Reactive Eccrine Syringofibroadenomatosis Presenting as Bilateral Plantar Hyperkeratosis.

Eccrine syringofibroadenoma (ESFA) is a rare cutaneous tumor with eccrine differentiation with varied clinical manifestations. We report a case of reactive eccrine syringofibroadenomatosis associated with chronic bilateral plantar ulcers in a patient with diabetes mellitus presenting as plantar hyperkeratosis and verrucous growth at margins.

What was known?

Patients of diabetes mellitus with long standing plantar ulcers may develop reactive eccrine syringofibroadenomatosis.

Introduction

Eccrine syringofibroadenoma (ESFA) is a rare cutaneous tumor with eccrine differentiation with varied clinical manifestations.[1] ESFA was first described by Mascaro[2] in 1963 as a solitary nodule characterized histopathologically by anastomosing strands of epithelial cells embedded in a fibrovascular stroma. Starink[1] classified ESFA into four subtypes, which includes solitary ESFA, multiple ESFA with hidrotic ectodermal dysplasia, multiple ESFA without associated cutaneous findings and nevoid (nonfamilial, unilateral) ESFA. This classification has been modified by French[3] to include reactive ESFA associated with inflammatory or neoplastic dermatoses as the fifth subtype of ESFA. Reactive ESFA is better termed as “reactive eccrine syringofibroadenomatosis (ESFa)” to highlight that it is a reactive process and not a neoplasm. ESFA may present as solitary nodule or multiple papules, nodules, and plaques, in a “streusel bread”-like appearance usually on extremities of an elderly.[4] But, it may present on face, trunk and rarely nails. We report a case of reactive eccrine ESFa associated with chronic ulcers of bilateral feet in a patient with long-standing diabetes mellitus.

Case Report

A 65-year-old female presented with non-healing ulcers over bilateral soles of 1 year duration and surrounding skin thickening of 6 months duration. She had been a known case of diabetes mellitus on oral hypoglycemic agents for the past 10 years. She gave history of repeated plantar ulcers and reduced sensation over bilateral feet up to the ankle region (diabetic neuropathy). There was no evidence of leprosy or past history of antileprosy treatment. Physical examination revealed two ulcers of size 1 × 2 cm and 2 × 3.5 cm over plantar aspect of bilateral feet. The skin surrounding the ulcers was hyperkeratotic and at the margin of hyperkeratotic area, multiple, coalescing, firm, flesh-colored nodules in “streusel bread”- like appearance were seen, more prominent on medial border of right sole [Figures 1 and 2]. Atrophic scars were present on plantar aspect of bilateral feet due to repeated multiple traumatic events and due to incision and drainage done before. There was no clinical or radiological evidence of osteomyelitis. A skin biopsy was taken from the flesh-colored nodule over right sole which on histopathological examination revealed hyperkeratosis, acanthosis, anastomosing thin cords of cuboidal epithelial cells extending from epidermis to dermis and a fibrovascular stroma [Figure 3]. Ductal structures were seen within the thin epithelial cords [Figure 4]. Immunohistochemistry revealed staining of ducts by S100 [Figure 5] but not by carcinoembryonic antigen (CEA) and cytokeratin 19 (CK19). These clinico-histopathological findings were characteristic of ESFa. The patient was offered treatment options - surgical excision and CO2 laser ablation of ESFa lesions but she refused both the procedures. She was advised regular cleaning and dressing of the ulcers, foot care measures and regular follow up.

Figure 1

Bilateral plantar ulcers with surrounding skin hyperkeratosis and a pink verrucous growth at medial border of bilateral sole

Figure 2

Pink verrucous growth over medial border of right sole

Figure 3

Photomicrograph showing anastomosing strands of epithelial cells embedded in a fibrovascular stroma (H and E, ×100)

Figure 4

Higher magnification photomicrograph showing thin epithelial strands with ductal structures (H and E, ×400)

Figure 5

Photomicrograph showing staining of eccrine ducts by S100 (S100, ×400)

Discussion

Reactive ESFa accounts for approximately a quarter of reported cases of ESFA.[5] Reactive ESFa occurs in cases with repeated tissue damage and repair which results in reactive hyperplasia of eccrine ducts. It has been proposed that reactive ESFA represents a hyperplastic and hamartomatous process and hence, “reactive eccrine syringofibroadenomatosis” may be the more appropriate terminology.[5] Reactive ESFa presents as a response to inflammatory and neoplastic dermatoses like chronic ulceration of feet (related to diabetes mellitus,[6] leprosy[7]), burn scars,[8] peristomal dermopathy,[9] erosive palmoplantar lichen planus,[10] bullous pemphigoid,[11] nail trauma,[12] nevus sebaceous[13] and squamous cell carcinoma.[14] Diabetes mellitus typically causes diabetic neuropathy and these patients frequently sustain traumatic injuries resulting in frequent skin repair and remodeling, which may result in abnormal epithelial changes and eccrine ductal proliferation, thus resulting in ESFa.[67] Scarring after recurrent infections may also predispose the skin to ESFa. It has also been postulated that reactive ESFa may be related to altered sympathetic nerve function possibly affecting regeneration of traumatized eccrine tissues and thus contributing to cellular proliferation.[7] Both diabetes mellitus and leprosy are known to affect autonomic nerves and lead to neuropathy. Our case had ESFa bilaterally which could be related to the diabetic neuropathy predisposing to frequent and recurrent plantar ulceration and alteration in sympathetic nerve function due to diabetes. Clinically, reactive ESFa usually presents as erythematous lesions unlike other types of ESFA. But, in our case the erythematous verrucous growth consisting of multiple, coalescing, firm, flesh-colored nodules in a “streusel bread”- like appearance was visible only along the medial border of right sole and instead there was predominant plantar hyperkeratosis which could be due to pressure effect of weight bearing of the sole. The histologic features of ESFA are diagnostic, which includes multiple thin anastomosing cords of cuboidal epithelial cells which forms a lattice and are embedded in fibrovascular stroma. These anastomosing cords of epithelial cells are connected to the undersurface of epidermis and characteristically show ductal differentiation. On immunohistochemistry, S100 stains the outer layer of eccrine ducts as was seen in our case.[15] CEA stains the luminal surface of eccrine ducts.[16] Cytokeratin 19 positivity has been reported to be confined to luminal ductal cells of ESFA.[17] But in our case it did not stain the luminal surface probably due to scarring. The clinical course of ESFA is benign, although malignant transformation to eccrine syringofibrocarcinoma and the association with squamous cell carcinoma has been reported. But there has been no report of malignancy in reactive ESFa yet, so probably the risk of malignant transformation in reactive ESFa is lower than other subtypes. Regular monitoring of reactive ESFa is preferable to surgical excision.[5] An alternative to surgical excision is CO2 laser ablation for ESFa lesions at difficult to treat anatomical sites or in cases of refusal of surgical excision.[18] Radiotherapy is also an option that can be considered for ESFa at difficult to treat locations.[19]

Conclusion

Reactive ESFA has been reported with diabetes mellitus but bilateral reactive ESFA presenting as plantar hyperkeratosis with verrucous growth at margins in a patient with diabetes mellitus is unique and an interesting finding.

What is new?

Reactive eccrine syringofibroadenomatosis can present as plantar hyperkeratosis with verrucous growth at margins in a patient with diabetes mellitus, sometimes even bilaterally.