Hailey-Hailey disease (HHD) is a rare, autosomal dominant intraepidermal blistering disorder characterized by recurrent vesicles and erosions affecting mostly the intertriginous areas. We report a case of HHD affecting exclusively the vulva from which an invasive squamous cell carcinoma developed after tacrolimus therapy.
A 44-year-old female patient was seen in February 2004 with a 6 month history of vulval erosion. Past medical history included a dysgerminoma of the ovary with peritoneal involvement at the age of 12 years. After laparotomy with tumor resection, she had been treated with radiotherapy of the right pelvis (Co 60 , 4.000 Ra) and chemotherapy (methotrexate, cyclophosphamide, and dactinomycin) every 2 months for 1 year. The vulva was not irradiated. At the age of 15 years, she was diagnosed to have primary amenorrhea because of ovarian failure (high luteinizing hormone level); since then she has been treated with estrogen.
Case Report
At presentation, physical examination revealed an ulceration within a well-defined whitish plaque-like lesion of the left labia minora, which was clinically diagnosed as herpetic infection ( Figure 1 , A). There was no involvement of other regions of the body in particular neck, axillae, groins, and nails were normal. A biopsy of the lesion revealed parakeratosis and dyskeratotic acantholytic cells with a suprabasal cleft; cells of the central layer of the epidermis showed partial separation from adjacent cells giving the appearance of a dilapidated brick wall ( Figure 1 , B). Direct immunofluorescence was negative.
Based on the clinical and histological examination, a diagnosis of Hailey-Hailey disease (HHD) of the vulva was made. She had no family history of HHD. Herpetic, candidal, and bacterial infections were excluded.
Treatment with topical tacrolimus 0.1% ointment once daily improved the HHD lesions (treatment period 2004: 7-8 months; period without tacrolimus therapy: 7 months; treatment period 2005: 2 months). However, over several months, a small scar-like lesion on the left labia minora developed, which was initially thought to be a wound-healing disturbance after the biopsy ( Figure 1 , C). This lesion gradually increased in size and hardened.
In June 2005, 1 year after diagnosis of HHD, the patient represented with a protruding tumour on the left side of the labia minora involving also the left paraclitoral region ( Figure 2 , A). Examination of the vagina, uterine cervix, inguinal lymph nodes, and perianal region showed no abnormalities. Cervical smears displayed no signs of malignancy. Routine laboratory investigations were within the normal ranges. Histological examination of a biopsy of the tumor showed a p53 immunoreactive, invasive squamous cell carcinoma (SCC) in which strands and masses of immature squamous cells with dyskeratosis infiltrated deeply into the dermis ( Figure 2 , B). Additionally, HHD was again present in the form of epidermal acantholysis on the edge of the section ( Figure 2 , C).
