Dermatology: Practical and Conceptual Observation | Dermatol Pract Concept 2016;6(1):3 5 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Introduction Eccrine syringofibroadenoma (ESFA) is a rare neoplasm that usually presents as a solitary, often large, hyperkeratotic nodular lesion with predilection for the extremities. Histo- logically, there are thin anastomosing epithelial cords and strands forming a lattice and connected to the undersurface of the epidermis. Ducts are presented within the tumor. Between the strands, there is a rich fibrovascular stroma. Eccrine syringofibroadenoma is typically a rare benign neoplasm. Eccrine syringofibroadenoma (ESFA) is of acro- syringeal or eccrine dermal duct differentiation. Histo- logically, there are multiple anastomosing cords of benign epithelial cells surrounded by a loose fibrovascular stroma. The epithelial cords demonstrate ductal differentiation. Occasional luminal eccrine ducts are noted within the anastomosing cords. The authors describe two cases with different subtypes of ESFA, a solitary ESFA and a reactive ESFA with squamous cell carcinoma. Case report Patient 1 A 77-year-old Thai male patient presented with asymptomatic erythematous plaques on both soles for a year. The lesions had slowly extended from the middle of his soles to heels and medial part of the feet (Figure 1A). He denied history Eccrine syringofibroadenoma (ESFA): a report of two cases Bhakinai Temnithikul1, Suthep Jerasutus2, Poonnawis Sudtikoonaseth1, Nataya Voravutinon1, Tanawatt Kootiratrakarn1, Pinnaree Kattipathananpong1 1 Institute of Dermatology, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand 2 Department of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Keywords: eccrine syringofibroadenoma (ESFA), syringofibroadenoma, eccrine syringofibroadenomatous hyperplasia, acrosyringeal adenomatosis, squamous cell carcinoma Citation: Temnithikul B, Jerasutus S, Sudtikoonaseth P, Voravutinon N, Kootiratrakarn T, Kattipathananpong P. Eccrine synringofibroadenoma (ESFA): a report of two cases. Dermatol Pract Concept 2016;6(1):3. doi: 10.5826/dpc.0601a03 Received: September 29, 2015; Accepted: October 6, 2015; Published: January 31, 2016 Copyright: ©2016 Temnithikul et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Bhakinai Temnithikul, MD, Institute of Dermatology, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand. Tel. +66 81719-2567. Email: arumuab@hotmail.com Figure 1A. The lesions slowly extended from the middle of the soles to the heels and medial part of the feet. [Copyright: ©2016 Tem- nithikul et al.] 6 Observation | Dermatol Pract Concept 2016;6(1):3 anastomosing slender elongated cords and strands of cuboi- dal cells embedded in fibrovascular stroma with a diagnosis of recurrent squamous cell carcinoma with eccrine syringo- fibroadenoma at the periphery of the specimen (Figure 2B and C). Immunohistochemical staining was done. Positive stain- ing was observed for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). Discussion Eccrine syringofibroadenoma (ESFA) (synonym: syringofi- broadenoma, eccrine syringofibroadenomatous hyperplasia [1], acrosyringeal adenomatosis [2]) is a rare benign adnexal of previous trauma. The patient had valvular heart disease and coronary artery disease. He had undergone valve and coronary bypass surgery 10 years ago. He is currently on oral warfarin treatment. Physical examination revealed bilateral, well-defined, firm, cobblestone-like, erythematous plaques on both soles with keratoderma. Histological examination was obtained. The histopa- thology showed thin reticular strands of proliferating cells connected to the epidermis and extending into the dermis, anastomosing irregularly. Small eccrine ducts could be seen within the cords. The area between the strands was filled with richly vascular fibrous stroma. Perivascular