Solitary Fibrous Tumor

Slide 1 · Solitary Fibrous Tumor

Pleural pathology · morphology · molecular diagnosis · risk assessment

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Recognize the characteristic gross and spindle-cell morphology.

Explain NAB2::STAT6 fusion and the diagnostic role of nuclear STAT6.

Distinguish SFT from pleural epithelial and other spindle-cell tumors.

Use morphology and validated risk factors without equating size with malignancy.

Slide 3 · A fibroblastic neoplasm, not a pleural mesothelioma

SFT is a mesenchymal soft-tissue neoplasm that commonly involves the pleura.

It may also arise within lung or at many extrathoracic anatomic sites.

Its defining molecular association is a NAB2::STAT6 fusion.

Its biological behavior ranges from indolent to recurrent or metastatic.

Slide 4 · Pleural location: Surface attachment matters

A pleural SFT may form a localized mass projecting from the pleural surface.

A pedicle may connect the lesion to visceral or parietal pleura.

This differs anatomically from a diffuse pleural rind typical of mesothelioma.

Location is an initial clue, not a stand-alone histologic diagnosis.

SCHEMATIC · not a histologic specimen

Pleural surface

Pedunculated mass

Slide 5 · Anatomic spectrum of solitary fibrous tumor

Pleura is a characteristic site but does not define the entity.

Tumors also occur in deep soft tissue, abdominal/retroperitoneal sites and head–neck regions.

Intrapulmonary SFT is less frequent than pleural SFT.

A similar molecular signature connects tumors across these locations.

Slide 6 · Pleural and intrapulmonary SFT are distinct locations

Pleural SFT is often attached to a serosal surface.

Feature

Pleural SFT

Intrapulmonary SFT

Origin

Pleural surface

Pulmonary parenchyma

Typical configuration

Surface-based ± pedicle

Intraparenchymal mass

Diagnostic implication

Mesothelioma differential

Spindle-cell lung tumors differential

Slide 7 · Terminology reflects a changing concept

Historic labels included localized fibrous pleural tumor and hemangiopericytoma.

A branching “hemangiopericytoma-like” vascular pattern is not entity-specific.

NAB2::STAT6 helps unify the variable morphologic appearances.

Modern diagnosis uses the designation solitary fibrous tumor.

Slide 8 · Asbestos exposure: A crucial negative association

SFT is not related to asbestos exposure.

Malignant pleural mesothelioma has a strong established asbestos association.

A history of asbestos exposure should not independently reclassify a spindle-cell lesion.

Morphology and lineage immunostains remain decisive.

Slide 9 · Clinical detection ranges from incidental to symptomatic

An indolent, localized SFT may be detected incidentally on imaging.

Large pleural tumors may produce breathlessness or discomfort through mass effect.

Clinical symptoms do not reliably establish histologic grade.

The relevant question is whether tumor compresses, invades or recurs.

Slide 10 · Why a large pleural mass causes symptoms

A growing mass occupies intrathoracic space.

Compression reduces expansion of adjacent lung tissue.

Displacement may cause dyspnea or chest discomfort.

The mechanism is mechanical; It does not require epithelial differentiation.

SCHEMATIC · not a histologic specimen

Pleural mass

Reduced adjacent lung volume

Slide 11 · Radiology localizes but does not confirm SFT

A circumscribed pleural-associated mass raises the possibility of SFT.

Imaging assesses size, site, relationship to pleura and neighboring structures.

Enhancement and vascularity may guide safe biopsy or operative planning.

Tissue morphology plus immunophenotype establish the diagnosis.

Slide 12 · Grossly: A firm, localized fibrous tumor

The cut surface is typically solid, firm and whitish to tan.

The prominence of fibrous stroma explains the firm consistency.

A pedicle is frequently described in pleural lesions.

Do not infer low metastatic risk from a well-circumscribed gross appearance alone.

SCHEMATIC · not a histologic specimen

Fibrous mass

Pedicle

Pleural surface

Slide 13 · Tumor size spans a broad spectrum

Examples only 1–2 cm in diameter.

Other lesions may become very large before detection.

Size influences pressure symptoms and validated risk assessments.

Absolute size alone does not define malignancy or determine outcome.

Slide 14 · Whorled and occasionally cystic cut surfaces

Intersecting collagen bundles can create a whorled cut-surface appearance.

Occasional cysts may contain viscous material in the Robbins description.

Hemorrhage, necrosis or irregular margins warrant additional sampling.

Grossly heterogeneous regions should be separately documented.

