Epithelial Sheath Neuroma: A Case Report and Discussion of the Literature

Abstract

Here, a case of a rare epithelial sheath neuroma (ESN) is reported. A 49-year-old white female presented with a 5 mm solitary, slightly raised, erythematous, itchy papule on her right upper back. The clinical impression was consistent with an inflamed nevus. The patient had no past medical history of malignancy or a family history of neurofibromatosis. There was no prior trauma, surgical procedures, or skin disease at the site. After excision, the patient has had no recurrence at the surgery site during a 4-months follow-up period. ESN is characterized by enlarged nerve fibers ensheathed by a sometimes keratinized squamous epithelium located in the superficial dermis where large nerves are not normally found. It is believed to be a benign neoplasm and simple excision is curative. The histologic differential diagnosis of ESN is presented, and possible mechanisms of its pathogenesis are discussed. It is important for the pathologist and dermatologist to be cognizant of this lesion to prevent misdiagnosis of perineural invasion.

Perineural growth of benign cutaneous sweat gland tumors: a hitherto unrecognized phenomenon unassociated with malignancy

“…Epithelial sheath neuroma is an exceedingly rare proliferation originally reported by Requena et al in 2000 . Upon microscopic examination, enlarged nerve endings were seen in the superficial dermis surrounded by normal appearing squamous epithelium lacking atypia, yet occasionally displaying mitotic activity . Distinction from true perineural invasion by well‐differentiated squamous cell carcinoma can be particularly challenging in small biopsies/shave excisions.…”

“…Reactive epithelial proliferations within the peripheral nerves occurring in the skin mimicking perineural invasion generally include epithelial sheath neuroma, re‐excision perineural invasion and reactive neuroepithelial aggregates . The main importance of these proliferations lies in their distinction from true perineural invasion developing in the background of malignant tumors of different lineage, a phenomenon usually associated with more aggressive clinical behavior, including increased risk for local recurrence with a potential for increased morbidity and mortality …”

Perineural Involvement: What Does it Mean?

“…44 Histologically, ESN is a superficial dermal proliferation composed of enlarged, mature nerve bundles surrounded by squamous epithelium with variable keratinization and lacking cytologic atypia. 21,44 There is minimal associated fibroplasia and a mild inflammatory cell infiltrate composed of lymphocytes and plasma cells. 44 The nerves stain for neural markers, such as: S100 protein, neurofilaments, CD57, nerve growth factor receptor while the perineural epithelial sheaths stain for cytokeratins.…”

“…21,44 There is minimal associated fibroplasia and a mild inflammatory cell infiltrate composed of lymphocytes and plasma cells. 44 The nerves stain for neural markers, such as: S100 protein, neurofilaments, CD57, nerve growth factor receptor while the perineural epithelial sheaths stain for cytokeratins. 45 ESN is not clinically aggressive and simple excision is curative.…”

“…21,44,46,47 Most importantly, the lack of scar formation, keratinocyte atypia, metastases, and the presence enlarged nerves argue against ESN representing a regressed malignancy. Despite the ambiguity in the histogenesis of ESN, dermatologists and pathologists should recognize ESN as a benign neoplasm that may exhibit PNI.…”