infiltration with lymphocytes, plasma cells and mast cells were noted (Figure 1B and 1C). Immunohistochemical staining was done. Positive stain- ing was observed for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). Patient 2 A 52-year-old Thai female patient presented with asymptom- atic erythematous exophytic masses on the dorsum of her left foot (Figure 2A). She had gradually developed asymptomatic erythematous exophytic masses on her left foot for several years. A surgical excision was performed on the lesions one year ago. Histopathological diagnosis revealed squamous cell carcinoma. This patient had developed dome-shaped reddish exophytic masses on top of the surgical scar after surgery 6 months ago. She denied history of trauma and never had previous keloidal scars. Physical examination revealed multiple well-defined firm dome-shaped exophytic erythematous masses on top of the surgical scar on the dorsum of her left foot. Histological examination from the lesion was obtained and showed proliferation of atypical squamous cells extend- ing to the superficial dermis. There was also aggregation of Figure 1B. Histopathologic findings. [Copyright: ©2016 Temnithi- kul et al.] Figure 1C. Histopathologic findings. [Copyright: ©2016 Temnithi- kul et al.] Figure 2A. Erythematous exophytic masses on dorsum of the left foot. [Copyright: ©2016 Temnithikul et al.] Observation | Dermatol Pract Concept 2016;6(1):3 7 sis. It may be the result of a somatic mutation in the early embryonic stage. 5. Reactive ESFA associated with inflammatory or neoplas- tic dermatosis is often in an acral location. This reactive change has been seen next to burn scar ulcer, erosive palmoplantar lichen planus [6], hidrotic ectodermal dys- plasia, bullous pemphigoid [1], diabetes mellitus with polyneuropathy and chronic ulcer, inflammatory psoriasis or persistent local infection, lymphedema (elephantiasis), nevus sebaceous and squamous cell carcinoma. The patho- genesis may be associated with a specific type of eccrine duct remodeling or repair. The co-existence of ESFA and squamous cell carcinoma has been reported [4,7]. It is unclear whether ESFA develops in response to squamous cell carcinoma or squamous cell car- cinoma represents a malignant degeneration of ESFA. The inci- dence of squamous cell carcinoma arising in ESFA is unknown. The histologic picture of coexistence of ESFA and squamous cell carcinoma have appeared as squamous cell carcinoma with ductal differentiation impinged by benign ESFA and squamous cell carcinoma surrounded by ESFA. The malignant degeneration of ESFA has been termed as eccrine syringofi- brocarcinoma (ESFAC) [7-9]. The mechanisms of underlying malignant transformation remain unclear. It is recommended that ESFA be completely excised to prevent malignant degen- eration, although the risk of this occurrence is unknown. Recurrences and metastatic disease have not been reported. Excision appears to be the definitive treatment. Trauner et al reported a patient with ESFA successfully treated with a dual pulse width flashlamp pumped pulsed dye laser [10]. In conclusion, the authors show two rare cases of eccrine syringofibroadenoma (ESFA) with different clinical manifes- tations. Patient 1 was diagnosed with ESFA by histological findings. The immunohistochemical demonstration was consistent with ESFA. He had no associated findings or sign of ectodermal dysplasia and he was therefore classified as tumor arising most often on the extremities of elderly indi- viduals with characteristic histopathology. The tumor consists of anastomosing cords of cuboidal epithelial cells surrounded by a fibrovascular stroma containing plasma cells and duc- tal structures [3]. Although the exact site of origin of ESFA remains controversial, it is believed to be derived from the acrosyringium or eccrine dermal duct. ESFA stains positively with