Solitary Fibrous Tumor of the Stomach: Diagnostic Pitfalls and Clinical Implications

ABSTRACT

INTRODUCTION

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that most commonly originates in the pleura but can also occur at extrapleural sites, including the abdominal cavity. Among these, primary SFT of the stomach is exceptionally rare. Due to overlapping clinical, endoscopic, and radiologic characteristics, distinguishing SFT from gastrointestinal stromal tumor (GIST) can be particularly challenging. Misdiagnosis may result in inappropriate treatment, such as unnecessary administration of imatinib. Therefore, accurate preoperative differentiation is essential for appropriate management.

CASE PRESENTATION

A 74-year-old man was incidentally found to have a submucosal gastric tumor during a routine health checkup and was referred to our hospital for further evaluation and treatment. Upper gastrointestinal endoscopy revealed a 30-mm subepithelial lesion on the greater curvature of the gastric fundus. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) demonstrated isolated and clustered cells with ovoid to spindle-shaped nuclei. Although not definitive, the combined endoscopic and cytological findings led to a preoperative diagnosis of suspected GIST, and laparoscopy and endoscopy cooperative surgery (LECS) was subsequently performed for local resection. Histopathological examination of the resected specimen revealed an irregular proliferation of spindle cells and nuclear immunopositivity for signal transducer and activator of transcription 6 (STAT6), leading to a final diagnosis of SFT of the stomach. According to Demicco’s risk stratification model, the tumor was classified as low risk. The patient underwent complete resection via LECS and has remained free of recurrence for more than 2.5 years postoperatively.

CONCLUSIONS

This case highlights the difficulty in differentiating SFT from GIST preoperatively and underscores the importance of obtaining sufficient tissue samples to allow for immunohistochemical analysis, particularly STAT6 staining. Recognizing gastric SFT as part of the differential diagnosis is critical to avoid misdiagnosis and ensure appropriate therapeutic decision-making.

Abbreviations

BMI

body mass index

EUS-FNA

endoscopic ultrasound-guided fine-needle aspiration

GIST

gastrointestinal stromal tumor

LECS

laparoscopy and endoscopy cooperative surgery

NAB2–STAT6

NAB2–STAT6 fusion gene

N/C

nuclear-to-cytoplasmic (ratio)

SFT

solitary fibrous tumor

SMA

smooth muscle actin

STAT6

signal transducer and activator of transcription 6

TKI

tyrosine kinase inhibitor

VEGF

vascular endothelial growth factor

WHO

World Health Organization

INTRODUCTION

SFT is a relatively rare mesenchymal neoplasm that most commonly originates in the pleura; however, it can occur at various extrathoracic sites. Although extrapleural SFTs have become increasingly recognized, primary involvement of the gastrointestinal tract—particularly the stomach—remains exceptionally rare. In this report, we describe a rare case of primary SFT of the stomach that was initially misdiagnosed as a GIST based on endoscopic and cytological findings. This case highlights the diagnostic challenges associated with this entity and is accompanied by a brief review of the literature to underscore key clinical considerations, particularly the serious consequences of pretreatment misdiagnosis.

CASE PRESENTATION

A 74-year-old man was referred to our hospital for evaluation of a submucosal gastric tumor incidentally detected during a routine health checkup. His medical history was notable for diabetes mellitus. He had no known allergies or significant family history. At the time of presentation, he was asymptomatic. His height was 172 cm, weight 60 kg, and BMI was 20.3. Physical examination revealed no abdominal tenderness or palpable masses. Laboratory investigations, including tumor markers, showed no significant abnormalities.

Abdominal ultrasonography demonstrated a well-circumscribed, hypoechoic mass measuring 26 mm in the fundus of the stomach. Upper gastrointestinal series and endoscopy revealed a 30-mm, smooth-surfaced, subepithelial lesion located on the greater curvature of the gastric fundus (Fig. 1). EUS-FNA showed isolated and clustered cells with ovoid or spindle-shaped nuclei. While these findings were insufficient for a definitive diagnosis, the possibility of a neoplastic lesion, including GIST, remained. Contrast-enhanced CT demonstrated a 28-mm submucosal mass with mild heterogeneous enhancement on the posterior wall of the gastric body (Fig. 2), without evidence of lymphadenopathy or distant metastasis.

Fig. 1. Upper gastrointestinal endoscopic findings. A 30-mm, subpedunculated submucosal tumor was observed on the greater curvature of the gastric fundus during routine endoscopy. The lesion showed a smooth surface and tense appearance without ulceration or bleeding. These non-specific features made preoperative differentiation from gastrointestinal stromal tumor (GIST) difficult.

