Mucinous tubular and spindle cell carcinoma

• A distinctive renal epithelial malignancy of elongated tubules, bland spindle cells and variable extracellular mucinous/myxoid stroma.
• Uncommon: generally <1% of renal malignancies.
• Usually well circumscribed, low grade and indolent.
• Classic picture: packed elongated tubules merging seamlessly with fascicles of bland spindle cells in a blue-grey matrix.
• Neither conspicuous mucin nor an extensive spindle cell component is obligatory in every case.
• PAX8, CK7 and AMACR positive, with marked immunophenotypic overlap with papillary RCC.
• Molecular hallmark: multiple whole-chromosome losses (1, 4, 6, 8, 9, 13, 14, 15, 22) and recurrent Hippo pathway alterations.
• Rare tumours show high-grade or sarcomatoid transformation and metastasise; it is a carcinoma, not a tumour of low malignant potential.

Diagnostic pearl: the key feature is the transition between elongated tubules and bland spindle cells, not the mucin alone.

Clinical

• Adults, usually middle-aged or older; female predominance.
• Mostly incidental on imaging; some present with haematuria, flank pain or a mass.
• May arise in end-stage kidney disease, but this is not a defining association.

Gross

• Solitary, well-circumscribed solid mass, often with a fibrous pseudocapsule.
• Tan-grey, grey-white or pale yellow; gelatinous or translucent when mucin is abundant.
• Haemorrhage, cystic change or necrosis are occasional.
• Extensive necrosis or infiltrative growth should prompt a search for high-grade transformation or another RCC.

Diagnostic pearl: a pale, circumscribed, somewhat gelatinous renal mass fits MTSCC, but gross appearance is not specific.

Tubular component

• Closely packed, elongated, branching or anastomosing tubules with slit-like lumina.
• Cuboidal to low columnar cells with uniform nuclei; some tubules compressed into cords.

Spindle cell component

• Bland spindle cells in short fascicles, parallel bundles or streaming cords.
• Merge imperceptibly with the tubules; elongated uniform nuclei without significant atypia.
• These are epithelial cells, not a sarcomatous component.

Mucinous stroma

• Pale blue-grey extracellular matrix separating cords and fascicles; Alcian blue positive.
• Amount varies widely.

Cytology

• Pale eosinophilic to amphophilic cytoplasm, fine chromatin, inconspicuous nucleoli, low mitotic activity.

Diagnostic pearl: bland spindle cells merging with compact elongated tubules are highly suggestive of MTSCC even when mucin is scarce.

• Elongated tubular: the most characteristic pattern; parallel or anastomosing tubules with compressed lumina.
• Compact tubular / cord-like: little stroma, can resemble solid or tubular PRCC; look for subtle spindle cell transitions.
• Spindle cell-predominant: may mimic a mesenchymal tumour; even focal tubules establish the biphasic picture.
• Papillary / tubulopapillary: tufts or true fibrovascular papillae; extensive papillae create major overlap with PRCC.
• Nested or solid: focal is acceptable; extensive expansile solid growth warrants assessment for high-grade transformation.
• Cystic / dilated tubules: can obscure the packed tubular look; lining stays bland.

Diagnostic pearl: a papillary, spindle cell or compact tubular tumour may still be MTSCC if characteristic areas or molecular evidence are present.

• Recognised morphologic variant with inconspicuous or absent extracellular mucin on H&E.
• Describes the stroma, not a distinct molecular subtype.
• Compact tubules and cords are prominent; the background is fibrous or minimally myxoid.
• May be virtually indistinguishable from low-grade tubular PRCC on limited samples.
• Alcian blue (pH 2.5) may reveal scant acidic mucin: supportive, not specific; a negative stain does not exclude the diagnosis.
• Approach: search for tubule-to-spindle transitions, take more sections, interpret CK7/AMACR cautiously, consider copy-number profiling.

Diagnostic pearl: mucin-poor does not mean spindle cell-poor. The two components vary independently.

• Cytoplasm: focal clear cell change or oncocytic/granular eosinophilic phenotype can mimic other RCCs.
• Nuclei: mild variability and occasional nucleoli occur; marked pleomorphism or brisk mitoses suggest high-grade transformation.
• Foamy macrophages: focal or extensive, PRCC-like, not diagnostic in isolation.
• Psammoma bodies: occasional; do not automatically redirect to PRCC.
• Lymphoplasmacytic inflammation: may obscure the characteristic morphology.
• Other stroma: fibrosis, hyalinisation, calcification or metaplastic bone; myxoid matrix may be uneven.

