- May be described as tubulopapillary.
- Hobnail pattern - cell width smaller at basement membrane than free surface.[76]
- High grade nuclear features (nuclear pleomorphism).
- High mitotic rate.
Notes:
- Benign urothelium must present to excluded urothelial carcinoma.
- Desmoplastic stroma may be prominent.
DDx:
IHC
Features:[3]
- CD117 +ve.
- E-cadherin +ve.
- CD10 -ve.
- AMACR -ve.
Renal medullary carcinoma
General
- Rare.
- Usually young adults.
- Associated with sickle cell trait (heterozygotes for the sickle cell allele).[77]
- Aggressive/poor prognosis.[78]
Aside:
- Kidney disease assoc. with sickle cell disorders:[77]
- Papillary necrosis.
- Nephrotic syndrome.
- Renal infarction.
- Pyelonephritis.
Gross
Features:[78]
- Well circumscribed.
- Renal medulla.
Microscopic
- 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:
Image:
IHC
- SMARCB1 (INI1) -ve.[79]
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.
References
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 288. ISBN 978-0781765275.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 281-304. ISBN 978-0443066771.
- ↑ 3.0 3.1 3.2 Srigley, JR.; Delahunt, B. (Jun 2009). "Uncommon and recently described renal carcinomas.". Mod Pathol 22 Suppl 2: S2-S23. doi:10.1038/modpathol.2009.70. PMID 19494850. Cite error: Invalid
<ref>tag; name "pmid19494850" defined multiple times with different content - ↑ Tickoo, SK.; Amin, MB. (Dec 1998). "Discriminant nuclear features of renal oncocytoma and chromophobe renal cell carcinoma. Analysis of their potential utility in the differential diagnosis.". Am J Clin Pathol 110 (6): 782-7. PMID 9844591.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 291. ISBN 978-0781765275.
- ↑ URL:http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001544/. Accessed on: 14 July 2011.
- ↑ 7.0 7.1 7.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 289. ISBN 978-0781765275.
- ↑ Schmid HP, Szabo J (May 1997). "[Renal cell carcinoma--a current review]" (in German). Praxis (Bern 1994) 86 (20): 837?3. PMID 9312811.
- ↑ 9.0 9.1 9.2 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1016. ISBN 0-7216-0187-1.
- ↑ 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.
- ↑ Delahunt, B.; Bethwaite, PB.; Nacey, JN. (Oct 2007). "Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype.". Pathology 39 (5): 459-65. doi:10.1080/00313020701570061. PMID 17886093.
- ↑ 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.
- ↑ 13.0 13.1 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.
- ↑ 14.0 14.1 Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R (February 2004). "Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases". Mod. Pathol. 17 (2): 180?. doi:10.1038/modpathol.3800032. PMID 14657952.
- ↑ 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.
- ↑ Pan CC, Chen PC, Ho DM (November 2004). "The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases". Histopathology 45 (5): 452?. doi:10.1111/j.1365-2559.2004.01962.x. PMID 15500648.
- ↑ 17.0 17.1 Geramizadeh B, Ravanshad M, Rahsaz M (2008). "Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma". Indian J Pathol Microbiol 51 (2): 167?1. PMID 18603673. http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2008;volume=51;issue=2;spage=167;epage=171;aulast=Geramizadeh.
- ↑ 18.0 18.1 Memeo L, Jhang J, Assaad AM, et al. (February 2007). "Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma". Am. J. Clin. Pathol. 127 (2): 225–9. doi:10.1309/9KWEA4W9Y94D1AEE. PMID 17210525. http://ajcp.ascpjournals.org/cgi/pmidlookup?view=long&pmid=17210525.
- ↑ Mazal PR, Exner M, Haitel A, et al. (January 2005). "Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma". Hum. Pathol. 36 (1): 22–8. doi:10.1016/j.humpath.2004.09.011. PMID 15712178.
