Low-grade oncocytic tumour

• A recently recognised renal tumour of bland oncocytic cells with diffuse CK7 and absent/minimal CD117.
• An emerging entity in WHO 2022; formerly called oncocytoma, eosinophilic ChRCC or unclassified oncocytic neoplasm.
• Architecture: tightly packed small nests with abrupt transitions into oedematous stroma.
• Granular eosinophilic cytoplasm, round–oval nuclei, inconspicuous nucleoli, variable perinuclear halos.
• Recurrent MTOR / TSC1 alterations — an mTOR-pathway neoplasm.
• Indolent in published series (no recurrence or metastasis), though long-term data are limited.
• Diagnosis rests on morphology + immunophenotype; molecular confirmation is usually unnecessary.

Diagnostic pearl: small nests + stromal oedema + bland nuclei + CK7 diffuse + CD117 negative strongly favours LOT.

Architecture

• Well circumscribed, compact small-nested growth separated by delicate capillaries.
• Abrupt transition from compact to loose oedematous areas; capsule absent or incomplete.

Cells

• Finely granular eosinophilic cytoplasm; round–oval nuclei with smooth or mildly irregular membranes.
• Uniform chromatin, inconspicuous nucleoli, variable halos; borders lack the plant-cell look of ChRCC.

Stroma

• Oedematous, hypocellular, sometimes haemorrhagic areas with elongated cords or single cells.
• No coagulative necrosis or significant mitoses.

Diagnostic pearl: compact small nests switching abruptly to loose oedema is one of the most useful clues.

• Compact small-nested — the prototype; unlike the broad sheets and trabeculae of ChRCC.
• Solid — usually alongside nested areas; a uniformly solid tumour without stromal transitions needs care.
• Trabecular / cord-like — near oedematous zones, sometimes single-cell thin.
• Tubular — minor; extensive tubules suggest another tumour.
• Oedematous / loose — dispersed cells can mimic infiltration.
• Cystic change — focal only; extensive cysts warrant reassessment.

Diagnostic pearl: LOT is often recognisable at low power from its small-nested pattern and stromal transitions.

• Conventional cells — granular eosinophilic cytoplasm, uniform nuclei, small nucleoli.
• Perinuclear halos — focal to extensive; may look chromophobe-like or nearly clear.
• Mild nuclear irregularity — scattered cells only; widespread raisinoid nuclei favour ChRCC.
• Binucleation — occasional, not defining.
• Elongated cells in oedema — not sarcomatoid.
• Clear-cell-like areas — differ from ccRCC by vasculature and immunophenotype.

Diagnostic pearl: the overall low-grade nuclear phenotype matters more than an isolated atypical cell.

• Central oedema — often conspicuous, abrupt, sometimes with haemorrhage.
• Delicate capillaries — not the diffuse chicken-wire network of ccRCC.
• Dispersed cells — can look infiltrative; bland cytology reassures.
• No aggressive features — pleomorphism, mitoses, necrosis, sarcomatoid or rhabdoid change require reconsideration.

Diagnostic pearl: abrupt oedema is characteristic but not pathognomonic — oncocytoma can show it too.

Start with CK7 and CD117; L1CAM and GATA3 are second line.

• CK7 — strong, diffuse (nearly every cell); rare LOTs focal/patchy.
• CD117 — negative or very focal/weak (<5% cells); check mast cells as internal control.
• L1CAM — strong membranous; 32/32 LOT vs 0/37 eosinophilic ChRCC (2024).
• GATA3 — frequently nuclear positive; supportive, not specific.
• GPNMB — frequently cytoplasmic positive; supportive.

Diagnostic pearl: CK7+/CD117− is the practical screen; L1CAM adds discrimination, especially against eosinophilic ChRCC.

