Juxtaglomerular cell tumour

• Rare renal mesenchymal neoplasm (reninoma) differentiating toward renin-producing juxtaglomerular cells, related to modified smooth muscle cells of the afferent arteriole.
• Mostly adolescents and young adults, often with secondary hypertension; renin excess activates RAAS and may cause hypokalaemia.
• Uniform round, polygonal or short spindle glomoid cells in sheets, nests and trabeculae with a conspicuous delicate vascular network.
• PAS-positive, diastase-resistant renin granules may be present.
• Renin IHC (granular cytoplasmic) is the most direct marker; CD34 and SMA are frequent but overlap with glomus tumour; GATA3 helps against glomus tumour; PAX8 and keratins negative.
• Usually benign after excision; rare infiltrative and malignant cases exist; MAPK-RAS activation in a subset.

Diagnostic pearl: a circumscribed renal tumour of uniform glomoid cells and delicate branching vessels, especially in a young hypertensive patient, should prompt JGCT.

• Classical functional: adolescents or young adults, more often female; persistent or resistant hypertension; headache, dizziness, visual disturbance, palpitations, fatigue; secondary hyperaldosteronism and hypokalaemia.
• Atypical functional: hypertension without hypokalaemia; renin and aldosterone vary with medication, posture, sodium intake, sampling and assay; one normal renin value does not exclude it.
• Nonfunctioning: normotensive, incidental, yet renin-expressing; function cannot be inferred from morphology.

Diagnostic pearl: hypertension, high renin and hypokalaemia are highly suggestive but not obligatory.

• Usually solitary, well-demarcated cortical mass, often small; partial capsule or compressed parenchyma.
• Solid, grey-white, tan or yellow-tan, fairly homogeneous; focal haemorrhage or cystic degeneration; sometimes multinodular or lobulated.
• Large lesions may distort the parenchyma or collecting system; rare tumours infiltrate.

Diagnostic pearl: circumscription does not prove benignity, and a non-cortical location does not exclude JGCT.

Architecture

• Solid sheets, rounded nests, short trabeculae and lobules separated by delicate fibrovascular septa with many thin-walled vessels; occasional tubular, pseudopapillary or microcystic foci.

Cells

• Uniform round to polygonal or short spindle cells, moderate pale eosinophilic cytoplasm, central round nuclei, fine chromatin, small nucleoli, little pleomorphism.

Mitoses

• Absent or rare; no atypical mitoses; low Ki-67.

Stroma

• Delicate vascular connective tissue, hyalinised or sclerotic areas, oedema or myxoid change, mast cells and inflammatory cells.

Diagnostic pearl: bland glomoid cells + compact solid/trabecular growth + delicate branching vessels is the recognisable H&E phenotype.

• Thin-walled branching vessels: numerous anastomosing channels; haemangiopericytoma-like or staghorn.
• Perivascular arrangement: cells applied to vessel walls, concentric or radial; glomus-like.
• Thick-walled vessels: may be interspersed and suggest AML or a smooth muscle tumour; not defining.
• Hyalinised walls: focal perivascular sclerosis, more in degenerated tumours.

Diagnostic pearl: staghorn vessels are not diagnostic; they occur in glomus tumour, SFT and other spindle-cell neoplasms.

• Fine cytoplasmic granules, often subtle on H&E.
• PAS-positive, diastase-resistant; negative or equivocal PAS does not exclude JGCT; PAS is not specific.
• Electron microscopy: membrane-bound renin secretory granules with rhomboid crystalline structures; rarely needed when renin IHC is convincing.

Diagnostic pearl: renin granules are characteristic, but renin IHC is more practical than EM.

• Renin may be heterogeneous with secretory activity and fixation; native JG cells are internal controls.
• CD34 stains the tumour cells diffusely, not just vessels; it cannot separate JGCT from glomus tumour or SFT.
• SMA can be weak or absent in molecularly confirmed tumours; do not exclude JGCT on SMA alone.

Diagnostic pearl: renin + CD34 + GATA3, with SMA as support, is the most useful combination.

• Native JG cells in adjacent kidney stain; assess the tumour nests.
• Negative or equivocal renin may reflect fixation or assay; integrate morphology, GATA3, CD34, SMA and clinical data; consider molecular work or expert review.
• Tissue expression is not endocrine function: reninomas can be normotensive, and renin abnormalities are not specific.
• CD117: mast cells stain strongly; all 12 JGCTs in a 2022 series were CD117 negative.

