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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Oncology · Clear Cell Sarcoma of Soft Tissue

Understanding Clear Cell Sarcoma of Soft Tissue

At a Glance

Clear Cell Sarcoma of Soft Tissue (CCS-ST), formerly known as melanoma of soft parts, is a rare soft tissue cancer, not a skin cancer. It is defined by the EWSR1-ATF1 gene fusion and requires specialized treatment at a dedicated sarcoma center.

If you have been told you have “melanoma of soft tissue,” it is natural to be confused and overwhelmed. You may have searched for information on skin cancer and found that it does not seem to match your experience. It is important to know that while the names sound similar, Clear Cell Sarcoma of Soft Tissue (CCS-ST) is a distinct and ultra-rare type of cancer that is very different from the common skin cancer known as cutaneous melanoma [1][2].

Understanding the Name Confusion

Historically, doctors called this disease malignant melanoma of soft parts or melanoma of soft tissue [3][2]. This was because, under a microscope, CCS-ST cells look remarkably like melanoma cells; both can produce melanin (the pigment that colors our skin) and share certain chemical markers like S-100 and HMB45 [3][2][4].

However, modern science has proven they are not the same. CCS-ST is a sarcoma—a cancer that begins in the connective tissues like muscles, fat, or tendons—rather than a skin cancer that has spread [2][5]. It is a high-grade cancer, meaning its cells look very abnormal under a microscope and tend to grow and spread aggressively [2].

Three Stabilizing Facts

  1. It is not skin cancer: CCS-ST is a primary soft tissue sarcoma. It does not start in the skin and is not caused by sun exposure [2][3].
  2. It has a unique genetic “signature”: Unlike melanoma, CCS-ST is defined by a specific genetic change called a translocation (specifically t(12;22)(q13;q12)t(12;22)(q13;q12)), which creates the EWSR1-ATF1 gene fusion [6][7]. Testing for this signature allows doctors to confirm the diagnosis with certainty [6][8].
  3. It requires specialized care: Because this is an “ultra-rare” cancer (representing about 1% of all sarcomas), it is standard for patients to be treated at specialized sarcoma centers where the doctors have specific expertise in this rare subtype [1].

Who Typically Gets CCS-ST?

CCS-ST is most often diagnosed in young adults, typically between the ages of 20 and 40 [2][9]. While it is found in both men and women, some data suggests it may be slightly more common in females [4][10]. Because it is so rare, many local doctors may never have seen a case in their entire careers [1].

Where Does It Usually Start?

This cancer has a strong preference for the deep “soft tissues” of the body, particularly in the extremities [2].

  • Common Locations: The foot and ankle are the most frequent sites, though it can also appear in the knees, hands, or arms [11][12].
  • Connection to Tendons: It is often found attached to tendons (the cords that connect muscle to bone) or aponeuroses (the flat sheets of pearly-white fibrous tissue that attach muscle to the parts they move) [9][2].
  • Growth Pattern: It usually appears as a slow-growing, often painless lump deep under the skin [9][13].

Why the Distinction Matters

Classifying this correctly as a sarcoma rather than a melanoma is critical for your treatment plan. Most common melanoma treatments (like certain targeted pills) may not work the same way for CCS-ST [1][14]. Additionally, while most sarcomas rarely spread to the lymph nodes (part of the body’s immune system), CCS-ST is unique because it frequently does [15][16]. Your care team will need to monitor your lymph nodes closely as part of your overall management [17][15].

To understand how doctors confirm this diagnosis, continue to Biology and Diagnosis: Telling CCS Apart from Melanoma. Or return to the Home Page.

Common questions in this guide

What is the difference between melanoma and clear cell sarcoma of soft tissue?
Clear cell sarcoma of soft tissue (CCS-ST) is a rare sarcoma that starts in connective tissues like tendons, while melanoma is typically a skin cancer. Although they look similar under a microscope, they have different genetic causes and require different treatments.
Why was CCS-ST formerly called melanoma of soft parts?
Under a microscope, CCS-ST cells look very much like melanoma cells. Both can produce melanin, the pigment that colors our skin, and share certain chemical markers, which led to the historical confusion between the two diseases.
How do doctors confirm a diagnosis of clear cell sarcoma?
Doctors confirm the diagnosis by testing the tumor for a specific genetic change called the EWSR1-ATF1 gene fusion. This unique genetic signature proves the tumor is CCS-ST rather than skin melanoma.
Where does clear cell sarcoma of soft tissue usually grow?
This cancer strongly prefers the deep soft tissues of the body, particularly in the extremities. It is most frequently found as a slow-growing lump in the foot and ankle, often attached to tendons.
Does clear cell sarcoma spread to lymph nodes?
Yes, unlike most soft tissue sarcomas, clear cell sarcoma of soft tissue frequently spreads to the lymph nodes. Your care team will need to monitor your lymph nodes closely as part of your overall treatment plan.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Has my tumor been tested for the t(12;22) translocation or the EWSR1-ATF1 gene fusion to confirm it is CCS-ST?
  2. 2.Since this is an ultra-rare sarcoma, how many cases of CCS-ST has this hospital or care team treated in the last five years?
  3. 3.Will you be checking my regional lymph nodes for spread, given that this type of sarcoma behaves differently than others?
  4. 4.Is my case being reviewed by a multidisciplinary sarcoma tumor board?
  5. 5.How does the specific location of my tumor (near tendons or fascia) affect the surgical plan?

