Deep penetrating naevus
DPN; "plexiform spindle cell naevus"; combined deep penetrating naevus (when combined with conventional naevus); now recognised as a distinct molecular entity within WHO 2018 classification
Deep penetrating naevus (DPN) is an uncommon benign melanocytic lesion characterised clinically by a heavily pigmented, dark brown to blue-black, dome-shaped or polypoid papule on the head, neck or upper trunk of a young to middle-aged adult, and histologically by an alarming "plexiform" / wedge-shaped infiltration of pigmented spindled and epithelioid melanocytes deep into the dermis (and sometimes into subcutis). The lesion is benign, but the deep extension, brisk pigmentation, focal atypia and frequent mitoses make DPN one of the principal histological mimics of vertical-growth-phase melanoma โ and benign DPN is repeatedly reported as misdiagnosed as melanoma in real-world dermatopathology audits. Modern molecular characterisation has identified ฮฒ-catenin (CTNNB1) gain-of-function activation of the Wnt pathway in DPN, often combined with co-occurring activating BRAF or MAP2K1 mutations โ placing DPN in a defined molecular bucket distinct from conventional acquired naevi, Spitz family lesions and BAP1-inactivated naevi.
Clinical features
- Solitary, dark brown to blue-black, dome-shaped or polypoid papule, 5โ15 mm.
- Distribution โ head, neck, upper trunk, shoulders, upper arms.
- Onset โ typically young adulthood (15โ30 years); slow growth over years.
- F>M slightly.
- Surface โ smooth or slightly verrucous.
- Differential โ pigmented Spitz naevus, blue naevus, melanoma (especially nodular pigmented), pigmented BCC, dermatofibroma with haemosiderin.
- Excisional biopsy with full histology is essential โ clinical and dermoscopic features cannot reliably distinguish DPN from melanoma.
Histology & pitfalls
- Wedge-shaped (apex pointing deep), plexiform infiltration of heavily pigmented spindled and epithelioid melanocytes extending from the papillary dermis deep into the reticular dermis or subcutis.
- Cells arranged in fascicles around adnexal structures (perifollicular, perineural, perieccrine).
- Heavy melanin pigmentation, abundant melanophages.
- Mild to moderate cytological atypia; mitoses present but few; no atypical mitoses; no necrosis.
- Symmetric, well-circumscribed at low power.
- Critical pitfall โ frequently misdiagnosed as vertical-growth-phase melanoma due to:
- Deep dermal extension.
- Brisk pigmentation.
- Focal cytological atypia.
- Occasional mitoses.
- Discriminating features supporting DPN over melanoma:
- Symmetric architecture.
- Absence of pagetoid spread.
- Absence of atypical mitoses, necrosis, lymphovascular invasion.
- Maturation with depth (cells become smaller).
- Low Ki-67.
- Combined nuclear and cytoplasmic ฮฒ-catenin (CTNNB1) staining on IHC.
- Equivocal cases โ refer to specialist dermatopathologist; molecular profiling (CGH, FISH).
Molecular profile
- Wnt-ฮฒ-catenin pathway activation โ characteristic.
- CTNNB1 gain-of-function activating mutations.
- APC loss-of-function mutations (less commonly).
- Combined nuclear and cytoplasmic ฮฒ-catenin staining on IHC โ useful diagnostic adjunct.
- Frequently co-occurs with classical melanoma driver mutations:
- BRAF V600E in many cases.
- MAP2K1 (MEK1) activating mutations.
- Less commonly NRAS.
- Distinct from Spitz family lesions (kinase fusions, HRAS) and BAP1-inactivated naevi (BRAF + BAP1 loss).
Management
- Complete excisional biopsy with 1โ2 mm clinical margin and full histology โ the standard of care for any clinically suspicious pigmented lesion that may be DPN, melanoma or pigmented Spitz naevus.
- Re-excision to clear margins for any equivocal histological features (focal atypia at the edge, expansive growth, atypical Spitz tumour features) โ the threshold should be lower than for unequivocal benign naevi.
- Specialist dermatopathology review for any "atypical DPN" or DPN-melanoma differential โ molecular profiling (CTNNB1, BRAF, MAP2K1, BAP1, kinase fusion panel) increasingly available.
- Counsel patients about the benign nature of the diagnosis.
- No specific cancer surveillance after complete excision.
References
- Seab JA et al. Deep penetrating nevus. Am J Surg Pathol; 1989.
- Yeh I et al. Combined activation of MAP kinase pathway and ฮฒ-catenin signaling causes deep penetrating nevi. Nat Commun; 2017.
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