Renal papillary adenoma

• A small, low-grade renal epithelial neoplasm with papillary, tubular or tubulopapillary architecture.
• WHO 2022 maximum diameter: 15 mm.
• Bland cells with low-grade nuclei — generally WHO/ISUP grade 1–2.
• Most closely resembles classic-pattern papillary RCC (formerly type 1), with shared morphology, immunophenotype and genetics.
• Size is the principal criterion separating it from an otherwise identical low-grade PRCC.
• Often an incidental microscopic finding in kidneys removed for other tumours or non-neoplastic disease.

Diagnostic pearl: the 15-mm threshold is a classification boundary, not a proven biological point at which a benign lesion becomes malignant.

Architecture

• Well-circumscribed, usually unencapsulated proliferation of small, closely packed papillae, tubules or both.
• Papillae have delicate fibrovascular cores; tightly packed tubules may look deceptively solid.

Cells

• Single layer of small cuboidal cells with scant to moderate, basophilic or amphophilic cytoplasm.
• Round to oval, uniform nuclei; nucleoli inconspicuous or mildly prominent.
• Prominent stratification, marked atypia or high-grade nuclei are not characteristic.

Additional features

• Foamy macrophages in papillary cores; psammoma bodies or focal calcification.
• Background kidney may show chronic injury or cystic change; destructive infiltration is absent.

Diagnostic pearl: classic papillary adenoma is almost indistinguishable from a very small, low-grade classic-pattern PRCC.

Papillary-predominant

• Small, delicate, sometimes branching papillae lined by a single layer of uniform cuboidal cells.

Tubular-predominant

• Small round or elongated tubules with narrow lumina; tangential sections may mimic solid nests.
• High power usually reveals luminal differentiation.

Tubulopapillary

• Mixed papillae and tubules — common, not a separate entity.

Compact / solid-appearing

• Closely packed tubules and compressed papillae; cells stay bland.
• A genuinely solid proliferation of primitive-looking cells → think metanephric adenoma.

Cytoplasm

• Typically scant and basophilic/amphophilic; focal eosinophilic or pale cytoplasm may occur.
• Extensive oncocytic cytoplasm or reverse nuclear polarity → consider another tumour.

Diagnostic pearl: the diagnosis rests on architecture, nuclear features and size together — not on papillae alone.

Foamy macrophages

• Supportive of conventional papillary differentiation; absence does not exclude.

Psammoma bodies

• Occasional, may be conspicuous in tiny lesions; not specific.

Multifocality

• Multiple adenomas are common in kidneys with PRCC, acquired cystic disease or hereditary papillary predisposition.
• Separate microscopic nodules are not automatically intrarenal metastases.

Other renal tumours

• Found next to or apart from RCCs of various types; coexistence with PRCC is well documented.
• Supports a precursor relationship without implying that every adenoma progresses.

Background renal disease

• Seen in chronic parenchymal injury and acquired cystic kidney disease, where small papillary proliferations may differ biologically and immunophenotypically.

Usually unnecessary for classic lesions — most useful to exclude metanephric adenoma or another low-grade tumour.

• CK7 — usually positive · classic papillary differentiation.
• AMACR (P504S) — usually positive · supportive.
• WT1 — usually negative · separates from metanephric adenoma.
• CD57 — usually negative/variable · interpret with the panel.

Key points

• CK7/AMACR co-expression is shared with classic PRCC and does not indicate benign versus malignant behaviour.
• AMACR may be absent in some adenomas associated with acquired cystic kidney disease.
• Metanephric adenoma: WT1+, CD57+, CK7/AMACR negative or limited.

Diagnostic pearl: no immunohistochemical marker reliably separates papillary adenoma from an otherwise identical low-grade PRCC.

Chromosomal alterations

• Gains of chromosomes 7 and 17, often with loss of Y in men — shared with classic PRCC.
• Similar changes can be found in spatially separate small papillary tumours.

MET pathway

• MET sits on chromosome 7; copy gain may activate the pathway.
• Activating MET mutations characterise a subset of PRCC (especially hereditary) but are not required for papillary adenoma.

Heterogeneity

• Separate microscopic lesions in one kidney may arise independently.
• PRCC-type alterations do not by themselves establish malignancy.

Diagnostic pearl: neither trisomy 7/17 nor a MET-pathway alteration distinguishes papillary adenoma from PRCC.

Papillary RCC (classic pattern)

• May be identical morphologically and immunophenotypically.
• >15 mm excludes adenoma; grade 3–4 nuclei or destructive invasion exclude it regardless of size.
• Pitfall: low-grade PRCC need not look more atypical than an adenoma.

Metanephric adenoma

• Tightly packed small tubules/acini, glomeruloid structures; high N:C ratio, primitive-looking nuclei.
• WT1+ and CD57+, CK7/AMACR negative; most carry BRAF V600E.
• Pitfall: psammoma bodies and glomeruloid or solid areas occur in both.

Papillary renal neoplasm with reverse polarity

• Delicate papillae lined by eosinophilic cells with nuclei toward the lumen; GATA3+, KRAS-mutated.
• Small adenoma-like analogues exist — size should not override this phenotype.

Mucinous tubular and spindle cell carcinoma

• Anastomosing tubules, spindle cells and mucinous/myxoid stroma; AMACR may overlap.

Incidental lesions

• Assess architecture, nuclear grade, circumscription and maximum size.
• Diagnosis is made on H&E; IHC is not needed for classic lesions.

Renal mass biopsy

• Size and full architecture cannot be established on a core — separation from low-grade PRCC is limited.
• For a small bland papillary proliferation, prefer “low-grade papillary renal neoplasm”.
• Do not rely on bland cytology or CK7/AMACR alone.

A 2024 discussion of renal cytology terminology also favoured the broader term “papillary neoplasm” in selected biopsy settings.

• A recognised precursor — a 2026 ISUP consensus called papillary adenoma arguably the best-established RCC precursor; this does not imply inevitable progression.
• 15 mm remains pragmatic — separation from low-grade PRCC rests on size, grade and lack of a capsule rather than a unique alteration; very small higher-grade papillary tumours lack a validated progression model.
• Not all small papillary lesions are alike — reverse-polarity lesions carry KRAS mutations instead of 7/17 gains; recognise distinctive morphology before applying a size-based label.
• Acquired cystic kidney disease — the 2026 ISUP consensus proposed cyst with epithelial proliferation for tufted, hyperplastic or cribriform cyst lining without a solid tumour, rather than calling it papillary adenoma.

• Classic low-grade papillary morphology and a maximum diameter of 15 mm.
• May be indistinguishable from classic PRCC except for size.
• Tubular and tubulopapillary architectures are acceptable; overt papillae are not mandatory.
• WHO/ISUP grade 1–2 nuclei; often unencapsulated.
• Foamy macrophages and psammoma bodies are supportive, not required.
• CK7 and AMACR positive — overlapping with PRCC; WT1 helps against metanephric adenoma.
• 7/17 gains support the PRCC relationship but do not establish malignancy.
• Reverse polarity with oncocytic cytoplasm → PRNRP spectrum.
• Multifocal adenomas may arise independently and often coexist with PRCC.
• Small size never justifies calling a high-grade tumour an adenoma.