title: Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6.
abstract: 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.
authors.affiliation: *Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY; †Ohio State University Comprehensive Cancer Center, Columbus, OH; and ‡NYC Dermatology and Cosmetic Center, New York, NY.
authors.forename: James Y
authors.initials: JY
authors.lastname: Wang
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kline
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001415:Back; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy / Q000009:adverse effects*; D002921:Cicatrix / Q000209:etiology / Q000473:pathology*; D004416:Dysplastic Nevus Syndrome / Q000473:pathology / Q000601:surgery*; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006965:Hyperplasia; D015850:Interleukin-6 / Q000032:analysis*; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009463:Neuroma / Q000737:chemistry / Q000209:etiology / Q000473:pathology*; D010525:Peripheral Nerves / Q000737:chemistry / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology / Q000601:surgery*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6; D007633:Keratins