SCHEMATIC · not a histologic specimen

Whorled collagen-rich cut surface

Slide 15 · Macroscopic sampling: What the pathologist seeks

Record maximum dimension and relation to pleural attachment.

Examine tumor–pleura and tumor–lung interfaces.

Sample soft, hemorrhagic, necrotic or unusually cellular regions.

Assess margins in a resection specimen and document heterogeneity.

Slide 16 · The basic histologic triad

Spindle or ovoid tumor cells are distributed in collagenous stroma.

Cellularity is variable, even within a single tumor.

Prominent branching blood vessels may be present.

No single morphologic feature is by itself pathognomonic.

SCHEMATIC · not a histologic specimen

Cells + collagen + vessels

Slide 17 · Spindle cells: Restrained cytology in conventional SFT

Conventional tumors often contain uniform elongated nuclei.

Cytoplasm is usually inconspicuous relative to the dense stroma.

The cells may form short, irregular fascicles or loose aggregates.

Marked pleomorphism should prompt closer evaluation for aggressive change.

SCHEMATIC · not a histologic specimen

Elongated spindle cells

Slide 18 · Patternless architecture is a useful low-power clue

Tumor cells may appear haphazard rather than arranged in parallel fascicles.

Areas of relatively high and low cellularity can alternate.

Collagen separates cells and cell clusters.

Patternless architecture must be integrated with vessels and immunostains.

SCHEMATIC · not a histologic specimen

Haphazard cell arrangement

Slide 19 · Collagen and reticulin dominate the classic pattern

Whorls of collagen and reticulin fibers.

Variable fiber abundance produces fibrous and more cellular zones.

Dense collagen may resemble keloidal bands or show tissue clefting.

This stromal architecture helps explain the firm gross cut surface.

Slide 20 · Branching vascular channels: “staghorn” pattern

Dilated thin-walled vessels can branch at acute angles.

This vascular configuration was historically called hemangiopericytoma-like.

The pattern occurs in other mesenchymal neoplasms as well.

A vascular pattern cannot substitute for lineage markers.

SCHEMATIC · not a histologic specimen

Branching thin-walled vessels

Slide 21 · Perivascular fibrosis modifies vessel appearance

Concentric or irregular collagen may surround vascular channels.

This can accentuate the boundary between vessel and tumor stroma.

The finding complements the branching-vessel pattern.

Interpret the feature as part of a broader SFT morphologic spectrum.

Slide 22 · Cellularity varies within the same neoplasm

Hypocellular zones may appear collagen-rich and deceptively scar-like.

Cellular zones may appear densely packed and less obviously fibrous.

Focal sampling can therefore misrepresent the whole lesion.

Compare morphology across multiple blocks before judging risk.

SCHEMATIC · not a histologic specimen

Hypocellular

Hypercellular

Slide 23 · Myxoid stromal change can obscure classic features

Some SFTs show mucin-rich, pale or myxoid background matrix.

The spindle-cell population may then appear more dispersed.

A broad myxoid differential requires immunophenotypic correlation.

Myxoid change alone is not proof of aggressive behavior.

Slide 24 · Cellular SFT: Less conspicuous collagen

Hypercellular tumors may have rounded-to-spindled cells.

More closely packed nuclei can mask the characteristic fibrous stroma.

A vascular hemangiopericytoma-like pattern may become prominent.

Use STAT6, other immunostains and the sampled context for classification.

Slide 25 · Fat-forming SFT: Mature fat within the lesion

A recognized variant contains admixed mature adipocytes.

Clue

Fat-forming SFT

A possible mimic

Stroma

SFT-type spindle cells and collagen

Lipomatous tumor architecture

Molecular axis

NAB2::STAT6

Alternative entity-specific changes

Useful test

Nuclear STAT6 in context

Marker panel guided by morphology

Slide 26 · Giant-cell-rich SFT: An established variant

Multinucleated stromal giant cells may line pseudovascular spaces.

This appearance overlaps with the historical “giant cell angiofibroma” term.

Recognize the background SFT-like spindle cells and vasculature.

Use nuclear STAT6 and a targeted differential panel.

Slide 27 · Dedifferentiation: A sharp morphologic transition

Some rare SFTs contain a conventional area adjoining high-grade sarcoma.

The boundary between components may be abrupt.

High-grade regions may show marked pleomorphism and brisk mitoses.

Immunophenotypic markers may be reduced or lost in dedifferentiated areas.

SCHEMATIC · not a histologic specimen

Conventional component

High-grade component

Slide 28 · Conventional and aggressive histology differ

Conventional SFT: Bland cells, limited atypia, often low mitotic activity.

