Dermatology Online Journal

Basal cell carcinoma does metastasize
Doruk Ozgediz MD¹, EB Smith¹, Jie Zheng¹, Jose Otero MD², Z Laura Tabatabai MD², Carlos U Corvera MD¹
Dermatology Online Journal 14 (8): 5

1. Department of Surgery, University of California San Francisco, VA Medical Center San Francisco, California. carlos.corvera@med.va.gov
2. Department of Pathology, University of California San Francisco, VA Medical Center San Francisco, California

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Abstract

Basal cell carcinoma (BCC) rarely metastasizes. However, this unfortunate outcome can occur, usually in neglected tumors. We report a 52-year-old man with a BCC on the left chest that enlarged and then ulcerated over a 6-year period. Metastasis of the tumor to lymph nodes in the left axilla resulted, but the patient remains free of disease 24 months after wide excision, lymph node dissection, and local radiation therapy to the axilla.

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Case Description

Figure 1
Figure 1A. Ulcerated mass over manubrium with satellite lesion (arrow) over right clavicular head Figure 1B. Skin dimpling associated with left axillary mass

A healthy 52-year-old man with no family history of skin cancer presented with a 5 x 6cm painful, ulcerative mass over his manubrium with an adjoining 1.5 x 0.5cm satellite lesion (arrow, Fig. 1A) over the right clavicular head. The tumor started as a small black lesion on the left chest six years earlier and progressively grew, developing ulceration two years prior to presentation. A painful lump that developed in his left axilla (arrowhead, Fig. 1B) within the previous year, was red, mildly tender on exam and caused skin dimpling. The patient had Fitzpatrick skin type 1, reported significant sun exposure, a 15-pack-year smoking history, and was not immunocompromised. He reported no fevers, chills, night sweats, or weight loss. Complete skin examination revealed other skin lesions: a 4 x 1cm ulcerated, linear erosion on the left shoulder, a 1.2cm glabellar nodule, and a 1cm crusted plaque on the right upper back. All lesions had smooth pearly borders and were minimally erythematous with telangiectasias. There were no signs of basal cell nevus syndrome. Shave biopsies of the anterior chest and left shoulder lesions all confirmed a diagnosis of basal cell carcinoma. Staging evaluation by magnetic resonance imaging (MRI) showed the cavitary lesion over the manubrium with a soft tissue density superior to the right clavicular head but no clear invasion of bone or involvement of pectoralis (Fig. 2).

Figure 2	Figure 3
Figure 2. MRI of the thorax showing the cavitary lesion over the manubrium (arrow) without involvement of pectoralis muscle or bone, sagittal view Figure 3: CT scan of the thorax showing the left axillary mass (arrow), coronal view

Figure 4
Figure 4. PET Scan showing uptake over the tumor at the manubrium (arrowhead), left axillary lymph nodes (arrow), and additional areas of uptake across the left superior chest wall to the axilla

Computed tomography (CT) confirmed nodal involvement of the left axilla (Fig. 3). Further staging by18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), demonstrated intense uptake over the manubrium corresponding to the cavitary primary lesion (arrowhead), left axillary lymph nodes (arrow), and additional areas across the left chest wall from the infraclavicular region to the left axilla (Fig. 4). Computed tomography of the chest showed several small 3-4 mm non-specific left lung nodules that were not visible on PET. The patient underwent Mohs micrographic surgical removal of the glabellar and shoulder lesions. The primary lesion over the manubrium was widely excised, including some periostium, and complete wound coverage was achieved by bilateral rotational pectoral flaps. Several intra-operative frozen histological sections were reported to be clear of tumor. A concomitant left axillary lymphadenectomy was performed. However, final histological evaluation revealed a 5.3 x 3.6cm area of nodular and infiltrative basal cell carcinoma with tumor extension into the deepest margin. Detailed microscopic evaluation of anterior chest wall lesion showed an area of ulceration (Fig. 5, double arrows).

Figure 5	Figure 6

Figure 7
Figure 7. 24 months post-op

Adjacent to the ulcer is an infiltrative neoplasm derived from the basal epidermal cells (Fig. 5, single arrow). These cells have hyperchromatic nuclei, scant cytoplasm, and grow in a nodular architecture with classical palisading of nuclei on the periphery of the lesion. These features are diagnostic of basal cell carcinoma. No squamous cell features were present. In the left axillary specimen, eleven of fourteen lymph nodes were positive. Histology showed displacement of lymphoid cells by metastatic basal cell carcinoma (Fig. 6). The final TNM classification was T4N1MX.

Discussion

Basal cell carcinoma (BCC) is the most common human malignancy worldwide, with a lifetime risk of 30 percent in the United States [1]. Metastatic BCC (MBCC) is extremely uncommon, with fewer than 300 reported cases of MBCC in the literature and an estimated rate of metastasis ranging from 0.0028 percent to 0.5 percent [2]. The formal diagnostic criteria for MBCC defined by Lattes and Kessler in 1951 include the following conditions: 1) the primary lesion must originate in the epidermis or follicular skin and not mucinous tissue, 2) spread must be to a distant site and not represent simple extension, 3) the primary and metastatic lesions must have a similar histologic appearance of BCC, and 4) no squamous cell features may be present [3]. Risk factors associated with the rare occurrence of metastasis include tumor size of less than 2cm, multiple primary tumors in the region of the head and neck, significant tumor depth, fair skin, middle age, and male gender [4, 5]. Risk of metastasis has been further shown to specifically correlate with the size of the primary tumor; tumors greater than 3cm conferring 2 percent risk, greater than 5cm conferring 25 percent risk, and greater than 10cm conferring 50 percent risk [6]. Immunocompromised patients and those with primary BCC of the head and neck (65-88% of all BCC) are also more likely to have metastatic disease. Our patient had several of these risk factors.

Metastasis can occur hematologically or through subcutaneous infiltration, but spread is lymphatic in 70 percent of cases [7]. Common sites of distant metastasis include lungs, bones, and skin [8]. All histological forms of BCC, including superficial, nodular, and sclerosing, have been shown to metastasize [9]. Unfortunately, adjuvant treatment of metastatic BCC has been largely unsuccessful. Mean survival for patients with metastatic disease is 8 months [1], although those with spread limited to the lymph nodes alone have an average survival of up to 3.6 years [10, 11]. Metastatic disease has historically been treated with a combination of bleomycin, vincristine, and methotrexate or prednisone, a regimen that was uniformly unsuccessful [10]. More recently, cisplatin has been administered as an adjuvant agent alone or in combination with agents such as methotrexate, 5-fluorouracil, and paclitaxel [10]. Case reports have documented disease remission with cisplatin-based therapy in patients with lung metastases [12, 13]. Localized, nodular BCC has been successfully treated with perilesional interferon alpha 2b, but the effects of systemic treatment of metastatic disease with this drug have not been assessed. Our patient received the standard dose of 60 Gray units of external beam radiation therapy. At 24 months post-op, he is well and without evidence of recurrent disease.

As the worldwide incidence of BCC continues to increase [12], so will the occurrence of MBCC. While adjuvant treatment of MBCC is improving, there continues to be significant associated morbidity and mortality. Traditionally oncologists are trained to regard BCC strictly as a local malignancy, but our case illustrates that, in fact, BCC does metastasize and if left untreated, can have a very grim prognosis. Tumor size and depth are two of the primary risk factors for lymphatic and hematogenous spread of disease, indicating that the longer a lesion remains untreated, the more likely it is to metastasize. As the incidence of BCC continues to rise, it is imperative that physicians recognize BCC lesions early and recommend prompt excision of the primary lesion to prevent metastatic spread.

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