Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6

Am J Dermatopathol. 2017 Jan;39(1):49-52. doi: 10.1097/DAD.0000000000000671.


Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Back
  • Biomarkers, Tumor / analysis*
  • Biopsy / adverse effects*
  • Cicatrix / etiology
  • Cicatrix / pathology*
  • Dysplastic Nevus Syndrome / pathology
  • Dysplastic Nevus Syndrome / surgery*
  • Epithelial Cells / chemistry
  • Epithelial Cells / pathology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Hyperplasia
  • Interleukin-6 / analysis*
  • Keratins / analysis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neuroma / chemistry
  • Neuroma / etiology
  • Neuroma / pathology*
  • Peripheral Nerves / chemistry
  • Peripheral Nerves / pathology*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / surgery*
  • Up-Regulation


  • Biomarkers, Tumor
  • IL6 protein, human
  • Interleukin-6
  • Keratins