Acta Chir Belg, 2008, 108, 269-272
Metastatic Basal Cell Carcinoma M. Akinci*, S. Aslan*, F. Markoç**, B. Cetin*, A. Cetin* Department of General Surgery*, Department of Pathology**, Oncology Hospital, Ankara, Turkey.
Key words. Basal cell carcinoma ; metastasis ; non-melanoma skin cancer.
Introduction Basal cell carcinoma (BCC) is one of the most prevalent forms of cancer worldwide. Despite the large number of BCCs diagnosed each year, the rate of metastatic BCC ranges from 0.003-0.5% (1). Metastatic BCC typically occurs in middle-aged men with a history of a recalcitrant BCC that has been refractory to conventional methods of treatment. The median age of onset of the primary BCC is approximately 45 years. Although the time interval between tumour onset and metastasis is approximately 9-12 years, once metastasis has been identified, the average life expectancy is around 8 months (2). Metastasis is usually to regional lymph nodes (60%), lung (42%), bone (20%), skin (10%), and other sites (2%). In this article, we present a case with metastatic basal cell carcinoma. Case report A 67-year-old man was admitted to the oncological surgery ward for basal cell carcinoma (BCC). He was diagnosed during 2000 in another hospital when a total excisional biopsy from a 30*25 cm partially ulcerated lesion in the back, with a 5-year history, showed BCC. His skin was closed with a graft. He came to our hospital two years later in June 2002 with a recurrence of the lesion in his back. When he was first seen in our hospital, he had a 3*5 cm ulcerated, hard, cream-white colored lesion with elevated borders in the right scapular region. The patient was in good health without any symptoms except the lesion in his back. There was no family history of skin cancer and no personal basal cell nevus syndrome. Abdominal ultrasonography was normal but thorax computed tomography showed mediastinal, carinal, subcarinal, aorticopulmonary lymphadenopathy. Chronic nodular changes were observed in lung parenchyma and inhomogeneous infiltrations were present in the right lower lobe anterior segment. Peribronchial and septal thickening were observed in the basal portions of the lungs.
Fig. 1 Computerised Tomography showing defective area after scapulectomy.
Follow-up with thoracic computed tomographies was planned because of these findings. His lesion was excised with at least 2 cm of disease-free margins plus scapulectomy (Fig. 1). Pathology from this 21*16*8 cm specimen revealed basal cell carcinoma of the kerototic type. Microscopically, the tumour was composed of nodular masses of basoloid cell groups with spiky outlines, displaying a rather uniform, large, oval, elongated nucleus (Fig. 2). In the centre of the cell groups, there were horn cysts with fully keratinized cells, which were surrounded by parakeratotic nuclei. The cell groups had irregular infiltrating edges, while peripheral palisading and clefting was obvious. There were also large strands of cells in a desmoplastic stroma. The tumour was ulcerative, had invaded the scapular bone and was metastatic
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Fig. 3 Computerised Tomography showing pulmonary metastatic deposits. Fig. 2 Skin tumour on the back showing features of a basal cell carcinoma (HE, 40).
to the lung. Tissue obtained from the scapular bone and bronchial wall showed tumour with features similar to those described in the primary tumour. The tumour had invaded to the bone inferolaterally, and was positive at the margins in the bone. Two of the three subcapular lymphadenopathies were positive for metastasis. Radiotherapy was started. The operation site was closed with a free skin graft, 40 days later. At his admission to our surgical ward in February 2003, he had a new, ulcerated lesion with a serous discharge on 10 cm*8 cm area on the controlateral left axilla. Ten days before this admission, this lesion had been excisionally biopsied in a peripheral hospital, showing basal cell carcinoma. All the previous biopsies were reviewed in our pathology department and keratotic basal cell carcinoma was confirmed with virtually identical histology to that seen in the right scapular region. The patient was complaining of cough, dyspnea, weakness and weight loss. Physical examination revealed the lesion on the axilla, the operation scar on the back and bilateral rhonchi. His admission chest X-ray showed bilateral nodular infiltrations and thorax computed tomography revealed a striking increase in inhomogeneous infiltrations with pleural retractions compared to the previous tomography suggesting pulmonary metastasis (Fig. 3). His forced vital capacity (FVC) was 1.41 liters (44% predicted), forced expiratory volume at 1 second (FEV1) was 0.97 liters (38% predicted), peak expiratory flow (PEF) was 3.95 liters/sec (55% predicted) and FEV1/FVC was 69% (91% predicted). Arterial blood gas analysis, complete blood count and serum biochemistry were within normal limits. Bronchoscopy revealed hyperemic mucosa starting from the right main bronchus. Middle lobe lateral segment ostium
