Papillary renal cell carcinoma

Papillary renal cell carcinoma
  • It is a malignant tumor having papillary and tubulopapillary architecture with tumor cells having origin from renal tubular epithelial cells
  • Incidence – 10-15% of all RCC
  • Sex- Predominance in males (with male to female ration of 2:1)
  • Age – early adulthood to oldage
  • Etiology – No specific etiological factors but found to be associated with  acquired cystic disease and end stage renal disease with scarring. Some cases are found to be associated with syndromes
  • Genetics – common chromosomal abnormality is trisomy or tetrasomy of 7 and 17
  • Bilaterality and multifocality is common in this tumor
Morphology
Gross-
  • Grossly tumors are well circumscribed and are situated eccentrically in renal cortex
  • In few cases distinct fibrous capsule may be seen
  • Cut surface may be gray to red brown granular or golden yellow due to lipid laden macrophages in the stroma
  • Intratumoral hemorrhage and necrosis may be present in 2/3rds of cases
  • These tumors are usually associated with cortical adenoma or can present in wall of cyst
  • They are often multiple
  • Numerous tumors are seen in hereditary type RCC
Microscopically :
  • Papillary RCC is usually surrounded by fibrous capsule
  • Tumor is characterised by papillae having fibrovascular stalks lined by single layered or pseudo stratified layers of tumor cells
  • Most of the tumor shows papillae but in some case tubules may also be seen
  • Tightly packed papillae and tubules may give solid appearance
  • Accumulation of foam cells or xanthoma cells or lipid laden macrophages in the papillary stalk is characteristic
  • Papillary cores are expanded and can be hyalinised or thickened
  • Tumor necrosis and psammomatous calcification may be seen
  • Mucin secretion is seen in small percentage of cases
  • Tumor cells are basophilic, amphophilic and clear
  • Papillary RCC has been separated into two subtypes based on morphologic features by Delahunt and Eble
    • Type-1
    • Type 2
  • Type-1 tumors:
    • Constitutes 2/3rds of cases
    • Composed of small cells having scanty basophilic or pale cytoplasm
    • Nuclei are small and ovoid with inconspicuous nucleoli (Grades 1& 2)
    • Nuclear grooves may be seen
    • Cells form single layer on papillae
    • Foamy macrophages and psammoma bodies are abundant
  • Type -2 tumors:
    • Constitutes less than 1/3rd of cases
    • Composed of large cells with abundant acidophilic cytoplasm
    • Cytoplasmic clearing is typically apical
    • Nuclei are large spherical with prominent nucleoli (grade3)
    • Focal pseudo stratification of cells are seen
    • Few cells may show intracytoplasmic lumen
    • In cases with mixture of two types, classification is dependent on the predominant type
  • Hereditary papillary RCC’s are composed of small cells with scant basophilic cytoplasm & low grade nuclei. Areas of haemorrhages necrosis,psammoma bodies and numerous foamy macrophages are seen.
Immunohistochemical findings
  • Tumor cells are strongly positive for – Pancytokeratins, Low molecular weight cytokeratin antibodies
  • Type1 tumors – strongly reactive for Cytokeratin 7 than type2 tumors
  • Tumor cells are positive for-
    • Vimentin
    • CD9
    • CD10
    • Parvalbumin
    • Beta-defensin1
  • Few tumors are reactive for CEA
Prognosis
  • papillary RCC’s have better prognosis than clear cell type
  • Type 1 has better prognosis than type 2 type
  • These tumors have propensity for metatsasis and late recurrence
Differential diagnosis
  • Papillary adenoma
    • Size of tumor is less than 5mm
    • tumor shows tubulopapillary architecture line by cells having scant amphophilic to basophilic cytoplasm and low grade nuclei
    • Immunohistochemistry – Cells are positivr for AMACR, CK 7, EMA and high molecular weight cytokeratins
  • Clear cell papillary RCC
    • Clear cells are cytologically low grade showing reverse polarity with subnuclear clearing and linear arrangement of nuclei
    • More solid and nested areas are seen with areas of papillary tufts
    • Immunohistochemistry – 
      • Strong positivity with CK 7
      • CD 10 and Racemase are typically negative
      • PAX 8 and high molecular weight keratin are often positive
  • Metanephric adenoma
    • Benign tumor with female predominance showing tightly packed primitive tubules and acini intermingled with papillary or glomeruloid structures
    • Tumor cells are small and uniform with round to oval nuclei, inconspicuous nucleoli and absent or rare mitosis
    • Immunohistochemistry
      • Positive for – WT 1, PAX 2, CD57
      • Negative for – CK7, CD56, AMACR
Reference
  1. William M.Murphy ,David J.Grignon,ElizabethJ.Perlman. Renal cell carcinoma,papillary type . In tumors of the kidney ,bladder and related urinary structures.AFIP atlas odf tumor pathology.Series 4.123-129
  2. John N.Eble,Robert H.Young.TUmors of urinary tract. In diagnostic histopahology of tumors by Christopher.D.M. Fletcher.Third edition Volume1.485-566.
  3. Mario F.Serrano and peter A.Humphrey .Adult renal neoplasms.In surgical diseases of kidney.The Washington manual of surgical pathology.By: peterA.Humphrey,Louis P.Dehner John D.Pfeifer.second edition 2016.357-371