Clinical-Pathologic Correlation in Nail Disorders: New Developments in Nail Pathology

Conclusions

• Careful clinical-pathologic correlation is essential in nail disorders, and the best diagnostic yield comes from photographing the nail from surface, lateral, and free-margin views while submitting well-oriented specimens.
• Multiple onychopapillomas should prompt consideration of BAP1 tumor predisposition syndrome, but onychopapilloma itself does not appear to require BAP1 immunohistochemistry.
• A painful, draining, enlarging, or otherwise atypical onychopapilloma-like lesion should raise concern for malignant onychopapilloma or another squamous neoplasm rather than being assumed benign.
• Nail clippings are highly informative and should be routinely examined and reported because they can reveal onychomycosis, psoriasis, melanocytic remnants, onychomatricoma, and occult squamous pathology.
• Atypical parakeratosis in nail plate or shallow nail biopsies is an important clue that should be reported because it can be associated with nail unit squamous cell carcinoma, though it is not fully specific.
• Nail unit squamous cell carcinoma often masquerades as a wart or other benign lesion, so refractory wart-like nail disease, lateral nail fold hyperkeratosis, or unexplained onycholysis should prompt biopsy.
• Shallow or superficial nail biopsies can miss invasive disease, so pathologists should caution clinicians when the specimen is insufficient to exclude squamous cell carcinoma.
• Nail unit squamous cell carcinoma is frequently HPV-associated, especially in basaloid lesions, and clinicians should consider evaluation for possible genitodigital HPV transmission.
• Pseudoepitheliomatous or pseudocarcinomatous hyperplasia can mimic nail squamous cell carcinoma, including in gout or other reactive conditions, making deep sampling and careful histology crucial.
• Proliferating onychomatricoma is a newly recognized benign variant that can resemble squamous neoplasia, but its fibroepithelial stroma and low proliferative profile help distinguish it from nuSCC.
• For nail unit melanoma, immunostains should be interpreted only in context, with a combination approach preferred when needed because marker performance differs between epithelium and dermis.
• In longitudinal melanonychia, biopsy decisions must balance risk and benefit, and benign melanocytic activation in children should not be overcalled as melanoma based on nail plate melanocyte remnants alone.