Questions For You

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References

References (17)
  1. 1

    Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network.

    Smrke A, Frezza AM, Giani C, et al.

    ESMO open 2022; (7(3)):100522 doi:10.1016/j.esmoop.2022.100522.

    PMID: 35717681
  2. 2

    Morphology quiz: Cytology of a palmar swelling with axillary lymphadenopathy.

    Gupta P, Rajwanshi A

    Cytopathology : official journal of the British Society for Clinical Cytology 2018; (29(6)):592-594 doi:10.1111/cyt.12603.

    PMID: 29923360
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    Clear cell sarcoma-A review.

    Ibrahim RM, Steenstrup Jensen S, Juel J

    Journal of orthopaedics 2018; (15(4)):963-966 doi:10.1016/j.jor.2018.08.039.

    PMID: 30210202
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    Clear cell sarcoma of soft tissue in right parapharyngeal region: report of a rare case.

    Fan C, Yu J, Yang L, et al.

    International journal of clinical and experimental pathology 2015; (8(9)):10935-40.

    PMID: 26617810
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    Primary intraretinal clear cell sarcoma presenting as an amelanotic circumpapillary tumor.

    Steinkerchner MS, Mukai S, Stagner AM

    American journal of ophthalmology case reports 2025; (37()):102251 doi:10.1016/j.ajoc.2025.102251.

    PMID: 39895874
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    Metastatic clear cell sarcoma of the pancreas: A sporadic cancer.

    Gebbia V, Carnaghi C

    World journal of clinical cases 2024; (12(18)):3291-3294 doi:10.12998/wjcc.v12.i18.3291.

    PMID: 38983428
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    Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor.

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    Diagnostic pathology 2018; (13(1)):73 doi:10.1186/s13000-018-0752-6.

    PMID: 30219084
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    Clear cell sarcoma in unusual sites mimicking metastatic melanoma.

    Obiorah IE, Ozdemirli M

    World journal of clinical oncology 2019; (10(5)):213-221 doi:10.5306/wjco.v10.i5.213.

    PMID: 31205866
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    Navigating diagnostic challenges-distinguishing malignant melanoma and clear cell sarcoma of soft tissues: a case report and review of the literature.

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    Journal of medical case reports 2024; (18(1)):249 doi:10.1186/s13256-024-04542-y.

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    Clear cell sarcoma of the scalp: A case report.

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    Clear Cell Sarcoma of the Soft Tissue in the Distal Phalanx of the Great Toe: A Case Report.

    Park H, Kang WY, Woo OH, Kim A

    Journal of the Korean Society of Radiology 2024; (85(6)):1189-1193 doi:10.3348/jksr.2024.0083.

    PMID: 39660322
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    CD151 confers metastatic potential to clear cell sarcoma of the soft tissue in animal model.

    Kawashima K, Saigo C, Kito Y, et al.

    Oncology letters 2019; (17(6)):4811-4818 doi:10.3892/ol.2019.10164.

    PMID: 31186687
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    A rare case of primary dermal clear cell sarcoma with focal epidermotropism: An entity difficult to distinguish from melanoma.

    Nawrocki S, Fitzhugh VA, Groisberg R, et al.

    Journal of cutaneous pathology 2020; (47(7)):621-624 doi:10.1111/cup.13659.

    PMID: 32012324
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    Clear cell sarcoma in Japan: an analysis of the population-based cancer registry in Japan.

    Takemori T, Ogura K, Morizane C, et al.

    Japanese journal of clinical oncology 2024; (54(12)):1281-1287 doi:10.1093/jjco/hyae112.

    PMID: 39196756
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    Trends of lymph node sampling and metastasis in pediatric and young adult patients with clear cell, epithelioid, and synovial sarcomas.

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    Factors associated with survival in patients with clear cell sarcoma.

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    PMID: 37907082

This page provides educational information about Clear Cell Sarcoma of Soft Tissue (CCS-ST). It is not a substitute for professional medical advice from a specialized sarcoma care team.

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