Domain

Conventional morphology

Concerning morphology

Cytology

Often bland

Atypia / pleomorphism

Proliferation

Often low mitotic activity

Increased mitoses

Viability

Necrosis absent

Necrosis may be present

Interface

Often circumscribed

May be infiltrative

Slide 29 · Necrosis: Distinguish true tumor necrosis

Coagulative tumor necrosis is an adverse feature in risk models.

Document the presence and extent of necrosis in the resection.

Do not mistake biopsy-related injury for spontaneous tumor necrosis.

Necrosis must be interpreted with age, size and mitotic rate.

Slide 30 · Mitotic activity requires systematic assessment

Evaluate representative viable, cellular tumor regions.

Count mitoses with a standardized area rather than relying on vague adjectives.

The Demicco model explicitly includes mitotic activity.

A small biopsy may underrepresent the highest proliferative focus.

Slide 31 · Infiltrative borders raise concern but are not a stage

SFT may appear sharply delineated in gross sections.

An infiltrative interface can accompany locally aggressive biology.

Document involvement of adjacent tissue and margin status.

Do not confuse infiltrative growth with proven distant metastasis.

Slide 32 · The diagnostic synthesis has three complementary axes

Morphology suggests a spindle-cell fibroblastic neoplasm.

Nuclear STAT6 strongly supports the NAB2::STAT6-linked entity.

CD34 and exclusionary markers refine the lineage differential.

Clinical site and tissue sampling resolve discordant cases.

SCHEMATIC · not a histologic specimen

Morphology

Immunophenotype

Molecular

Convergent interpretation

Slide 33 · Chromosome 12 rearrangement defines the molecular axis

NAB2 and STAT6 are neighboring genes on chromosome 12q13.

A recurrent intrachromosomal rearrangement generates NAB2::STAT6.

The alteration as a cryptic inversion.

A fusion transcript encodes a chimeric transcriptional regulator.

SCHEMATIC · not a histologic specimen

NAB2

STAT6

NAB2::STAT6

Intrachromosomal rearrangement · chromosome 12

Slide 34 · NAB2::STAT6 is hypothesized to drive tumorigenesis

The fusion brings functional regions of NAB2 and STAT6 together.

The chimeric product affects transcriptional regulation.

Its driver role as a hypothesis, not an experimentally complete mechanism.

Nuclear STAT6 immunoreactivity serves as a practical surrogate signal.

SCHEMATIC · not a histologic specimen

NAB2::STAT6 fusion

Chimeric transcription factor

Altered gene regulation

Putative oncogenic driver

Slide 35 · Diagnostic specificity comes from fusion context

An individual immunostain is not equivalent to direct sequencing.

A characteristic morphologic phenotype increases the weight of STAT6 positivity.

Some non-SFT tumors may show nuclear STAT6 staining.

Fusion testing is useful when morphology and immunophenotype conflict.

Slide 36 · Nuclear STAT6: The most informative routine stain

Strong, diffuse nuclear staining is characteristic of conventional SFT.

The localization matters: Evaluate tumor nuclei, not merely background cells.

STAT6 is a surrogate for NAB2::STAT6, not direct proof of the gene fusion.

Rare mimics and high-grade marker loss require interpretation.

SCHEMATIC · not a histologic specimen

Dark nuclei represent IHC nuclear signal

Slide 37 · CD34: Common but insufficient by itself

Conventional SFTs are commonly CD34 positive.

CD34 is not specific: Multiple other spindle-cell lesions also stain.

Loss of CD34 may occur in malignant or dedifferentiated components.

Use CD34 in concert with nuclear STAT6 and tumor morphology.

Slide 38 · CD99 and BCL2 are supporting, nonspecific stains

CD99 and BCL2 are often positive in SFT.

Both are expressed in other spindle-cell neoplasms.

They may contribute when the differential is wide.

Neither substitutes for a specific molecular or convincing STAT6 result.

Slide 39 · Keratin negativity supports separation from mesothelioma

Keratin negativity in usual SFT.

Mesothelioma generally expresses epithelial keratins.

A broad-spectrum cytokeratin stain is part of a pleural spindle-tumor panel.

Rare focal keratin expression in SFT means interpretation needs context.

Slide 40 · Pleural SFT versus malignant mesothelioma

SFT is generally localized; Mesothelioma often diffusely invests pleura.

