Syringocystadenoma papilliferum (ORPHA:840)
A rare non-malignant adnexal neoplasm that originates from the apocrine or eccrine sweat glands and is characterized histologically by cystic, papillary, and ductal invaginations into the dermis lined by double-layered outer cuboidal and luminal high columnar epithelium and connected to the epidermis. Dilated capillaries and a dense infiltrate of plasma cells are characteristic. Clinically, lesions are asymptomatic with a heterogeneous, non-distinctive appearance ranging from skin-colored to pink papules or plaques, occurring most commonly in the head and neck area.
Epidemiology
To date, approximately 730 cases have been reported in the literature. The condition has been reported worldwide.
Clinical description
Syringocystadenoma papilliferum (SCAP) may be present at birth (50% of cases) or develop around puberty (15-30% of cases). SCAP typically presents as slow developing, non-specific, smooth, skin-colored to pink papule, verruca or nodule, which may be exudative. It may also be seen as hairless plaques, smooth or raised, usually less than 4 cm in diameter, skin-colored to brown. It is rarely pigmented. In the majority of cases, it is asymptomatic, but it may grow progressively and has been occasionally associated with pruritus, pain, and/or bleeding. Three clinical types have been described: the plaque type, the linear type and the solitary nodular type. The plaque type usually presents as an alopecia plaque on the scalp which may increase in size at puberty and often transforms to nodular or verrucous lesions. The linear type consists of multiple pink to reddish, firm papules or umbilicated nodules, 1-10 mm in diameter, and is extremely rare. The solitary type includes dome-shaped, pedunculated nodules, 5-10 mm in diameter, with a predilection for the trunk, shoulder and axillae. Rarely, segmental variants are found. In 75% of cases, SCAP is located on the head or cervical region and less frequent in other regions, or on a postoperative scar. SCAP develops in existing nevus sebaceous in about one-third of cases, 10% of which are associated with he development of basal cell carcinoma and more rarely other carcinomas. SCAP can also be associated with other benign lesions. Transition to malignancy is rare but, possible. Syringocystadenocarcinoma papilliferum is the malignant counterpart to this lesion and may develop in a long-standing case of SCAP.
Etiology
The etiology of SCAP has not been elucidated. It seems to arise from the pluripotent cells with the potential to exhibit either apocrine or eccrine lineage, although apocrine differentiation is more common. The pathogenesis of SCAP remains unclear although, both in sporadic cases and lesions arising in nevus sebaceous, the human papillomavirus (HPV) DNA and mutations in the RAS/mitogen-activated protein kinase signaling pathway have been detected. BRAF V600E mutation or activating mutations in HRAS (or in one case KRAS) have been reported in sporadic forms.
Diagnostic methods
Diagnosis is suspected on clinical presentation of non-distinctive lesions and confirmed on biopsy showing the characteristic histology. Immunohistochemically, the tumor cells stains positively for carcinoembryonic antigen. Dermatoscopy is not diagnostic.
Differential diagnosis
The differential diagnosis is broad, requiring histological confirmation of cases. The main diagnostic issue is the distinction of SCAP from hidradenoma papilliferum. Other conditions to be considered include basal cell carcinoma, cutaneous lymphoma, factitious dermatitis, viral warts, subcutaneous fungal infection, linear verrucous nevus, pyogenic granuloma, warty dyskeratoma, inverted follicular keratosis, as well as eccrine nevus, nevus comedonicus, cylindroma, and basaloid follicular hamartoma.
Management and treatment
Treatment involves complete surgical excision. However, recurrence is common. Carbon dioxide laser treatment can be useful for lesions in anatomic areas not favorable for excision and grafting. SCAP has also been successfully treated with Mohs micrograhic surgery.
Prognosis
The condition is mostly benign but extensive lesions may have an impact on quality of life and transformation to malignancy cannot be ruled out.

                            Last update: 
                            February 2021


                            - Expert reviewer(s): 
                            Pr Alexander KATOULIS  - Pr Efstathios RALLIS