Diagnostic pearl: foamy macrophages, psammoma bodies and focal papillae are compatible with MTSCC and do not by themselves establish PRCC.

No routine marker definitively separates MTSCC from PRCC.

• PAX8: usually positive in tubules and spindle cells; very helpful when spindle cells dominate.
• CK7: usually diffuse in both components; does not discriminate from PRCC.
• AMACR: often diffuse; not proof of PRCC.
• CK19, EMA: usually positive; EMA may highlight lumina and cords.
• CD10: usually negative or focal; diffuse strong staining favours PRCC (in one 9-case comparison only 1 MTSCC was CD10+, versus 8 of 10 PRCCs), but results vary across cohorts.
• Spindle cells retain CK7, CK19, EMA and PAX8; interpret SMA/desmin cautiously (entrapped myofibroblasts or smooth muscle).

Diagnostic pearl: CK7+/AMACR+/PAX8+ is typical of MTSCC but equally compatible with PRCC. Morphology and chromosomal findings decide.

Multiple chromosomal losses

• Whole-chromosome losses of 1, 4, 6, 8, 9, 13, 14, 15 and 22 in varying combinations; 1, 6, 9, 14, 15 and 22 are particularly recurrent.
• Contrasts with the +7/+17 gains of many PRCCs.
• Broad copy-number profiling is more useful than single-chromosome FISH.

Hippo pathway

• Recurrent biallelic inactivation of PTPN14, NF2 and SAV1, leading to nuclear YAP1 activity.
• In a multi-institutional study of 22 tumours: Hippo alterations 85%, PTPN14 31%, NF2 23%; nuclear YAP1 in about 90%.
• NF2 or PTPN14 mutations alone are not specific, and YAP1 IHC is not an established routine test.

Diagnostic pearl: a characteristic multi-chromosome loss pattern is stronger molecular support than an isolated Hippo pathway alteration.

• VSTM2A: upregulated in transcriptomic studies; RNA in situ hybridisation may help separate MTSCC from PRCC when morphology and IHC overlap. Not routinely available.
• YAP1: nuclear expression reflects Hippo dysregulation; not specific enough as a standalone marker.
• CDKN2A/CDKN2B (9p21) deletion: reported in aggressive and high-grade MTSCC; not a feature of conventional tumours; prognostic value unvalidated.

Diagnostic pearl: the two core molecular concepts are multiple chromosomal losses and Hippo dysregulation; VSTM2A is a promising adjunct.

The most common and practically important mimic, especially with compact tubules, scant mucin or papillae.

• Architecture: elongated tubules, cords and bland spindle cells (MTSCC) vs papillary, tubular, tubulopapillary (PRCC).
• Mucin: usually present, may be minimal (MTSCC) vs usually absent (PRCC).
• Spindle cells: characteristic (MTSCC) vs not typical (PRCC).
• Foamy macrophages: may occur in MTSCC; common in PRCC.
• CK7, AMACR: positive in both.
• CD10: usually negative/focal (MTSCC) vs more often positive (PRCC).
• Molecular: multiple whole-chromosome losses (MTSCC) vs +7/+17, subset MET (PRCC).

Pitfall: do not use the old PRCC type 1/type 2 distinction; the differential rests on full architecture and molecular profile.

FH-deficient RCC

• Tubular, papillary, solid, cribriform or tubulocystic; infiltrative tubules can mimic MTSCC.
• Viral inclusion-like nucleoli with perinucleolar halos (may be focal); myxoid or desmoplastic stroma possible.
• FH loss and/or 2SC positivity; retained FH does not exclude every case, molecular testing may be needed.

Collecting duct carcinoma

• Irregular tubules in desmoplastic stroma, high-grade nuclei, markedly infiltrative, often inflamed.
• Conventional MTSCC is circumscribed and bland; high-grade MTSCC may need molecular testing.

Diagnostic pearl: uniform bland spindle cells merging with low-grade tubules support MTSCC; prominent nucleoli, heterogeneous architecture and destructive infiltration point elsewhere.

Sarcomatoid RCC vs the ordinary spindle cells of MTSCC

• MTSCC spindle cells: uniform, bland, low mitotic activity, seamless transition from tubules.
• Sarcomatoid change: marked atypia, frequent and atypical mitoses, necrosis, expansile or destructive sheets.

