Zosteriform palisaded encapsulated neuroma: an unusual presentation.

Palisaded encapsulated neuroma (PEN) is an infrequent benign cutaneous neural tumor, which usually presents as solitary, asymptomatic, papule or nodule, often localized on the faces, around the orifices, in middle age with no sex preponderance. Rarely, it can be multiple. Both solitary and multiple lesions are not associated with neurofibromatosis or multiple endocrine neoplasica syndrome type 2B (MEN 2B). We hereby report, a rare case of multiple cutaneous PEN in a 30-year-old female who presented with multiple asymptomatic soft-to-firm papules and nodules in a dermatomal distribution on the face along the supply of the ophthalmic division of the trigeminal nerve with no signs of neurofibromatosis or MEN 2B.

What was known?

Palisaded encapsulated neuroma (PEN) is a benign neural tumor, which usually presents as small, solitary, asymptomatic, firm, skin-colored, or pink papule, or nodule, almost always present on the face or close to a mucocutaneous junction. Rarely, it can present with multiple lesions.

Introduction

Palisaded encapsulated neuroma (PEN) is a distinctive benign neural tumor, which usually presents as small, solitary, asymptomatic, firm, rubbery, skin-colored or pink papule or nodule, almost always present on the face or close to a mucocutaneous junction. [1] It commonly occurs in middle-aged adults with female to male ratio of 1:1. Rarely it can present with multiple lesions. [2] Despite the fact that it is not uncommon, it has received minimal attention and is very poorly known among pathologists. Clinically, PEN is most commonly confused with neurofibroma, basal cell carcinoma, nevus, or skin appendage tumor. [13] PEN has histological appearance between that of a neurofibroma and a schwannoma situated predominantly in the dermis. Differentiation from neurofibromas is essential, because the latter is often associated with neurofibromatosis, and has a propensity for malignant transformation. PEN has no association with neurofibromatosis or multiple endocrine neoplasia syndrome type 2B (MEN 2B). Even after incomplete excision PEN does not recur, a fact supporting a reactive rather than a neoplastic origin. Here, we present a rare case of multiple cutaneous PEN in a dermatomal distribution on the face not associated with neurofibromatosis or MEN 2B.

Case Report

A 30-year-old female patient presented to us with asymptomatic skin lesions on the face of 4 years duration. These lesions began as pinhead sized elevations and gradually grew in size to the present state. On examination, lesions were multiple, discrete, mostly multi-lobulated, flesh colored, soft to firm, papules, and nodules arranged in a curvilinear fashion on the face [Figure 1] starting from tip of the nose and gradually deviating to the left along the nose, left eyebrow, and forehead region along the distribution of the ophthalmic division of the trigeminal nerve. There was no accompanying history of hearing defect or other neurological disorders. None of the family members were affected. On thorough cutaneous examination, there was no café au lait macules, axillary freckling or plexiform neurofibromas. Hair nails and mucous membranes were normal. On ophthalmological examination no signs of neurofibromatosis were detected. No other clinical sign suggestive of systemic neurofibromatosis was noted. Routine blood investigations, chest X-ray, ultrasonography of the whole abdomen were normal. Skin biopsy specimen showed a tan granular surface of the base and histopathological examination revealed a normal epidermis. In the dermis, there was a partially encapsulated, well-circumscribed nodule [Figure 2] composed of fascicles of small spindle cells with wavy nuclei interlaced with small slits and clefts [Figure 3]. There was no nuclear pleiomorphism or mitoses. The tumor cells were positive for S-100 protein [Figure 4]. These findings and the clinical presentation were consistent with a diagnosis of PEN. We had sent the patient to the plastic surgery out patient departmentfor excision of the lesion.

Figure 1

Multiple, discrete, flesh colored, soft to firm, papules and nodules arranged in a curvilinear fashion on the face

Figure 2

Multiple partially encapsulated, well-circumscribed nodules in the dermis (H and E, ×40)

Figure 3

Fascicles of small spindle cells with wavy nuclei interlaced with small slits and clefts (H and E, ×100)

Figure 4

Tumor mass showing positive S-100 (immunohistochemical staining, ×100)

Discussion

PEN of the skin was first described by Reed et al. in 1972. [1] It is an infrequent, benign cutaneous neural tumor, clinically misdiagnosed as a neurofibroma, basal cell carcinoma, melanocytic nevus, epidermal cyst, or skin appendage tumor, with a histological appearance between that of a neurofibroma and a schwannoma. [13] Common differentials of papule/nodules on the face are presented in Table 1. Despite the relatively high-incidence of this tumor, it remains under-diagnosed by many pathologists.

Table 1

Common differentials of papule/nodules on the face

PEN clinically presents as solitary, asymptomatic, firm, sessile, immobile, rubbery, skin-colored or pink dome-shaped papule or nodule, commonly present on the face or close to a mucocutaneous junction. [14] The lesions have also been found on the trunk, shoulder, arm, oral mucosa, eyelid, and glans penis. [15] It is usually found in middle-aged adults with equal incidence in both sexes. The size of the lesion typically ranges between 2 and 6 mm. Rarely, it can present with multiple lesions. [5] Usually, the lesions have no overlying hairs, with minimal to absent telangiectasia. It has no association with neurofibromatosis or MEN 2B. Clinically, it is difficult to differentiate PEN from neurofibroma because of their similar clinical presentation; though the lesions of PEN are commonly present on the face, usually firm with absence of “buttonhole” sign; whereas in neurofibroma the lesions are mostly present on the trunk, usually soft where “buttonhole” sign can be elicited.

Histopathologically, the tumors are well circumscribed nodule and situated predominantly in the dermis. They are composed of a partially encapsulated mass of schwann cells arranged in interlacing fascicles separated by small clefts, interspersed with a variable amount of tiny axons. [6] There is lack of nuclear pleiomorphism or mitoses. Although the nodular growth pattern is most frequently encountered, other types include epithelioid, plexiform, multi-nodular and fungating. [7]

Immunohistochemical analyses reveal that tumor cells stain positively for S100 protein, collagen type IV and vimentin characteristic of Schwann cell differentiation. The capsule is composed of elongated perineural cells that stain positively for epithelial membrane antigen. [8]

The histological differential diagnosis for PEN includes neurofibroma, schwannoma, traumatic neuroma and leiomyoma. [9] Unlike PEN, neurofibromas lack a capsule, contain mucopolysaccharide ground substance, and have fewer axons with myelin sheaths. [6] Schwannomas are typically found subcutaneously, contain Antoni A and B type tissue with Verocay bodies, and do not have axons. [10] Overall, the PEN accounts for approximately 25% of all nerve sheath tumors of the dermis. True schwannomas rarely occur in the dermis. Traumatic neuromas have axonal and Schwann cell proliferation, however, scarring and inflammatory cells are evident as well. Leiomyomas are spindle cell tumors composed of muscle cells readily differentiated by immunohistochemistry where they are consistently positive for desmin.

PEN is a benign tumor and recurs rarely. So patients can be reassured that excision is curative with a minimum possibility of recurrence, which reduces unnecessary further testing or concern to search for systemic diseases or malignancy.

This case is a rare presentation of a multiple PEN that can be misdiagnosed. A similar presentation of linearly arranged papules, and nodules on the neck and forehead with diagnosis of collagenoma was reported. [11] Clinicians should include PEN in the differential diagnosis of fleshy papules presenting on the nose and forehead for the purpose of obtaining wider recognition of the tumor, which responds well to excision.

What is new?

Multiple cutaneous PEN in a dermatomal distribution on the face in a middle aged female is a very rare presentation.