- ↑ Krueger S, Sotlar K, Kausch I, Horny HP (2005). "Expression of KIT (CD117) in renal cell carcinoma and renal oncocytoma". Oncology 68 (2-3): 269-75. doi:10.1159/000086783. PMID 16015044.
- ↑ Martignoni G, Brunelli M, Gobbo S, et al (February 2007). "Role of molecular markers in diagnosis and prognosis of renal cell carcinoma". Anal. Quant. Cytol. Histol. 29 (1): 41?. PMID 17375873.
- ↑ Avery AK, Beckstead J, Renshaw AA, Corless CL (February 2000). "Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms". Am. J. Surg. Pathol. 24 (2): 203?0. PMID 10680888. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=24&issue=2&spage=203.
- ↑ Kim MK, Kim S (December 2002). "Immunohistochemical profile of common epithelial neoplasms arising in the kidney". Appl. Immunohistochem. Mol. Morphol. 10 (4): 332–8. PMID 12613443.
- ↑ 24.0 24.1 24.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 290. ISBN 978-0781765275.
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 136850
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 135150
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 314310
- ↑ 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.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 282. ISBN 978-0443066771.
- ↑ 30.0 30.1 Delahunt, B.; Sika-Paotonu, D.; Bethwaite, PB.; McCredie, MR.; Martignoni, G.; Eble, JN.; Jordan, TW. (Jun 2007). "Fuhrman grading is not appropriate for chromophobe renal cell carcinoma.". Am J Surg Pathol 31 (6): 957-60. doi:10.1097/01.pas.0000249446.28713.53. PMID 17527087.
- ↑ AE. June 2010.
- ↑ 32.0 32.1 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1017-8. ISBN 0-7216-0187-1.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 291. ISBN 978-0781765275.
- ↑ AFIP Renal Tumours Book.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 285. ISBN 978-0443066771.
- ↑ Latta. 27 January 2009.
- ↑ 37.0 37.1 37.2 37.3 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 292. ISBN 978-0781765275.
- ↑ Agarwal, S.; Agrawal, U.; Mohanty, NK.; Saxena, S. (Mar 2011). "Multilocular cystic renal cell carcinoma: a case report of a rare entity.". Arch Pathol Lab Med 135 (3): 290-2. doi:10.1043/2010-0243-LE.1. PMID 21366448.
- ↑ You, D.; Shim, M.; Jeong, IG.; Song, C.; Kim, JK.; Ro, JY.; Hong, JH.; Ahn, H. et al. (Jul 2011). "Multilocular cystic renal cell carcinoma: clinicopathological features and preoperative prediction using multiphase computed tomography.". BJU Int. doi:10.1111/j.1464-410X.2011.10247.x. PMID 21722289.
- ↑ 40.0 40.1 40.2 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 289. ISBN 978-0443066771.
- ↑ Fogo, Agnes B.; Kashgarian, Michael (2005). Diagnostic Atlas of Renal Pathology: A Companion to Brenner and Rector's The Kidney 7E (1st ed.). Saunders. pp. 438. ISBN 978-1416028710.
- ↑ ALS Feb 9, 2009.
- ↑ Granter SR, Perez-Atayde AR, Renshaw AA (October 1998). <303::AID-CNCR6>3.0.CO;2-7 "Cytologic analysis of papillary renal cell carcinoma". Cancer 84 (5): 303?8. PMID 9801205. http://dx.doi.org/10.1002/(SICI)1097-0142(19981025)84:5<303::AID-CNCR6>3.0.CO;2-7.
- ↑ 44.0 44.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 288. ISBN 978-0443066771.
- ↑ ALS Feb 9, 2009.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 292. ISBN 978-0781765275.
- ↑ 47.0 47.1 47.2 47.3 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 293. ISBN 978-0443066771.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1016-7. ISBN 0-7216-0187-1.
- ↑ URL: http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html. Accessed on: 9 October 2011.
