Ganglion cell like cells, diagnostic dilemma

Abstract

We report a case of cutaneous swelling found on the left anterior axillary fold of a 41-year-old man. Gross examination of specimen excised from the dermis showed a well-circumscribed nodule histologically composed of spindle cells with interspersed ganglion cell like cells. On hematoxylin and eosine (H and E) staining it was diagnosed as ganglioneuroma. Ganglioneuromas are rare, benign, fully differentiated tumors that contain mature schwann cells, ganglion cells, fibrous tissue, and nerve fibers. They are commonly found along the paravertebral sympathetic ganglia and sometimes in the adrenal medulla. However primary cutaneous ganglioneuroma is an extremely rare tumor. Immunohistochemical workup revealed a fibroblastic origin and hence the case was diagnosed as fibromatosis with ganglion cell like fibroblasts. This case report suggests that the features considered diagnostic of ganglioneuromas can occur in other cutaneous lesions and, therefore, this diagnosis cannot be offered only on the basis of H and E.

Introduction

What was known?

1. Fibromatosis is characterized by infiltrative pattern of growth, variable amount of collagen, bland cytological features, scant or absent mitotic activity and aggressive clinical behavior.

2. A well circumscribed tumor composed of spindle cells with numerous large mononuclear rounded basophilic ganglion cells having prominent nuclei and eosinophilic nucleoli suggests possibility of ganglioneuroma.

Ganglioneuroma is a peripheral neuroblastic tumor arising mainly from the sympathetic nervous system and is found in the pediatric population. However primary cutaneous ganglioneuroma is an exceedingly rare neoplasm.[1] They are slow-growing, well-differentiated tumors.[2] Immunohistochemical study in our case was in favor of fibroblastic origin of the lesion. Thus the earlier H and E based diagnosis of ganglioneuroma was revised as fibromatosis with ganglion cell like giant cells.

Case Report

A 41 year old man, otherwise healthy, presented with an asymptomatic, painless, solitary, nontender, cutaneous swelling over the left anterior axillary fold [Figure 1]. It was measuring 2 cm in size. There were no local inflammatory changes. The nodule was firm with relatively well defined borders. Regional lymphnodes were not palpable. The patient had no constitutional symptoms. An excision biopsy was performed without any complications. The specimen was sent for histopathologic examination.

Figure 1.

(a) Lump in the left anterior axillary fold and (b) showing a relatively well circumscribed mass with a solid grey white glistening appearance on cut surface

Pathological finding

Gross examination revealed a relatively well circumscribed mass measuring 2 × 1.5 × 1.5 cm with a solid grey white glistening appearance on the cut surface [Figure 1]. Microscopy showed a relatively well circumscribed tumor composed of spindle cells arranged in whorls and fascicles with thin elongated nuclei interspersed with few blood vessels lined by plump endothelial cells. There were numerous large ganglion-like mononuclear rounded basophilic cells with prominent nuclei and nucleoli. Compressed fibro-adipose tissue and blood vessels were seen outside the margin of the tumor [Figure 2]. Based on these histologic features a diagnosis of ganglioneuroma was made. However, immunohistochemical studies showed strong positive staining for vimentin and negative for smooth muscle actin, CD34, S100 protein and chromogranin [Figure 2]. Based on these immunohistochemistry finding a final diagnosis of fibromatosis with ganglion cell like cells was offered.

Figure 2.

Photomicrographs showing H and E and immunohistochemical studies (a) H and E stain showing spindle cells, few blood vessels and ganglion-like cells (b) negative for smooth muscle actin (c) negative for S100 protein (d) negative for CD34 (e) Strong positive staining for vimentin (f) negative for chromogranin

Discussion

Ganglioneuroma is an uncommon benign, peripheral neuroblastic tumor arising mainly from developing neuronal cells of the sympathetic nervous system and is found in childhood or early adult life.[2] The most commonly involved sites are the posterior mediastinum, retroperitoneum, adrenal gland and head and neck soft tissue.[3] On rare occasions they may be encountered in the gastrointestinal tract as initially documented in 1928.[4] However primary cutaneous ganglioneuroma is a very rare neoplasm first described by Collins et al. in 1972. These tumors are usually solitary, asymptomatic and noninvasive. Our case differs from the other cases reported in terms of location and age.[2,3] Very uncommon site and age group of our case prompted us to undertake detailed immunohistochemical study. A fibroblastic origin of the lesion was confirmed by these studies. A negative staining for smooth muscle actin, CD34, S100 protein and chromogranin ruled out the smooth muscle, vascular, neural and neuroendocrine origin. Thus the H and E based ganglioneuroma diagnosis, was withdrawn and the final diagnosis based on the histochemical study was offered as fibromatosis with ganglion cell like giant cells. These ganglion cell like cells are also seen in myofibroblastoma, inflammatory myofibroblastic tumor of soft tissue, ischemic fasciitis of soft tissue, myxoinflammatory fibroblastic sarcoma of soft tissue, nodular fasciitis of soft tissue, proliferative fasciitis, proliferative myositis of soft tissue and some of the benign fibrous lesions of the umbilicus.[5,6,7] However these lesions differ from fibromatosis in clinical presentation and microscopic appearance.

Stout described Fibromatosis, as a broad group of benign fibrous tissue proliferations of similar microscopic appearance whose biologic behavior is intermediate between that of benign fibrous lesions and fibrosarcoma[8] These lesions are characterized by presence of well differentiated fibroblasts, infiltrative pattern of growth, variable amount of collagen, bland cytological features, scant or absent mitotic activity and aggressive clinical behavior. These lesions never metastasize. In our case the lesion was relatively well circumscribed and showed ganglion like cells. To the best of our knowledge fibromatosis with ganglion like cells are not reported in the literature.

Conclusion

This case report suggests that the features considered diagnostic of ganglioneuromas can occur in other cutaneous lesions and, therefore, this diagnosis cannot be offered only on the basis of H and E and a thorough immunohistochemistry workup is necessary to diagnose such lesions.

What is new?

Well circumscription and ganglion-like cells will neither exclude the possibility of fibromatosis nor confirm the lesion as ganglioneuroma.