Clear cell renal cell carcinoma

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Clear cell renal cell carcinoma
Diagnosis in short

Clear cell renal cell carcinoma. H&E stain.

Synonyms conventional renal cell carcinoma

LM solid or trabecular pattern, polygonal cells usually with clear cytoplasm (may be eosinophilic - esp. in high grade tumours), central nucleus, delicate branching vasculature (chicken wire-like), +/-hyaline bodies
LM DDx chromophobe renal cell carcinoma, clear cell papillary renal cell carcinoma, Xp11.2 translocation carcinoma, adrenocortical carcinoma, alveolar soft part sarcoma
Stains Hale's colloidal iron stain -ve
IHC CA9 +ve, CK7 -ve, CK20 -ve, TFE3 -ve, PAX8 +ve, vimentin +ve
Gross golden/yellow colour, +/-hemorrhagic, +/-cystic, +/-necrosis
Grossing notes total nephrectomy for tumour grossing, partial nephrectomy grossing
Staging kidney cancer staging
Site kidney - see kidney tumours

Syndromes von Hippel-Lindau syndrome, familial clear cell renal cell carcinoma

Signs +/-hematuria, +/-abdominal mass
Prevalence common
Radiology renal mass
Prognosis good-to-poor - dependent on stage and grade
Clin. DDx other renal tumours
Treatment surgery, targeted therapies, other drugs

Clear cell renal cell carcinoma, abbreviated CCRCC, is the most common type of renal cell carcinoma.

It is also known as conventional renal cell carcinoma (abbreviated CRCC).

General

  • Most common subtype of RCC.
  • May be associated with Von Hippel-Lindau syndrome.
  • Familial clear cell renal cell carcinoma[1] - usually VHL gene mutation.[2]
    • VHL gene not mutated in all cases.[3]

Treatment:

Gross

Features:

  • Golden/yellow colour.
  • +/-Haemorrhage (common).
  • +/-Necrosis (common in large tumours).
  • +/-Calcification.
  • +/-Cysts.
  • Usually unifocal. ‡

Note:

  • ‡ Approximately 4% of CCRCCs are multifocal (based on a set of 5378 patients).[7]

Image

Microscopic

Features:[8]

  • Clear cytoplasm.
    • May have eosinophilic cytoplasm (in high-grade tumours) - usually focal.
  • Delicate branching vasculature - key feature.
    • Often called "chicken wire-like" vasculature.
  • Solid or trabecular pattern.
  • Polygonal cells.
  • Central nucleus.
  • +/-Rhabdoid cells:
    • Eccentric nucleus.
    • Abundant eosinophilic cytoplasm.

Notes:

  • Cytoplasm may be eosinophilic.[9]
    • This change is typically focal - other areas have a classic appearance.
    • Chicken wire-like vasculature present - helps distinguish from other tumours.
  • Hyaline bodies common.[10]
    • Not common in papillary RCC.
  • Clear cytoplasm - due to lipid content.
  • Necrosis is independent predictor of outcome - if present in a significant quantity:[11]
    • >30% is significant for pT3a tumours.
    • >20% is significant for pT1-2 pN0 tumours.

DDx:

Images

Case 1

Case 2

Case 3

Stains

Note: Hale's colloidal iron does not stain iron... it stains hemosiderin.[13]

Clear cell vs. chromophobe:

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

IHC

A panel to confirm the diagnosis:

  • CK7 (-ve), CD10 (+ve), PAX8 (+ve), vimentin (+ve).

CCRCC versus chromophobe RCC

ISUP recommends:[17]

  • CD117 -ve (+ve in ChRCC).
    • Aguilar-León et al. found ~8% of CCRCC are CD117 +ve.[18]
    • Liu et al. found ~80% of ChRCC are CD117 +ve.[19]
  • CA9 (carbonic anhydrase 9) +ve (membranous).[20]
  • CK7 -ve (+ve in ChRCC).

May also be useful:

  • Vimentin +ve.

CCRCC versus CCPRCC

ISUP recommends:[17]

Others:

CCRCC versus Xp11.2 translocation carcinomas

ISUP recommends:[17]

  • Cathepsin K -ve.[21]
  • TFE3 -ve.
  • TFEB -ve.

Sign out

Biopsy

Kidney Mass, Left, Core Biopsy:
- Clear cell renal cell carcinoma
- ISUP nucleolar grade 2 (based on biopsy)
- No renal parenchyma identified

Comment:
The quantity of tissue available at microscopy is very limited.
Immunostains confirm the morphologic impression (see microscopic).

MDA form

Kidney Mass, Left, Core Biopsy:
- CLEAR CELL RENAL CELL CARCINOMA, preliminary ISUP nucleolar grade 2 (see comment).
- No renal parenchyma identified.

Comment:
The quantity of tissue at microscopy is limited, and may not be representative 
of the lesion identified radiologically.

Resection

Note:

  • The surgeon wants the diagnosis and margin status; thus, these are included in the diagnosis line with the tumour stage.
Left Kidney, Radical Nephrectomy:
     - CLEAR CELL RENAL CELL CARCINOMA.
     -- Margins clear.
     -- Please see synoptic report.

Block letters

KIDNEY, LEFT, NEPHRECTOMY:
- CLEAR CELL RENAL CELL CARCINOMA, FUHRMAN GRADE 2, pT1a, pNx.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.