was narrowed and its mucosa was oedematous. Punch biopsy from the right lung also showed the malignant epithelial tumour with a similar histologic structure to the primary basal cell carcinoma. Chemotherapy was started with Cisplatin 125 mg/m2/day and 5-fluorouracil 1000 mg/m2/day for 3 days once in every 21 days. Hospital discharge was possible on the twenty-fifth postoperative day. However, the patient suffered from progressive haemoptysis and died of pulmonary metastases after six months. Discussion Metastasis from basal cell carcinoma is extremely rare, unlike that from squamous cell carcinoma (3). According to Latess’ and Kessler’s guidelines for establishing the diagnosis of metastatic BCC, the primary lesion must be a basal cell carcinoma originating from the skin, not from mucous membrane. Metastasis must be to a distant site and not due to extensive local growth of the primary tumour, and finally the primary and metastatic lesion must have a similar histologic structure (3, 4). The size and site of the tumour, depth of invasion, duration and recurrence of the disease, play important roles in predicting metastasis from basal cell carcinoma (3). SNOW et al. analysed the size and distribution of tumours of 45 patients with metastatic BCC. They found the mean diameter of the primary BCC to be 8.7 cm and that large (T2 and T3) and deep (T4) BCC accounts for approximately 75% of metastatic tumours (2). In a review of 78 metastatic BCC cases, the site of the primary tumour was mainly in the head and neck region. Insufficient non-radical excision and radiation therapy of the primary lesion may lead to the occurrence of metastasis (3, 5). Our patient had a large, deep lesion in the back and suffered direct bone invasion that led to distant metastasis. Deeply invasive trunk BCC and genital BCC
Metastatic Basal Cell Carcinoma also appear to have a relatively high rate of metastasis, given the low incidence of BCC originating from these general lesions compared with the facial region (2). Our patient had recurrence, lymph node metastasis, contralateral axilla skin metastasis and pulmonary metastasis two years after excision of the primary lesion with a 5-year history. In a cumulated series by Sakula of 30 cases with pulmonary metastatic BCC, the average duration of the disease was 11.4 years when metastasis occurred (6). In previous case reports, good outcome was reported after resection of the solitary pulmonary metastasis from BCC (3, 7). In our case, the metastatic nodules were bilateral and were not appropriate for surgical resection. Metastatic BCC has been described with many histologic subtypes of BCC. There is no consensus as to whether any histologic subtype of the primary tumour predisposes to metastatic BCC (1). Nodular, micronodular, morpheaform, metatypical or basosquamous, and keratotic histologies have all been reported (8). But BCC which contains keratotic foci, as reported here, has a prevalence of aggressive feature of 39%, and is observed in 78% of basosquamous carcinomas (9). In the present case, microscopically infiltrative tumour nests in the desmoplastic stroma showed an aggressive growth pattern, peripheral palisading and clefting. In the centre of the cell groups, there were horn cysts with fully keratinized cells. In the present case there was also a severe clinical course. In the literature, squamous differentiation is reported to be more frequent in the metastasizing, than in the non-metastasizing BCC (10). The keratotic foci found in the present case support this concept. In conclusion, metastatic BCC is a complication of BCC with high morbidity and mortality rates. Patients with metastatic BCC often begin with long-standing primary BCCs that are either large or recurrent and have a higher incidence of the more aggressive histologic patterns (morpheic, infiltrating, metatypical and basosquamous) (1, 11, 12). Perineural spread, blood vessel invasion and squamous differentiation were found to be evident in the primary lesions of metastatic cases (13). Conventional surgical treatment of basal cell cancer is an important issue, since inadequately excised basal cell cancer may be a cause of recurrence and the recurring tumour is a prognostic parameter of metastatic potential (1, 11). Two distinct surgical approaches are practiced in BCC excisions : en bloc excision and Mohs micrographic surgery. A 4-mm surgical margin of clinically normal skin is the current standard for elliptical excision of basal cell carcinomas (14). Histologic studies have confirmed that the sub-clinical extension of disease varies from 1-6 mm (15). Prior studies have shown a recurrence rate as high as 35-38% for inadequately excised tumours (16, 17). BISSON et al. have shown that, given a 3 mm margin, 96% of lesions would have been excised completely (18). However, a 4-mm surgical
271 margin is often not feasible on lesions which are large, recurrent and have deep structural invasion. Tumours larger than 2 cm have wider sub-clinical invasion than smaller lesions ; therefore, a tumour smaller than 2 cm would require a margin of only 4 mm to achieve adequate clearance. Larger morpheaform BCC requires a resection margin of 1-2 cm. The incidence of recurrence following surgical excision is 30% for patients with a positive margin, 12% with a close margin, and less than 5% for complete excision (15). To avoid repetitive operations and the risk of recurrence these tumours should be treated with standard wide margins. The principal aim of surgical treatment should be to obtain complete excision of the tumour with uninvolved margins. Cosmetic and functional concerns are secondary. The extent of the surgical margin required depends on the histological type, and the clinician should expect deeper and/or wider infiltration in patients with recurrent tumours.
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