Cutaneous benign epithelioid peripheral nerve sheath tumour: a rare entity.

Benign epithelioid peripheral nerve sheath tumor, a rare entity is an umbrella term describing benign, neural origin tumors with epithelioid morphology. Clinically indistinguishable from other benign cutaneous lesions, histopathology offers the only source of accurate diagnosis. Morphologic mimics include many benign and malignant soft tissue lesions. Besides a predominant epithelioid component, the lesion can also show a fair share of spindle cells. A circumscribed nodular tumour of low mitotic activity, it often exhibits areas resembling schwannoma or neurofibroma. An awareness of this entity and its varied morphological aspects helps to arrive at the correct diagnosis and hence avoid unnecessary extensive surgical procedures. This case presents features of this benign tumor which occurred in a 47 years old man.

What was known?

Benign Peripheral nerve sheath tumours with epithelioid morphology, are known to be rare cutaneous lesions of neural origin, closely mimicking malignant epithelioid soft tissue tumours.

Introduction

Benign peripheral nerve sheath tumors with epithelioid morphology (BEPNST) are uncommon entities; a cutaneous location and epithelioid morphology often leading to misdiagnosis. Many tumors fall under this umbrella term, with some researchers separating out epithelioid Schwannoma into a distinct entity. A few epithelioid lesions have overlapping features of neurofibroma and schwannoma, while some lesions have features typical of neither. Non neural, epithelioid benign and malignant soft tissue tumors are close mimics and would fall into the differential diagnoses of this lesion.[1]

The epithelioid variant of malignant peripheral nerve sheath tumor (EMPNST) is a well categorised lesion with distinct features. The benign counterpart though is rarely reported, and often under various terms like ‘Cutaneous epithelioid Schwannoma’[2] ‘Benign Epithelioid Schwannoma’[34] depending on dominant histological features supporting schwannoma, co-existence of conventional Neurofibroma, or relationship with a nerve. Few tumors reported have features of Schwannoma/Neurofibroma or fall into a ‘grey’ zone in between. To avoid such confusion, all these tumors were clubbed under the term ‘BEPNST’ by Laskin and colleagues[4] in their landmark study, which elucidated features classic to this category.

Case Report

A male patient aged 47 years, gives history of sudden increase in the size of a nodular lesion over the knee, following a minor trauma. The swelling had been present for the last 35 years and was slowly increasing in size. A history of trauma sustained to the site at the age of 12 was elicited, which healed with a small bleb sized lesion over the lateral end of scar. It was associated with pain following pressure at that site with full range of movements of the knee joint. Presently, the swelling had become painful following trauma to the lesion. The surgeon noted a nodular cutaneous lesion over the lateral aspect of the knee joint measuring 2.5 cm across, which was freely movable over the underlying structures. Skin over the lesion was stretched, hypopigmented and smooth [Figure 1]. A clinical diagnosis of sebaceous cyst was made and local excision performed. Specimen received in the pathology department was a single skin covered nodular tissue measuring 2 × 1 cm. Cut section showed a single cyst with luminal areas of haemorrhage and thick wall with solid white areas. Histopathological examination (HPE) showed a mid to deep dermal lesion with central cystic degeneration and coagulative necrosis. Short fascicles of spindle and epithelioid cells were seen [Figures 2 and 3], with moderate eosinophilic cytoplasm, vesicular fusiform nucleus, prominent eosinophilic nucleolus and an occasional mitotic figure, vaguely resembling Antoni A areas [Figure 4]. Areas of haemorrhage rimmed by hemosiderrin laden macrophages, stromal hyalinisation and chronic inflammation were noted. Tumor cells were S100 positive diffusely [inset [Figure 3], and SMA and CD68 negative. MIB count was low. Based on these findings, a diagnosis of Cutaneous Benign Epithelioid Peripheral Nerve sheath tumor was offered.

Figure 1

Single, skin covered nodule over knee joint; skin is stretched over the lesion

Figure 2

Photomicrograph of lesion. (a) Epithelioid and spindle cells (H and E, ×400), (b) Epithelioid cells (H and E, ×400)

Figure 3

Photomicrograph of spindle cells (H and E, ×100) Inset: S100 positive tumor cells

Figure 4

Photomicrograph of Antoni A areas (H and E, ×50)

Discussion

The cutaneous benign peripheral epithelioid nerve sheath tumor (BEPNST), as endorsed by Laskin and colleagues, is an umbrella term reserved for morphological entities of neural origin with a predominance of epithelioid cells. Falling into this category include lesions with partial resemblance to Schwannoma, Neurofibroma, features of both or neither, with IHC being positive for neural markers. A tumor found in various sites and not restricted to any age group, it's characteristic clinical features include a benign behavior, superficial location and small size (< 3 cm).[34] Usually solitary, multiple lesions with Schwannoma like morphology have been described in association with Carney's syndrome and Neurofibromatosis.[2] The lesions have a wide distribution, with the lower limb being the preferred site.[4] Laskin and colleagues in their landmark study described the histological features characterising this lesion. With a predominant dermal/subcutaneous location, these lesions may rarely be attached to nerves. Circumscription with or without encapsulation is the rule. Tumors are surrounded by thick connective tissue mantle, and comprise one or more closely apposed nodules of uniform population of epithelioid ‘nevus like’ cells with moderate to abundant eosinophilic cytoplasm, vesicular nucleus, small nucleolus, low mitotic activity (0-6/50 HPF) forming nests, cords, trabeculae, clusters in a myxohyaline matrix. A minor spindle cell component in clusters/fascicles is seen merging with the epithelioid cells. The tumor cells demonstrate immunohistochemical positivity for S100, GFAP, Laminin, Collagen IV. Permeative intraneural growth and rosette like structures, are additional features supportive of neural origin.[4] A collagen rich variant exhibiting hyalinised collagen rich nodules has also been described.[5]

The present case was a dermal circumscribed, nonencapsulated lesion with epithelioid cell predominance, minor spindle cell component, with other features and IHC helping us decide in favor of BEPNST. Follow up of the patient revealed a benign clinical nature.

Clinically not different from other benign cutaneous lesion associated with pain, like angioleiomyoma, HPE remains the mainstay for diagnosis in such cases.

Histological differential diagnoses include the rare EMPNST, myopericytoma, leiomyoma and benign fibrous histiocytoma (BFH), the latter two with epithelioid morphology. Similar to BEPNST on microscopy and IHC to some extent, features that favor EMPNST include hyperchromasia, large nucleoli, increased mitoses (often atypical), and necrosis. It is difficult to distinguish the latter three differentials from this tumor. IHC an integral part of current pathological diagnoses offers some succor, with S100 and GFAP being negative in these tumors, pointing towards their non-neural origin. Myopericytoma shows cells closely apposed to numerous blood vessels besides being SMA positive,[6] as also a leiomyoma.[7] BFH should be CD68 and CD34 positive.[8]

This case represents a rare lesion of neural origin with features partially resembling it's more common soft tissue counterparts. The benign clinical nature and the strong resemblance to the malignant counterpart with epithelioid morphology, necessitates the need for the dermatologist/dermatopathlogist to consider this lesion in the differential diagnoses of benign cutaneous painful lesions exhibiting epithelioid morphology.

What is new?

A rare neural lesion with epithelioid cells on morphology, this case of BEPNST presented with a history of post traumatic occurrence over a prolonged period.