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Metastatic basal cell carcinoma: A case report and literature review. How accurate is our incidence data?

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Metastatic basal cell carcinoma: A case report and literature review. How accurate is our incidence data?
Akhil Wadhera MD, Michael Fazio MD, Gregory Bricca MD, Oliver Stanton MD
Dermatology Online Journal 12 (5): 7

University of California, Davis Department of Dermatology.


A 55-year-old man presented to Skin Cancer Surgery Center of Sacramento in 1995 for Mohs micrographic surgery of a 1.5-cm nodular basal cell carcinoma located on the right superior antihelix and scaphoid fossa. The tumor was excised by Mohs micrographic surgery. A recurrent basal cell carcinoma developed at the same site 5 years later and was treated also by Mohs micrographic surgery. One year later (approximately 6 years after the diagnosis of the initial basal cell carcinoma), a right parotid mass was noted on routine physical exam. CT scan and fine needle aspiration of the mass revealed metastatic basal cell carcinoma. The patient underwent excision of the parotid mass followed by radiation therapy. He has done well for the past 2 years since the diagnosis of his metastatic lesion. Basal cell carcinoma is the most common malignancy in the world. The metastatic potential of this tumor has been a cause for concern to many of our patients. We report a case of basal cell carcinoma metastatic to the parotid gland and critically review the incidence data reported in the literature. We recommended the collection of more current and accurate incidence data for basal cell carcinoma and metastatic basal cell carcinoma.

Clinical synopsis

Figure 1
Location of recurrent BCC after MMS.

A 55-year-old man with a prior history of malignant melanoma underwent Mohs micrographic surgery (MMS) for a 1.5-cm nodular basal cell carcinoma (BCC) located on the right superior antihelix and scaphoid fossa in late 1995. He underwent four stages of MMS to obtain tumor-free margins in early 1996. The wound was then reconstructed with a full-thickness skin graft. The patient had a recurrence of the BCC in the same area with identical histopathology 5 years postoperatively, treated with a second MMS procedure (Fig. 1 and 2). The tumor was very superficial and cleared with one stage of MMS.

Figure 2AFigure 2B
Two views of the histopathology of tumor at primary site on ear. (H&E, original magnification × 100).

Figure 3aFigure 3b
Two views of the histopathology of the metastatic tumor in the parotid gland. The tumor shows peripheral palisading, clefting and a sclerotic stroma similar to that seen in the primary tumor (H&E, original magnification × 100).

Approximately 6 years after the diagnosis of his initial BCC, a right parotid mass was noted on routine physical examination. A CT scan of the soft tissues of the neck revealed an approximately 1.5-cm mass adjacent to the right parotid gland. A fine-needle aspiration biopsy was done, and the findings were suspicious for a monomorphic adenoma of the parotid gland. The patient then underwent a superficial parotidectomy, revealing a 1.0-cm mass. The pathology of the excised mass revealed an invasive carcinoma with basaloid features and stromal response identical in appearance to the primary BCC (Fig. 3). A panel of immunohistochemistry stains that included actin, carcinoembryonic antigen, epithelial membrane antigen, glial fibrillary acidic protein, cytokeratin 20, cytokeratin 7, and S100 supported the diagnosis of metastatic basal cell carcinoma (MBCC). A work-up for metastases including a complete blood cell count, comprehensive chemistry panel, CT scan of the chest, abdomen, and pelvis, and a whole-body PET scan, did not reveal any other areas of metastasis. After excision of the parotid mass, the patient received radiation therapy (approximately 5,000 cGy to ipsilateral neck and 6,600 cGy to the parotid bed) to reduce the risk of occult microscopic disease. He has done well for 2 years since the diagnosis of his metastatic lesion.


Basal cell carcinoma is the most common human malignancy in the world. In the United States more than 1 million new cases are diagnosed each year, accounting for 65-75 percent of all skin cancers [1, 2]. Although rare MBCC is a definite entity with more than 300 cases reported in the literature [3]. Review of the literature reveals the reported incidence of this entity to range from 0.0028 percent to 0.55 percent [2, 4, 5, 6]. The upper limit of this range appears to be exceedingly high; i.e., 1 out of 185 people diagnosed with BCC may have a metastasis of this tumor. Even the lower limit of this range of 1 in 35,000 patients may be an overstatement. We believe that this statistic does not reflect the true incidence of MBCC and is very disconcerting to patients who have been recently diagnosed with BCC. These discrepancies may be a result of selection bias, and poor reporting of BCC and MBCC. BCC is not included in the conventional cancer registries. Large population-based retrospective studies or a MBCC registry may help to better estimate its incidence.

In 1894 Beadles reported the first case of MBCC in a 46-year-old man with an extensive rodent ulcer on the face that metastasized to his submaxillary lymph node [7]. Since then, approximately 300 cases of MBCC have been reported in the scientific literature over the last 110 years. There are three essential criteria for a lesion to be classified as a MBCC (see Table 1) [8]. Most BCCs and hence MBCCs occur in light-skinned persons, although there are a few reports of MBCC arising in chronic wounds in those of darker skin [9]. The male:female ratio of MBCC has been reported to be 2:1 [6]. Most MBCCs arise from the head and neck region (65 percent-85 percent) with the ear being the most common location for the primary tumor, as in our case [5, 6]. BCCs are known to metastasize via both lymphatic and hematogenous routes. The usual sites of metastasis include lymph nodes, lungs, bones, skin and parotid glands. There are case reports of MBCC lesions occurring in almost every viscera, although lymph nodes are the most common site [6].