Adrenal gland present

KIDNEY, RIGHT, RADICAL NEPHRECTOMY:
- CLEAR CELL RENAL CELL CARCINOMA, FUHRMAN GRADE 2, pT1a, pNx.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.
- ADRENAL GLAND WITHIN NORMAL LIMITS.
KIDNEY, RIGHT, RADICAL NEPHRECTOMY:
- CLEAR CELL RENAL CELL CARCINOMA, FUHRMAN GRADE 3, pT1b, pNx.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.
- ADRENAL GLAND WITHIN NORMAL LIMITS.

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 wispy. Papillae are not evident.

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

Alternate

The sections show cohesive mildly atypical clear cells with a columnar morphology. Small cystic spaces are present. The nuclei are basal stratified. Nucleoli are not prominent. Siderophages are present. Blood is present.

No perinuclear halos are apparent. No papillary structures are identified. No definite renal parenchyma is seen.

See also

References

  1. Keefe, SM.; Nathanson, KL.; Rathmell, WK. (Aug 2013). "The molecular biology of renal cell carcinoma.". Semin Oncol 40 (4): 421-8. doi:10.1053/j.seminoncol.2013.05.006. PMID 23972705.
  2. Foster, RE.; Abdulrahman, M.; Morris, MR.; Prigmore, E.; Gribble, S.; Ng, B.; Gentle, D.; Ready, S. et al. (Apr 2007). "Characterization of a 3;6 translocation associated with renal cell carcinoma.". Genes Chromosomes Cancer 46 (4): 311-7. doi:10.1002/gcc.20403. PMID 17205537.
  3. Woodward, ER.; Clifford, SC.; Astuti, D.; Affara, NA.; Maher, ER. (May 2000). "Familial clear cell renal cell carcinoma (FCRC): clinical features and mutation analysis of the VHL, MET, and CUL2 candidate genes.". J Med Genet 37 (5): 348-53. PMID 10807693.
  4. Elaidi, R.; Harbaoui, A.; Beuselinck, B.; Eymard, JC.; Bamias, A.; De Guillebon, E.; Porta, C.; Vano, Y. et al. (Feb 2015). "Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma.". Ann Oncol 26 (2): 378-85. doi:10.1093/annonc/mdu552. PMID 25467013.
  5. Verma, J.; Jonasch, E.; Allen, P.; Tannir, N.; Mahajan, A. (Nov 2011). "Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma.". Cancer 117 (21): 4958-65. doi:10.1002/cncr.26138. PMID 21484781.
  6. Singer, EA.; Gupta, GN.; Srinivasan, R. (May 2011). "Update on targeted therapies for clear cell renal cell carcinoma.". Curr Opin Oncol 23 (3): 283-9. doi:10.1097/CCO.0b013e32834479c0. PMID 21330923.
  7. Siracusano, S.; Novara, G.; Antonelli, A.; Artibani, W.; Bertini, R.; Carini, M.; Carmignani, G.; Ciciliato, S. et al. (Dec 2012). "Prognostic role of tumour multifocality in renal cell carcinoma.". BJU Int 110 (11 Pt B): E443-8. doi:10.1111/j.1464-410X.2012.11121.x. PMID 22502873.
  8. 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.
  9. 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.
  10. AFIP Renal Tumours Book.
  11. Renshaw, AA.; Cheville, JC. (Jan 2015). "Quantitative tumour necrosis is an independent predictor of overall survival in clear cell renal cell carcinoma.". Pathology 47 (1): 34-7. doi:10.1097/PAT.0000000000000193. PMID 25474516.
  12. 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.
  13. Latta. 27 January 2009.
  14. Williamson, SR.; Gupta, NS.; Eble, JN.; Rogers, CG.; Michalowski, S.; Zhang, S.; Wang, M.; Grignon, DJ. et al. (Nov 2015). "Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis.". Am J Surg Pathol 39 (11): 1502-10. doi:10.1097/PAS.0000000000000514. PMID 26457355.
  15. Ozcan, A.; Shen, SS.; Zhai, QJ.; Truong, LD. (Aug 2007). "Expression of GLUT1 in primary renal tumors: morphologic and biologic implications.". Am J Clin Pathol 128 (2): 245-54. doi:10.1309/HV6NJVRQKK4QHM9F. PMID 17638658.
  16. Hu, H.; Chen, JW.; Xu, KX.; Wang, D.; Wang, Y.; Wang, GW.; Zhang, SY.; Wang, XF. (Aug 2013). "[Expressions of CMTM8 and E-cadherin in primary and metastatic clear cell renal cell carcinoma].". Beijing Da Xue Xue Bao 45 (4): 537-41. PMID 23939157.
  17. 17.0 17.1 17.2 Amin MB, Epstein JI, Ulbright TM, et al. (August 2014). "Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): 1017–22. doi:10.1097/PAS.0000000000000254. PMID 25025364.
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  19. 19.0 19.1 Liu, L.; Qian, J.; Singh, H.; Meiers, I.; Zhou, X.; Bostwick, DG. (Aug 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): 1290-7. doi:10.1043/1543-2165(2007)131[1290:IAOCRC]2.0.CO;2. PMID 17683191.
  20. Al-Ahmadie HA, Alden D, Fine SW, et al. (July 2011). "Role of immunohistochemistry in the evaluation of needle core biopsies in adult renal cortical tumors: an ex vivo study". Am. J. Surg. Pathol. 35 (7): 949–61. doi:10.1097/PAS.0b013e31821e25cd. PMID 21677535.
  21. Martignoni G, Gobbo S, Camparo P, et al. (October 2011). "Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions". Mod. Pathol. 24 (10): 1313–9. doi:10.1038/modpathol.2011.93. PMID 21602817.