Fig. 2. Contrast-enhanced computed tomography findings. Contrast-enhanced CT revealed a 28-mm ovoid submucosal tumor with mild heterogeneous enhancement in the posterior wall of the gastric body (arrow). No evidence of lymphadenopathy or distant metastasis was observed. The tumor was well-circumscribed and lacked invasive features, radiologically resembling a gastrointestinal stromal tumor (GIST).

Based on these findings, GIST was the primary diagnostic consideration, and LECS was subsequently performed. The patient underwent classical LECS, with an operation time of 280 minutes and estimated blood loss of 50 mL. Gross examination of the resected specimen revealed a well-demarcated submucosal tumor measuring 2.6 × 2.4 × 2.1 cm (Fig. 3A). Histologically, spindle to stellate tumor cells with pleomorphic, chromatin-rich nuclei proliferated in irregular fascicles (Fig. 3B). Nuclear atypia was observed, including intranuclear inclusions and multinucleated cells.

Fig. 3. Macroscopic and microscopic findings of the surgically resected specimen. (A) Grossly, a submucosal tumor measuring 26 × 24 × 21 mm was located in the central portion of the resected specimen. The cut surface was solid, well-demarcated, and grayish-white in color. (B) Histological examination revealed irregular fascicular proliferation of spindle-shaped and stellate tumor cells with pleomorphic, hyperchromatic nuclei. These findings were suggestive of a spindle cell tumor.

Immunohistochemical staining was negative for SMA, KIT (CD117), DOG1, and S100; partially positive for CD34; and strongly and diffusely positive for STAT6 in both the nucleus and cytoplasm, confirming the diagnosis of SFT (Fig. 4).

Fig. 4. Immunohistochemical staining findings. Tumor cells were immunonegative for KIT (CD117), DOG-1, S-100, and smooth muscle actin (SMA), ruling out gastrointestinal stromal tumor (GIST) and neural tumors. CD34 showed focal positivity. Strong and diffuse nuclear positivity for signal transducer and activator of transcription 6 (STAT6) confirmed the diagnosis of solitary fibrous tumor (SFT).

According to the risk stratification model proposed by Demicco et al.,^1,2) which incorporates age (<55 or ≥55 years), tumor size (<5, 5–<10, 10–<15, or ≥15 cm), mitotic count (per 10 high-power fields: 0, 1–3, or ≥4), and tumor necrosis (<10% or ≥10%) (Table 1), only one adverse factor—age—was applicable in this case. The tumor was therefore classified as low risk. The postoperative course was uneventful, and the patient has remained free of recurrence for more than 2.5 years following R0 resection via LECS.

Table 1. Risk stratification and clinical outcomes of solitary fibrous tumors proposed by Demicco et al.

A. Risk factors and scoring criteria
		Three-variable model	Four-variable model
Risk factor		Score	Score
Age	<55	0	0
	≥55	1	1
Tumor size (cm)	<5	0	0
	5 to <10	1	1
	10 to <15	2	2
	≥15	3	3
Mitotic count (/10 high-power fields)	0	0	0
	1–3	1	1
	≥4	2	2
Tumor necrosis	<10%	–	0
	≥10%	–	1
		Total score	Total score
Risk class	Low	0–2	0–3
	Intermediate	3–4	4–5
	High	5–6	6–7

B. Stratified risk classes and long-term prognostic outcomes
Risk group	Score	N (%)	5 years metastasis-free survival rate
Three-variable model
Low	0–2	23 (46%)	100%
Intermediate	3–4	17 (34%)	93%
High	5–6	10 (20%)	49%
Four-variable model
Low	0–3	28 (56%)	100%
Intermediate	4–5	15 (30%)	90%
High	6–7	7 (14%)	27%

DISCUSSION

SFT is a mesenchymal tumor classified as an intermediate-grade malignancy and categorized as a fibroblastic tumor in the WHO classification of soft tissue tumors.³⁾ Although initially described as a pleural tumor, SFT is now known to occur at various anatomical sites. Among extrapleural cases, the majority arise either in the soft tissues of the extremities or in the abdomen, pelvis, and/or retroperitoneum, with each region accounting for approximately 30%–40% of cases.³⁾ SFTs can occur across a wide age range but are most commonly diagnosed in adults between 40 and 70 years of age, with no clear sex predilection observed.³⁾ In particular, primary SFT of the stomach is extremely rare. A review of the literature identified only 12 previously reported cases. ^4–15) The median age at diagnosis among these cases was 68 years (range, 26–85 years), and tumor size ranged from 1 to 16 cm, with a median diameter of 5.4 cm (Table 2).

