Cutaneous sarcomas (overview)

Heterogeneous group of malignant mesenchymal tumours originating in the cutis or subcutis (see also under benign cutaneous soft tissue tumours - soft tissue tumours, cutaneous).

Primary sarcomas of the skin are rare. In principle, however, all deep soft tissue sarcomas can also occur in the skin with varying incidence.

Sarcomas are classified according to their respective tissue of origin or their similarity to existing tissue types (sarcomas of fat, muscle, connective tissue, blood vessels and nerves) and their degree of differentiation.

According to the WHO classification of 1994 about 15 clinically significant subgroups of sarcomas are described which may be of different dermatological relevance.

• Fibrös
  • Fibrosarcoma
  • dermatofibrosarcoma protuberans
• Fibrohistiocyte
  • Malignant fibrous histiocytoma (pleomorphic/myxoid - see below sarcoma, myxofibrosarcoma / giant cell / inflammatory)
  • Sarcoma, myxofibrosarcoma
  • Atypical fibroxanthoma
  • sarcoma, acral myxoinflammatory fibroblastic
• Fatty tissue
  • Liposarcoma (well differentiated/ myxoid/ round cell/ pleomorphic/ undifferentiated)
• Sarcomas of the musculature
  • Skeletal muscles
    • Rhabdomyosarcoma (embr./ botryoid/ spindle cell/ alveolar/ pleomorph/ ectomesenchymoma)
  • Smooth musculature
    • Leiomyosarcoma
• Sarcomas of the vessels (endothelial tumours)
  • "Actinic" angiosarcoma (classic angiosarcoma, especially of the scalp)
  • Kaposi's Sarcoma
    • Epidemic Kaposi sarcoma
    • Endemic Kaposi's sarcoma
  • Angiosarcoma in lymphedema
  • Angiosarcoma after radiotherapy (see also lymphangiosarcoma after mastectomy)
• Perivascular tumors
  • Hemangiopericytoma
  • Malignant glomus tumor (see below glomus tumor)
• Synovial tumors
  • Malignant tendosynovial giant cell tumor
• Mesothelial tumors
  • Mesothelioma (epithelial/spindle cell/biphasic)
• Neurogenic sarcomas
  • Malignant granular cell tumor (see Schwannom below)
  • clear cell sarcoma, cutaneous
  • Malignant melanocytic schwannoma
  • Neuroblastoma
  • Ganglioneuroblastoma
• Cartilage/bone tumours (dermatological affection extremely rare)
  • Extraskeletal chondrosarcoma (well differented/ myxoid/ mesenchymal/ undifferentiated)
  • Extraskeletal osteosarcoma
• pluripotent mesenchymal tumors
  • malignant mesenchymoma
• Various tumours
  • Alveolar soft tissue sarcoma
  • Epithelioid cell sarcoma
  • Extraskeletal Ewing sarcoma
  • Synovial sarcoma (monophasic)
  • Malignant (extrarenal) rhabdoid tumor
  • Desmoplastic round cell tumors
• Unclassified tumours (NOS)
  • Sarcoma, undifferentiated pleomorphic

• Tumours with complex genomic aberrations with detectability of various chromosomal "gains and losses". These are often associated with p53 gene mutations (genome guard function). These include:
• Leiomyosarcoma
• Atypical fibroxanthoma
• Angiosarcoma
• Tumors with simple genomic aberrations:
• Here the product of such a translocation is a functional fusion gene. In the typical case, the "new" gene product is a new transcription factor due to the fusion of the regulatory sections (promoter) of a gene A and the DNA binding domain of a transcription factor gene. This puts the complex function of a transcription factor under completely incorrect control. The example of the DFSP ( Dermatofibrosarcoma protuberans) is a good illustration of this: chromosomal translocation mutations ("ring chromosomes") are created by a fusion of chromosome regions 17q22 and 22q13. The fused COL1A1-PDGFß gene is removed from the other genes as a "ring chromosome". As a result, under the influence of transcription factors, excessive amounts of functional growth factor PDGF-beta are formed, which drive the tumor to grow autocrine via PDGF receptor stimulation. This dysfunction is highly characteristic of DFSP (detection in >90%) and is also the key to molecularly targeted therapy with tyrosine kinase inhibitors of the imatinib type (Gleevec).
• Besides DFSP, this group includes:
• Clear Cell Sarcoma
• Myxoid round cell liposarcoma

• Well differentiated less aggressive
• tumours
• and
• poorly differentiated, very aggressive tumours.

