Practical Approach to Diagnosis of Oncocytic Renal Tumors

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Overview of Oncocytic Renal Tumors

These tumors include Oncocytoma, Chromophobe RCC, Eosinophilic Variant of Chromophobe RCC, Low-Grade Oncocytic Tumor (LOT), Succinate Dehydrogenase Deficient RCC, Fumarate Hydratase Deficient RCC, and others. Diagnosis relies on morphology first, IHC often required, low threshold for molecular testing/expert consultation.

Key Features

  • Clusters of eosinophilic cells in background of edematous connective tissue ("archipelago").
  • Diffuse/sheets, acini, cystic/microcystic patterns might be present.
  • Majority of nuclei have regular nuclear membrane, may have prominent nucleoli.
  • No brisk mitotic activity, coagulative necrosis, overt high-grade atypia.
  • Degenerative cytologic changes may be present.
  • Definitive diagnosis depends on resources & expertise.

Tumor Types

Oncocytoma Chromophobe RCC Eosinophilic Variant Low-Grade Oncocytic Tumor SDH Deficient RCC FH Deficient RCC BHD-associated Hybrid Tumors

Diagnostic Algorithm

Structured flow for diagnosing oncocytic renal tumors based on morphology.

Morphological Evaluation
Start: Is the tumor oncocytic?
Yes → Proceed to evaluate high-grade features.
↓ (If confirmed oncocytic)
Are high-grade features present?
(Increased cytologic atypia, infiltrative growth, desmoplasia, coagulative necrosis, prominent mitotic activity)
Yes → Possible diagnoses: Clear cell RCC, Epithelioid AML/PEComa, Fumarate hydratase deficient RCC, TFEB amplified RCC, ALK rearranged RCC, SMARCB1 deficient RMC, Papillary RCC with oncocytic features, Solid papillary RCC.
↓ (If no high-grade features)
Is papilla formation observed?
Yes → Possible diagnoses: Papillary RCC with oncocytic features, Papillary neoplasm with reverse polarity.
↓ (If no papilla formation)
Does the tumor exhibit low nuclear grade?
Possible diagnoses: Oncocytoma, Eosinophilic chromophobe RCC, Low grade oncocytic tumor (LOT), Low grade FH-def RCC, SDH-def RCC, BHD-associated hybrid tumors, Oncocytic renal neoplasm of low malignant potential.

KIT Distribution for IHC

Distribution based on KIT and KRT7 status.

KIT Positive KIT Negative
Oncocytoma (KRT7 rarely positive)
Chromophobe RCC (KRT7 mostly positive)
EVT (CathepsinK, CD10, GPNMB+) 		LOT (KRT7+, GATA3+)
ESC RCC (KRT20+, GPNMB+)
SDH RCC (GATA3+, KRT7-, SDHB loss)
PRNRP (KRT7+, GATA3+)

Key Points

  • KIT positivity is strongly associated with oncocytoma and chromophobe RCC
  • KIT negative tumors require additional IHC markers for classification
  • GATA3 is a useful marker for KIT negative tumors

IHC Profile Table

Comprehensive immunohistochemical profile of renal oncocytic tumors.

Tumor Type KRT7 KIT CA9 Cathepsin K SDHB KRT20 GATA3 L1CAM FH 2SC GPNMB TTF1 CyclinD1
Oncocytoma Rare + +++ - - Retained - - - Retained - - - ±
Chromophobe RCC, eosinophilic ++ +++ - - Retained - /+ - Retained - - -
Low-grade Eosinophilic Tumor +++ - - - Retained - +++ +++ Retained - +++ - -
Eosinophilic Vacuolated Tumor /+ ++ ++ + Retained - ND ND Retained - ++ - -
Eosinophilic Solid and Cystic RCC /+ /+ - /+ Retained ++ ND ND Retained - ++ - -
Hybrid Tumors (BHD patients) Variable Variable - - Retained - Variable Variable Retained - - - -
Succinate Dehydrogenase Deficient Renal Cell Carcinoma - - - - Loss - +++ +++ Retained - - - -
Fumarate Hydratase Deficient Renal Cell Carcinoma, Low-Grade /+ - - - Retained - ± ND Loss Over Expressed - - -
Thyroid Follicular Like Renal Cell Carcinoma +++ - - ND Retained - ND ND Retained - ND - +++

Marker Interpretation

  • +++: Strong/diffuse positivity
  • ++: Moderate positivity
  • +/±: Weak/focal positivity
  • -: Negative
  • ND: Not determined

Morphology and Key Features

Descriptions and features of oncocytic renal tumors.