Feature

Solitary fibrous tumor

Mesothelioma

Architecture

Localized mass ± pedicle

Often diffuse pleural rind

STAT6 nuclei

Usually positive

Usually negative

CD34 tumor cells

Commonly positive

Usually negative

Cytokeratin

Usually negative

Usually positive

Slide 41 · Sarcomatoid carcinoma is another pleural mimic

Spindle-cell epithelial malignancy can simulate sarcoma morphology.

Broad keratin expression favors an epithelial process.

SFT morphology plus nuclear STAT6 supports the alternative lineage.

Interpret staining within the clinical and imaging context.

Slide 42 · Soft-tissue spindle-cell differential is broad

Schwannoma or MPNST: Neural-lineage morphology and marker context.

Mimic

Overlapping feature

Useful discriminator

Schwannoma

Spindle-cell architecture

Neural marker pattern

GIST

CD34-positive spindle cells

KIT / DOG1 context

Desmoid fibromatosis

Collagen-rich spindle cells

β-catenin / clinical pattern

Synovial sarcoma

Monomorphic spindle cells

Keratin / SS18 fusion

Slide 43 · STAT6 positivity is not absolutely specific

Dedifferentiated liposarcoma can exhibit nuclear STAT6 positivity.

Other mesenchymal tumors may rarely show nuclear immunoreactivity.

MDM2 amplification testing may be needed in a liposarcoma differential.

Fusion detection offers added confidence in an equivocal case.

Slide 44 · Diagnostic pitfalls intensify after dedifferentiation

A high-grade focus may lose CD34, STAT6 or both.

Sampling only this area may conceal the conventional SFT component.

Search for a lower-grade area and compare different tumor blocks.

Confirm the diagnosis molecularly when necessary.

Slide 45 · When to request molecular confirmation

Consider fusion-directed testing if immunophenotype is discordant.

Consider it in unusual site, high-grade morphology or competing STAT6-positive mimic.

A positive NAB2::STAT6 fusion supports SFT identity.

Assay sensitivity depends on method, fusion partners and specimen quality.

Slide 46 · Small biopsy: Identity is easier than risk prediction

A core biopsy can show the characteristic cell/vessel/stroma triad.

A limited fragment may miss necrosis, focal hypercellularity or dedifferentiation.

Immunostains can narrow the lineage diagnosis on small material.

Complete risk stratification is most reliable with the resection specimen.

Slide 47 · Report the features that affect clinical interpretation

Specify site, tumor size and margins when assessable.

Describe mitotic activity using a defined counting area.

Record necrosis, pleomorphism and dedifferentiation if present.

Include relevant STAT6/CD34/keratin results and molecular results when performed.

Slide 48 · A practical workflow for a pleural spindle-cell lesion

Step 1: Locate the mass and evaluate its architecture.

Step 2: Assess spindle cytology, collagen and vascular pattern.

Step 3: Perform STAT6, CD34 and exclusionary epithelial-lineage stains.

Step 4: Resolve discordance through additional markers or fusion testing.

SCHEMATIC · not a histologic specimen

Localize lesion

Spindle-cell morphology

STAT6 / CD34 + keratin

Integrate or test fusion

Slide 49 · “Malignant” morphology and metastasis risk are distinct

Histologic atypia is evidence, not certainty, of future progression.

Metastasis can occur in a minority without striking early atypia.

Risk assessment incorporates clinical and morphologic predictors.

Communicate a risk category rather than promising a deterministic outcome.

Slide 50 · The Demicco model uses four variables

Patient age provides a clinical dimension.

Tumor size quantifies growth burden.

Mitotic rate reflects proliferative activity.

Tumor necrosis supplies another adverse morphologic variable.

SCHEMATIC · not a histologic specimen

Age

Size

Mitotic rate

Necrosis

Combined prognostic stratification

Slide 51 · Risk categories must be applied to the right setting

The revised Demicco model stratifies non-meningeal SFT by metastatic risk.

Its categories are low, intermediate and high risk.

It complements—but does not replace—histologic interpretation.

A model is calibrated to studied populations, not every site or scenario.

Slide 52 · Do not use a single adverse feature as a binary verdict

A large tumor may still follow a relatively indolent course.

A mitotically active, necrotic tumor deserves greater concern.

Risk estimates depend on combined factors and appropriate sampling.

Avoid presenting an isolated measurement as a categorical diagnosis.

Slide 53 · Metastasis remains possible after apparently complete excision

A minority of SFTs metastasize, sometimes after a prolonged interval.

Distant spread indicates clinically malignant behavior.

Long-term surveillance is justified even for seemingly bland primary tumors.

Follow-up should reflect location, resection status and validated risk.

