Soft tissue
Fibrohistiocytic tumors
Undifferentiated pleomorphic sarcoma

Author: Vijay Shankar, M.D.

Revised: 30 January 2018, last major update August 2012

Copyright: (c) 2003-2018,, Inc.

PubMed Search: Undifferentiated pleomorphic sarcoma [title]
Cite this page: Shankar, V. Undifferentiated pleomorphic sarcoma. website. Accessed July 16th, 2018.
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
  • Terminology
  • Also called pleomorphic undifferentiated sarcoma
  • 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
  • Epidemiology
  • 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 post-radiation are usually osteosarcoma or MFH (Mod Pathol 2001;14:969)
  • Radiology images

    Images hosted on other servers:

    Tumor surrounds intramedullary nail

    Case reports
  • 60 year old man with liver tumor (Hepatobiliary Pancreat Dis Int 2009;8:541)
  • 63 year old man with concurrent scrotal Fourniers gangrene (Appl Immunohistochem Mol Morphol 2010;18:473)
  • 67 year old man with 1.5 cm excised scalp nodule (Case of the Week #387)
  • 76 year old man with a breast tumor (J Breast Cancer 2011;14:241)
  • Treatment
  • 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:

    Shoulder tumor

    Sternal mass

    Images hosted on Nature servers:

    Implant related MFH is tan and fleshy and surrounds femur

    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

    Scroll to see all images.

    Images hosted on PathOut server:

    Striking low power appearance due to cellularity,
    whorled pattern, marked pleomorphism with bizarre nuclei

    Tumor cells have abundant eosinophilic cytoplasm
    and bizarre nuclei, and resemble a muscle tumor

    Characteristic giant cells with bizarre nuclei

    Mixture of fibroblasts and histiocyte-like cells including multinucleated forms

    Vague storiform pattern is often present, at least focally

    Strap like cells resemble rhabdomyoblasts

    Numerous mitotic figures, some bizarre forms

    Frequent tumor cell necrosis, not seen in benign fibrous histiocytoma

    Case of the Week #387:

    H&E images: low

    H&E images: high








    Images hosted on other servers:

    Various images

    Breast mass (recurrent)

    Hard palate tumor (vimentin, CD68)

    Hard palate tumor (H&E)

    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
  • Note: positive stains are usually not helpful for diagnosis
  • Vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, Factor XIIIa, CD68 (may be due to lysosomal granules in non-histiocytic cells); also CD10, CD34, CD99 (35%, J Cutan Pathol 2006;33 Suppl 2:24) very rarely aberrant expression of MelanA (J Cutan Pathol 2011;38:954)
  • Negative stains
  • Keratin (usually), melanocytic markers, CD45, S100, muscle markers
  • Electron microscopy description
  • No features of a specific lineage
  • Relatively undifferentiated fibroblastic, myofibroblastic or primitive mesenchymal cells, some with phagocytic properties
  • Electron microscopy images

    Images hosted on Nature servers:

    Tumor cell has fibroblastic features

    Molecular / cytogenetics description
  • Highly complex karyotype, usually triploid or tetraploid
  • Gene expression profiles may be somewhat similar to other sarcomas (Mod Pathol 2007;20:749)
  • Frequent alterations in G1/S checkpoint genes (Genes Chromosomes Cancer 2011;50:291)
  • Differential diagnosis
  • Anaplastic large cell lymphoma: CD30+
  • Atypical fibroxanthoma: cutaneous, small and superficial
  • Leiomyosarcoma, pleomorphic: smooth muscle differentiation
  • Leprosy, histiocytoid: prominent histiocytes but no prominent atypia or atypical mitotic figures, special stains may reveal mycobacteria
  • Liposarcoma, pleomorphic: lipoblasts, often S100+ or smooth muscle actin+
  • MFH-giant cell: numerous osteoclast-like giant cells
  • MFH-inflammatory: marked inflammatory cells
  • Myxofibrosarcoma: 10%+ myxoid foci
  • Renal cell carcinoma, metastatic: keratin+
  • Rhabdomyosarcoma, pleomorphic: evidence of skeletal muscle differentiation