Oncocytoma of the kidney

• A benign renal epithelial neoplasm of oncocytic cells with abundant granular eosinophilic cytoplasm and uniform round nuclei.
• Thought to arise from intercalated cells of the collecting duct — sharing a putative origin with chromophobe RCC.
• Classic: nests, acini and tubules in oedematous, myxoid or hyalinised stroma.
• Smooth nuclear contours, inconspicuous cell borders, finely granular (mitochondria-rich) cytoplasm.
• Focal degenerative atypia, limited chromophobe-like cytology and unusual patterns may occur without malignancy.
• Main differential: eosinophilic ChRCC, then LOT, EVT and hybrid oncocytic/chromophobe tumours.
• A morphologic diagnosis — CK7 and CD117 are the most useful first-line markers.

Architecture

• Well-circumscribed, mostly solid; nested, acinar, tubular and trabecular growth.
• Nests separated by loose, oedematous or myxoid stroma; a central scar may be present but is neither required nor specific.

Cells

• Round to polygonal cells with dense granular eosinophilic cytoplasm and indistinct borders.
• Central, uniform round nuclei with smooth membranes; nucleoli may be conspicuous.

Stroma & other features

• Oedema, myxoid change, fibrosis; cells may be dispersed as cords or single cells.
• Mitoses absent or very rare; coagulative necrosis is not a feature.

Diagnostic pearl: uniform round nuclei + granular eosinophilic cytoplasm + nests in oedematous stroma is more characteristic than any single pattern.

• Nested / solid — packed nests; the oedematous background may be inconspicuous.
• Tubular / acinar — round or branching tubules, sometimes with eosinophilic secretions.
• Trabecular / cord-like — strands in loose stroma; discohesive without being infiltrative.
• Microcystic / cystic — focal cysts lined by oncocytic cells; marked cystic change → evaluate other eosinophilic tumours.
• Pseudopapillary — focal abortive papillae are acceptable; extensive true papillae suggest PRCC.
• Stromal-rich — scattered nests in oedema/fibrosis can look deceptively infiltrative.
• Small-cell — less cytoplasm, higher N:C ratio, but bland nuclei and no mitoses.

Diagnostic pearl: a classic nested appearance helps but is not obligatory throughout the tumour.

Degenerative atypia

• Enlarged, hyperchromatic, irregular or multinucleated cells with smudged chromatin, often clustered near hyalinised stroma.
• No significant mitoses — not WHO/ISUP grade 4 and not malignant transformation.

Chromophobe-like changes

• Focal membrane irregularity and perinuclear clearing occur in otherwise typical oncocytomas.
• Widespread raisinoid nuclei, halos and prominent cell borders favour ChRCC.

Other

• Occasional binucleated cells do not establish ChRCC.
• Extensive large vacuoles with prominent nucleoli → consider EVT.

Diagnostic pearl: degenerative atypia can be striking but lacks organised nuclear abnormalities, mitoses and other malignant features.

• Perinephric fat extension — rare; not by itself malignant if strict criteria are met, but sample thoroughly and exclude ChRCC.
• Vascular involvement — rare; not consistently adverse; exclude artefact and other subtypes.
• Prominent central scar — dispersed cells with increased CK7 or vimentin near the scar can be a pitfall.
• Haemorrhage — acceptable; true coagulative necrosis with atypical viable tumour warrants reassessment.
• Multifocality — numerous bilateral oncocytic tumours → oncocytosis, Birt–Hogg–Dubé and hybrid tumours.

Diagnostic pearl: fat or vascular involvement does not automatically mean malignancy, but demands a convincing overall diagnosis.

Keep the first panel limited — CK7 and CD117 do most of the work.

• CD117 (KIT) — diffuse membranous · shared with ChRCC.
• CK7 — negative or scattered single cells (often <5%) · separates from ChRCC and LOT.
• S100A1 — frequently diffuse · supportive against ChRCC in difficult cases.
• Cyclin D1 — variable nuclear · ancillary, not specific.

Key points

• CK7 may increase near the central scar or hyalinised stroma.
• Diffuse contiguous CK7 raises ChRCC or LOT; no universal % threshold exists.
• CD117 negative with diffuse CK7 favours LOT.
• Eosinophilic ChRCC may show less CK7 than classic ChRCC.

Diagnostic pearl: CD117 positivity with CK7 restricted to scattered cells is the characteristic immunophenotype — morphology remains essential.

• Loss of chromosome 1 (1p) and Y — among the most characteristic changes; often a simple genome.
• CCND1 rearrangements — 11q13, e.g. t(5;11)(q35;q13), with cyclin D1 overexpression; not required or routinely tested.
• Diploid tumours — a near-diploid profile is compatible.
• Mitochondrial alterations — mtDNA and respiratory-chain dysfunction underlie the granular cytoplasm; not used diagnostically.
• Versus ChRCC — ChRCC shows multiple whole-chromosome losses; oncocytoma 1/Y loss, CCND1 rearrangement or near-diploidy.

