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.

Renal specimens

  • Renal biopsy - usually of medical disease (see medical kidney).
  • Partial nephrectomy.
  • Nephrectomy.
  • Nephroureterectomy (includes ureter) - done for urothelial cell carcinoma (UCC) of the renal pelvis and ureteric UCC.
  • Radical nephrectomy (includes the adrenal gland).

In excisions done for tumours, a comment should be made about kidney distant from the tumour. People with less renal mass, i.e. less kidney, are predisposed to focal segmental glomerulosclerosis (FSGS).[1]

Renal cell carcinoma

General

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

Origin

  • Proximal renal tubule.

Clinical

  • Classically described as a triad:[2]
    • Hematuria (most common symptom).
    • Abdominal mass.
    • Flank pain.
  • Frequently picked-up on imaging (incidentaloma) ~ 1/3 of cases.

Risk factors

  • Smoking.
  • Some chemicals.
  • Hemodialysis.
  • Male>female (~2:1).
  • Hereditary - familial syndromes (see Hereditary RCC).

Subtypes

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

  • Clear cell carcinoma (70-80% of RCC) -- abbrev. CCRCC,
  • Papillary renal cell carcinoma (10-15% of RCC) -- abbrev. PRCC,
  • Chromophobe renal carcinoma (5% of RCC) -- abbrev. ChRCC,
  • Collecting duct (Bellini duct) carcinoma (1% of RCC).

Notes:

  • Subtype is an independent predictor of mortality - but adds very little to multivariate models with staging information.[4]
  • CCRCC tends to be worse than ChRCC and PRCC, probably due to higher incidence of mets.[5]

IHC - is it RCC?

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

IHC - differentiation of types

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

Notes:

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

Tabular comparison

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

Clear cell RCC Papillary RCC
type 1		 Papillary RCC
type 2		 Chromophobe RCC
classic variant		 Chromophobe RCC
eosinophilic variant		 Oncocytoma
Gross Golden yellow, solid friable friable light brown light brown mahogany/brown, +/-central scar
Architecture nests, sheets papillary, simple papillary,
pseudostratified		 nests, sheets nests, sheets nests, sheets
Nuclear atypia low-high
typically medium-high		 low-medium medium-high low-high low-high low-medium, round nuclei
Cytoplasm clear eosinophilic eosinophilic cobwebs/clear eosinophilic/cobwebs eosinophilic/
granular & abundant
Other delicate vessels,
necrosis common		 histiocytes
in fibrovascular cores		 histiocytes
in fibrovascular cores		 perinuclear clearing, thick vessels perinuclear clearing, thick vessels in loose fibrous/hyaline stroma
IHC CK7-, EMA+ AMACR+, EMA+, CK7+ AMACR+, E-cadherin+, CK7- CD117+, CK7+ (membrane) CD117+, CK7+ (membrane) Vimentin-, EMA+
Main DDx chromophobe
classic variant		 PaRCC type 2, mets PaRCC type 1, mets clear cell RCC oncocytoma chromophobe
eosinophilic variant
Key features clear cells, vascular papillae, histiocytes
simple epithelium		 papillae, histiocytes,
stratified		 perinuc. clearing
wispy cytoplasm		 wispy eosinophilic
cytoplasm		 eosinophilic, granular cytoplasm

Notes:

  • Cell shape: all have epithelioid morphology.

Hereditary RCC

  1. Von Hippel-Lindau syndrome (clear cell tumours),
  2. hereditary clear cell carcinoma (VHL gene),
  3. hereditary papillary carcinoma (MET proto-oncogene mutation)

Note: all of the above are autosomal dominant[17]

Grading

Grading based on Fuhrman system which considers:[18]

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

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: 2 has granular chromatin, 2 nucleoli visible @ 5x objective.[19]
  • 2 vs. 3: 3 has nucleoli @ 10x objective.
  • 3 vs. 4: 4 has pleomorphism/hyperchromasia.

Clear cell carcinoma

Gross

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

Histo.[20]

  • Clear cells,
  • Solid or trabecular pattern,
  • Delicate branching vasculature.
  • Hyaline bodies common[21]
    • Not common in papillary RCC.

