Childhood Soft Tissue Sarcoma Treatment (PDQ®) 2/7 —Health Professional Version - National Cancer Institute

Childhood Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Childhood Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version

Histopathological Classification of Childhood Soft Tissue Sarcoma

In This Section

• World Health Organization (WHO) Classification of Soft Tissue Sarcomas

World Health Organization (WHO) Classification of Soft Tissue Sarcomas

The WHO classification system for cancer represents the common nomenclature for cancer worldwide. In the United States, it has been adopted by the American Joint Committee on Cancer (AJCC) for sarcoma staging and the College of American Pathologists (CAP) cancer protocols for bone and soft tissue sarcomas. The fourth edition of the WHO Classification of Tumors of Soft Tissue and Bone was published in February 2013.[1]

The grading of soft tissue tumors has always been a controversial issue. While the WHO does not strictly state a preference in grading systems, one of the major modifications made to the WHO classification was the designation of two distinct types of intermediate malignancy in terms of biological potential—locally aggressive and rarely metastasizing.[1]

The WHO acknowledged the poorly defined nature of malignant fibrous histiocytoma (also known as undifferentiated pleomorphic sarcoma) and hemangiopericytoma (now considered within the spectrum of solitary fibrous tumors).[1]

With the current advances in molecular and genetic studies, a subset of tumors has been moved into new sections, including angiomatoid malignant fibrous histiocytoma and extraskeletal myxoid chondrosarcoma, which were previously classified as tumors of uncertain differentiation. Multiple entities were newly recognized, and a few entities belonging to tumors of skin were also added to this book. A few entities that were found to most likely represent morphologic variants of other tumors were deleted from the current classification or subsumed into other sections.[1]