Smooth muscle tumours

• Organised intersecting fascicles, cigar-shaped nuclei, diffuse smooth muscle markers.
• PAX8 and keratin in the spindle cells favour MTSCC; sample extensively for focal tubules.

Metanephric adenoma

• Packed small tubules and acini of primitive cells with scant cytoplasm.
• WT1 and CD57 positive, BRAF V600E; lacks the spindle cell/myxoid continuum.

Diagnostic pearl: before diagnosing a sarcomatoid or mesenchymal renal tumour, exclude spindle cell-predominant MTSCC with PAX8/keratin and a search for tubules.

High-grade features

• Pleomorphic nuclei, prominent nucleoli, increased and atypical mitoses.
• Extensive solid growth, coagulative necrosis, vascular invasion, destructive infiltration.
• Sarcomatoid differentiation: an overtly malignant spindle cell population, focal or extensive; conventional areas may need extensive sampling.

Molecular

• Additional genomic alterations, including CDKN2A/CDKN2B deletion, in some aggressive tumours; no validated predictor of progression.

Behaviour

• Conventional low-grade MTSCC: excellent outcome after resection.
• Recurrence and metastasis are documented, sometimes in tumours without overt sarcomatoid change.

Diagnostic pearl: bland morphology is reassuring but not an absolute guarantee against metastasis.

1. Tubules: elongated, packed or anastomosing, slit-like lumina, bland cells.
2. Spindle cell continuum: gradual transition to uniform spindle cells in short fascicles.
3. Mucin: pale blue-grey stroma; Alcian blue and more sections if subtle.
4. Targeted IHC: PAX8, CK7, AMACR, CD10 as the differential requires; CK7/AMACR overlap with PRCC.
5. Atypical findings: nucleoli, necrosis, infiltration or high-grade spindle cells: consider FH-deficient RCC, sarcomatoid RCC or high-grade MTSCC.
6. Molecular in ambiguous cases: multiple losses favour MTSCC; +7/+17 favours PRCC.

On biopsy

• May sample only compact tubules, spindle cells or papillae; mucin-poor tumours can be indistinguishable from PRCC.
• A spindle cell-predominant core can mimic a mesenchymal tumour.
• Focal high-grade transformation can be missed.
• When key features are absent or discordant, a descriptive diagnosis with the main differential is preferable.

Diagnostic pearl: one unequivocal tubular, spindle and mucinous area is often more informative than an expanded IHC panel.

• Hippo pathway is central: PTPN14/NF2/SAV1 inactivation and YAP1 activation separate MTSCC biologically from PRCC; ambiguous MTSCC/PRCC cases benefit more from copy-number profiling than from extra epithelial stains.
• High-grade MTSCC: a 2024 report in a haemodialysis patient; CDKN2A/B deletion implicated in aggressive cases. High-grade morphology does not exclude MTSCC, but convincing conventional areas and, if needed, molecular support are required.
• Metastasis without sarcomatoid change: a 2026 report of mucin-poor MTSCC with bone metastasis. Mucin-poor is a diagnostic variant, not an established adverse prognostic factor.
• Checkpoint inhibitor response: a 2025 case of molecularly confirmed high-grade MTSCC with MLH1/PMS2 loss responding to immunotherapy. A single case, not a treatment standard.
• VSTM2A remains a promising adjunct for the MTSCC vs PRCC problem pending validation and wider availability.

• Elongated tubules merging with bland spindle cells in variable mucinous stroma.
• Mucin may be abundant, scant or inconspicuous; Alcian blue highlights acidic mucin.
• Mucin-poor MTSCC is a morphologic variant, not a separate molecular entity.
• Papillae, foamy macrophages, psammoma bodies, oncocytic or clear cell change can occur.
• CK7 and AMACR positive, overlapping with PRCC; CD10 usually negative or focal.
• Losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15 and 22; PRCC more often shows +7/+17.
• Biallelic Hippo alterations (PTPN14, NF2, SAV1); YAP1 is a biological correlate, not a routine marker.
• The bland spindle cells are part of the tumour and must not be called sarcomatoid.
• True sarcomatoid change is overtly malignant and aggressive; most MTSCCs do well, but metastases occur.
• Copy-number analysis is most valuable in mucin-poor, PRCC-like or high-grade tumours.