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A 42-year-old man presents with a slow-growing, indurated, blue-red-brown plaque on his anterior abdominal wall that has been present for 5 years and has recently developed multinodular protuberant change. He reports occasional tenderness but no other symptoms. There is no preceding trauma. On examination, the lesion is 4 x 3 cm, firm, fixed to the overlying skin, and mobile over the deep fascia. There is no regional lymphadenopathy. A punch biopsy shows a monotonous storiform pattern of spindle cells infiltrating subcutaneous fat in a honeycomb pattern, with strong diffuse CD34 positivity and Factor XIIIa negativity.
Questions
a) What is the most likely diagnosis, and which clinical and histological features support it? (2 marks)
b) Which immunohistochemical and molecular investigations would you arrange, and what is the molecular hallmark of this disease? (2 marks)
c) Outline your definitive surgical management, including the rationale for your choice of technique. (3 marks)
d) If this tumour showed fibrosarcomatous transformation on biopsy, how would your management change, and what is the prognosis? (2 marks)
e) If the lesion recurred locally and was not amenable to further surgical resection, which systemic therapy would you offer, and what is its mechanism of action? (1 mark)
Model Answer
[4]a) Diagnosis (2 marks)
- Diagnosis: Dermatofibrosarcoma protuberans (DFSP).
- Supporting clinical features: slow growth over years (5-year history is typical), trunk location (anterior abdominal wall; the commonest site), indurated blue-red-brown plaque with multinodular protuberant progression (the 'protuberans' phase), tethering to overlying skin with mobility over deep fascia, and absence of lymphadenopathy at presentation.
- Supporting histological features: monotonous storiform (cartwheel) pattern of uniform spindle cells, honeycomb (lace-like) infiltration of subcutaneous fat, strong diffuse CD34 positivity (the hallmark), and Factor XIIIa negativity (the discriminator from dermatofibroma).
[1][4]b) IHC and molecular work-up (2 marks)
- Complete the IHC panel - CD34+ (strong, diffuse; HALLMARK), Factor XIIIa-, S100-, SOX10-, SMA-, desmin-, STAT6-. The panel excludes dermatofibroma (Factor XIIIa+), melanoma (S100+/SOX10+), leiomyosarcoma (SMA+/desmin+), and solitary fibrous tumour (STAT6+).
- Molecular confirmation - FISH for the COL1A1-PDGFB fusion (break-apart probes on 17q22 and 22q13), or RT-PCR for the fusion transcript on FFPE tissue, or NGS sarcoma panel for rare fusion variants.
- Molecular hallmark: the t(17;22)(q22;q13) translocation (or r(17;22) ring chromosome) fuses the COL1A1 gene on 17q22 with the PDGFB gene on 22q13, placing PDGFB under the COL1A1 promoter and producing constitutive PDGFB overexpression with autocrine PDGFR-beta activation (the target of imatinib).
[3]c) Definitive surgical management (3 marks)
- Mohs micrographic surgery (MMS) is the standard of care - complete 100 percent margin examination using horizontal frozen sections (or immunostained MMS with CD34 to highlight tumour cells at the margin); reported 5-year local control 95-100 percent, recurrence 1 percent.
- Alternative: wide local excision (WLE) with 2-3 cm peripheral margins to the deep fascia (or the next anatomical barrier - periosteum, perichondrium) with CD34 immunostaining of the specimen margins; reported 5-year local control 80-90 percent, recurrence 10-20 percent.
- Rationale: DFSP has subclinical honeycomb infiltration that extends 1-3 cm beyond the clinical margin; standard WLE with bread-loaf sectioning examines <1 percent of the margin; Mohs examines 100 percent and conserves tissue.
- Reconstruction: primary closure for small defects; local flap, skin graft, or free tissue transfer for larger defects; multidisciplinary planning with a reconstructive surgeon.
- Sarcoma-MDT discussion is recommended for all DFSPs; the case should be discussed pre-operatively.
[2]d) Fibrosarcomatous transformation (2 marks)
- FS-DFSP in 10-15 percent of cases - higher-grade areas with increased cellularity, >5 mitoses per 10 HPF, herringbone pattern; CD34 may be lost in the FS areas (but the fusion persists).
- Management change:
- Wider surgical margins (2-3 cm or more; consider Mohs with immunostaining).
- Adjuvant radiotherapy (50-60 Gy in 2 Gy fractions) for positive margins or unresectable disease.
- Consider imatinib (response less predictable than in classic DFSP; case-by-case at sarcoma MDT).
- CT chest staging for pulmonary metastases; MRI of the primary site.
- Prognosis: metastatic risk rises from <5 percent (classic) to 15-30 percent (FS-DFSP); aggressive management improves local control but metastatic disease may still develop.
[1]e) Systemic therapy for unresectable recurrence (1 mark)
- Imatinib 400 mg orally once daily (continuous; can be escalated to 400 mg twice daily for progression).
- Mechanism: small-molecule tyrosine kinase inhibitor of PDGFR-beta (and PDGFR-alpha, BCR-ABL, KIT); in DFSP the relevant target is the PDGFR-beta encoded by the PDGFB portion of the COL1A1-PDGFB fusion. The fusion is the molecular target; imatinib is FDA- and EMA-approved for unresectable, recurrent, or metastatic DFSP.
- Efficacy: objective response ~50 percent; disease control ~80 percent; median time to response 2-3 months.
- Monitoring: FBC and LFTs every 2 weeks for 2 months, then monthly; weight, oedema, and symptom check at every visit.
References4ShowHide
- [1]Das S, et al. Beyond COL1A1::PDGFB: Rare fusions and their clinical implications in dermatofibrosarcoma protuberans World J Clin Cases, 2025.PMID 41356086
- [2]Das S, et al. Beyond COL1A1::PDGFB: Rare fusions and their clinical implications in dermatofibrosarcoma protuberans World J Clin Cases, 2025.PMID 41356086
- [3]Das S, et al. Beyond COL1A1::PDGFB: Rare fusions and their clinical implications in dermatofibrosarcoma protuberans World J Clin Cases, 2025.PMID 41356086
- [4]Saiag P, Lebbe C, Brochez L, et al. Diagnosis and treatment of dermatofibrosarcoma protuberans. European interdisciplinary guideline - update 2024 Eur J Cancer, 2025.PMID 39904126