1. Adipocytic tumors.
   1. Benign.
      • Lipoma.
      • Lipomatosis.
      • Lipomatosis of nerve.
      • Lipoblastoma/lipoblastomatosis.
      • Angiolipoma.
      • Myolipoma.
      • Chondroid lipoma.
      • Extra-renal angiomyolipoma.
      • Extra-adrenal myelolipoma.
      • Spindle cell/pleomorphic lipoma.
      • Hibernoma.
   2. Intermediate (locally aggressive).
      • Atypical lipomatous tumor/well-differentiated liposarcoma.
   3. Malignant.
      • Dedifferentiated liposarcoma.
      • Myxoid liposarcoma.
      • Pleomorphic liposarcoma.
      • Liposarcoma, not otherwise specified (NOS).
2. Chondro-osseous tumors.
   • Soft tissue chondroma.
   • Extraskeletal mesenchymal chondrosarcoma.[2]
   • Extraskeletal osteosarcoma.
3. Fibroblastic/myofibroblastic tumors.
   1. Benign.
      • Nodular fasciitis.
      • Proliferative fasciitis.
      • Proliferative myositis.
      • Myositis ossificans.
      • Fibro-osseous pseudotumor of digits.
      • Ischemic fasciitis.
      • Elastofibroma.
      • Fibrous hamartoma of infancy.
      • Fibromatosis colli.
      • Juvenile hyaline fibromatosis.
      • Inclusion body fibromatosis.
      • Fibroma of tendon sheath.
      • Desmoplastic fibroblastoma.
      • Mammary-type myofibroblastoma.
      • Calcifying aponeurotic fibroma.
      • Angiomyofibroblastoma.
      • Cellular angiofibroma.
      • Nuchal-type fibroma.
      • Gardner fibroma.
      • Calcifying fibrous tumor.
   2. Intermediate (locally aggressive).
      • Palmar/plantar fibromatosis.
      • Desmoid-type fibromatosis (previously called desmoid tumor or aggressive fibromatoses).
      • Lipofibromatosis.
      • Giant cell fibroblastoma.
   3. Intermediate (rarely metastasizing).
      • Dermatofibrosarcoma protuberans.
        • Fibrosarcomatous dermatofibrosarcoma protuberans.
        • Pigmented dermatofibrosarcoma protuberans.
      • Solitary fibrous tumor.
        • Solitary fibrous tumor, malignant.
      • Inflammatory myofibroblastic tumor.
      • Low-grade myofibroblastic sarcoma.
      • Myxoinflammatory fibroblastic sarcoma/atypical myxoinflammatory fibroblastic tumor.
      • Infantile fibrosarcoma.[3]
   4. Malignant.
      • Adult fibrosarcoma.
      • Myxofibrosarcoma.
      • Low-grade fibromyxoid sarcoma.[4]
      • Sclerosing epithelioid fibrosarcoma.
4. Skeletal muscle tumors.
   • Rhabdomyoma.
   • Rhabdomyosarcoma (embryonal, spindle cell/sclerosing, alveolar, and pleomorphic forms). (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.)
5. Smooth muscle tumors.
   1. Benign.
      • Deep leiomyoma.
   2. Malignant.
      • Leiomyosarcoma (excluding skin).
      Angioleiomyoma was reclassified under perivascular tumors.
6. So-called fibrohistiocytic tumors.
   1. Benign.
      • Tenosynovial giant cell tumor.
        • Localized type.
        • Diffuse type.
        • Malignant.
      • Deep benign fibrous histiocytoma.
   2. Intermediate (rarely metastasizing).
      • Plexiform fibrohistiocytic tumor.
      • Giant cell tumor of soft tissue.
      The malignant counterpart of so-called fibrohistiocytic tumors, formerly known as malignant fibrous histiocytoma and its subtypes was renamed undifferentiated sarcoma and was previously classified under the undifferentiated/unclassified sarcomas section.
7. Nerve sheath tumors.
   1. Benign.
      • Schwannoma (including variants).
      • Melanotic schwannoma.
      • Neurofibroma (including variants).
        • Plexiform neurofibroma.
      • Perineurioma.
        • Malignant perineurioma.
      • Granular cell tumor.
      • Dermal nerve sheath myxoma.
      • Solitary circumscribed neuroma.
      • Ectopic meningioma.
      • Nasal glial heterotopia.
      • Benign Triton tumor.
      • Hybrid nerve sheath tumor.
   2. Malignant.
      • Malignant peripheral nerve sheath tumor.
      • Epithelioid malignant peripheral nerve sheath tumor.
      • Malignant Triton tumor.
      • Malignant granular cell tumor.
      • Ectomesenchymoma.
8. Pericytic (perivascular) tumors.
   • Glomus tumor (and variants).
     • Glomangiomatosis.
     • Malignant glomus tumor.
   • Myopericytoma.
     • Myofibroma (hemangiopericytoma are now included in recent WHO classification).
     • Myofibromatosis.
     • Infantile myofibromatosis.
   • Angioleiomyoma.
9. Tumors of uncertain differentiation.
   1. Benign.
      • Acral fibromyxoma.
      • Intramuscular myxoma (including cellular variant).
      • Juxta-articular myxoma.
      • Deep (aggressive) angiomyxoma.
      • Pleomorphic hyalinizing angiectatic tumor.
      • Ectopic hamartomatous thymoma.
