Soft tissue
Uncertain differentiation
PRRX1 rearranged mesenchymal tumors
Author: Laura Warmke, M.D.
Editorial Board Member: Josephine K. Dermawan, M.D., Ph.D.
Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.
Last author update: 8 April 2025
Last staff update: 8 April 2025
Copyright: 2024-2025, PathologyOutlines.com, Inc.
PubMed Search: PRRX1 rearranged mesenchymal tumors
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2Cite this page: Warmke L. PRRX1 rearranged mesenchymal tumors. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissueprrx1rearranged.html. Accessed April 29th, 2025.
Definition / general
- First formally described in 2019 in a series of 4 cases by Lacambra et al. and at least 20 cases have been described to date (Genes Chromosomes Cancer 2019;58:705)
- Distinctive mesenchymal neoplasm, likely of fibroblastic origin with the possibility of partial neural or neuroectodermal differentiation, with gene fusions involving PRRX1 and various fusion partners including NCOA1, NCOA2 and KMT2D
Essential features
- Lobulated hypocellular growth of bland spindle to stellate cells in a myxocollagenous stroma
- Often has peripheral staghorn-like vessels with perivascular hyalinization
- Has gene fusions involving PRRX1 and either NCOA1/2 or KMT2D
Terminology
- PRRX::NCOAx rearranged fibroblastic tumor
Epidemiology
- Adults with a median age of 40 years (range: 20 - 76 years) (Virchows Arch 2023;483:207)
- Roughly equal sex distribution (J Cutan Pathol 2022;49:802, Virchows Arch 2023;483:207)
Sites
- Often involves superficial subcutaneous tissues of middle aged adults (J Cutan Pathol 2022;49:802)
- Develops in diverse anatomic sites including the abdominal wall, head and neck, groin, shoulder, thigh, axilla and hip (J Cutan Pathol 2022;49:802)
- Rare cases can be intramuscular and involve deeper soft tissue (Virchows Arch 2023;483:207)
Pathophysiology
- When PRRX1 is fused to NCOA1, the nuclear receptor binding protein of NCOA1 is lost and is replaced by exon 1 of PRRX1, whereas the transcriptional activation domains of NCOA1 remain intact (Virchows Arch 2023;483:207)
Etiology
- Unknown
Clinical features
- Frequently presents as a slow growing subcutaneous nodule (Virchows Arch 2023;483:207, Histopathology 2021;79:997)
- Duration of lesion varies from weeks to years, with 1 patient reporting a 4 - 5 year history of a slow growing mass prior to presenting for excision (Virchows Arch 2023;483:207)
Diagnosis
- Molecular testing to confirm presence of PRRX1 gene rearrangement
Radiology description
- Computed tomography (CT) scan may reveal heterogeneous enhancement (Virchows Arch 2022;481:111)
- Magnetic resonance imaging (MRI) shows an ovoid, superficial mass with low to intermediate T1 signal intensity and heterogeneous T2 signal intensity (Histopathology 2021;79:997)
Radiology images
Contributed by Laura Warmke, M.D.
Axial CT scan
Prognostic factors
- Best considered to be a benign mesenchymal tumor (J Cutan Pathol 2022;49:802)
- None of these tumors are associated with local recurrence of metastasis (Genes Chromosomes Cancer 2019;58:705)
Case reports
- 23 year old man with a 2.5 cm pigmented subcutaneous nodule on the shoulder (J Cutan Pathol 2022;49:802)
- 46 year old man with a tender left groin mass (Virchows Arch 2022;481:111)
- 65 year old woman with a soft tissue mass involving the left posterior chest wall (Virchows Arch 2023;483:207)
Treatment
- Simple excision (Genes Chromosomes Cancer 2019;58:705)
Gross description
- Encapsulated nodule with lobulated cut surface (Histopathology 2021;79:997)
- Grayish white cut surface, fibromyxoid to rubbery in consistency (Virchows Arch 2022;481:111)
- Size ranges from 2.3 to 14.0 cm (average: 5.8 cm) (Genes Chromosomes Cancer 2019;58:705)
Gross images
Contributed by Nasir Ud Din, M.B.B.S.
Resection specimen
Microscopic (histologic) description
- Well circumscribed with a nodular or multinodular growth pattern
- Predominantly hypocellular with focal areas of increased cellularity (Genes Chromosomes Cancer 2019;58:705)
- Monomorphic spindle to stellate cells with bland ovoid nuclei and scant eosinophilic cytoplasm
- Only rare mitotic activity (0 - 1 per 10 high power field [HPF])
- Prominent collagenous or hyalinized to myxoid stroma with rope-like collagen bundles
- Occasional multinucleation may be seen
- Necrosis is not identified
- Rarely contains pigmented melanocytes (J Cutan Pathol 2022;49:802)
- Dilated staghorn-like vessels with variable perivascular hyalinization are more prominent at the periphery of tumor nodules (J Cutan Pathol 2022;49:802)
- Minimal to mild cytologic atypia
- Rare mast cells and rare cases with entrapped benign adipose tissue (Virchows Arch 2023;483:207)
- May have collagenous rosettes (Virchows Arch 2022;481:111)
Microscopic (histologic) images
Contributed by Laura Warmke, M.D.