- ↑ 50.0 50.1 50.2 50.3 Rohan, SM.; Xiao, Y.; Liang, Y.; Dudas, ME.; Al-Ahmadie, HA.; Fine, SW.; Gopalan, A.; Reuter, VE. et al. (Sep 2011). "Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway-related proteins.". Mod Pathol 24 (9): 1207-20. doi:10.1038/modpathol.2011.80. PMID 21602815.
- ↑ Argani, P.; Olgac, S.; Tickoo, SK.; Goldfischer, M.; Moch, H.; Chan, DY.; Eble, JN.; Bonsib, SM. et al. (Aug 2007). "Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum.". Am J Surg Pathol 31 (8): 1149-60. doi:10.1097/PAS.0b013e318031ffff. PMID 17667536.
- ↑ 52.0 52.1 52.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 285. ISBN 978-0781765275.
- ↑ Prasad, SR.; Humphrey, PA.; Catena, JR.; Narra, VR.; Srigley, JR.; Cortez, AD.; Dalrymple, NC.; Chintapalli, KN.. "Common and uncommon histologic subtypes of renal cell carcinoma: imaging spectrum with pathologic correlation.". Radiographics 26 (6): 1795-806; discussion 1806-10. doi:10.1148/rg.266065010. PMID 17102051.
- ↑ Ishihara, A.; Yamashita, Y.; Takamori, H.; Kuroda, N. (Sep 2011). "Renal carcinoma with (6;11)(p21;q12) translocation: Report of an adult case.". Pathol Int 61 (9): 539-45. doi:10.1111/j.1440-1827.2011.02711.x. PMID 21884304.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 281. ISBN 978-0781765275.
- ↑ 56.0 56.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 302. ISBN 978-0443066771.
- ↑ Seyam, RM.; Bissada, NK.; Kattan, SA.; Mokhtar, AA.; Aslam, M.; Fahmy, WE.; Mourad, WA.; Binmahfouz, AA. et al. (Nov 2008). "Changing trends in presentation, diagnosis and management of renal angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated forms.". Urology 72 (5): 1077-82. doi:10.1016/j.urology.2008.07.049. PMID 18805573.
- ↑ Abrams, J.; Yee, DC.; Clark, TW. (Jul 2011). "Transradial embolization of a bleeding renal angiomyolipoma.". Vasc Endovascular Surg 45 (5): 470-3. doi:10.1177/1538574411408352. PMID 21571778.
- ↑ Zhang, SH.; Cong, WM.; Xian, ZH.; Wu, WQ.; Dong, H.; Wu, MC. (Oct 2004). "[Morphologic variants and immunohistochemical features of hepatic angiomyolipoma.]". Zhonghua Bing Li Xue Za Zhi 33 (5): 437-40. PMID 15498214.
- ↑ 60.0 60.1 Crapanzano, JP. (Jan 2005). "Fine-needle aspiration of renal angiomyolipoma: cytological findings and diagnostic pitfalls in a series of five cases.". Diagn Cytopathol 32 (1): 53-7. doi:10.1002/dc.20179. PMID 15584043.
- ↑ Nelson, CP.; Sanda, MG. (Oct 2002). "Contemporary diagnosis and management of renal angiomyolipoma.". J Urol 168 (4 Pt 1): 1315-25. doi:10.1097/01.ju.0000028200.86216.b2. PMID 12352384.
- ↑ Aydin, H.; Magi-Galluzzi, C.; Lane, BR.; Sercia, L.; Lopez, JI.; Rini, BI.; Zhou, M. (Feb 2009). "Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association.". Am J Surg Pathol 33 (2): 289-97. doi:10.1097/PAS.0b013e31817ed7a6. PMID 18852677.
- ↑ 63.0 63.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 324. ISBN 978-0443066771.
- ↑ Ooi, SM.; Vivian, JB.; Cohen, RJ. (2009). "The use of the Ki-67 marker in the pathological diagnosis of the epithelioid variant of renal angiomyolipoma.". Int Urol Nephrol 41 (3): 559-65. doi:10.1007/s11255-008-9473-1. PMID 18839327.