   2. Intermediate (locally aggressive).
      • Hemosiderotic fibrolipomatous tumor.
   3. Intermediate (rarely metastasizing).
      • Atypical fibroxanthoma.
      • Angiomatoid fibrous histiocytoma.
      • Ossifying fibromyxoid tumor.
        • Ossifying fibromyxoid tumor, malignant.
      • Mixed tumor NOS.
      • Mixed tumor NOS, malignant.
      • Myoepithelioma.
      • Myoepithelial carcinoma.
      • Phosphaturic mesenchymal tumor, benign.
      • Phosphaturic mesenchymal tumor, malignant.
   4. Malignant.
      • Synovial sarcoma NOS.
        • Synovial sarcoma, spindle cell.
        • Synovial sarcoma, biphasic.
      • Epithelioid sarcoma.
      • Alveolar soft part sarcoma.
      • Clear cell sarcoma of soft tissue.
      • Extraskeletal myxoid chondrosarcoma.
      • Extraskeletal Ewing sarcoma. (Refer to the PDQ summary on Ewing Sarcoma Treatment for more information.)
      • Desmoplastic small round cell tumor.
      • Extra-renal rhabdoid tumor.
      • Neoplasms with perivascular epithelioid cell differentiation (PEComa).
        • PEComa NOS, benign.
        • PEComa NOS, malignant.
      • Intimal sarcoma.
10. Undifferentiated/unclassified sarcomas.
    • Undifferentiated spindle cell sarcoma.
    • Undifferentiated pleomorphic sarcoma.
    • Undifferentiated round cell sarcoma.
    • Undifferentiated epithelioid sarcoma.
    • Undifferentiated sarcoma NOS.[5]
    Genetic subgroups are emerging within this family and this work is ongoing:
    • Undifferentiated round cell and spindle cell sarcoma.
      In this group, EWSR1 is involved in non-ETS fusions with genes such as PATZ1, POU5F1, SMARCA5, NFATC2, or SP3. Another recurrent rearrangement involves the CIC-DUX4 fusion gene resulting in the chimeric CIC-DUX4 protein, which upregulates genes of the PEA3 subclass of ETS family. (Refer to the Genomics of Ewing Sarcoma section of the PDQ summary on Ewing Sarcoma Treatment for more information.)
      It is unclear whether these cases represent one or more separate entities, or whether they are better classified as variants of Ewing sarcoma.
    • Undifferentiated pleomorphic sarcoma.
      Undifferentiated pleomorphic sarcoma was most often called malignant fibrous histiocytoma in the past. Historically, this entity has been difficult to evaluate because of the shifting diagnostic criteria. Analysis of 70 cases diagnosed as malignant fibrous histiocytosis of no specific type, storiform or pleomorphic malignant fibrous histiocytoma, pleomorphic sarcoma or undifferentiated pleomorphic sarcoma showed a highly complex karyotype with no specific recurrent aberrations.[6]
      Undifferentiated sarcomas with 12q13–15 amplification, including MDM2 and CDK4, are best classified as dedifferentiated liposarcomas;[6] the relationship between this tumor and the family of undifferentiated/unclassified tumors with spindle cell morphology remains relatively undefined.
11. Vascular tumors.
    1. Benign.
       • Hemangioma. (Refer to the PDQ summary on Childhood Vascular Tumors Treatment for more information.)
         • Synovial.
         • Venous.
         • Arteriovenous hemangioma/malformation.
         • Intramuscular.
       • Epithelioid hemangioma.
       • Angiomatosis.
       • Lymphangioma.
    2. Intermediate (locally aggressive).
       • Kaposiform hemangioendothelioma.
    3. Intermediate (rarely metastasizing).
       • Retiform hemangioendothelioma.
       • Papillary intralymphatic angioendothelioma.
       • Composite hemangioendothelioma.
       • Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma.
       • Kaposi sarcoma.
    4. Malignant.
       • Epithelioid hemangioendothelioma.
       • Angiosarcoma of the soft tissue.

References

1. Fletcher CDM, Bridge JA, Hogendoorn P, et al., eds.: WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon, France: IARC Press, 2013.
2. Dantonello TM, Int-Veen C, Leuschner I, et al.: Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer 112 (11): 2424-31, 2008. [PUBMED Abstract]
3. Steelman C, Katzenstein H, Parham D, et al.: Unusual presentation of congenital infantile fibrosarcoma in seven infants with molecular-genetic analysis. Fetal Pediatr Pathol 30 (5): 329-37, 2011. [PUBMED Abstract]
4. Evans HL: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 35 (10): 1450-62, 2011. [PUBMED Abstract]
5. Alaggio R, Collini P, Randall RL, et al.: Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol 13 (3): 209-17, 2010 May-Jun. [PUBMED Abstract]
6. Le Guellec S, Chibon F, Ouali M, et al.: Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas? Am J Surg Pathol 38 (3): 293-304, 2014. [PUBMED Abstract]