Circumscribed mass
Multilobular mass
Spindle cells
Bland spindle cells
Ropy collagen bundles
Hypocellular lesion
Myxoid change
Scattered vessels
S100 protein
Negative stains
- Pancytokeratin
- Epithelial membrane antigen (EMA)
- Smooth muscle actin (SMA)
- Calponin
- H-caldesmon
- Desmin (very limited expression in 1 case) (Histopathology 2021;79:997)
- CD34
- RB1 (retained expression)
- STAT6
- Beta catenin
- CD31
- CD117
- MUC4
- MDM2
- CDK4
- ALK
- Rare cases may be positive for pan-TRK (Virchows Arch 2023;483:207)
Molecular / cytogenetics description
- Most common fusion partner for PRRX1 is NCOA1, followed by KMT2D and NCOA2
- PRRX1::NCOA1 resulting from t(1;2)(q24.2;p23.3)
- PRRX1::NCOA2 resulting from t(1;8)(q24.2;q13.3)
- PRRX1 breakpoint is usually located at exon 1 (Genes Chromosomes Cancer 2019;58:705)
- NCOA1 breakpoint is often located at exon 13 and the NCOA2 breakpoint at exon 15 (Genes Chromosomes Cancer 2019;58:705)
- Corresponding reciprocal fusions may be identified
- Targeted sarcoma fusion panels may not identify the fusion (Virchows Arch 2023;483:207)
- Unsupervised clustering using RNA sequencing data shows that cases appear to cluster closely to solitary fibrous tumor (Genes Chromosomes Cancer 2019;58:705)
Molecular / cytogenetics images
Images hosted on other servers:
PRRX1::NCOA1 and PRRX1::NCOA2 fusions
Sample pathology report
- Soft tissue, shoulder mass, excision:
- PRRX1 rearranged mesenchymal tumor, 3.2 cm, completely excised (see comment)
- Comment: Sections show a well circumscribed multinodular spindle cell neoplasm composed of bland spindle cells in collagenous stroma with rope-like collagen bundles. Scattered staghorn-like vessels with perivascular hyalinization are present at the periphery of the lesion. No marked cytologic atypia, no necrosis and no significant mitotic activity is identified. Immunohistochemical stains show that the lesional cells are focally positive for S100 protein and SOX10, while they are essentially negative for pancytokeratin, SMA, desmin and CD34. Next generation sequencing revealed a PRRX1::NCOA2 gene fusion, supporting the above diagnosis. All control slides stained appropriately.
Differential diagnosis
- Soft tissue angiofibroma:
- Solitary fibrous tumor:
- Low grade fibromyxoid sarcoma (LGFMS):
- Positive for MUC4
- Often has FUS::CREB3L2 gene fusion
- May have giant collagen rosettes
- Collagenous stroma transitioning to myxoid areas
- YAP1::KMT2A rearranged sarcoma:
- Negative for MUC4
- Morphology can mimic sclerosing epithelioid fibrosarcoma (SEF)
- Presence of YAP1::KMT2A and KMT2A::YAP1 gene fusions
- Ossifying fibromyxoid tumor (OFMT):
- Dermatofibrosarcoma protuberans (DFSP):
- Spindle cells with a storiform to whorled pattern
- Centered in the dermis or subcutis
- Diffusely positive for CD34
- Presence of COL1A1::PDGFB gene fusions
- May have pigmented cells (i.e., Bednar tumor)
- Spindle cell melanoma:
- NTRK rearranged spindle cell neoplasm:
- Fat poor spindle cell lipoma:
- Schwannoma:
Practice question #1
Which of the following immunohistochemical stains can be focally positive in PRRX1 rearranged mesenchymal tumor?
- CD34 and STAT6
- DOG1 and CD117
- S100 protein and SOX10
- SMA and desmin
Practice answer #1
C. S100 protein and SOX10. Both S100 protein and SOX10 have been reported to be focally positive in PRRX1 rearranged mesenchymal tumor, raising the possibility of partial neural or neuroectodermal differentiation. Answer A is incorrect because expression of CD34 and STAT6 are usually seen in solitary fibrous tumor. Answer B is incorrect because both DOG1 and CD117 are typically positive in gastrointestinal stromal tumor (GIST). Answer D is incorrect because SMA and desmin are positive in smooth muscle tumors.
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Practice question #2
Which of the following fusion partners have been reported in gene fusions involving PRRX1 in PRRX1 rearranged mesenchymal tumor?
- AHRR and GTF2I
- NAB2 and STAT6
- NCOA1/2 and KMT2D
- YAP1 and KMT2A
Practice answer #2
C. NCOA1/2 and KMT2D. Both PRRX1::NCOA1/2 and PRRX1::KMT2D fusions have been reported in PRRX1 rearranged mesenchymal tumor. Answer D is incorrect because YAP1::KMT2A fusions have been reported in YAP1::KMT2A rearranged sarcomas with a sclerosing epithelioid fibrosarcoma-like morphology. Answer A is incorrect because AHRR::NCOA2 and GTF2I::NCOA2 fusions have been reported in soft tissue angiofibroma. Answer B is incorrect because NAB2::STAT6 fusions are associated with solitary fibrous tumor.
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