Diagnostic pearl: molecular testing is rarely needed for a typical oncocytoma; no single alteration is diagnostic.

Eosinophilic ChRCC

• Conspicuous borders, perinuclear halos, irregular raisinoid nuclei, binucleation.
• Diffuse CK7 favours ChRCC; CD117 positive in both; S100A1 supports oncocytoma.
• Pitfall: eosinophilic ChRCC may show subtle irregularity and limited CK7.

Hybrid oncocytic/chromophobe tumour

• Mixed features, heterogeneous CK7; relevant in Birt–Hogg–Dubé or oncocytosis.
• Do not label every oncocytoma with focal chromophobe-like cells as hybrid.

Others

• Oncocytic PRCC — true papillae, foamy macrophages; CK7/AMACR+, CD117−.
• Eosinophilic ccRCC — branching vessels, clear areas, box-like CAIX, CD117−.
• SDH-deficient RCC — flocculent cytoplasmic inclusions; SDHB loss; hereditary implications.

• Low-grade oncocytic tumour (LOT) — bland, oedematous, perinuclear halos; CK7 diffuse, CD117 negative; GATA3, L1CAM, GPNMB; MTOR/TSC1 alterations.
• Eosinophilic vacuolated tumour (EVT) — large vacuoles, prominent nucleoli, thick-walled vessels; CD117+, CK7 limited, cathepsin K+; TSC/MTOR.
• ESC RCC — solid and cystic, coarse basophilic stippling; CK20+, CK7/CD117 negative or focal; TSC1/TSC2.
• FLCN-associated tumours — bilateral/multifocal, oncocytoma-like, chromophobe-like or hybrid; Birt–Hogg–Dubé.

Diagnostic pearl: CK7 and CD117 are an efficient first step but cannot separate oncocytoma from every emerging entity.

• 1 · Cytology & architecture — uniform oncocytic cells, round smooth nuclei, nests/tubules in oedematous or fibrotic stroma.
• 2 · Nuclei — separate smudged degenerative atypia from widespread chromophobe-like irregularity or true high grade.
• 3 · CK7 / CD117 — scattered/+ → oncocytoma · diffuse/+ → ChRCC · diffuse/− → LOT · limited/+ with vacuoles → EVT (patterns, not rules).
• 4 · Extra markers only when indicated — S100A1, cathepsin K, SDHB.
• 5 · Heterogeneity & heredity — solitary vs multifocal; multiple populations; syndromic tumours.

• Oncocytic tumours are among the hardest biopsy categories — benign, indolent and malignant tumours look alike.
• A definitive diagnosis is reasonable when morphology and immunophenotype are convincing and nothing conflicts.
• Limited sampling may miss chromophobe-like areas or vacuolated cells.
• Prefer “oncocytic renal neoplasm” when distinction is not possible; “favour oncocytoma” conveys preference without certainty.
• Clinical–radiologic correlation is key when surveillance is considered.

Histopathology, April 2026: 145 biopsy-diagnosed oncocytic neoplasms — 92.9% overall concordance with nephrectomy, 81.4% for oncocytoma; 5 of 9 discordant tumours were LOT or EVT.

• An expanding family — LOT, EVT and pathway-based (mTOR-, FLCN-associated) classification shrink the indeterminate category (2026 review).
• Better concordance — recognising LOT and EVT explains many biopsy–resection discordances.
• LOT refined — consistent GATA3, GPNMB, L1CAM and mTOR alterations (2025); a 2026 study proposed a principal-cell lineage and the term “renal eosinophilic principal cell adenoma” — investigational.
• Atypia ≠ malignancy — degenerative atypia, occasional chromophobe-like cells and rare fat/vascular extension remain compatible.
• Selective molecular testing — for unusual tumours, suspected hereditary predisposition or new entities.

• Round nuclei, smooth membranes and abundant granular eosinophilic cytoplasm are central.
• Nests, acini and tubules in oedematous or hyalinised stroma; a central scar is characteristic but not required.
• Marked degenerative atypia does not imply malignancy.
• Focal chromophobe-like cells do not make ChRCC or HOCT.
• Scattered single-cell CK7 is typical; diffuse CK7 → reconsider. Watch CK7 near the scar.
• CD117 is shared with ChRCC and EVT.
• LOT: CK7 diffuse, CD117 negative. EVT: CK7-low/CD117+ with vacuoles and big nucleoli.
• Flocculent cytoplasmic inclusions → SDHB.
• Multiple bilateral oncocytic tumours → FLCN / Birt–Hogg–Dubé.
• Biopsies may miss heterogeneity; integrate morphology and immunophenotype.