Table 2. Summary of case reports.

Author	Year	Age	Sex	Tumor size (cm)	Preoperative pathological methods	Preoperative diagnosis	Medical treatment	Positive IHC markers	Negative IHC markers	Follow-up period	Recurrence
Shidam13)	1998	77	F	3	FNA (cell block)	SFT	Close follow-up	CD34, Bcl-2, Vimentin, SMA, Collagen IV, Factor XIIIa, HLA DR, CD68	MSA, desmin, pancytokeratin, S-100, CD31, EMA	Not mentioned	Not mentioned
Lee10)	2004	70	M	8.5 × 7 × 6	Not performed	Gastric tumor	Wedge resection (open)	CD34, Vimentin	CD117, S-100, Desmin, Pancytokeratin, SMA, CD99	Not mentioned	Not mentioned
Park12)	2007	26	M	5.4 × 5.2 × 4	Biopsy	Barium granuloma	Wedge resection	CD34, S-100	CD117, Desmin, SMA	12 months	No
Nabeshima11)	2015	43	F	2.7 × 2 × 1.5	Biopsy	Sarcoma	Wedge resection (LECS)	CD34, Bcl-2, MIC-2	CD117, DOG-1, SMA, ALK-1, ALK-EML4	8 months	No
Bosković6)	2015	65	F	2.5 × 2.3 × 1	Not mentioned	GIST	Surgical resection	CD34, Vimentin	CD117, DOG-1, S-100, Desmin, SMA, PDGFRA	Not mentioned	Not mentioned
Xiang15)	2016	56	M	4.5 × 3	Not mentioned	Not mentioned	Wedge resection (LECS)	CD34, Bcl-2, CD99, Vimentin	CD117, DOG-1, S-100, Desmin, ALK	3 months	No
Inayat8)	2017	55	M	7.1 × 6.7	EMR	Submucosal tumor	EMR	CD34, Bcl-2	CD117, DOG-1, S-100, Desmin, ALK	6 months	No
Voth14)	2018	68	M	16 × 9	Initial: FNA (cytology) Second: Biopsy	Initial: GIST Second: SFT	Partial gastorectomy	STAT6, CD34	CD117, DOG-1	4 months	Yes (Liver metastasis)
Kimmel9)	2019	81	F	7.5	Biopsy (No tumor tissue)	Gastric tumor	Sleeve gastorectomy	STAT6, CD34, Bcl-2, Vimentin, PDGFRA	CD117, DOG-1, S-100, Desmin, SMA, Calponin, ERG, CAM5.2	Not mentioned	Not mentioned
Ababneh4)	2020	79	F	6.6	FNA (cell block)	SFT	Not mentioned	STAT6, CD34, Bcl-2	CD117, DOG-1, S-100, Desmin, CD31, ERG-ENDO, AE1/AE3, Synaptophysin	Not mentioned	Not mentioned
Aslam5)	2025	85	F	1	EMR	Submucosal tumor	EMR	STAT6, CD34	CD117, DOG1, S100, Desmin, SMA, SOX10	18 months	No
Dong7)	2025	67	M	3.1 × 1.7	Not performed	GIST	Laparoscopic gastrectomy	STAT6, CD34, Bcl-2, CD99, Vimentin	CD117, DOG1, S100, CK, SMA, β-catenin	18 months	No
Ao	2025	74	M	2.6 × 2.4	FNA (cytology)	GIST	Wedge resection (LECS)	STAT6, CD34	CD117, DOG-1, S-100, SMA	30 months	No

EMR, endoscopic mucosal resection; F, female; FNA, fine needle aspiration; GIST, gastrointestinal stromal tumor; IHC, immunohistochemical; LECS, laparoscopy and endoscopy cooperative surgery; M, male; MSA, muscle specific actin; SFT, solitary fibrous tumor; SMA, smooth muscle actin; STAT6, signal transducer and activator of transcription 6

There are no specific serum biomarkers for SFT, and the diagnosis is typically based on a combination of imaging and histopathological findings. On contrast-enhanced CT, SFTs often appear as well-circumscribed masses with enhancement equal to or greater than that of the surrounding muscle tissue.¹⁶⁾ MRI generally shows low to isointense signals on T1-weighted images and heterogeneous signals on T2-weighted images, with post-contrast images revealing variable enhancement.¹⁷⁾ However, these findings are non-specific, and histological examination is essential for a definitive diagnosis.

