Papillary renal cell carcinoma

Papillary renal cell carcinoma
Diagnosis in short
Papillary renal cell carcinoma. H&E stain.
LM	cuboidal or low columnar cells (simple or pseudostratified) on papillae, interstitial foam cells in the vascular cores
Subtypes	no World Health Organization recognized subtypes; defunct subtypes: "type 1" and "type 2", oncocytic variant
LM DDx	clear cell renal cell carcinoma, clear cell papillary renal cell carcinoma, metanephric adenoma (esp. solid PaRCC type 1), collecting duct carcinoma (esp. PaRCC type 2), renal papillary adenoma, acquired cystic disease-associated renal cell carcinoma, urothelial carcinoma, renal mucinous tubular and spindle cell carcinoma, ALK translocation renal cell carcinoma, Xp11 translocation renal cell carcinoma
Molecular	MET mutation (hereditary papillary renal cell carcinoma), FH mutation (hereditary leiomyomatosis and renal cell cancer)
Gross	may be multifocal, must be >1.5 cm (if low ISUP grade), often necrotic-appearing (brown, soft, friable)
Grossing notes	total nephrectomy for tumour grossing, partial nephrectomy grossing
Staging	kidney cancer staging
Site	kidney - see kidney tumours
Associated Dx	acquired renal cystic disease (end-stage renal disease)
Syndromes	hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell cancer
Prevalence	relatively common
Clin. DDx	other kidney tumours
Treatment	surgical excision, ablation

Papillary renal cell carcinoma, abbreviated PRCC, PaRCC and papillary RCC, is the second most common type of renal cell carcinoma.

General

• Historically, PaRCC was subclassified into type 1 and type 2.
  • Type 1 and Type 2 are different on a cytogenetic and molecular basis.

Epidemiology

• Associated with acquired renal cystic disease.
• May be familial - uncommon.
  • MET mutation - autosomal dominant transmission (previously PaRCC type 1).

Gross

• Renal cortical mass usually >1.5 cm.
• May be multifocal. ‡
• Often necrotic appearing - light-to-dark brown, soft/mushy, friable.

Note:

• ‡ Approximately 10% of PaRCCs are multifocal (based on a set of 5378 patients); it is the renal tumour that is most commonly multifocal.

Microscopic

Features:

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

Size criterion:

• Papillary lesions with low ISUP grade must be >1.5 cm to be called carcinoma; smaller lesions (<=1.5 cm) with low ISUP grade are called papillary adenomas. †

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

Note:

• † The diagnostic size cut-off in the 2004 WHO GU (blue) book was 0.5 cm.

DDx:

• Clear cell RCC.
  • Papillary: histiocytes, intracellular hemosiderin, CK7 +ve.
• Clear cell papillary renal cell carcinoma - apical nuclei, usu. no true papillae.
• Metanephric adenoma (esp. solid PaRCC type 1) - no histiocytes, WT-1 +ve.
• Collecting duct carcinoma - esp. PaRCC type 2.
• Urothelial carcinoma.
• Renal papillary adenoma - doesn't fulfill size criterion for PaRCC.
• Acquired cystic disease-associated renal cell carcinoma.
• Renal mucinous tubular and spindle cell carcinoma.
• Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma - for type 2 PaRCC; CK7 -ve, prominent eosinophilic nucleoli.
• ALK translocation renal cell carcinoma.
• Mixed epithelial and stromal tumour.
• Papillary renal neoplasm with reverse polarity (PRNRP) - nuclei at luminal aspect of cell (rather than closer to the basement membrane).
  • May be considered a subtype of papillary renal cell carcinoma (rather than a distinct entity).
• Xp11 translocation renal cell carcinoma.

Images

• 

  PaRCC - intermed. mag. (WC/Nephron)

• 

  PaRCC - high mag. (WC/Nephron)

• 

  PaRCC - very high mag. (WC/Nephron)

• 

  PaRCC - intermed. mag. (WC)

• 

  PaRCC - high mag. (WC)

• 

  PaRCC - very high mag. (WC)

• 

  PaRCC - high mag. (WC/Nephron)

• 

  PaRCC - very high mag. (WC/Nephron)

Histological subtyping

Historically, PaRCC was subtyped:

• Type 1 - single layer of cells on basement membrane - most important.
  • Usually low grade nuclear features, i.e. low ISUP nucleolar grade.
  • Other characteristics:
    • Clear cytoplasm.
    • Foamy macrophages - common.
    • Cells smaller.
• Type 2 - pseudostratification of cells - most important.
  • Usually high grade nuclear features, i.e. high ISUP nucleolar grade.
  • Other characteristics:
    • Eosinophilic cytoplasm.
    • Foamy macrophages - uncommon.
    • Cells larger.

The WHO GU Blue Book 5th Ed. recommends against subtyping.

Another subtype:

• Oncocytic - oncocytic cytoplasm.
  • Extremely rare ~ a few dozen reported.
    • One "large" series was 14 cases.

IHC

Features:

• AMACR +ve.
• HMWCK (34betaE12) +ve.
• Panker (AE1/AE3) +ve.
• CK7 +ve ~90% of type 1, 20% of type 2.
• CD10 +ve.

Others:

• GATA3 +ve - oncocytic variant of PaRCC; negative in other PaRCC subtypes.

Type 1 versus Type 2:

• CK7:
  • Type 1 ~ 100%.
  • Type 2 ~ 19%.
• CK19:
  • Type 1 ~ 100%.
  • Type 2 ~ 53%.

Metanephric adenoma vs. PaRCC type 1:

• AMACR +ve.
• WT-1 -ve.
• CD57 -ve.

Molecular

Features:

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

Note:

• Not used for diagnosis.

Sign out

Kidney Tumour, Left, Partial Nephrectomy: 
- PAPILLARY RENAL CELL CARCINOMA. 
-- Surgical margins NEGATIVE. 
-- ISUP nucleolar (Fuhrman) Grade 3. 
-- TNM stage: pT1a pNx. 
-- Please see tumour summary. 

Block letters

KIDNEY, RIGHT, RADICAL NEPHRECTOMY:
- PAPILLARY RENAL CELL CARCINOMA, WHO/ISUP NUCLEOLAR GRADE 3, pT2a(2), pNx.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
- RENAL PAPILLARY ADENOMAS.

Micro

The sections show a tumour in the kidney with fibrovascular cores (papillae) that focally contain macrophages. Psammoma bodies are present. Siderophages are present.

The papillae predominantly have a single layer of tumour cells and the cytoplasm of the tumour cells is predominantly clear.

Nucleoli are visible focally with the 10x objective (ISUP nucleolar grade 3).

A second tumour with the same morphology is present and measures 8 millimetres.

Multiple small lesions, like the largest tumour, less than 1.5 cm are present.

Oncocytic variant

KIDNEY, RIGHT, NEPHRECTOMY:
- PAPILLARY RENAL CELL CARCINOMA, ONCOCYTIC -- SEE COMMENT;
- WHO/ISUP 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.

See also

• Kidney tumours.
• Acquired cystic disease-associated renal cell carcinoma.