IHC

  • CK7-
  • CK20-
  • Hale's colloidal iron-
    • +ve in chromophobe

Note: Hale's colloidal iron does not stain iron... it stains hemosiderin.[22]

Clear cell vs. chromophobe

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

Clear cell vs. adrenocortical carcinoma

  • ACC: EMA- (epithelial membrane antigen), cytokeratin mostly neg., inhibin+ (neg. in RCC).[23]

Papillary RCC

General

  • Often subclassified[24] into type 1 and type 2 -- see below.
  • May be abbreviated PRCC.

Epidemiology

  • Associated with dialysis associated cystic disease.[25]

Microsopy

Histo.[26]

  • Cuboidal or low columnar cell in papillae.
  • Interstitial foam cells in vascular cores - key feature.[27]
    • Most sensitive and specific feature of PRCC.[28]
  • Highly vascular.

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

Histological subtyping:[29]

  • 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:[30]

  • AMACR +ve.[31]
  • HMWCK (34betaE12) +ve.
  • Panker (AE1/AE3) +ve.
  • CK7 +ve ~90% of type 1, 20% of type 2.

More reading:

Clear cell vs. papillary

  • Papillary: +histiocytes, +intracellular hemosiderin, CK7+.

Chromophobe RCC

General

  • Sometimes abbreviated ChRCC.

There are two subtypes:[32]

  • Classic (type I???)
  • Eosinophilic variant (type II???)

Gross

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

Microscopy

Classic Histo.[33][34], 3 P's mnemonic:

  • Pale cytoplasm, with wisps of eosinophilic material; the cells are not completely clear, they have "cobwebs".
  • Perinuclear clearing, i.e. a pale halo surrounds the nucleus - key feature.
  • Periphery of cell distinct, i.e. cell membrane is easy to discern.

Eosinophilic variant:[35]

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

Image: Oncocytic chromophobe RCC (wikimedia.org).

IHC

  • CK7+ cell membrane[36]

DDx:

  • May appear similar to oncotyoma -- particularily the eosinophilic variant.
    • IHC: CK7: chromophobe = cell membrane CK7+; oncoctyoma = patchy cytoplasmic +ve
  • Classic ChRCC may be challenging to differentiate from clear cell RCC.
    • Perinuclear clearing is not seen in clear cell RCC.
    • ChRCC has wisps in the cytoplasm

Collecting duct carcinoma

Epidemiology

  • Rare.

Microscopy

Features:[37]

  • Tubular structures with tapered ends.
  • High grade nuclear features (nuclear pleomorphism).
  • High mitotic rate.
  • Hobnail pattern - cell width smaller at basement membrane than free surface ??? [38]


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 = nephrectomy or radical nephrectomy.

Benign & mimics

Oncocytoma

General

  • Can be difficult to distinguish radiologically from RCC (chromophobe subtype).
    • ... and pathologists occasionally struggle like the radiologists.
  • Benign tumour - the reason it is excised is... one cannot be certain it isn't a RCC.

Gross

  • Brown, mahogany brown.
  • 1/3 have a characteristic central scar.[39]

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

Histology

  • Eosinophilic cytoplasm key feature.
  • Cells arranged in nests.
  • Slightly enlarged nuclei, but no significant pleomorphism (size variation).
  • Nuclei uniform and round.[40]

Notes:

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

Images:

Angiomyolipoma

General

  • Mostly benign mesenchymal tumour.
  • Presentations: flank pain, hematuria, incidentaloma.[41]
  • AMLs occur may be elsewhere in the body, e.g. liver,[42] but are most common in the kidney.

Epidemiology

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

Microscopy

  • Muscle.
  • Adipose tissue - not always present.[43]
  • Blood vessels.

Cytologic features[44]

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

IHC

  • Melanocytic markers +ve[45] (e.g. HMB-45 +ve).
  • Epithelial markers -ve.[46]
  • SMA +ve.
  • CD117 +/-.

Additional paper: [43]

Notes:

  • There is a suggestion that an epithelioid variant is more worisome,[47] but this is not the case in all studies.[48]

Ki-67 can be used to help distinguish btw 'em -- epithelioid variant Ki-67 +ve.[49]

Xanthogranulomatous pyelonephritis

General

  • May mimic RCC (esp. radiologically).
  • Usually lower pole ???
  • Associated with:
    • Diabetes mellitus,
    • History of UTI,[50]
    • Nephrolithiasis,
    • GU obstruction.[51]
  • Occasionally an indication of nephrectomy.[50][51]
  • Most common organism (in the context of nephrectomy specimens) - Proteus mirabilis.[51]

Microscopy

  • Abundant macrophages.
  • +/-Giant cells.

