Surgical Pathology Criteria

Renal Cell Carcinoma Associated with Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome

Definition
Renal cell carcinomas with inclusion-like nucleoli and perinucleolar clearing that occur in the setting of skin and uterus leiomyomatosis and demonstrate germline fumarate hydratase (FH) mutations

Common abbreviation
HLRCC-associated RCC

Diagnostic Criteria

 

Supplemental studies

Grading/Staging

Use WHO/ISUP grading system for clear cell and papillary renal cell carcinomas

Grade 1

Nucleoli are absent or inconspicuous and basophilic at 400x magnification

Grade 2

Nucleoli are conspicuous and eosinophilic at 400x and visible but not prominent at 100x

Grade 3

Nucleoli are conspicuous and eosinophilic at 100x

Grade 4

Extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation

 

Clinical

 

Differential diagnosis
Papillary renal cell carcinoma
Tubulocystic renal cell carcinoma
Collecting duct carcinoma

Hereditary Leiomyomatosis RCC Papillary Renal Cell Carcinoma

FH Negative, 2SC Overexpressed

FH intact, No 2SC over expression

CK7 negative

CK7 positive

Prominent eosinophilic nucleoli
with a clear perinucleolar halo

May have prominent nucleoli

Foamy macrophages uncommon

Foamy macrophages common

Average age 36

Average age 60

  • Both may show predominantly papillary architecture
  • HLRCC-associated RCC more likely to resemble Type 2 PRCC with larger tumor cells, often with higher nuclear grade and eosinophilic cytoplasm
  • Hereditary Leiomyomatosis RCC Tubulocystic Carcinoma of the Kidney

    FH Negative, 2SC Overexpressed

    FH intact, No 2SC over expression

    Papillary architecture predominates

    Tubulocystic architecture predominates (small to intermediate-sized tubules with admixed larger cysts)

    Mean age 36

    Mean age 58

    Prominent eosinophilic nucleoli
    with a clear perinucleolar halo

    May have prominent nucleoli

  • Both can show tubulocystic architecture and have similar cytologic features including prominent nucleoli and eosinophilic cytoplasm
  • Both may have poorly-differentiated areas
  • Given dramatic differences in prognosis, may consider doing immunohistochemistry especially if there are dedifferentiated areas
  • Hereditary Leiomyomatosis RCC Collecting Duct Carcinoma

    FH Negative, 2SC Overexpressed

    FH intact, No 2SC over expression

    CK7 and HMWCK negative

    CK7 and HMWCK positive

    Predominant papillary morphology

    Predominantly tubular morphology

    Predominantly located in renal cortex

    Must have medullary involvement

    Both may be high nuclear grade and incite desmoplastic response

    Bibliography

     

     

    Kurt Schaberg MD
    John P Higgins MD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting 12/29/16

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