epithelial membrane antigen (EMA) and carcinoembry- onic antigen (CEA). Cytokeratin studies have been inconsis- tent [4]. Human papillomavirus 10 (HPV-10) may also play a role in the development of eccrine syringofibroadenomas. Cases of ESFA have been divided into five distinct subtypes due to clinical manifestations: solitary lesions, multiple lesions associated with an ectodermal dysplasia, lesions with no additional cutaneous pathology, nevoid lesions, and reac- tive lesions: 1. Solitary ESFA is typically a nonhereditary solitary nodule or verrucous mass normally found on the lower extremi- ties of the middle-aged and elderly. 2. Multiple ESFA without associated cutaneous finding (eccrine syringofibroadenomatosis) are nonfamilial pal- moplantar lesions without significant associated cutane- ous finding. 3. Multiple ESFA with hidrotic ectodermal dysplasia (HED) presents in two different variants, Schöpf-Schulz-Passarge syndrome and Clouston’s syndrome. Schöpf -Schulz- Passarge syndrome (SSPS) is a rare autosomal dominant ectodermal dysplasia, characterized by hypodontia, hypo- trichosis, nail dystrophy, palmoplantar keratoderma, and periocular and eyelid margin apocrine hidrocystoma. Clouston’s syndrome is autosomal dominant ectodermal dysplasia, characterized by dystrophic nails and sparse hair. HPV-10 has been detected in the lesions occurring in Clouston’s syndrome [5]. 4. Nevoid ESFA (nonfamilial unilateral linear ESFA) is a rare genetic mosaicism, producing diffuse plantar hyperkerato- Figure 2B. Histopathologic findings. [Copyright: ©2016 Temnithi- kul et al.] Figure 2C. Histopathologic findings. [Copyright: ©2016 Temnithi- kul et al.] 8 Observation | Dermatol Pract Concept 2016;6(1):3 5. Carlson JA, Rohwedder A, Daulat S, Schwartz J, Schaller J. Detec- tion of human papillomavirus type 10 DNA in eccrine syringofi- broadenomatosis occurring in Clouston’s syndrome. J Am Acad Dermatol. 1999;40:259–62. 6. French LE, Masgrau E, Chavaz P, Saurat JH. Eccrine syringofi- broadenoma in a patient with erosive palmoplantar lichen planus. Dermatology. 1997;195:399-401. 7. Bjarke T, Ternesten-Bratel A, Hedblad M, Rausing A. Carcinoma and eccrine syringofibroadenoma: a report of five cases. J Cutan Pathol. 2003;30:382-92. 8. González-Serva A, Pró-Rísquez MA, Oliver M, Caruso MG. Syringofibrocarcinoma versus squamous cell carcinoma involving syringofibroadenoma: is there a malignant counterpart of Mas- caro’s syringofibroadenoma? Am J Dermatopathol. 1997;19:58- 65. 9. Katane M, Akiyama M, Ohnishi T, Watanabe S, Matsuo I. Car- cinomatous transformation of eccrine syringofibroadenoma. J Cutan Pathol. 2003; 30:211-4. 10. Trauner, MA, Narurkar VA, Ruben BS. Eccrine syringofibroad- enoma treated with a dual pulse width flashlamp pumped pulsed dye laser. Dermatol Surg. 1999;25:418-20. multiple EFSA without associated cutaneous findings. Patient 2 was classified as reactive ESFA and diagnosed as ESFA with squamous cell carcinoma by typical histological and immu- nohistological findings. Excision of the ESFA was the defini- tive treatment to prevent the malignant degeneration. Mohs surgery was done for squamous cell carcinoma. She has been evaluated with a complete skin examination every 6 months. References 1. Nomura K, Hashimoto I. Eccrine syringofibroadenoma in two patients with bullous pemphigoid. Dermatology. 1997;195:395-8. 2. Hara K, Mizuno E, Nitta Y, Ikeya T. Acrosyringeal adenomatosis (eccrine syringofibroadenoma of Mascaro). A case report and review of the literature. Am J Dermatopathol. 1992;14:328-39. 3. Starink TM. Eccrine syringofibroadenoma: Multiple lesion repre- senting a new cutaneous marker of the Schöpf syndrome, and soli- tary nonhereditary tumors. J Am Acad Dermatol. 1997;36:569-76. 4. Schadt CR, Boyd AS. Eccrine syringofibroadenoma with co- existent squamous cell carcinoma. J Cutan Pathol. 2007;34:71-4.