Eosinophilic vacuolated tumour

• A distinctive renal neoplasm of large eosinophilic cells with prominent intracytoplasmic vacuoles and enlarged nuclei with conspicuous nucleoli.
• Formerly “high-grade oncocytic tumour” (HOT) and “sporadic RCC with eosinophilic and vacuolated cytoplasm”.
• Named by GUPS in 2021 and included in WHO 2022 among emerging “other oncocytic tumours”.
• Solid, nested or compact acinar growth, often with thick-walled peripheral vessels.
• Immunophenotype: CD117+, cathepsin K+, CK7 negative or very focal.
• Most harbour TSC1, TSC2 or MTOR alterations.
• Usually indolent, but metastatic cases have now been reported.

Diagnostic pearl: vacuoles + prominent nucleoli + thick-walled vessels + CD117+/CK7-low should raise strong consideration of EVT.

Architecture

• Well circumscribed, usually without a well-formed capsule; solid, nested or compact acinar.
• Delicate septa or oedematous stroma; thick-walled vessels at the periphery; entrapped tubules at the edge.

Cells

• Large polygonal cells with abundant granular eosinophilic cytoplasm, often condensed at the periphery.
• Numerous large intracytoplasmic vacuoles; borders often well defined.

Nuclei

• Round to oval, enlarged, with prominent, sometimes inclusion-like, nucleoli.
• Smooth membranes with focal irregularity; mitoses very rare; no coagulative necrosis.

Diagnostic pearl: high-grade-looking nucleoli contrast with low mitotic activity, nucleoli alone do not make an aggressive RCC.

• Solid / sheet-like: the most common; vacuoles give a perforated look at low power.
• Nested: around thick-walled vessels and oedematous areas.
• Compact acinar: may resemble oncocytoma or eosinophilic ChRCC.
• Trabecular / tubular: usually minor components.
• Microcystic / tubulocystic: focal; extensive macrocysts suggest ESC RCC.
• Stromal-rich: nests in oedematous, myxoid or hyalinised stroma.

Diagnostic pearl: EVT is not purely solid, but large intracytoplasmic vacuoles in at least part of the tumour remain central.

• Large, round, sharply defined vacuoles, solitary or multiple, sometimes a single central vacuole; bubbly or spider-cell-like cytoplasm.
• Surrounding cytoplasm finely granular and deeply eosinophilic, condensed toward the membrane.
• Ultrastructure: abundant mitochondria and dilated rough endoplasmic reticulum.

Not to be confused with

• Fine perinuclear halos of ChRCC and LOT.
• Coarse basophilic stippling of ESC RCC.
• Pale flocculent inclusions of SDH-deficient RCC.

Diagnostic pearl: large vacuoles within densely eosinophilic cytoplasm are far more suggestive of EVT than nonspecific perinuclear clearing.

• Prominent nucleoli: visible at low/intermediate power; the reason for the old “high-grade” name.
• Nuclear irregularity: mild; widespread raisinoid nuclei favour ChRCC.
• Thick-walled vessels: often hyalinised, peripheral; supportive, not specific.
• Entrapped peripheral tubules: can mimic infiltration.
• Hyalinised / myxoid stroma: can mimic oncocytoma or LOT.

Diagnostic pearl: nucleoli, thick-walled vessels and vacuoles form a useful triad, none alone is diagnostic.

• CD117: usually strong membranous · shared with oncocytoma and ChRCC.
• CK7: negative or scattered cells (≤10% in a 19-case study) · against LOT and classic ChRCC.
• Cathepsin K: usually cytoplasmic positive · against oncocytoma and most ChRCC; also positive in ESC RCC, MiT RCC, PEComa.
• CK20: usually negative or rare cells · against ESC RCC.
• PAX8: positive.

Others

• CD10 often positive (nonspecific); GPNMB and CD56 emerging; HMB45/Melan-A negative; SDHB retained.

Diagnostic pearl: CD117+, CK7-negative/focal, cathepsin K+ is characteristic, but cytology and architecture are still required.

