Palisaded Encapsulated Neuroma (PEN): An often misdiagnosed neural tumor
Published Web Locationhttps://doi.org/10.5070/D39wm665kr
Palisaded Encapsulated Neuroma (PEN): An often misdiagnosed neural tumorUniversity of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. firstname.lastname@example.org
Marissa D Newman MD, Sandy Milgraum MD
Dermatology Online Journal 14 (7): 12
We describe a unique case of a young man with concomitant Fragile X syndrome who presented with a dome-shaped pearly papule under the nose that had enlarged over 9 months. Histology demonstrated a smoothly contoured spindle cell neoplasm of the dermis with neuroid structures and foci of palisaded growth, consistent with a diagnosis of palisaded encapsulated neuroma (PEN). Palisaded encapsulated neuroma is a benign neural neoplasm of the skin or mucosa that displays histologic features of both a neurofibroma and a schwannoma. However, unlike these tumors, PEN lacks the implications for underlying systemic disease or malignancy. Palisaded encapsulated neuroma is a commonly underdiagnosed and misdiagnosed tumor that, once identified clinically and histologically, can be easily excised without recurrence.
First described by Reed et al. in 1972, palisaded encapsulated neuroma (PEN) of the skin is a benign, solitary, firm, dome-shaped, non-pigmented papule that occurs preferentially near mucocutaneous junctions of the face, although not limited to the face . PEN most frequently presents in patients 40 to 60 years of age and exhibits a slight predilection for women as compared with men. The diagnosis of PEN may be confounded by similarities that PEN shares with schwannomas and neurofibromas. Differentiation of PENs from neurofibromas is imperative because neurofibromas are characteristic of Neurofibromatosis 1 (Von Recklinghausen disease), a disease with serious implications for internal neurofibromas of the peripheral and central nervous system, systemic disease, and the potential for malignancy (neurofibrosarcoma). Conversely, PEN is not known to represent a sign of underlying disease and may be excised without recurrence.
|Figure 1. Solitary pearly papule (5 x 4 mm) under the nose|
A 37-year-old man presented with a rubbery papule under his nose that gradually increased in size over 9 months. The patient sought evaluation because the lesion bled when he shaved, but was not painful. There was no history of similar lesions. The patient had been diagnosed with Fragile X syndrome via Southern blotting and PCR testing. The patient was otherwise healthy.
Physical examination revealed a well circumscribed, firm, pearly 5 x 4 mm papule with overlying telangiectasia under the nose (Fig. 1). The remainder of the skin examination was normal.
|Figure 2||Figure 3|
|Figure 2. Well circumscribed dermal papule (hematoxylin & eosin 40x)|
Figure 3. Fascicles of spindle cells embedded in an eosinophilic fibrillar matrix (hematoxylin & eosin 200x)
The solitary papule was clinically thought to be a fibroma. Biopsy of the specimen revealed a tan granular surface of the base. Microscopic examination revealed a smoothly contoured spindle cell neoplasm within the dermis comprised of scattered small neuroid structures and focal suggestions of palisaded growth (Figs. 2 & 3). There was no atypia or mitotic evidence of malignancy. The histopathologic diagnosis in the context of the clinical picture was consistent with a palisaded encapsulated neuroma. The lesion was definitively removed with a shave excision that was well tolerated. There was no recurrence of the lesion.
Palisaded encapsulated neuroma of the skin, also referred to as solitary circumscribed neuroma, is a benign cutaneous tumor of the skin that clinically presents as a firm, flesh-colored, dome-shaped papule with loss of overlying skin markings . The lesions typically measure between 2 and 6 mm and have slowly enlarged over several years. Although hairs, ulcerations, and telangiectasias are typically absent or minimal, our patient presented with a single telangiectasia. Such dilated capillaries and venules have been reported to occur in PENs with recurrent trauma, such as in shaving. While PENs overwhelmingly occur on the face particularly at mucocutaneous junctions, reports have described these lesions occurring on the eyelid, oral mucosa, nasal fossa, shoulder, arm, hand, foot, and glans penis [2, 3, 4]. The clinical differential diagnosis of PEN includes neurofibroma, basal cell carcinoma (BCC), melanocytic nevus, epidermal cyst, and skin appendage tumor [1, 5]. Features that distinguish PEN from BCC are the longer presence and relative lack of telangiectasias and ulceration of the PEN .
Histopathologic examination of the PEN reveals a solitary, well circumscribed, partially encapsulated, intradermal nodule comprised of interdigitating spindle cells grouped in distinct fascicles . Additionally, there is a lack of nuclear pleomorphism and mitoses. Although the nodular growth pattern occurs most frequently, others include epithelioid, plexiform, multinodular and fungating .
Immunohistochemical analyses demonstrate positive tumor cell staining for S100 protein, collagen type IV and vimentin characteristic of Schwann cell differentiation . The capsule is comprised of elongated perineural cells that stain positively for epithelial membrane antigen (EMA). Based on histologic similarities, the differential diagnosis includes neurofibroma, schwannoma, traumatic neuroma and leiomyoma [8, 9]. Dissimilar to PEN however, neurofibromas that are associated with Neurofibromatosis 1 lack a capsule, contain mucopolysaccharide ground substance and possess fewer ensheathed axons . Schwannomas are usually subcutaneous, contain Antoni A and B type tissue with Verocay bodies and lack axons . Although traumatic neuromas display abundant Schwann cells and axons, inflammatory cells and scaring are also visualized. Leiomyomas are distinguished by the presence of muscle cells in the tumor and positive staining for vimentin.
The proposed pathophysiology of the PEN focuses on a hamartomatous growth of Schwann cells predominating over the number of axons . However, the stimulus that triggers these Schwann cells to proliferate has not been identified.
Most important is the recognition and biopsy of these lesions such that a definitive diagnosis can be made. In the case of the PEN, patients can be reassured that excision is curative with a low probability of recurrence, which alleviates unnecessary further testing or concern for systemic disease or malignancy. While neurofibromas have been associated with Neurofibromatosis 1 and underlying neurofibrosarcoma, mucosal neuromas are linked with the tumors of multiple endocrine neoplasia II. To date, there are no reports of PENs in patients with Fragile X, and thus we do not believe that the PEN is part of the Fragile X syndrome. However, this case highlights that well circumscribed solitary papules, particularly near mucocutaneous junctions, necessitate definitive histologic diagnosis because they can mimic tumors with underlying systemic disease or malignant potential.
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