Recurrent Diffuse Neurofibroma of Nose Associated with Neurofibromatosis Type 1: A Rare Case Report with Review of Literature.

Diffuse neurofibroma is an unusual variant of neurofibroma with the head and neck being the common sites of involvement. It is benign in nature and spreads superficially and has many ectatic blood vessels. Histologically it is similar to conventional neurofibromas except for a few peculiar distinguishing features. We report a case of a 14-year-old boy who presented with a diffuse recurrent painless swelling over the dorsum of the nose with the clinical stigmata of neurofibromatosis. Microscopy revealed a diagnosis of diffuse neurofibroma with a few foci showing differentiation towards Meissner's type of tactile corpuscles. It is important to recognize this entity as it has a tendency to recur, yet hardly ever become malignant and is almost always associated with neurofibromatosis type 1.

What was known?

Diffuse neurofibroma is an uncommon but distinctive type of neurofibroma. It is seen mostly in the head and neck region especially the scalp, and is known for its recurrent nature.

Introduction

Diffuse neurofibroma is a recently recognized entity and an unusual variant of neurofibroma, occurring primarily in children and young adults. The head and neck are common sites of involvement.[1] It is benign in nature and spreads superficially and has many ectatic blood vessels. Histologically it is similar to conventional neurofibromas except for a few peculiar distinguishing features. We report a case of diffuse neurofibroma in a 14-year-old boy presenting as a diffuse recurrent painless swelling over the dorsum of the nose with the clinical stigmata of neurofibromatosis.

Case Report

A 14-year-old boy presented with a diffuse swelling over the dorsum of the nose which was gradually increasing in size over the past 5 months. There was no history of pain, nasal block, nasal discharge or bleeding. He was operated for a similar swelling in the same site 7 months back and the same was diagnosed as neurofibroma. The swelling recurred after 2 months and was progressively increasing in size. On examination, there was a diffuse swelling over the dorsum of the nose, nasal supratip and right lateral nasal wall, measuring about 4 × 3 × 2 cm. The swelling was soft, mobile and not fixed to the underlying nasal septal cartilage or nasal bones, but adherent to the overlying skin of the nose. The skin over the swelling was normal with no sinuses or dilated veins. A healed surgical scar of about 2 cm in length was seen over the columella and right nasal rim [Figure 1]. He also had multiple café-au-lait spots over the anterior and posterior aspects of the trunk [Figures 2 and 3]. A slit-lamp examination of the eye showed multiple Lisch nodules in the iris [Figure 4].

Figure 1

Diffuse swelling over the dorsum of nose and skin over the swelling appearing normal

Figure 2

Multiple café-au-lait spots over the trunk

Figure 3

Café-au-lait spot over the back

Figure 4

Slit lamp examination of the eye showing multiple Lisch nodules in the iris

Ultrasound of the nasal region showed a superficial ill-defined hyperechoic lesion in the right side of the nasal bridge without any evidence of vascularity, altered echogenecity or inflammation. Remaining investigations were normal. A provisional diagnosis of recurrent neurofibroma was then made.

He was then subjected to open rhinoplasty with a bilateral infracartilaginous incision with a stair step columella incision. The lesion was carefully dissected from the adherent nasal skin and the surrounding structures and was completely excised.

The specimen received for histopathological examination consisted of two gray white soft tissue fragments measuring 3 × 2 × 0.5 cm in aggregate. The cut surface was solid gray white with gelatinous areas.

Microscopic examination revealed a diffuse neoplasm encompassing the entire tissue and composed of spindle-shaped cells with wavy, buckled nuclei and some with oval nuclei arranged in a haphazard pattern with entrapment of lobules of mature adipocytes and skeletal muscle fibers [Figures 5–7]. Scattered ectatic blood vessels were also seen interspersed between the tumor cells. Few foci showed differentiation toward Meissner's type of tactile corpuscles [Figure 8].

Figure 5

Diffuse neoplasm composed of spindle shaped cells with wavy buckled nuclei with entrapment of adipocytes and scattered ectatic blood vessels (H and E ×100)

Figure 7

High power view of tumor cells (H and E ×400)

Figure 8

Foci showing differentiation towards Meissner's type of tactile corpuscles (arrow) (H and E ×400)

Neoplasm with entrapment of normal appearing skeletal muscle fibers (arrow) and adipocytes (H and E ×100)

The tumor cells showed diffuse positivity for S100 immunomarker confirming the diagnosis of diffuse neurofibroma [Figure 9].

