News, Views & Reviews. A Biopsy Diagnosis? Clinical Clues and Patterns to Help Distinguish Cutaneous Metastases: Part I of II

Metastasis is an unfortunate consequence of many visceral and hematogenous malignancies. Although metastatic lesions may be the first indication of cancer they often represent an advanced stage of disease.^1,2 There are four methods of metastasis that allow malignant cells to infiltrate virtually any part of the body: direct tissue invasion, lymphatic, hematogenous and iatrogenic.² Although visceral to visceral metastases are more common, cutaneous metastases do occur with an overall incidence of 0.7-10.4 percent of patients with primary visceral malignancies.^3-8 Cutaneous metastases are commonly metachronous, and occur months or years after the diagnosis of the primary cancer.¹ However, they may represent the first evidence of an internal malignancy in 0.8⁴-23.3 percent⁹ of patients. Regardless, skin metastases have serious and often grave consequences for the patient, and it is important for physicians to be cognizant of this condition in patients with a recent, remote or nonexistent diagnosis of cancer. In this review, the authors will discuss clinical considerations and common histopathologic features of cutaneous metastases.

Based largely upon autopsy studies and tumor databases, the reported incidence of cutaneous metastasis in patients with cancer ranges from 0.7-10.4 percent.^3-8 This wide range may result not only from errors inherent to these studies, such as the exclusion of microscopic metastases on autopsy,² but also from variations in the definition of cutaneous metastasis and the inclusion of different primary malignancies. For example, Brownstein and Helwig defined cutaneous metastasis as cancer that had spread to the skin by lymphatic or hematogenous routes or by direct extension,¹⁰ while Hu et al. included lesions caused by iatrogenic implantation.⁵ Lookingbill specified cutaneous metastasis as cancer involving the dermis or subcutaneous tissue, not contiguous with the primary neoplasm.³ Most studies excluded lesions that affected mucocutaneous areas, instead including only those patients with metastatic lesions to "true skin."^3,10 In terms of the exclusion of primary malignancies, many studies omitted malignancies originating in lymph nodes or bone marrow, such as lymphoma and leukemia, as well as sarcomas.^3,4,7,10-13 In one analysis of 7,518 autopsied patients that included these primary malignancies, the incidence of skin metastasis among cancer patients was 9 percent, higher than previously reported.¹⁴ Incidence was also dependent on the inclusion or exclusion of melanoma. Using a tumor registry with over 7,000 cancer patients, Lookingbill et al. reported a 4.7 percent total incidence of skin metastasis when excluding melanoma⁴ but an incidence of 5.5 percent when including melanoma.³ Given these discrepancies, the exact incidence of cutaneous metastases is not entirely clear.

When considering cutaneous metastases as a whole, several studies have examined the primary tumors from which known skin metastases are most likely to be derived. Among primary visceral tumors, lung and breast carcinomas most commonly result in cutaneous metastasis in men and women, respectively. This is perhaps not surprising considering that these tumors occur with high frequency in the general population.^{1,3-6,10,11,15,16} In men, carcinoma of the lung accounts for 11.8 percent of skin metastases, followed by cancer of the colon (11%), oral cavity (8.7%) and kidney (4.7%).³ In women 70.7 percent of all cutaneous metastases are derived from breast cancer, followed by cancer of the colon (9%), ovary (3.3%) and oral cavity (2.3%).^3,6,10,16 Similarly, the likelihood of skin metastasis varies based upon the primary cancer type, and will be addressed in the "Specific Cutaneous Metastases" section in Part II of this article.

These patterns of cutaneous metastasis are also influenced by age, much like the patterns of primary malignancy in the general population. For instance, among women over the age of 40, a relatively larger proportion of cutaneous metastases are derived from breast and colon cancers as compared to that seen in women under age 40 (72% versus 59% breast, and 10% versus 6% colon).¹¹ Overall, cutaneous metastases are more likely derived from visceral tumors after the fourth decade of life¹⁷ and more commonly derived from melanoma in patients under the age of 40, reflecting the relative incidence of the primary tumor.¹¹ Cutaneous metastases, however, can