Skin metastases of cervical cancer: two case reports and review of the literature

Carcinoma of the uterine cervix is the most common gynecological cancer in developing countries. The most frequently reported metastases sites are lungs, bone, and liver [1, 2]. Skin metastases are extremely rare even in the late stages of disease; they have an incidence range from 0.1 to 2 % [3, 4]. The presence of metastatic disease in the skin is a strong predictive of poor prognosis, as skin metastases are usually associated with local or regional recurrence. The treatment is usually palliative with very poor outcomes. We report here the cases of two patients with locally advanced cervical cancer who developed cutaneous metastasis.

In Morocco, cervical cancer is the second most common cancer in the country and the third most common cause of death [5]. Hematogenous spread is uncommon, presenting either in a recurrence setting or initially in advanced stages; it is often localized in the liver, lung, and bone, in order of decreasing frequency [1, 2, 6].

The incidence of cutaneous metastasis from solid tumors ranges from 0.7 to 9 % [1]. The most common solid tumors metastasizing to the skin in women include breast (60 to 69 %), gastrointestinal tract (9 %), lung, and ovary [2]. Cutaneous metastases from carcinoma of the cervix are exceptional, even in the late stages of disease, with an incidence not exceeding 2 % [3, 4]. Imachi et al. [7] in a review of 1190 patients with cervical cancer reported that 15 patients developed skin metastasis. The incidence of skin metastasis varied according to the initial tumor stage, it was 0.8 % in stage I, 1.2 % in stage II, 1.2 % in stage III, and 4.8 % in stage IV. The incidence of skin metastasis seemed to be higher in patients with adenocarcinoma and undifferentiated carcinoma than in patients with squamous cell carcinoma.

On macroscopic examination, three common patterns of skin metastasis, such as nodules, plaques, and inflammatory telangiectasic lesions, have been reported [2, 7‐9]. Lesions may be single or multiple. Our patients had multiple nodular lesions. The most common differential diagnoses include benign dermatitis, subcutaneous phycomycosis, plaque-like mycosis fungoides, and Kaposi’s sarcoma [10]. A pathological study establishes the diagnosis.

The abdominal wall and vulva are the most common sites for skin lesions, followed by the anterior chest wall [2, 11, 12]. However, cases presenting at the scalp [13, 14], extremities [15], umbilicus [16], and face [17] have been reported. In our cases, it was mainly localized in the chest and abdominal areas. The mechanism behind this type of metastases is not well established, the possible reason could be attributable to a retrograde spread of tumor secondary to lymphatic obstruction [18].

To date, no effective treatment has been identified. Treatment is nearly always palliative, and consists of using radiation, chemotherapy, or surgery, either alone or in combination [16, 19]. Electrochemotherapy (ECT) can provide immediate clinical benefit in patients with advanced cutaneous and subcutaneous metastases [20]. ECT combines the administration of a poorly permeant cytotoxic agent, such as bleomycin or cisplatin regardless of histological type, with the local application of electric pulses that induce reversible electroporation, thus improving drug diffusion into cells [21, 22]. ECT was introduced in 2006, demonstrating a high rate of efficacy and favorable toxicity profile in a European multicenter study on skin metastases from different tumor histotypes [23]. In this study, the objective response rate on treated tumor nodules was 89.0 % with complete regression in 73.3 % of cases. For our patients who had multiple metastases, we opted for palliative chemotherapy.

Skin metastasis from cervical carcinoma occurs predominantly in cases of tumor recurrences, with metastasis developing up to 10 years after initial diagnosis and averaging less than 1 year [24, 25]. In the largest series [7], the mean interval between the diagnosis of the primary tumor and skin metastasis was 16.9 months. Only two cases of cutaneous metastasis at initial presentation have been reported in the literature [12, 26]. In our report, both of the patients presented skin metastasis during the treatment or in the first months following treatment completion.

Prognosis in such cases is poor and is considered a sign for preterminal disease. The mean survival being 3 months and survival for more than 1 year seen in only 20 % of patients [7, 8, 16]. The cases that we have reported are consistent with these findings.

Skin metastasis of cervical cancer remains extremely rare. Physicians should pay more attention to cutaneous lesions in patients with cervical cancer that can be the first sign of the disease, and should perform a biopsy whenever they are doubtful.