Table 1. Lattes criteria for metastatic basal cell carcinoma[8]
  1. Primary tumor originated from the skin and not from mucous membranes or other glands
  2. Metastasis occurred to a distant site from the primary tumor and could not result from direct extension
  3. Both metastatic and primary tumors have identical histopathology

On the basis of a review of 170 cases, von Domarus et al. found that the median age of onset of BCC was 45 years, the median interval between the diagnosis of the primary tumor and the diagnosis of metastatic lesions was 9 years, and the median age at the time of metastasis was 59 years [6]. Based on the same review, the median survival after the diagnosis of metastasis was found to be only 8 months. For our patient, age of onset of MBCC was 61, and the time between the diagnosis of the primary tumor and metastasis was 6 years. Based on a retrospective review of 67 patients by Snow et al., high-risk patients include those with primary tumors located on the head and neck, primary tumors larger than 10 cm, and tumors with deeper penetration [10]. Evidence of perineural spread and invasion of blood vessels are other factors that enhance metastatic potential [11]. The histopathologic subtype does not appear to be predictive regarding the likelihood of a BCC to metastasize, although basosquamous cell tumors appear to have a high rate of metastasis even when compared to squamous cell carcinoma [12].

Work-up of patients diagnosed with MBCC includes a thorough physical examination with special emphasis on lymph nodes that lie in the drainage basin of the primary tumor. Laboratory work-up includes CBC, chemistry panel, liver functions tests, bone scan, and computed tomography of the chest, abdomen, and pelvis. Treatment of this devastating complication depends on the age of the patient, location of the metastasis and the overall health status. The three modalities that have been used either individually or in combination include surgery, radiotherapy and chemotherapy. Because there are so few cases of MBCCs and the survival of these patients is very poor, there is very little evidence-based data on any of the above treatment modalities. Surgical resection in cases of local spread as was true in our case seems to provide the best outcome [13]. However, for more generalized metastases, radiotherapy and chemotherapy may be the only options. A review of systemic chemotherapy for basal cell carcinoma by Pfeiffer et al. found cisplatin to be the most effective chemotherapeutic agent [14].

A review of the world literature on MBCC reveals that the incidence spans two orders of magnitude (0.0028 % to 0.55 %). This range is not only too wide (ranging from 1 in 35,000 to 1 in 185) but also appears to be higher than the incidence seen in clinical practice. Using the lower end of the range (0.0028 %) and using the United States annual incidence of BCC of approximately 1 million cases based on 1994 estimates, there should be at least 30 cases of MBCC a year. This would result in 300 cases of MBCC over the last 10 years just in the United States alone. However, there have been only about 300 cases reported in total for the world over the last 110 years, and thus even the lower limit of this range may also be an overestimation. These numbers were obtained from very small case studies and need to be reevaluated.

In his 1940 book on treatment of malignant disease with radium, Cade reported a MBCC incidence rate of 0.55 percent. This is based on his observation that 1 out of 183 patients with rodent ulcers that he had treated with radium over a period of 13 years developed MBCC [15]. However, this observation was reported 10 years prior to Lattes' publication of the classification criteria for MBCC [8]. Moreover, the cases of BCC seen by Cade were from a selected population that had very large and difficult-to-manage BCCs. The lower limit of the incidence range of 0.0028 percent was calculated by Paver et al. in 1973 and was based on a questionnaire survey sent to practicing dermatologists in Australia in which they recorded all BCCs seen in 1 month, years in practice, and the number of metastases that they had observed over their lifetime. On the basis of a 52 percent response to the survey they determined that the dermatologists would have seen approximately 28 MBCCs out of 1 million cases of BCC in the 1,095 years of their combined dermatologic practice, thus giving an incidence rate of 0.0028 percent. Table 2 lists other sources and methods used to calculate the incidence of MBCC that we encountered in our literature review.

In addition to the selection bias and limited size of studies reporting MBCCs, another reason for this discrepancy may be the low rate of reporting by physicians around the world. However, we feel that this alone would not account for this discrepancy. Therefore, we would encourage our colleagues to report cases of MBCCs that they encounter in their clinical practice.

Table 2. MBCC incidence data and the extrapolated number of MBCCs expected over the last 10 years based on published rates
# AuthorsYearStudy DesignpercentExtrapolated number of MBCC
1. Cade 1940 Case series 0.55 55,000
2. Cotran 1961 Case series 0.1 10,000
3. Wronkowski 1969 Case series 0.14 14,000
4. Paver 1973 Questionnaire 0.0028 280
5. Weedon 1975 Case series of pathology specimens 0.002 200
6. von Domarus 1984 Case series0.1 10,000
1. One case of MBCC out of 183 cases of BCC seen over a period of 13 years in England [15].
2. Nine cases of MBCC out of 9050 cases of BCC seen over a period of 14 years in Boston, US [16].
3. Six cases of MBCC out of 4188 cases of BCC seen over a period of 18 years in Warsaw, Poland [17].
4. Twenty-eight cases of MBCC out of 1,000,000 cases of BCC in Australia [18].
5. One case of MBCC out of 50,000 cases of BCC in Australia [19].
6. Five cases of MBCC out of 3634 cases of BCCs diagnosed over a period of 8 years in Europe [6].


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17. Wronkowski Z. [Metastases in dermal basal cell carcinoma]. Nowotwory. 1968 Jan -Mar;18(1):51-5. Polish. No abstract available. PubMed

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19. Weedon D, Wall D. Metastatic basal cell carcinoma. Med J Aust. 1975 Aug 2;2(5):177-9. PubMed

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