SRF 重排肌样肿瘤SRF rearranged myoid neoplasm

Definition / general

• Usually benign myoid neoplasm defined by SRF fusion

Essential features

• Monomorphic ovoid to spindle cells with fibrillary cytoplasm
• Demonstrate myoid or immature smooth muscle differentiation
• Expression of 1 or multiple smooth muscle markers
• Detection of SRF gene fusion

Terminology

• Myoid neoplasm of somatic soft tissue

ICD coding

• No unique, standalone code

Epidemiology

• Rare
• Wide age range at presentation
• Most cases occur in pediatric patients (Am J Surg Pathol 2020;44:1725)
• Overall relatively equal gender distribution

Sites

• Anatomic distribution is quite broad
• Most common in deep soft tissue
• May involve subcutis
• Often involves the head and neck, trunk and extremities (Am J Surg Pathol 2017;41:677, Am J Surg Pathol 2020;44:1725, Pediatr Dev Pathol 2023;26:65, Mod Pathol 2025;38:100722)
• Rare cases reported in visceral organs (Am J Surg Pathol 2017;41:677)

Pathophysiology

• SRF gene encodes for serum response factor, a transcription factor that regulates multiple genes involved in cardiac, skeletal and smooth muscle development (Dev Biol 1998;194:18, Eur J Transl Myol 2016;26:6008)
• Most tumors harbor similar SRF breakpoints, resulting in SRF mRNA upregulation at the transcription level

Etiology

• Unknown

Diagnosis

• Myoid or immature smooth muscle differentiation
• Expression of 1 or multiple smooth muscle markers (Semin Diagn Pathol 2026;43:150997)
• Detection of SRF gene fusion

Radiology description

• MRI shows an ovoid mass with hyperintense signal on T2 FS (fat suppressed) and heterogeneous contrast enhancement on T1 FS (Virchows Arch 2021;478:597)

Prognostic factors

• Most cases follow a benign course
• Behavior in children appears to be indolent
• Only 1 patient to date has developed lung metastases, indicating rare potential for malignant behavior (Am J Surg Pathol 2020;44:55)

Case reports

• 3 month old girl with chest wall soft tissue mass (Am J Surg Pathol 2017;41:677)
• 6 year old boy with right buccal mucosa lesion and 12 year old girl with palmar soft tissue mass (Semin Diagn Pathol 2026;43:150997)
• 15 year old boy with left forearm mass (Virchows Arch 2021;478:597)

Treatment

• Surgical resection

Gross description

• Homogeneous tan-white, nodular appearance
• Most are well circumscribed but not encapsulated
• May show infiltrative borders
• Most measure < 5 cm
• Rare cases are > 15 cm (Am J Surg Pathol 2020;44:55, Am J Surg Pathol 2020;44:1725)

Gross images

Gross image of an SRF::ICA1L positive tumor from the original topic was hosted on other servers and was not archived locally.

Microscopic (histologic) description

• Uniform ovoid to spindle cells arranged in short fascicles
• Lesional cells have bland nuclei and fibrillary cytoplasm
• No marked cytologic atypia
• Perivascular arrangement of lesional cells
• Vague nested pattern with a rich vascular network
• Small nodules may appear to bulge into vascular lumina
• Variable cellularity and mitotic rate
• Lack atypical mitotic figures
• Small subset have > 10 mitotic figures per 2 mm 2 and focal necrosis
• Variable collagenous stroma and calcification may be present (Mod Pathol 2025;38:100722)
• May have areas of infarction with dystrophic calcification

Microscopic (histologic) images

Cytology description

• Scattered bland ovoid to spindle cells

Cytology images

Original topic includes “Bland spindle cells” and “Bland ovoid cells” images contributed by Laura Warmke, M.D.; not archived locally.

Negative stains

• EMA
• SOX10
• MyoD1 (Am J Surg Pathol 2020;44:1725)
• CD34 (may be focally positive) (Am J Surg Pathol 2017;41:677)
• Myogenin
• HMB45
• Pancytokeratin: may show focal to multifocal positivity in a subset
• Fumarate hydratase (FH) / 2SC: retained FH expression with negative 2SC staining helps exclude FH deficient leiomyoma
• S100: variable expression has been reported in SRF::ICA1L tumors (Am J Surg Pathol 2020;44:55, Biomolecules 2022;12:1678)

Molecular / cytogenetics description

• Confirmation of SRF gene rearrangement recommended for definitive diagnosis
• Most common gene partners include RELA, ICA1L, CITED1 / CITED2 and NCOA2 (Am J Surg Pathol 2017;41:677, Am J Surg Pathol 2020;44:55, Pediatr Dev Pathol 2023;26:65, Mod Pathol 2025;38:100722)
• Alternative partners include MKL2, C3orf62, ARGFXP1, ARNTL2, NFKBIE, STAT6, NCOA3 and RGAG1 (Am J Surg Pathol 2020;44:1725, Pediatr Blood Cancer 2023;70:e30675, Mod Pathol 2025;38:100722, Virchows Arch 2021;478:597, Hum Pathol 2023;138:41, Semin Diagn Pathol 2026;43:150997)

Molecular / cytogenetics images

SRF::ICA1L and SRF::RELA fusion images from the original topic were hosted on other servers and were not archived locally.