Slide 54 · Local recurrence has several possible drivers

Incomplete excision can leave microscopic residual disease.

High-risk morphology can indicate greater propensity to recur.

Anatomic constraints may complicate obtaining negative margins.

A recurrence should be resampled for evolution or dedifferentiation.

Slide 55 · Surgery is the principal treatment for localized disease

Complete excision with negative margins is the usual primary objective.

Resection strategy depends on pleural attachment and involved structures.

The pathology report guides multidisciplinary risk discussion.

There is no universal fixed follow-up schedule in the Robbins excerpt.

Slide 56 · Long-term follow-up is a biological, not decorative, add-on

SFT outcome can be delayed and is not fully predicted by bland histology.

Clinical surveillance should be individualized by risk and site.

Review new masses for local recurrence versus metastasis.

Avoid declaring cure solely because the initial lesion was circumscribed.

Slide 57 · Doege–Potter syndrome: Uncommon paraneoplastic hypoglycemia

A subset of SFTs produces insulin-like growth factor 2 (IGF2).

The resulting non-islet-cell tumor hypoglycemia may be clinically significant.

Recurrent unexplained hypoglycemia can provide a clue to an occult SFT.

This syndrome is supplementary to, not described in, the supplied Robbins excerpt.

Slide 58 · Why excess IGF2 can cause hypoglycemia

Tumor-related IGF2 exerts insulin-like metabolic effects.

Glucose consumption and reduced hepatic glucose output contribute to low glucose.

Definitive management focuses on the underlying tumor when feasible.

The clinical phenotype does not independently grade the lesion.

SCHEMATIC · not a histologic specimen

Tumor-associated IGF2

Insulin-like metabolic effects

Hypoglycemia

Slide 59 · Case 1: Circumscribed pleural mass

An adult has a large, localized pleural-based mass on imaging.

The resection is firm and attached by a narrow pedicle.

Histology shows bland spindle cells, dense collagen and branching vessels.

Question: What marker pair most strongly supports SFT?

Diagnostic reasoning case — synthesized educational vignette

Slide 60 · Case 1: Morphology plus markers resolves the lesion

Diffuse nuclear STAT6 and tumor-cell CD34 support SFT.

Keratin negativity makes an epithelial pleural tumor less likely.

Pedunculated growth supports localization but does not establish lineage.

Final interpretation integrates site, morphology and staining.

Slide 61 · Case 2: A pleural spindle-cell lesion stains for keratin

The lesion extensively coats the pleural surface rather than forming a solitary mass.

Spindle cells show keratin reactivity without convincing nuclear STAT6.

Question: Which competing diagnosis is prioritized?

What additional mesothelial markers or molecular work-up would be appropriate?

Diagnostic reasoning case — synthesized educational vignette

Slide 62 · Case 2: Avoid mistaking a pleural malignancy for SFT

Sarcomatoid mesothelioma is an important diagnostic consideration.

A cytokeratin-positive, STAT6-negative profile argues against typical SFT.

Extend the mesothelial versus carcinoma differential according to findings.

Clinical asbestos exposure is contextual, never a substitute for pathology.

Slide 63 · Case 3: Atypia, necrosis and brisk mitoses

A resected SFT contains a region of marked atypia with tumor necrosis.

Several blocks show higher mitotic activity than the bland component.

Question: Is “large” alone an adequate final risk assessment?

What additional parameters belong in the report?

Risk-assessment case — synthesized educational vignette

Slide 64 · Case 3: Combine variables and document heterogeneity

No: Size alone does not classify metastatic risk.

Document age, size, mitoses and tumor necrosis for the Demicco model.

Report dedifferentiation, margins and other relevant pathology findings.

Discuss high-risk features without claiming inevitable metastasis.

Slide 65 · Five diagnostic and prognostic principles

Think SFT for a localized collagen-rich, vascular spindle-cell mass.

Recognize the defining NAB2::STAT6 molecular association.

Use nuclear STAT6 with CD34 and an appropriate exclusionary panel.

Separate SFT from asbestos-associated mesothelioma.

Combine clinical and pathologic variables when assessing risk.

Slide 66 · References and scope of evidence

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 15, pp. 661–662.

Tariq MU, et al. Diagnostic Pathology. 2021;16:32. doi:10.1186/s13000-021-01095-2.

Demicco EG, et al. Modern Pathology. 2017;30:1433–1442. doi:10.1038/modpathol.2017.54.

Supplementary reviews address variants, molecular differential diagnoses and clinical management; Robbins remains the primary teaching source.