Histologically, SFT is characterized by a prominent, branching, thin-walled, dilated (staghorn) vasculature.³⁾ The tumor cells are typically short and spindle-shaped, exhibiting a high N/C ratio and relatively scant cytoplasm.³⁾ In 2013, the NAB2–STAT6 fusion gene was identified in the majority of SFT cases, providing a pivotal molecular hallmark for this tumor entity.^18,19) Subsequently, the 2020 revision of the WHO classification of soft tissue tumors incorporated the presence of this fusion gene as a defining diagnostic criterion for SFT. As a surrogate marker, nuclear expression of STAT6 detected by immunohistochemistry has emerged as a highly sensitive and specific tool for diagnosis.³⁾ Most SFTs demonstrate strong and diffuse nuclear positivity for STAT6, making this marker indispensable for distinguishing SFT from its histologic mimics.^20–22)

In the present case, EUS-FNA was performed preoperatively; however, only conventional cytological smears were prepared without cell block specimens, and immunohistochemical analysis was not performed. While immunostaining generally requires formalin-fixed, paraffin-embedded cell block specimens, EUS-FNA material is generally unsuitable for this diagnostic process due to insufficient cellularity. In this context, the diagnosis of SFT was confirmed postoperatively based on histopathological examination of the resected specimen obtained via LECS. To avoid this diagnostic pitfall, when SFT is included in the differential diagnosis, it is recommended that clinicians consider alternative sampling methods—such as deep biopsy—to obtain adequate tissue for definitive pathological and immunohistochemical evaluation.

The mainstay of treatment for SFT is complete surgical resection with negative margins. Incomplete resection is associated with an increased risk of local recurrence. Lymph node metastasis is exceedingly rare, even in pleural SFTs, where nodal involvement has been reported in up to 7% of cases.²³⁾ Notably, none of the reported cases of gastric SFT demonstrated lymph node metastasis. These findings suggest that nodal involvement in SFT of the stomach is also uncommon; therefore, routine lymphadenectomy is not considered necessary.

Local recurrence occurs in approximately 10% of cases, and distant metastases develop in 5%–10%.²⁴⁾ In cases of unresectable SFT, chemotherapy is considered a treatment option for the dedifferentiated subtype, whereas VEGF inhibitors and TKIs are regarded as potential therapeutic options for differentiated tumors.²⁵⁾ Among TKIs, imatinib primarily targets the KIT receptor, which is typically not expressed in SFT, and thus its efficacy is generally limited.^26,27)

Among previously reported cases of SFT of the stomach, there is one instance in which the tumor was initially misdiagnosed as a GIST based on findings from FNA. The patient received preoperative imatinib therapy, which failed to achieve tumor reduction. A subsequent biopsy revealed nuclear STAT6 positivity, confirming the diagnosis of SFT, and the patient ultimately underwent surgical resection.¹⁴⁾ In the present case, had the tumor been larger or considered unresectable, a similar misdiagnosis could have led to inappropriate administration of imatinib. As SFTs are typically c-KIT negative and unresponsive to imatinib, misdirected therapy would likely delay appropriate surgical intervention and expose patients to unnecessary drug-related side effects. Therefore, especially when neoadjuvant treatment is being considered, accurate differentiation between SFT and GIST is essential through the acquisition of adequate tissue for immunohistochemical analysis.

CONCLUSIONS

We presented a rare case of SFT of the stomach, diagnosed by histopathological and STAT6 immunohistochemical analysis following LECS. This case highlights the challenge of differentiating SFT from GIST based on cytological or imaging findings, and underscores the importance of obtaining sufficient tissue for STAT6 immunostaining to ensure an accurate diagnosis. Maintaining a high index of suspicion for SFT in the differential diagnosis of gastric submucosal tumors is essential, as an inaccurate preoperative diagnosis may lead to inappropriate therapeutic decisions.

DECLARATIONS

Funding

None declared.

Authors' contributions

All authors have read and approved the final manuscript. TA: Writing–original draft; ES: Supervision, Writing–review & editing.

TI, KI, TS, SM, HA, TK, MN, and KN: Writing–review & editing; KK and HT: Histopathological diagnosis and interpretation.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Ethics approval and consent to participate

This work does not require ethical considerations or approval.

Consent for publication

Informed consent for publication of this case report was obtained from the patient.

Competing interests

The authors declare that there are no conflicts of interest.