Diagnostic pearl: lack of hypokalaemia or one normal plasma renin does not exclude a reninoma.

Gupta et al., Human Pathology 2022: 15 JGCTs vs 9 renal glomus tumours; median age 27 vs 51 years.

• SMA, CD34 and collagen IV overlap; renin is most discriminatory; GATA3 adds value; integrate with the clinical context.

Diagnostic pearl: SMA+/CD34+ does not separate JGCT from glomus tumour; renin and GATA3 do.

Lobo et al., Mod Pathol 2024 (10 tumours, WES)

• Gain-of-function RAS-family alterations in a subset; no alteration shared by all.
• Three tumours with concerning histology had uneventful follow-up.

Michalova et al., AJSP 2025 (15 tumours, DNA, RNA, methylation)

• Gains of 1p, 10, 17, 19; losses of 9, 11, 21; one pathogenic HRAS mutation; no recurrent fusion.
• One suspected JGCT with NAB2::STAT6 was reclassified as SFT.
• Methylation separated JGCT from glomus tumour and SFT.

• RAS/MAPK activation is relevant in a subset; no universal driver or validated molecular test; convincing cases do not need sequencing.

NOTCH1 rearrangements were reported in reninoma (Nat Commun 2023) and NOTCH signalling has been linked to JG cell transformation (Hum Pathol 2025), but no recurrent fusion was found in the 2025 multi-institutional series.

Diagnostic pearl: molecular studies support JGCT as a distinct neoplasm, but MAPK-RAS alterations are neither universal nor required.

Diagnostic pearl: a glomus-like renal lesion in a hypertensive patient needs renin and GATA3 before calling it glomus tumour.

Overlap

• Patternless spindle cells, staghorn vessels, hyalinisation, circumscribed renal or perirenal mass.

Favours SFT

• More spindled cells, alternating collagenous and cellular areas, ropy collagen, nuclear STAT6, NAB2::STAT6.

Favours JGCT

• Uniform round glomoid cells, granular renin, GATA3, renin-mediated hypertension.

In the 2025 molecular series a suspected JGCT with NAB2::STAT6 on RNA sequencing was reclassified as SFT.

Diagnostic pearl: staghorn vessels do not establish JGCT; strong nuclear STAT6 means SFT work-up.

Shared

• Perivascular differentiation, SMA, eosinophilic cells, thick-walled vessels, solid mass.

Favours AML

• Mature fat, dysmorphic vessels, spindle or epithelioid myoid cells, HMB45/Melan-A, TSC/mTOR alterations.

Favours JGCT

• Compact uniform glomoid cells, thin-walled branching capillaries, renin, CD34 and GATA3, no melanocytic phenotype.

Diagnostic pearl: smooth muscle and thick vessels without fat are not enough for AML; renin and melanocytic markers resolve it.

• Solid oncocytic RCC: uniform eosinophilic cells with rich vessels; PAX8 and keratins positive; renin not a tumour marker.
• Clear cell RCC: nested alveolar growth, diffuse membranous CAIX, VHL/3p loss.
• EVT: large vacuoles, prominent nucleoli, CD117 and cathepsin K positive.
• Papillary RCC: solid or trabecular areas; CK7, AMACR and PAX8.

Diagnostic pearl: a circumscribed tumour of bland epithelioid cells is not necessarily epithelial; PAX8/keratin negativity plus renin redirects to JGCT.

• Haemangiopericytoma-like tumours: decide the lineage of the tumour cells; CD31/ERG in tumour cells means endothelial.
• Leiomyoma: fascicles, SMA and desmin, no renin-positive glomoid cells, usually not diffusely CD34+.
• Paraganglioma: organoid nests, sustentacular S100/SOX10, neuroendocrine markers; catecholamine rather than renin secretion.
• Metanephric stromal tumour: peritubular onion-skinning, angiodysplasia, entrapped nephrons; native JG cells stain for renin.

Diagnostic pearl: in a perivascular-looking tumour, identify which compartment is neoplastic before reading CD34, SMA, endothelial markers or renin.

