Metastatic Disease

Abstract

Metastatic disease to the skin is not uncommon. Skin metastases may be the first sign of an internal malignancy and may offer the most accessible site for diagnosis. In addition, in patients with a known underlying cancer, skin metastasis may be the presenting symptom of extranodal disease, thus impacting therapeutic decisions.

Keywords

Breast cancer, Cutaneous metastases, Lung cancer, Metastatic melanoma, Melanoma

Key Points

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Cutaneous metastases are not uncommon, and are usually a late finding with poor prognosis.
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Cutaneous metastases can be the first sign of an internal malignancy or of extranodal disease in a known malignancy.
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Breast cancer is the most common cause of cutaneous metastases in women, whereas melanoma and lung cancer are the most common causes in men.
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Cutaneous metastases most often present with solitary or multiple skin-colored or erythematous to violaceous dermal nodules.
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Cutaneous metastases can have a wide variety of clinical presentations, particularly in breast cancer.

Metastatic disease to the skin is not uncommon. Skin metastases may be the first sign of an internal malignancy and may offer the most accessible site for diagnosis. In addition, in patients with a known underlying cancer, skin metastasis may be the presenting symptom of extranodal disease, thus impacting therapeutic decisions.

Epidemiology

Studies regarding cutaneous metastases vary greatly in methodology (case reports, series, meta-analyses) and in the patient populations investigated (autopsies, cancer registries). Furthermore, some studies exclude particular cancers, such as melanoma or hematopoietic malignancies, while others exclude tumors with local extension or direct invasion, including only local or distant metastases. The incidence of cutaneous metastases in the literature ranges from 0.2% to 10%. In a retrospective study of 7316 patients with carcinoma (excluding melanoma, leukemia, lymphoma, and sarcoma), 5% of patients developed cutaneous metastases. In the follow-up study of 4020 patients that included melanoma, 10% of patients had cutaneous metastases. The average age of patients with locally invasive and/or cutaneous metastases in one study was 62 years.

Skin metastases were the presenting sign of an internal malignancy in 0.8% of patients, and were the presenting sign of extranodal metastatic disease in patients with a known underlying malignancy in 7.6% of patients (6.4% if melanoma was excluded).

The most frequent neoplasm associated with cutaneous metastases varies by study and inclusion of particular cancers. In most studies, breast cancer has the highest incidence of skin metastases. However, some studies include direct extension, while others include only local or distant metastases. In one series, metastasis occurred in 6.3% of patients with breast cancer and was the presenting sign in 3.5% of patients. In another study, skin involvement occurred in 23.9% of patients with breast cancer and was the presenting sign in 8% of patients. In patients who developed cutaneous infiltration or metastases after the diagnosis of breast cancer, it was a late finding, occurring an average of 101 months after diagnosis. In another study of 1287 patients with internal malignancy, hematologic cancers were the most frequent source of cutaneous metastases, while in another that included melanoma (but excluded hematologic malignancies), melanoma was the most frequent. Cancers of the upper respiratory tract metastasized to the skin at a high incidence as well. Lung, colon, and rectal cancers uncommonly metastasize to the skin, but given the high prevalence of these cancers, they are a common cause of metastases. Cutaneous metastases are often the presenting sign in lung cancer, and it is proposed that this type of malignancy spreads more quickly to the skin than many other cancers. Based on gender, breast, colon, and ovarian cancer are the most common causes of cutaneous metastases in women, whereas lung and colon cancer are the most common causes in men. However, if melanoma is included, it has been reported to be the most frequent source of cutaneous metastases in men, and second in women (preceded by breast cancer). The primary malignancies for cutaneous metastases based on percentage and gender are shown in Table 19-1 . Prostate cancer has a very low incidence of cutaneous metastases even with its high prevalence. Neuroblastoma and leukemia are the most frequent cause of cutaneous metastases in children. In neonates, leukemia, multisystem Langerhans cell histiocytosis, and neuroblastoma, in order of rank, were the most frequent cause of cutaneous metastases.

TABLE 19-1

Cutaneous Involvement by Carcinoma (Including Melanoma) ^∗( Lookingbill et al., 1993 )

Distribution in Men ( n = 127)		Distribution in Women ( n = 300)
Primary Site	Rounded (%)	Primary Site	Rounded (%)
Melanoma	32	Breast	71
Lung (13/19 adenocarcinoma, 2/19 oat cell carcinoma)	12	Melanoma	12
Colon/rectum	11	Ovary, unknown primary, oral cavity, lung ^†	5-2
Oral cavity	9	Colon/rectum, endometrium, bladder, uterine cervix, stomach, bile duct, pancreas, endocrine ^†	<2
Unknown primary	9	––	––
Larynx	6	––	––
Kidney, upper digestive tract, breast, nasal sinuses, bladder, esophagus ^†	5-2	––	––
Endocrine, stomach, pancreas, liver ^†	<2	––	––