Figure 9

Tumor cells showing diffuse positivity for a S100 marker. (×100)

Discussion

Neurofibroma is a benign peripheral nerve sheath tumor arising from a mixture of Schwann cells and perineural fibroblasts. It is seen either as a sporadic (solitary) lesion or as a part of a generalized syndrome of neurofibromatosis type 1. Neurofibromas associated with neurofibromatosis type 1 are usually seen in the third to fourth decades of life presenting as slow growing, soft, painless lesions varying in size.[2]

Diffuse neurofibroma is an uncommon but distinctive type of neurofibroma that is recognized as a separate entity from 1997. It typically involves the skin and the subcutaneous tissues occurring primarily in children and young adults between the ages of 10 and 30 years of either sex.[1] The trunk is the most common site followed by the head and neck region and the extremities.[3] It is not as well defined as the typical neurofibroma and shows diffuse infiltration of the dermis and subcutaneous tissue, often extending along the connective tissue septae.[4] Histologically, it is characterized by a diffuse replacement of the dermis and subcutis by interlacing bundles of spindle-shaped cells with round or fusiform buckled nuclei and eosinophilic cytoplasm within a loose matrix of fine fibrillary collagen.[1] Despite the infiltrative growth, it does not destroy but envelops or entraps the normal structures that it encompasses, such as the skin adnexal structures, adipose tissue or the skeletal muscle fibers. Meissner's bodies are characteristic of diffuse neurofibroma and are virtually seen in almost all the cases, in contrast to typical neurofibromas. However, rarely Meissner's bodies can be absent as reported in few studies.[1] Diffuse neurofibromas are usually associated with other mesenchymal elements including ectatic blood vessels and mature-entrapped adipose tissue. A comparative review of the present case with the cases of diffuse neurofibroma reported in the literature is presented in Table 1.

Table 1

Comparison between present case and cases of diffuse neurofibroma reported in the literature

It differs from the conventional neurofibroma in that it has a uniform matrix of fine fibrillary collagen. In addition, the Schwann cells which lie suspended in the matrix are usually less elongated than those of conventional neurofibroma and have short fusiform to even round contours.

When the entrapped mesenchymal elements like adipose tissue and ectatic blood vessels are more in number, they may be mistaken for exuberant granulation tissue on histology.

Due to the diffuse manner in which these lesions infiltrate the dermis and subcutaneous fat superficially, they may be mistaken for a dermatofibrosarcoma. Dermatofibrosarcoma shows a more storiform pattern histologically with CD34 positivity and S100 negativity, in contrast to diffuse neurofibromas which are S100 positive. In addition, Meissner's bodies are absent in dermatofibrosarcoma in contrast to diffuse neurofibroma.[56]

Entrapment of subcutaneous fat in diffuse neurofibroma may also mimic an extremely rare condition, lipomatous neurofibroma, in which there is an aberrant development of adipose tissue in a neurofibroma, regarded as either a metaplastic change or aberrant adipose tissue differentiation from multipotential cells of neural crest origin.[7] Microscopically, it presents either as adipocytes focally intermingled with the spindle cells, or as spindle cell proliferation with regularly scattered adipocytes. It can be differentiated from diffuse neurofibroma by its localized or well-delineated nature, absence of entrapment of normal structures such as skeletal muscles or dermal appendages and the absence of Meissner's bodies in contrast to the latter.[7]

Several studies have reported that about 10% of the diffuse neurofibromas are associated with neurofibromatosis type 1.[89] Any patient with a lesion that is diagnosed as diffuse neurofibroma should be clinically evaluated for the possibility of neurofibromatosis. The treatment includes complete excision of the tumor depending on the extent and location of the tumor. If not excised completely, they may recur locally and require further local resection.[10] Long-term follow up after surgical intervention is also necessary, since many studies have reported that neurofibromas of the head and neck are twice as likely to recur as similar tumors in different locations. Extremely rare is the occurrence of malignant change over many years, in the form of a malignant peripheral nerve sheath tumor.[11]

Conclusion

Diffuse neurofibroma is a variant of conventional neurofibroma. It should be considered in the differential diagnosis of any cutaneous swelling seen in patients of neurofibromatosis type 1. The importance of recognizing this entity lies in the fact that it may microscopically mimic dermatofibrosarcoma, exuberant granulation tissue or a lipomatous neurofibroma. Moreover, in the absence of wide excision, the chances of recurrence are high. The case is reported for its rarity and its unique presentation. Due to the recurrent nature of this lesion, it is necessary to follow up these cases regularly, at least once a year.

What is new?

Diffuse neurofibroma may microscopically mimic dermatofibrosarcoma or a lipomatous neurofibroma. It can occur as a diffuse swelling in the external aspect of the nose.