Enlarging pigmented macule on the sole at the site of a prior 'benign' biopsy
A 54-year-old man presents with a 9-mm asymmetric, irregularly pigmented macule on the right sole that has enlarged over 18 months. Three years earlier, a shave biopsy from the same site was reported as a benign acral nevus with a nested junctional pattern, and no further treatment was given. The current 6-mm punch biopsy shows a lentiginous and nested intraepidermal melanocytic proliferation that extends beyond the clinical scar, with confluent nests along the crista profunda, pagetoid scatter of melanocytes above the basal layer, and moderate cytologic atypia; no dermal invasion is identified on three levels. The lesion is 9 mm wide and the margins are involved. Reflectance confocal microscopy was not performed. The patient is otherwise healthy, with no personal or family history of melanoma.
1. Which features in this biopsy drive a diagnosis of melanoma in situ rather than a persistent benign acral nevus, and which atypical features are unreliable at acral sites?
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Features favoring melanoma in situ:
- Pagetoid scatter of melanocytes well above the basal layer, especially when widespread and not confined to the center of nests.
- Confluent nests along the crista profunda and a lentiginous proliferation that extends beyond the scar and is poorly circumscribed.
- Cytologic atypia with enlarged, hyperchromatic nuclei and prominent nucleoli.
Features that are unreliable at acral sites:
- A nested junctional pattern alone: acral nevi commonly show well-defined square nests along the crista profunda.
- Mild suprabasal scatter: pagetoid melanocytosis can occur in benign acral nevi, particularly in younger patients and within the center of the lesion.
- Melanin incontinence and dermal fibrosis: these reflect the prior biopsy and scar, not malignancy.
The discriminating feature is the combination of poor circumscription, confluence, and atypia extending beyond the scar. A persistent nevus is typically confined to the scar and shows a shoulder of residual benign nevus. The extension past the clinical scar argues against a simple persistent nevus, and any single feature, especially nesting, should not drive the diagnosis.
2. FISH for 6p25, 11q13, 9p21, and 8q24 is negative, and PRAME shows weak patchy staining in 10% of cells. How do you use these results, and what are their limits?
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I would interpret the negative FISH as non-informative rather than exculpatory. These panels detect copy-number changes in roughly 60 to 70 percent of acral melanomas; a negative result does not exclude melanoma. Homozygous 9p21 deletion is highly specific when present but has limited sensitivity. PRAME immunohistochemistry is supportive when diffuse and strong, but weak patchy staining in 10 percent of cells is neither sensitive nor specific and should not be used to downgrade a morphologically convincing lesion.
So the ancillary tests are concordant with, but not proof of, a benign process. The diagnosis should rest on the H&E features and the clinical behavior. In a lesion that is enlarging, poorly circumscribed, and shows confluent nesting and pagetoid scatter beyond a scar, I would still call this melanoma in situ and treat it as such. I would document the limitations of testing in the report so the clinician does not over-interpret the negative FISH, and I would seek a second dermatopathology opinion if available.
3. What is your management plan, and how do the earlier biopsy and the involved margins affect it?
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Management:
- Complete excision with a 5-mm clinical margin to clear the involved margins. Acral melanoma in situ carries a meaningful risk of upsampling to invasive disease, and margins must be verified histologically on the re-excision specimen.
- Because no dermal invasion is seen on three levels, sentinel lymph node biopsy is not indicated at this stage. If the re-excision shows invasion, staging changes.
- Retrieve and review the 3-year-old slides and compare them with the current specimen. The earlier benign report does not exclude melanoma; a persistent or recurrent nevus can mimic melanoma, but a melanoma arising in or near a prior biopsy site is also well described.
- Consider a second dermatopathologist opinion and, if available, a molecular classifier before committing to wide excision on a sole.
- Follow-up with clinical surveillance, photography, and education about acral lesions.
The involved margins make re-excision mandatory regardless of the ancillary test results.