- ↑ 65.0 65.1 Afgan F, Mumtaz S, Ather MH (2007). "Preoperative diagnosis of xanthogranulomatous pyelonephritis". Urol J 4 (3): 169–73. PMID 17987581.
- ↑ 66.0 66.1 66.2 Al-Ghazo MA, Ghalayini IF, Matalka II, Al-Kaisi NS, Khader YS (October 2006). "Xanthogranulomatous pyelonephritis: Analysis of 18 cases". Asian J Surg 29 (4): 257–61. PMID 17098659.
- ↑ Le Nué, R.; Marcellin, L.; Ripepi, M.; Henry, C.; Kretz, JM.; Geiss, S. (Aug 2011). "Conservative treatment of metanephric adenoma. A case report and review of the literature.". J Pediatr Urol 7 (4): 399-403. doi:10.1016/j.jpurol.2010.09.010. PMID 21220212.
- ↑ 68.0 68.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 284. ISBN 978-0781765275.
- ↑ 69.0 69.1 69.2 Turbiner, J.; Amin, MB.; Humphrey, PA.; Srigley, JR.; De Leval, L.; Radhakrishnan, A.; Oliva, E. (Apr 2007). "Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term.". Am J Surg Pathol 31 (4): 489-500. doi:10.1097/PAS.0b013e31802bdd56. PMID 17414095.
- ↑ 70.0 70.1 Mai, KT.; Elkeilani, A.; Veinot, JP. (Apr 2007). "Mixed epithelial and stromal tumour (MEST) of the kidney: report of 14 cases with male and PEComatous variants and proposed histopathogenesis.". Pathology 39 (2): 235-40. doi:10.1080/00313020701230799. PMID 17454754. Cite error: Invalid
<ref>tag; name "pmid17454754" defined multiple times with different content - ↑ Geramizadeh B, Salehipour M, Moradi A (2009). "Mucinous tubular and spindle cell carcinoma of kidney: a rare case report and review of the literature". Indian J Pathol Microbiol 52 (4): 514–6. doi:10.4103/0377-4929.56144. PMID 19805959.
- ↑ Trabelsi A, Stita W, Yacoubi MT, Rammeh S, Hmissa S, Korbi S (December 2008). "Renal mucinous tubular and spindle cell carcinoma". Can Urol Assoc J 2 (6): 635–6. PMC 2593603. PMID 19066686. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593603/.
- ↑ Dhillon J, Amin MB, Selbs E, Turi GK, Paner GP, Reuter VE (January 2009). "Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid change". Am. J. Surg. Pathol. 33 (1): 44–9. doi:10.1097/PAS.0b013e3181829ed5. PMID 18941398.
- ↑ Ferlicot S, Allory Y, Compérat E, et al. (December 2005). "Mucinous tubular and spindle cell carcinoma: a report of 15 cases and a review of the literature". Virchows Arch. 447 (6): 978–83. doi:10.1007/s00428-005-0036-x. PMID 16231179.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 295. ISBN 978-0443066771.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1018. ISBN 0-7216-0187-1.
- ↑ 77.0 77.1 77.2 Davis CJ, Mostofi FK, Sesterhenn IA (January 1995). "Renal medullary carcinoma. The seventh sickle cell nephropathy". Am. J. Surg. Pathol. 19 (1): 1–11. PMID 7528470.
- ↑ 78.0 78.1 78.2 Watanabe, IC.; Billis, A.; Guimarães, MS.; Alvarenga, M.; de Matos, AC.; Cardinalli, IA.; Filippi, RZ.; de Castro, MG. et al. (Sep 2007). "Renal medullary carcinoma: report of seven cases from Brazil.". Mod Pathol 20 (9): 914-20. doi:10.1038/modpathol.3800934. PMID 17643096. http://www.nature.com/modpathol/journal/v20/n9/full/3800934a.html. Cite error: Invalid
<ref>tag; name "pmid17643096" defined multiple times with different content Cite error: Invalid<ref>tag; name "pmid17643096" defined multiple times with different content - ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 286. ISBN 978-0781765275.