Soft tissue
Uncertain differentiation
Undifferentiated / unclassified sarcoma
Author: Vijay Shankar, M.D.
Last author update: 1 August 2012
Last staff update: 19 September 2023 (update in progress)
Copyright: 2003-2023, PathologyOutlines.com, Inc.
PubMed Search: Undifferentiated / unclassified sarcoma
Table of Contents
Definition / general | Terminology | Epidemiology | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Shankar V. Undifferentiated / unclassified sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuemfhpleo.html. 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
Terminology
- 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
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 postradiation are usually osteosarcoma or MFH (Mod Pathol 2001;14:969)
Case reports
- 4 year old boy with chest wall swelling (Fetal Pediatr Pathol 2004;23:319)
- 5 year old boy with retroperitoneal tumor (Turk J Pediatr 2007;49:307)
- 45 year old woman with kidney tumor (Pathol Res Pract 2008;204:857)
- 46 year old man with tumor originating in thymus (Ann Thorac Surg 2010;89:2003)
- 53 year old man with laryngeal tumor (Rom J Morphol Embryol 2010;51:359)
- 59 year old man with vocal cord lesion on the vocal cord (Rom J Morphol Embryol 2009;50:481)
- 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)
- 65 year old woman with lumbar abscess (Case Rep Oncol 2011;4:343)
- 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)
- Disseminated tumor (Indian J Pathol Microbiol 2007;50:795)
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:
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
CD10+
CD68+
Vimentin+
CK-
CD34-
Desmin-
S100-
Contributed by @JMGardnerMD on Twitter
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
- 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)
Electron microscopy description
- No features of a specific lineage
- Relatively undifferentiated fibroblastic, myofibroblastic or primitive mesenchymal cells, some with phagocytic properties
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
Additional references
