Cutaneous sarcomas (CS) are classified as uncommon and highly invasive cancers that develop within the skin's soft tissues. Protheragen is dedicated to advancing the field of cutaneous sarcoma diagnostics and therapeutics. Our services include histological and molecular diagnostics, targeted therapy development, and preclinical research support.
Overview of Cutaneous Sarcoma (CS)
Cutaneous sarcomas (CS) are an uncommon group of tumors, with a diverse range of them arising from the skin and its appendages. These tumors exhibit different biological behavior, from being locally invasive to having metastatic potential. The more common ones are dermatofibrosarcoma protuberans (DFSP) and angiosarcoma, as well as leiomyosarcoma and Kaposi's sarcoma. Their specific subtypes exhibit particular histopathological characteristics and molecular modifications, which affect their phenotype and the way they are treated.
Fig.1 Pathogenesis of angiosarcoma and its modulation by epigenetic factors. (Mashima E.,
et al., 2021)
Diagnostics Development for Cutaneous Sarcoma (CS)
Histological Analysis
The foundation of diagnosing cutaneous sarcomas lies in histopathological examination. Certain histological features, like storiform patterns in DFSP or spindle cells in leiomyosarcomas, are key diagnostic clues. The distinction of these tumors from other neoplasms is also facilitated by some immunohistochemical markers like CD34 for DFSP or S100 for exclusion of melanoma.
Molecular Techniques
Molecular diagnostics are essential in verifying the diagnosis of cutaneous sarcomas. Specific chromosomal translocations and fusion genes are detected using fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). For instance, DFSP’s diagnosis of COL1A1-PDGFB fusion is made using these techniques, which helps in accurate diagnosis and targeted therapy.
Imaging Modalities
As with any other disease, imaging studies using magnetic resonance imaging (MRI) and computed tomography (CT) scans are important in diagnosing tumor involvement and metastasis of the disease. Also, MRI scans are especially helpful with soft tissues and in the planning of the surgical excision.
Therapeutics Development for Cutaneous Sarcoma (CS)
- Systemic Therapy
Like other advanced DFSPs, its imatinib targeted therapy has proven effective in shrinking and controlling the growth of cancerous tissues while increasing the chances of survival. Exerting its effects on the PDGFB fusion protein, imatinib prevents its action, thereby controlling abnormal cell proliferation. Other sunitinib and sorafenib are currently under study with sunitinib-resistant patients.
- Epigenetic Modulators
Drugs modifying epigenetic changes, like EZH2 inhibitors tazemetostat and histone deacetylase inhibitors vorinostat, are being investigated as possible therapies for cutaneous sarcomas. These agents can reverse epigenetic changes, and the correction of gene expression can lead to the cessation of tumor growth.
Table 1. Pathogenesis, histologic findings, and therapeutic strategy by tumor type. (Tillman B. N., et al., 2021)
| Tumor |
Pathogenesis |
Histology |
Therapeutics |
| Dermatofibrosarcoma Protuberans (DFSP) |
Dermal fibroblasts and dendrocytes
t (17;22) (q22:q13) translocation |
Monomorphic spindle cells with minimal atypia
(+) CD34 and (-) factor XIIIa |
Wide excision with 2–4 cm margins vs Mohs
MRI for extensive disease
Regional/distant imaging for fibrosarcomatous subtype
Radiation therapy vs imatinib for select cases |
| Atypical fibroxanthoma |
Myofibroblastic cells
P53 and telomerase reverse transcriptase mutations |
Dermal atypical spindle, pleomorphic, histiocytic, and multinucleated giant cells with occasional atypical mitosis
Diagnosis of exclusion |
Wide excision with at least 1–2 cm margins vs Mohs
Consider imaging for advanced disease |
| Pleomorphic dermal sarcoma |
Possibly a deeper and more aggressive variant of AFX
P53, HRAS, CDKN2A, PIK3CA mutations |
Resembles AFX with a predilection for subcutaneous structure invasion, perineural invasion, and necrosis
Diagnosis of exclusion |
Wide excision with at least 1–2 cm margins vs Mohs
Consider imaging given a 10% risk of metastasis |
| Cutaneous leiomyosarcoma |
Erector pili muscles of hair follicles |
Interlacing fascicles of spindle cells with mitotic figures
(+) Vimentin and smooth muscle actin
(+) Desmin, cytokeratin, S100 in some cases |
Wide excision with 3–5 cm margins vs Mohs
Consider imaging for advanced disease.
Adjuvant radiation therapy for tumors >5 cm
Multiple systemic regimens have been reported for advanced disease |
| Angiosarcoma |
Vascular endothelial cells |
Dilated disorganized vascular structures or high-grade epithelioid spindle cells without clear vessels
High mitotic rates |
Preoperative mapping biopsies
Wide excision with at least 3 cm margins
Consider imaging for advanced disease
Multiple systemic regimens have been reported for advanced and metastatic disease
Poor prognosis |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers comprehensive preclinical research services for the development of diagnostics and therapeutics for cutaneous sarcomas. Our services encompass histological analysis, molecular diagnostics, and advanced imaging techniques to provide accurate and reliable diagnostic solutions. We also specialize in the development of targeted therapies and epigenetic modulators tailored to address the specific needs of cutaneous sarcoma.
Disease Models
- Human Endothelial AS-M Cell Line
- Skin Fibrosarcoma Organoids
- Cell-Derived Xenograft Models
- Patient-Derived Xenograft (PDX) Models
Protheragen provides customized services to meet the unique requirements of each project. Our team of experts works closely with clients to design and implement tailored preclinical studies, ensuring that the most appropriate diagnostic and therapeutic strategies are employed. If you are interested in our services, please feel free to contact us.
References
- Mashima, Emi, and Yu Sawada. "Epigenetics of cutaneous sarcoma." International Journal of Molecular Sciences 23.1 (2021): 422.
- Tillman, Brittny N., and Jeffrey C. Liu. "Cutaneous sarcomas." Otolaryngologic Clinics of North America 54.2 (2021): 369-378.
- Llombart, B., et al. "Guidelines for diagnosis and treatment of cutaneous sarcomas: dermatofibrosarcoma protuberans." Actas Dermo-Sifiliográficas (English Edition) 109.10 (2018): 868-877.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