Renal Oncocytoma

Clusters of eosinophilic cells, archipelago pattern, focal pleomorphism, pseudoinclusion, clumped nuclei, bland round nuclei, nucleoli common, cellular membranes not distinct. Degenerative changes may be present. No brisk mitosis, coagulative necrosis, high-grade atypia.

Degenerative cytologic changes may be present (as long as it is within acceptable limits). Tumor cells entrapped in fibrous stroma (usually in the central scar) can have bizarre morphology.

Low-Grade Oncocytic Tumor (LOT)

KRT7 diffuse positive/KIT negative, GATA3 almost always positive (chromophobe RCC and some other tumors in the DDx can also be positive). L1CAM similar to GATA3 with similar precautions.

Succinate Dehydrogenase Deficient RCC

GATA3 (almost always) and L1CAM (frequently) expressed. Succinate dehydrogenase deficient renal cell carcinoma frequently expresses GATA3 and L1CAM.

Eosinophilic Tumor Diagnostics

Morphology first, IHC often required, low threshold for molecular testing/expert consultation.

Recognizable Morphologic Features

  • Oncocytoma: KIT Positive, KRT7 (rare)
  • Chromophobe RCC: KIT Positive, KRT7 (mostly +)
  • EVT: KIT Positive, Cathepsin K, CD10, (GPNMB) POS
  • LOT: KIT Negative, KRT7, GATA3 POS
  • ESC RCC: KIT Negative, KRT20, (GPNMB) POS
  • SDH RCC: KIT Negative, GATA3+, KRT7-, SDHB (L)
  • PRNRP: KIT Negative, KRT7, GATA3 POS

Unusual Morphologic Features

Common things = common: 1. Clear Cell RCC? (CA9) 2. Take more sections if applicable 3. Morphologic "variant" of a common subtype (PRCC, ChRCC...)

Unusual morphology, no common entity (usually KRT7/KIT dual negative): 1- Rosettes, basophilic stippling, pigment, calx? 2- High grade features? Consider molecularly defined RCC or epithelioid AML?

Practical Approach in Diagnosis

Practical approach to diagnosis of oncocytic tumors in the kidney. Anticipated outcomes in oncocytic tumors.

Diagnostic Pathway

  • Oncocytic Tumor → Morphologic Eval
  • High-Grade Features Present? → Yes: Clear Cell RCC, Epithelioid Angiomyolipoma, Fumarate Hydratase Deficient RCC, TFEB Amplified RCC, ALK Rearranged RCC, SMARCB1 Deficient RMC, Papillary RCC with Oncocytic Features, Solid Papillary RCC
  • No → Papilla Formation? → Yes: Papillary Renal Neoplasm with Reverse Polarity, Papillary RCC with Oncocytic Features
  • No → Low Nuclear Grade → Low Data: Oncocytoma, Eosinophilic Chromophobe RCC, Succinate Dehydrogenase RCC, Low Grade Fumarate Hydratase RCC, Hybrid Oncocytic Tumors (BHD patients), Oncocytic Renal Neoplasm of LMP

Challenges

  • Tumors with overlapping features and different outcomes
  • Under-documented experience
  • Rare tumors/lack of resources to define tumors
  • Unknown spectrum of morphology

Limited Resource Setting

Can you make a Dx in limited resource setting?

Tumor Type IHC Markers Biopsy Dx Resection Dx
Oncocytoma KIT++/KRT7(rare) Probably Yes
Eosinophilic Chromophobe Tumor KIT++/KRT7++/GATA3+ Probably Yes
Succinate Dehydrogenase RCC KIT-/KRT7-/SDHB loss No Lack IHC
Low Grade Fumarate Hydratase RCC KIT-/KRT7-/FH loss/2SC+ No Lack IHC
Hybrid Oncocytic Tumors (BHD patients) Clinical History No No/Lack XP
Oncocytic Renal Neoplasm of LMP Dx of Exclusion No No

Most Labs/Depts Lack SDHB FH 2SC CATHK. Low Nuclear Grade Confidence (=Experience) No: Chromophobe RCC KIT++/KRT7++, Eosinophilic Vacuolated Tumor KIT+/KRT7-/CATHK+, Eosinophilic Solid and Cystic RCC KIT+/KRT7+/KRT20+, Biphasic Papillary and Alveolar RCC KRT7++/AMACR++/KIT-/CYCD1+, Clear Cell RCC CA9++/KRT7-/KIT- . Biopsy/Resection: Varies from Yes to Lack XP.