Cutaneous undifferentiated pleomorphic sarcoma
Cutaneous UPS; previously "malignant fibrous histiocytoma" (MFH) — term retired by WHO in 2002
Undifferentiated pleomorphic sarcoma (UPS) is a high-grade soft-tissue sarcoma defined by the absence of specific lineage differentiation despite extensive immunohistochemical and molecular workup. The 2002 WHO classification retired the older term "malignant fibrous histiocytoma" (MFH), and many lesions previously called MFH are now reclassified as AFX (when superficial and indolent), PDS (AFX with one adverse feature) or leiomyosarcoma when smooth-muscle markers are positive. The diagnosis "cutaneous UPS" is reserved for high-grade dermal/subcutaneous pleomorphic sarcomas that exceed the AFX/PDS spectrum — typically deeper, larger, with substantial subcutaneous and fascial extension. These behave like deep soft-tissue UPS, with rates of distant metastasis (predominantly lung) of 30–40% and 5-year survival 50–65%.
Terminology & reclassification
- "MFH" was a wastebasket diagnosis for any pleomorphic sarcoma without obvious differentiation.
- WHO retired "MFH" as a stand-alone entity over successive editions — WHO 2002 (4th edn) downgraded its diagnostic utility, WHO 2013 (revised 4th edn) formalised "undifferentiated pleomorphic sarcoma" as the descriptor (Fletcher et al.), and WHO 2020 (5th edn, soft tissue & bone) retains that framing. Most cases formerly called MFH are now reclassifiable with modern IHC into:
- AFX — superficial, indolent, dermal-only, no adverse features.
- PDS — AFX-spectrum but with subcutis invasion / necrosis / LVI / perineural invasion.
- Pleomorphic leiomyosarcoma (smooth-muscle markers positive).
- Pleomorphic liposarcoma (lipoblasts identified).
- Pleomorphic rhabdomyosarcoma (skeletal-muscle markers).
- Cutaneous UPS — high-grade pleomorphic sarcoma without lineage differentiation, deeper than AFX/PDS spectrum.
- For cutaneous lesions, this distinction is therapeutically important: AFX is essentially benign, PDS has 10–20% metastatic risk, and UPS has 30–40% metastatic risk.
Clinical features
- Rapidly enlarging, often deeply seated dermal/subcutaneous mass.
- Most common in elderly Caucasian men on the head, neck, lower limbs and trunk.
- Strong association with chronic UV damage and prior radiotherapy.
- May ulcerate or fix to fascia, muscle or bone.
- Differential: AFX, PDS, leiomyosarcoma, melanoma, spindle-cell SCC, cutaneous metastasis.
Histology & molecular
- Highly pleomorphic spindled and epithelioid cells with bizarre nuclei, brisk mitoses (often atypical) and tumour necrosis.
- Storiform or fascicular architecture; deep dermal/subcutaneous extension.
- Negative for lineage-specific markers — S100, SOX10, Melan-A (excludes melanoma); pan-cytokeratin, p63 (excludes spindle SCC); desmin, SMA, h-caldesmon (excludes leiomyosarcoma); MDM2/CDK4 (excludes dedifferentiated liposarcoma); MyoD1, myogenin (excludes rhabdomyosarcoma).
- CD10 typically positive but non-specific; CD34 variable.
- Complex karyotype; recurrent TP53 mutations and copy-number alterations.
Imaging & staging
- MRI of the affected region — defines depth of subcutaneous, fascial and muscular invasion.
- CT chest/abdomen/pelvis — staging for distant metastasis (lung most common).
- USS or CT of regional nodal basin.
Management
- Sarcoma MDT involvement essential.
- Wide local excision with at least 2–3 cm clinical margins to fascia, en-bloc with deep fascia where involved; reconstruction with skin graft or free flap.
- Sentinel lymph node biopsy not routinely performed; nodal metastasis <10%.
- Adjuvant radiotherapy for incomplete margins, deep tumours or recurrent disease — significantly reduces local recurrence.
- Adjuvant chemotherapy (doxorubicin / ifosfamide) considered for high-grade large tumours; evidence base limited.
- Pulmonary metastasectomy can be curative for oligometastatic disease.
- Pembrolizumab and other immune checkpoint inhibitors active in selected cases.
Prognosis
Local recurrence 20–40%; regional or distant metastasis (predominantly lung) 30–40%. 5-year overall survival 50–65%. Adverse factors: large size (>5 cm), deep extension, high mitotic count, R1/R2 resection.
References
- Fletcher CDM. The evolving classification of soft tissue tumours — an update based on the new WHO classification. Histopathology; 2014.
- WHO Classification of Soft Tissue and Bone Tumours, 5th edn; 2020.
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