Sample pathology report

• Soft tissue, forearm mass, excision:
  • SRF rearranged myoid neoplasm (see comment)
  • Comment: Sections show a circumscribed myoid neoplasm composed of monomorphic spindle cells with a moderate amount of pale eosinophilic cytoplasm. Focal calcification and areas with hyalinized collagen deposition are present. No marked cytologic atypia and no tumor type necrosis is identified. Mitotic figures are inconspicuous. Immunohistochemical stains show that the lesional cells are positive for smooth muscle actin (SMA), h-caldesmon and desmin and essentially negative for pancytokeratin, S100 protein, myogenin, MyoD1 and CD34. Additionally molecular testing confirmed the presence of a SRF::RELA gene fusion. These results support the above diagnosis and all control slides stained appropriately.

Differential diagnosis

Low grade leiomyosarcoma

• Often arises in adults
• Elongated cigar shaped nuclei
• Nuclear atypia and hyperchromasia
• Overt pleomorphism
• Not associated with specific gene fusions

Congenital / infantile spindle cell rhabdomyosarcoma

• Long fascicles of spindle cells with scant cytoplasm
• Infiltrative borders, nuclear atypia and rhabdomyoblastic differentiation
• Occurs in infants and young children
• Preferentially involves the trunk and head and neck
• Gene fusions involving VGLL2 / TEAD1::NCOA2 / CITED2
• Subset with SRF::NCOA1 and SRF::FOXO1 fusions (Genes Chromosomes Cancer 2013;52:538, Am J Surg Pathol 2020;44:607)
• Positive for desmin, MyoD1 and myogenin
• Less aggressive than classic rhabdomyosarcoma

Low grade myofibroblastic sarcoma

• Frequently arises in the head and neck
• Nuclear atypia
• Does not express h-caldesmon
• Not associated with specific gene fusions

Myofibroma / myopericytoma

• Myopericytoma shows bland spindled cells growing in a concentric pattern around numerous small blood vessels
• Myofibroma shows a biphasic appearance with primitive cellular zones and nodules of myoid spindled cells
• Positive for SMA, h-caldesmon and muscle specific actin
• Characterized by PDGFRB mutations

Glomus tumor

• Uniform glomus cells forming nests, sheets and trabeculae
• Chromatin is homogeneous and bland
• Positive for SMA
• Collagen IV shows prominent pericellular positivity
• May harbor NOTCH fusions and BRAF mutations

EBV associated smooth muscle tumor

• Tends to arise in immunocompromised patients
• Often has prominent lymphocytic infiltrate
• Visceral location is common
• Positive for EBER ISH

Fumarate hydratase (FH) deficient leiomyoma

• May be sporadic or occur in the setting of hereditary leiomyomatosis and renal cell carcinoma syndrome
• Alveolar edema and staghorn-like vessels
• Ovoid nuclei with prominent eosinophilic nucleoli surrounded by perinuclear halos
• May have multinucleated cells and cells with bizarre nuclei
• Fumarate hydratase (FH) / 2SC: retained FH expression with negative 2SC staining helps exclude FH deficient leiomyoma

Solitary fibrous tumor (SFT)

• Diffusely positive for CD34 and STAT6
• Associated with NAB2::STAT6 gene fusions
• Lack of both biphasic pattern and myoid cytology

Additional references

No entries listed in this section of the original topic.

Practice question #1

SRF rearranged myoid neoplasms may be easily misdiagnosed as leiomyosarcoma or sarcoma with myogenic differentiation. Which of the following features is more characteristic of leiomyosarcoma than SRF rearranged myoid neoplasms?

1. Foci of infiltrative growth
2. Hypercellularity
3. Mitotic activity
4. Nuclear pleomorphism

Practice answer #1

D. Nuclear pleomorphism. SRF rearranged myoid neoplasms should not have marked cytologic atypia, nuclear pleomorphism or atypical mitotic figures. The presence of nuclear pleomorphism is more characteristic of leiomyosarcoma than an SRF rearranged myoid neoplasm. Answer B is incorrect because SRF rearranged myoid neoplasms may show a variable degree of cellularity. Answer C is incorrect because SRF rearranged myoid neoplasms may show a variable degree of mitotic activity. Answer A is incorrect because while most SRF rearranged myoid neoplasms are relatively well circumscribed, foci of infiltrative growth are frequently present.

Practice question #2

Which immunohistochemical profile fits best with an SRF rearranged myoid neoplasm?

1. Positive for CD34 and STAT6
2. Positive for desmin and MyoD1
3. Positive for SMA and calponin
4. Positive for SMA and collagen IV

Practice answer #2

C. Positive for SMA and calponin. SRF rearranged myoid neoplasms are typically positive for smooth muscle markers, including smooth muscle actin (SMA) and calponin. Answer D is incorrect because SMA and collagen IV are positive in glomus tumors. Answer B is incorrect because desmin and MyoD1 are positive in tumors with skeletal muscle differentiation, including rhabdomyosarcoma. Answer A is incorrect because while CD34 may be focally positive in SRF rearranged myoid neoplasms (and a rare case with SRF::STAT6 fusion demonstrated staining with STAT6), diffuse staining with CD34 and STAT6 is typically seen in solitary fibrous tumor.

Cite this page: Ghazy A, Warmke L. SRF rearranged myoid neoplasm. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuesrfmyoidneoplasm.html. Accessed September 15th, 2026.

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