Image:

IHC

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

DDx:

  • Malacoplakia.
  • RCC - esp. PaRCC (as this has foamy macrophages).
  • Granulomatous disease.

Malakoplakia

Main article: Malakoplakia

Medullary fibroma

General

  • Rare.

Epidemiology

  • Benign.

Gross

  • Small, white well circumscribed nodule in medulla.

Microscopy

  • Spindle cells.

Rare stuffs

Metanephric adenoma

  • Benign.

Micro

  • Nests of cells.

Cystic nephroma

  • AKA renal epithelial stromal tumour (REST) and mixed epithelial stromal tumour (MEST).
  • Rare - approx. 1.5% of renal neoplasms.[52]
  • Benign.
  • Prevalence: males > females.

Micro

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

Image: Cystic nephroma (wikimedia.org).

IHC

Features:[52]

  • ER +ve.
  • PR +ve.
  • CD10 +ve.

DDx

  • Tubulocystic carcinoma.

Mucinous spindle cell carcinoma

Microscopy

  • Mucin - may be scant.
  • Spindle cells.

See also

References

  1. ↑ NEED REF.
  2. ↑ Schmid HP, Szabo J (May 1997). "[Renal cell carcinoma--a current review]" (in German). Praxis (Bern 1994) 86 (20): 837?3. PMID 9312811.
  3. ↑ PBoD P.1016.
  4. ↑ PMID 19076149
  5. ↑ PMID 17886093
  6. ↑ Zhou M, Roma A, Magi-Galluzzi C (June 2005). "The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms". Clin. Lab. Med. 25 (2): 247?7. doi:10.1016/j.cll.2005.01.004. PMID 15848735.
  7. ↑ 7.0 7.1 Zhou M, Roma A, Magi-Galluzzi C (June 2005). "The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms". Clin. Lab. Med. 25 (2): 247?7. doi:10.1016/j.cll.2005.01.004. PMID 15848735.
  8. ↑ 8.0 8.1 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.
  9. ↑ Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG (August 2007). "Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis". Arch. Pathol. Lab. Med. 131 (8): 1290?. PMID 17683191. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=1290.
  10. ↑ 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.
  11. ↑ 11.0 11.1 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ GUP PP.281-304.
  16. ↑ 16.0 16.1 PMID 19494850. Cite error: Invalid <ref> tag; name "pmid19494850" defined multiple times with different content
  17. ↑ PBoD P.1016.
  18. ↑ GUP P.282.
  19. ↑ AE. June 2010.
  20. ↑ PBoD P.1017-8
  21. ↑ AFIP Renal Tumours Book.
  22. ↑ Latta Jan 27, '09
  23. ↑ GUP P.285.
  24. ↑ GUP P.289.
  25. ↑ PBoD PP.1017-8
  26. ↑ PBoD P.1017-8.
  27. ↑ ALS Feb 9, 2009.
  28. ↑ 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.
  29. ↑ GUP P.289.
  30. ↑ GUP P. 289.
  31. ↑ ALS Feb 9, 2009.
  32. ↑ GUP P.293.
  33. ↑ PBoD P.1016-7
  34. ↑ GUP P.293.
  35. ↑ GUP P.293.
  36. ↑ GUP P.293.
  37. ↑ GUP P.295.
  38. ↑ PBoD P.1018.
  39. ↑ GUP P.302.
  40. ↑ GUP P.302.
  41. ↑ PMID 18805573
  42. ↑ PMID 15498214
  43. ↑ 43.0 43.1 PMID 15584043
  44. ↑ PMID 15584043
  45. ↑ GUP P.324.
  46. ↑ GUP P.324.
  47. ↑ PMID 12352384
  48. ↑ PMID 18852677
  49. ↑ PMID 18839327
  50. ↑ 50.0 50.1 Afgan F, Mumtaz S, Ather MH (2007). "Preoperative diagnosis of xanthogranulomatous pyelonephritis". Urol J 4 (3): 169–73. PMID 17987581.
  51. ↑ 51.0 51.1 51.2 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.
  52. ↑ 52.0 52.1 PMID 17454754. Cite error: Invalid <ref> tag; name "pmid17454754" defined multiple times with different content
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