Kidney tumor
Adult renal cell carcinoma
Unclassified renal cell carcinoma

Author: Nicole K. Andeen, M.D.
Senior Author: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 7 November 2018, last major update August 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Unclassified renal cell carcinoma AND kidney AND (free full text[sb])

Cite this page: Andeen, N.K. Unclassified renal cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytumormalignantnos.html. Accessed November 20th, 2018.
Definition / general
Essential features
  • Heterogeneous group of RCC tumors that are not readily classifiable
  • Immunohistochemistry, fluorescent in situ hybridization and other molecular techniques may aid in classification
  • Important category enabling separation of unusual tumors from common subtypes and their further grouping / reclassification as distinct entities using advanced techniques
ICD-10 coding
  • C64.9: malignant neoplasm of unspecified kidney, except renal pelvis
Epidemiology
Sites
  • Kidney
Clinical features
Radiology description
  • Radiographic features similar to other RCCs
Prognostic factors
  • Outcome is often associated with grade, stage and clinicopathologic features known to be relevant in other forms of RCC (BJU Int 2012;110:786)
  • The majority of studies show that unclassified RCC is more aggressive with 1.6 - 1.7X the mortality of clear cell RCC (J Urol 2002;168:950, BJU Int 2007;100:802, BJU Int 2012;110:786), however one study showed that overall cancer specific survival is similar in matched cohorts after adjusting for grade, stage and other parameters (Urology 2010;76:580)
    • Despite that discrepancy, > 50% of high grade unclassified RCC are dead of disease within 2 years
    • For low grade tumors there may be an indolent course
Case reports
Treatment
  • No standardized treatment but whenever feasible immunotherapy with nephrectomy is warranted (J Urol 2002;168:950)
Gross description
Gross images

Images hosted on PathOut server:

Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.

Unclassified RCC

Microscopic (histologic) description
  • Histologic features which do not resemble any classified subtype or have features of multiple subtypes, pure sarcomatoid or rhabdoid morphology
  • High grade tumors often extremely heterogeneous with papillary, solid, sheet-like, nested, alveolar, tubular, glandular, rhabdoid or sarcomatoid architecture
  • Cytoplasm often variable from eosinophilic to clear to amphophilic to spindled
  • Majority are high nuclear grade, ISUP grade 3 or 4
  • Necrosis, mitoses and vascular invasion are common
  • May be purely sarcomatoid or rhabdoid, must exclude possibility of a distinct subtype RCC
  • Low grade tumors often resemble oncocytoma but with more solid architecture, increased pleomorphism, more than occasional mitoses and focal necrosis
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.

Unclassified RCC CDC like

Unclassified RCC

Initially unclassified RCC (chromophobe)

Initially unclassified RCC (clear cell)

Positive stains
Negative stains
  • Staining patterns characteristic of a specific type of RCC preclude the diagnosis of unclassified RCC
Molecular / cytogenetics description
  • A study of 62 high grade unclassified RCCs revealed mutations in NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%) (Nat Commun 2016;7:13131)
  • Chromosome genomic array testing (array CGH) and single nucleotide polymorphism (SNP) arrays are both useful tools in resolving 80 - 94% of unclassified RCCs with ~50% cases reclassified as clear cell RCC
  • Reclassified tumors show characteristic cytogenetic changes of certain subtype plus numerous additional copy number aberrations (Am J Surg Pathol 2009;33:1276)
Differential diagnosis
Board review question #1
    Which of the following is true about unclassified RCC?

  1. Any degree of staining for an immunohistochemical marker of interest (including TFE3, 2SC, CAIX) can establish the underlying diagnosis
  2. Areas with classic morphologic and immunophenotypic features of clear cell RCC or chromophobe RCC indicate the likely underlying etiology
  3. Unclassified RCC is a specific morphologic diagnosis
  4. Unclassified RCC is always high grade
Board review answer #1
B. Areas with classic morphologic and immunophenotypic features of clear cell RCC or chromophobe RCC indicate the likely underlying etiology
Board review question #2

    A renal carcinoma with marked morphologic heterogeneity including that seen in the image is best classified as:

  1. Chromophobe RCC
  2. Clear cell RCC
  3. MiT family RCC
  4. Papillary type 2 RCC
  5. Unclassified RCC
Board review answer #2
E. Unclassified RCC

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