• Rare concerning features: marked atypia, prominent nucleoli, increased or atypical mitoses, necrosis, destructive infiltration, sinus or pelvic extension, vascular invasion.
• Hogeboom et al. (Virchows Arch 2025): a relatively large, high-grade, locally infiltrative JGCT extending into the pelvis, with uncertain prognostic significance.
• Document these features and consider follow-up; no scoring model separates benign from malignant JGCT; atypia does not reliably predict metastasis.

Diagnostic pearl: atypical JGCT is not automatically malignant; report the concerning features rather than a definitive malignant label.

• Exceptionally rare but established: a 15 cm tumour with renal vein invasion developed bilateral lung metastases about six years later, with identical renin-positive morphology and renin granules on EM.
• Other aggressive cases: local recurrence, renal vein or lymphovascular invasion, distant metastases, rare paediatric metastatic tumours.
• Large size, necrosis, proliferation and vascular invasion may be concerning, but none is validated; bland tumours have occasionally behaved aggressively.

Diagnostic pearl: conventional JGCT is predominantly benign, but not incapable of metastasis.

1. Morphology: circumscribed tumour of uniform glomoid cells, solid/nested/trabecular growth, delicate branching vessels.
2. Clinical context: hypertension, hypokalaemia, high renin, secondary hyperaldosteronism; their absence does not exclude JGCT.
3. Immunophenotype: renin, CD34, SMA, GATA3; PAX8 and PanCK to exclude RCC.
4. Exclude mimics: glomus tumour, SFT, AML, leiomyoma, RCC; add STAT6 or melanocytic markers.
5. Equivocal cases: confirm cytoplasmic renin; expert review or molecular analysis if discordant.
6. Adverse features: size, necrosis, atypia, mitoses, vascular invasion, infiltration.
7. Report: JGCT, describing unusual features rather than assuming a validated risk category.

• A core may show only compact epithelioid cells without the vascular pattern; mistaken for oncocytic RCC or glomus tumour.
• Strong CD34 suggests SFT; SMA suggests AML or a smooth muscle tumour; renin may be unavailable or inconclusive; CD117+ mast cells mislead.
• Necrosis or infiltration may be unsampled; risk cannot be assessed reliably.

Suggested wording

• Conventional: “Juxtaglomerular cell tumour (reninoma). Uniform round to polygonal cells in solid nests and short trabeculae with a delicate branching vascular network and granular cytoplasmic renin; no significant atypia, necrosis or increased mitoses.”
• Atypical: “Juxtaglomerular cell tumour with atypical histological features: [specify]. Their significance is incompletely established; clinical correlation and follow-up are recommended.”
• Inconclusive core: “Renal perivascular neoplasm, favour juxtaglomerular cell tumour. Renin IHC and correlation with biochemical findings are recommended.”

• MAPK-RAS activation (Mod Pathol 2024): activating RAS-family alterations in a subset; not sensitive enough for routine confirmation.
• Methylation (AJSP 2025): JGCT, glomus tumour and SFT form distinct groups; recurrent gains and losses; no recurrent fusion.
• Spatial transcriptomics (2026, one paediatric tumour): REN, CD34, VIM, GATA3, KISS1, NOTCH3, PPARG; mast cells carried KIT expression, supporting the CD117 pitfall; needs validation.
• Atypical histology does not reliably predict behaviour: keep risk assessment descriptive.
• Metastatic reninoma (2026 case): lung metastases, ATRX alteration, reported olaparib response; a single case, not a standard of care.

• Rare renal mesenchymal tumour with renin-producing differentiation; mostly young adults; usually benign.
• Hypertension is characteristic but not universal; hypokalaemia and high aldosterone reflect RAAS activation; nonfunctioning tumours exist.
• Circumscribed; uniform glomoid cells in solid, nested and trabecular patterns with delicate branching vessels.
• PAS-D+ granules; rhomboid crystals on EM; granular renin IHC is the most direct marker.
• CD34 often diffuse, SMA frequent but variable, GATA3 valuable; PAX8 and keratins negative; CD117 marks mast cells only.
• Glomus tumour is the main mimic: renin and GATA3 discriminate, CD34 and SMA do not; exclude SFT when vessels are staghorn.
• MAPK-RAS in a subset; no defining fusion; rare infiltrative, recurrent and metastatic tumours; no validated risk model.