• GX Degree of differentiation cannot be determinedG1
• Well differentiated Low degree of malignancyG2
• Moderately differentiated Medium degree of malignancyG3
• Poorly differentiated High degree of malignancyG4
• Undifferentiated High degree of malignancyThe

• tumour cannot be assessedT0
• No evidence of primary tumourT1
• Tumour maximum 5 cm in its largest extensionga
• ) superficialb
• ) deepT2
• Tumour more than 5 cm in its largest extensionga
• ) superficialb
• ) deepStadia grouping

• IA (G1 or G2;
• Tumor < 5 cm superficial or deep localized; no lymph node or distant metastases)IB
• (G1 or G2; tumor > 5 cm superficial localized;
• no lymph node or distant metastases)
• IIA ( G1 or G2; tumour > 5 cm superficially or deeply localised; no lymph node or distant metastases)IIB
• ( G3 or G4; tumour > 5 cm superficially or deeply localised; no lymph node or distant metastases)IIC (G3
• or G4;

• Tumor > 5 cm superficially localized; no lymph node or distant metastases)III
• ( G3 or G4; tumor > 5 cm deep localized; no lymph node or distant metastases)IV ( Any

Soft tissue sarcomas occur in about 40% of cases on the legs, 15% each on the neck and arms, and 30% on the trunk, chest or abdomen. Only a smaller proportion of these patients become primarily dermatologically noticeable. The angiosarcomas (skin) have different preferred localisations (e.g. angiosarcoma of the head and facial skin), as do dermatofibrosarcoma protuberans (shoulder and back areas) or malignant fibrous histiocytoma (scalp).

The prognosis depends essentially on the type of sarcoma (e.g. dermatofibrosarcoma protuberans or angiosarcoma of the head and facial skin) and on the grade of the primary tumour. In the case of well differentiated tumours, 75% of patients have no relapse of their disease 5 years after completion of treatment, in moderately differentiated tumours it is only 50% and in poorly differentiated tumours 25%. Local recurrences at the site of the primary tumour occur in only 10 to 20% of patients. More frequent (40 to 60% of all patients) are metastases in other organs, mainly in the lung, less frequently in the bones or liver. Lymph node metastases are very unusual (except for synovial sarcoma and rhabdomyosarcoma).

• In the present chapter all sarcomas which may be of diagnostic importance for the dermatologist are summarized under "Sarcomas, cutaneous". It is not meant by this term that these tumors have their starting point in the skin.
• Relatively frequent sarcomas which the dermatologist should know in all details are:
• dermatofibrosarcoma protuberans
• Leiomyosarcoma
• Atypical fibroxanthoma
• "Actinic" angiosarcoma
• Undifferentiated pleomorphic sarcoma in distinction to malignant melanoma
• There is a certain risk that such highly malignant tumours will be misinterpreted as cutaneous sarcomas due to their clinical inhomogeneity and rarity (about 0.7% of malignancies in adults) and that a delayed start of therapy will lead to a worsening of the prognosis.

1. Darier F, Ferrand M (1924) Dermato-fibromes progressifs et récidivantes ou fibro-sarcomes de la peau Annales de dermatologie et de syphilographie (Paris) 5: 45-62
2. Grossmann AH et al (2012) Classification, molecular characterization, and the significance of pten alteration in leiomyosarcoma. Sarcoma: PubMed PMID: 22448121
3. Rao J et al (2003) Cutaneous angiosarcoma as a delayed complication of radiation therapy for carcinoma of the breast. J Am Acad Dermatol 49: 532-538
4. Schöfer H, Brockmeyer N (2002) German guideline: Kaposi's sarcoma.
5. Ugurel S et al (2008) Short guideline - dermatofibrosarcoma protuberans. JDDG 6 (Suppl1) S19-S20
6. Vogt T et al (2012) Malignant connective tissue tumor sarcomas. Act Dermatol 38: 248-264