A Fast-Growing Forearm Nodule: 'Favor AFX' on a Shave Biopsy
A 74-year-old man has a 1.6 cm rapidly growing, ulcerated nodule on the dorsal forearm that appeared over five months on severely sun-damaged skin. A deep shave biopsy shows a dermal nodular proliferation of large epithelioid and spindle cells with abundant eosinophilic cytoplasm, marked nuclear pleomorphism, and numerous atypical mitoses. There is no connection to the overlying epidermis, which is ulcerated. There is no myxoid stroma, no giant-cell collagenoma pattern, and no area of conventional squamous cell carcinoma. Tumor cells reach the deep edge of the specimen. The pathologist signs out "atypical dermal spindle/epithelioid neoplasm, favor atypical fibroxanthoma versus pleomorphic dermal sarcoma versus nodular melanoma" and asks what you need before definitive surgery.
1. Design the immunohistochemical work-up and explain what each result would rule in or out. State why the shave technique itself limits the diagnosis.
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Panel and rationale:
- S100, SOX10, Melan-A, HMB-45: if positive, this is melanoma. A dermal-only epithelioid proliferation with no epidermal component can be a nodular or metastatic melanoma.
- p63, p40, pan-cytokeratin (AE1/AE3, CK5/6): if positive, sarcomatoid squamous cell carcinoma - very common on sun-damaged forearm.
- Desmin, myogenin, h-caldesmon: excludes leiomyosarcoma and rhabdomyosarcoma.
- CD34, STAT6: excludes solitary fibrous tumor and dermatofibrosarcoma protuberans.
- CD10, CD68, vimentin, SMA, p53: the AFX/PDS profile is typically positive for CD10 and CD68 with aberrant p53 and negative for the lineage markers above. This is a diagnosis of exclusion.
Why the technique limits it: AFX and pleomorphic dermal sarcoma are the same morphologic spectrum separated by depth and by the presence of subcutaneous invasion, necrosis, perineural or lymphovascular involvement. A shave biopsy that reaches the deep margin cannot assess the subcutis, so "favor AFX" is not a defensible final diagnosis. A deep excision or deep punch is required, and the case should be reviewed at a multidisciplinary or expert pathology setting.
2. Assume the markers are negative for melanocytic and epithelial lineage and the deep margin is involved. Explain how the AFX-versus-PDS distinction changes your surgical plan and staging.
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The distinction is not academic - it changes margins and staging.
- If AFX (superficial, no subcutaneous invasion, no necrosis, no perineural or lymphovascular invasion): complete excision with a narrow clinical margin (typically 0.5–1 cm) and clinical follow-up is adequate. Metastatic risk is very low.
- If PDS (subcutaneous invasion, necrosis, perineural or lymphovascular involvement): re-excise with 2–3 cm margins down to fascia where feasible, and consider adjuvant radiotherapy for close or positive margins or perineural disease. Reported metastatic rates are in the range of 10–20%, so baseline staging imaging (CT of chest and regional nodes, or MRI for deep or perineural disease) and consideration of sentinel lymph node biopsy at a specialist center are reasonable.
If the final read is melanoma, the entire algorithm switches to Breslow-based wide local excision and sentinel node biopsy at >0.8 mm or with ulceration.
Practically: I would not close this defect with a small primary closure until the deep tissue has been examined; plan the excision so that re-excision is possible without compromising a reconstructive option.
3. How would you counsel the patient and structure follow-up given genuine diagnostic uncertainty at this stage?
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Uncertainty must be named honestly rather than hidden behind a label. I would tell him: the biopsy shows a malignant-looking tumour of uncertain lineage, the shave cannot tell us how deep it goes, and the next procedure is both diagnostic and therapeutic.
Counselling points:
- The chance it is melanoma or sarcomatoid SCC is real, and the treatment differs, so waiting is not safe.
- The definitive excision will be wider and deeper than a typical skin cancer excision, and may need a skin graft or flap.
- If it proves to be PDS, there is a meaningful risk of spread to nodes or lungs that warrants imaging.
Follow-up structure:
- Weekly wound review until healed, given the forearm and likely graft.
- Three-monthly skin and regional nodal examination for two years, then six-monthly to five years.
- Full skin examination each visit - he has field cancerisation and will develop further lesions.
- Strict photoprotection and self-examination instruction, with a low threshold for biopsying any new nodule.