We report a patient with vulvar lichen sclerosus, Langerhans cell histiocytosis (LCH), and later vulvar cancer. In LCH, high amounts of non functional Langerhans cells are present in the affected tissue, making it possible that LCH may have contributed to vulvar cancer development in this patient.
Langerhans cell histiocytosis (LCH), previously named histiocytosis X, is a disorder hallmarked by a clonal proliferation of Langerhans cells (LCs). These cells are bone marrow-derived, antigen-presenting cells, which differ from other histiocytes in being CD1a- and S-100-positive on immunohistochemical staining. This uncontrolled proliferation may affect many sites of the human body and may cause destruction of the involved tissues. Sites commonly involved include bone, skin, lung, and brain tissue. Disease presentation may vary from mild activity in 1 organ, to extensive systemic involvement with life-threatening consequences. The disorder was first described more than a century ago, but the cause still remains largely obscure.
LCH restricted to the vulvar area is a rare phenomenon. To our knowledge, only 12 cases are described in the current literature. We describe a new and unique case of vulvar LCH, preceded by lichen sclerosus (LS) and followed by the development of an invasive squamous cell carcinoma (SCC) of the vulva in a 33-year-old patient. Even though development of vulvar SCC is connected with LS, this case gives rise to the question of whether LCH possibly has contributed to the tumor development or progression in this young patient.
Case Report
A 33-year-old woman was referred to our tertiary vulvar clinic with painful, pruritic, and irritating lesions of the vulvar area existing more than 2 years, causing mild dyspareunia. Prior treatment with ultrapotent corticosteroids was ineffective. On physical examination, the right labium showed a 4-cm papillomatous tumor and the left labium showed multiple sharply limited hypertrophic spots, in the absence of regional lymphadenopathy.
The lesions were biopsied, and histology showed LS without dysplasia. Because ultrapotent corticosteroid treatment was ineffective, a skinning local excision was carried out, and histology showed a differentiated vulvar intraepithelial neoplasia (dVIN) lesion without invasive growth in addition to LS.
At follow-up, initially, there were no signs of vulvar recurrences, but 1 year later, the patient noticed a new verrucous lesion (1.5 cm large and 3 mm thick), which was situated on the right labium minus with a verrucous aspect ( Figure 1 ). The tumor grew slowly despite local immunosuppressive treatment with tacrolimus and hence it was decided to excise the lesion within one month. At the time of the procedure, the tumor had outgrown excisable size and extended from the right labium minus to the clitoris. Again, biopsies were taken and histology showed a tumorous monotonous proliferation of atypical cells, with cerebriform or grooved nuclei and abundant mitotic activity ( Figure 2 , A). Eosinophils were scattered throughout the proliferating cells. Immunohistochemistry was performed and showed that the monotonous cells were positive for CD1a ( Figure 2 , B), vimentin, and S-100 ( Figure 2 , C), all pointing to a diagnosis of LCH.
The patient was subjected to extensive metastatic workup to exclude systemic localizations of LCH, including computed tomography of the brain, the thorax, and abdomen, chest x-rays, bone marrow aspirate, and bone scintigraphy. This revealed no evidence of disease. Regarding the solitary vulvar lesion and patient’s age, the patient was treated locally with CO 2 laser vaporization, after which the lesion completely disappeared. The appearance of the vulva remained with signs of LS, showing white and papillomatous tissue.
During the follow-up period, 23 months after the diagnosis LCH was made, the patient had a suspicious lesion develop on the left labium minus ( Figure 3 , A), which was biopsied. Histology showed a poorly differentiated SCC with a depth of invasion of 1.6 mm. A dVIN lesion was found adjacent to the tumor. Additional imaging revealed no signs of metastatic disease. A wide local excision with sentinel node procedure was performed. Definitive pathology showed a 9-mm diameter SCC with a depth of invasion of 4 mm without the presence of LCH (International Federation of Gynecology and Obstetrics stage IB). There were no signs of metastatic disease or LCH in the sentinel nodes.
The patient was regularly seen in our clinic for follow-up of her vulvar SCC. Verrucous lesions that histologically turned out to be a dVIN frequently developed ( Figure 3 , B). The patient refused additional surgery to prevent future recurrence of a vulvar SCC and preferred occasional CO 2 laser vaporization treatments. In the following 11 months, the patient had a local recurrence develop on the clitoris and 2 metastatic groin nodes (bilateral). She was treated with surgery and radiotherapy.
Comment
In our case, the patient presented with LS of the vulva, followed by LCH. Eventually, she developed a vulvar SCC. LCH of the genital tract is rare, and lesions isolated to the vulva are seldom described in the current literature ( Table ). Apart from this being a new rare case of isolated vulvar LCH, the question emerges whether LCH could have played a role in tumor development of our young patient. The possible association between LCH and malignant neoplasms had been recognized many years ago. Cases in which LCH preceded both solid and hematologic malignancies have been described, although it remains unclear whether there was a causal relation or it was the consequence of LCH treatment.