• TSC–mTOR pathway: loss of TSC1/TSC2 or activating MTOR mutations increase mTORC1 signalling.
• Farcas et al., Mod Pathol 2022 (19 cases): MTOR 8, TSC2 7, TSC1 4; all altered, mutually exclusive; no significant copy-number changes; low TMB.
• Usually sporadic; rarely in tuberous sclerosis complex.
• Versus ChRCC: no multiple whole-chromosome losses; simple near-diploid genome.

Diagnostic pearl: a TSC1/TSC2/MTOR alteration supports EVT but cannot separate it from LOT, ESC RCC or other mTOR-driven tumours.

Oncocytoma

• Uniform round nuclei, smooth membranes, less conspicuous nucleoli, no large vacuoles.
• CK7 scattered and CD117+ in both, cathepsin K favours EVT.
• 1/Y loss, CCND1 rearrangement or diploid genome.

Eosinophilic ChRCC

• Wrinkled nuclei, perinuclear halos, binucleation.
• CK7 may be limited and CD117 positive in both; cathepsin K favours EVT.
• Multiple whole-chromosome losses in ChRCC.

Diagnostic pearl: a CK7-low/CD117+ eosinophilic tumour with crisp borders is not necessarily ChRCC, look for big vacuoles and nucleoli.

• LOT: smaller uniform cells, small nests with abrupt oedema; CK7 diffuse/CD117 negative; also mTOR-altered.
• ESC RCC: solid and cystic, coarse basophilic stippling; CK20+, CD117 negative; also TSC-altered and cathepsin K+.
• SDH-deficient RCC: flocculent inclusions; SDHB lost (retained in EVT).
• FLCN-associated tumours: mixed oncocytic/pale mosaic; may mimic EVT; Birt–Hogg–Dubé; FLCN alterations.
• TFEB-rearranged RCC / epithelioid AML: cathepsin K+; melanocytic markers; PAX8 favours renal epithelial origin.

Diagnostic pearl: cathepsin K and mTOR alterations are shared, morphology decides.

• 1 · Cytoplasm: large sharp vacuoles, not halos or stippling.
• 2 · Nuclei & vessels: prominent nucleoli, solid/nested growth, thick-walled peripheral vessels.
• 3 · IHC: CD117+/CK7 negative-focal + cathepsin K+ supports EVT; CK20 diffuse/CD117− → ESC RCC; CK7 diffuse/CD117− → LOT.
• 4 · Exclude mimics: SDHB, melanocytic markers, TFEB testing as needed.
• 5 · Molecular: for ambiguous cases; exclude FLCN.

On biopsy

• Recognisable when vacuolated cells are well represented; vessels and architecture may be missed.
• Do not diagnose on cathepsin K or an mTOR alteration alone.
• Consider “oncocytic renal neoplasm with EVT-like features” when uncertain.

• Rare metastasis: 2025: an 11.2 cm EVT in a 14-year-old metastasised to mediastinal nodes after 54 months, with a shared MTOR variant (VUS); Coiner et al. (Histopathology 2026) also addressed metastatic potential.
• Uncommon and usually indolent: 2025 review of 605 eosinophilic tumours: EVT ~0.8% vs LOT 5.5%; no aggressive behaviour, two on active surveillance.
• New markers: GPNMB and CD56 (Trpkov 2026 review); supportive only.
• FLCN mimics: 2026: five FLCN-mutated tumours overlapped with oncocytoma, ChRCC and EVT; one was initially called EVT.
• Renal sinus EVT: 2026 case mimicking urothelial carcinoma; unusual site does not exclude EVT.
• EVT vs LOT: shared mTOR biology, distinct morphology and immunophenotype.

• Large eosinophilic cells with big intracytoplasmic vacuoles and prominent nucleoli; formerly HOT.
• Solid, nested or compact acinar; thick-walled peripheral vessels.
• Prominent nucleoli do not by themselves indicate high-grade carcinoma.
• Vacuoles ≠ perinuclear halos ≠ coarse stippling ≠ flocculent inclusions.
• CD117+, CK7 negative/focal, cathepsin K+, CK20 negative.
• CK7-low/CD117+ overlaps with oncocytoma and eosinophilic ChRCC, cathepsin K helps.
• TSC1, TSC2, MTOR alterations; no extensive chromosome losses.
• FLCN-associated tumours can look EVT-like.
• Mostly indolent, but rare metastases reported since 2025.