Soft tissue

Uncertain differentiation

Undifferentiated / unclassified sarcoma

Last author update: 1 August 2012
Last staff update: 19 September 2023 (update in progress)

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PubMed Search: Undifferentiated / unclassified sarcoma

Vijay Shankar, M.D.
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Cite this page: Shankar V. Undifferentiated / unclassified sarcoma. website. Accessed September 29th, 2023.
Definition / general
  • Pleomorphic sarcoma composed of fibroblasts, myofibroblasts and histiocyte-like cells
  • Diagnosis of exclusion; must sample generously and search for other components to rule out a dedifferentiated tumor or evidence of specific differentiation other than fibroblasts or myofibroblasts
  • Previously called malignant fibrous histiocytoma (MFH), pleomorphic, myxoid or giant cell subtypes, but this terminology is no longer used
  • See also bone, eye-conjunctiva and heart-tumor chapters
  • First described in 1964 (Cancer 1964;17:1445)
  • Pleomorphic: variation in cytoplasmic and nuclear size throughout the tumor, not just funny looking cells
  • Historically considered the most common adult soft tissue sarcoma
  • Usually older adults (age 50+ years) with slight male predominance; more common in lower extremities, rarely retroperitoneum, head and neck, breast
  • Large and deep-seated with progressive enlargement
  • Sarcomas adjacent to orthopedic implants or postradiation are usually osteosarcoma or MFH (Mod Pathol 2001;14:969)
Case reports
  • Wide local excision is occasionally curative in extremities; adjuvant or neoadjuvant radiation and chemotherapy often used
  • Recurs locally, may metastasize to lungs or regional lymph nodes
  • Almost never presents as metastasis with unknown small primary
  • 5 year survival is 50 - 60% for all high grade pleomorphic sarcomas, better for some subtypes (dedifferentiated liposarcoma)
  • Call borderline if features are between fibrous histiocytoma and MFH, and treat with wide local excision
  • Good prognostic factors: superficial, small size, low grade
  • When occurs in skin, is difficult to differentiate from atypical fibroxanthoma or DFSP
Gross description
  • Large, may appear circumscribed (but is not); subcutaneous lesions are usually 5 cm or less, retroperitoneal lesions may be 20 cm
  • Cut surface is fibrous or fleshy with hemorrhage, necrosis or myxoid change
Gross images

Images hosted on other servers:

Sternal mass

Microscopic (histologic) description
  • Storiform pattern (cells emanate from a central focus), irregular fascicles, variable cellularity
  • Pleomorphic and bizarre tumor cells with foamy cytoplasm and marked atypia, in background of inflamed collagenous stroma
  • May represent end stage of various sarcomas with common morphologic features of pleomorphism and storiform growth pattern
  • Multinucleated giant cells may be seen; if prominent, classify as MFH-giant cell
  • Numerous mitotic figures, including atypical forms
  • Rarely metaplastic (not neoplastic) bone or cartilage
Microscopic (histologic) images

Contributed by Nikhil Sangle, M.D. (Case #387) and AFIP

Bizarre nuclei

Abundant eosinophilic cytoplasm

Characteristic giant cells

Mixture of fibroblasts and histiocyte-like cells

Vague storiform pattern

Strap-like cells

Numerous mitotic figures

Frequent tumor cell necrosis

Osteoclast-like giant cells with uniform nuclei in a pleomorphic MFH

Tumor cells may form neoplastic bone and osteoid

Acute inflammatory and histiocyte-like cells

Numerous histiocyte-like cells resembling lymphoma

Large histiocyte-like cells

H&E images: low

H&E image: low

H&E images: high








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Undifferentiated / unclassified sarcoma

Undifferentiated / unclassified sarcoma

Cytology description
  • Single cells to large storiform fragments
  • Cells are spindled, plasmacytoid and pleomorphic (often multinucleated), all with malignant nuclear morphology (Cancer 1997;81:228)
Cytology images

Images hosted on other servers:

Various images

Positive stains
Negative stains
Electron microscopy description
  • No features of a specific lineage
  • Relatively undifferentiated fibroblastic, myofibroblastic or primitive mesenchymal cells, some with phagocytic properties
Molecular / cytogenetics description
Differential diagnosis
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