• mTOR pathway — activating MTOR mutations and TSC1 (less often TSC2) loss increase mTORC1 activity.
• MTOR — dominant in some series (6/7 in a 2026 study); not exclusive to LOT.
• Chromosomes — no extensive whole-chromosome losses; simple or near-diploid, sometimes limited 1 or 19 losses.
• Use — not routine; helpful when morphology and IHC are discordant.

Diagnostic pearl: LOT is mTOR-driven, but an MTOR mutation alone cannot define it — EVT shares the pathway.

Oncocytoma

• Larger nests, acini and tubules in oedematous/hyalinised stroma; focal degenerative atypia.
• CK7 scattered cells, CD117 strongly positive; L1CAM helps.

Eosinophilic ChRCC

• Prominent borders, irregular raisinoid nuclei, binucleation; CD117 positive; multiple chromosome losses.

2024 comparison: 65 LOT vs 68 eosinophilic ChRCC

• Small-nested architecture: 100% vs 14%
• Irregular nuclear contours: 18% vs 99%
• Diffuse CK7: 98% vs 36%
• CD117 positive: 2% vs 94%
• Diffuse L1CAM: 100% vs 0%

Diagnostic pearl: halos were common in both (88% vs 86%) — contour, architecture and focused IHC discriminate better.

• EVT — large vacuoles, big nucleoli, thick-walled vessels; CD117+, cathepsin K+, CK7 limited.
• Hybrid oncocytic/chromophobe tumour — mixed nuclear phenotypes; Birt–Hogg–Dubé.
• ESC RCC — solid and cystic, coarse basophilic stippling; CK20+, CK7/CD117 negative.
• SDH-deficient RCC — flocculent inclusions; SDHB lost (retained in LOT).
• ccRCC — branching capillaries, box-like CAIX; LOT is CAIX negative with perinuclear (not diffuse) clearing.

Diagnostic pearl: do not confuse LOT’s perinuclear halos with the large intracytoplasmic vacuoles of EVT.

• 1 · Morphology — compact small nests, delicate septa, abrupt oedema.
• 2 · Nuclei & clearing — round nuclei favour LOT; raisinoid → ChRCC; vacuoles + nucleoli → EVT.
• 3 · CK7 / CD117 — diffuse/negative → LOT · scattered/positive → oncocytoma · diffuse/positive → ChRCC · limited/positive + vacuoles → EVT.
• 4 · L1CAM in equivocal cases.
• 5 · Molecular only for discordant tumours.

On biopsy

• Recognisable when morphology and IHC are typical, but stromal transitions may be missed.
• Use “low-grade oncocytic renal neoplasm, favour LOT” when uncertain; do not force LOT with atypia, mitoses or necrosis.

• L1CAM — 32/32 LOT vs 0/37 eosinophilic ChRCC (2024); 10/10 LOT vs none of oncocytoma, ChRCC, EVT (2025).
• Immunophenotypic exceptions — focal weak CD117 (<5%) in 2/13 and patchy CK7 in a minority.
• GATA3, GPNMB, L1CAM in all 20 LOTs (2025) — a distinct differentiation program.
• Principal-cell origin — an August 2026 study proposed “renal eosinophilic principal cell adenoma”; still a proposal.
• Molecular heterogeneity — one tumour with BRAF, LRP1B, XRCC1 instead of mTOR alterations; significance uncertain.
• Indolent follow-up — no recurrence up to 96 months (13 cases), ~4.5 years (20), 5.8 years median (65).

• Emerging WHO 2022 entity: CK7+/CD117−.
• Compact small nests with delicate capillaries and abrupt oedema.
• Granular eosinophilic cytoplasm, uniform round nuclei; halos frequent but nonspecific.
• Widespread raisinoid nuclei favour ChRCC.
• Rare LOTs show focal CK7 or weak focal CD117.
• L1CAM is a valuable second-line marker; GATA3 and GPNMB supportive.
• MTOR/TSC1 alterations; no extensive chromosome losses.
• Vacuoles + big nucleoli suggest EVT.
• Pleomorphism, mitoses and necrosis are not LOT.