Skin metastasis: a pathologist's perspective

Abstract

Skin metastasis is defined as the spread of malignant cells from a primary malignancy to the skin. It is one manifestation of systemic spread of cancer. The tumor cells originate either from an internal malignancy or from a primary skin cancer. This study presents a literature review concerning these issues as well as this author's experience encountered throughout 19 years of surgical pathology and dermatopathology practice. Several conclusions are evident. Generally, skin metastases are encountered in 0.7-9% of all patients with cancer and as such the skin is an uncommon site of metastatic disease when compared to other organs. There is usually a long-time lag between the diagnosis of the primary malignancy and the recognition of the skin metastases. However, these metastases may be the first indication of the clinically silent visceral malignancies. The regional distribution of the skin metastasis, although not always predictable, is related to the location of the primary malignancy and the mechanism of metastatic spread. The relative frequency of skin metastasis correlates with the type of primary cancer, which occurs in each sex. For instance, lung and breast carcinomas are the most common primaries that send skin metastasis in men and women, respectively. The head and neck region and the anterior chest are the areas of greatest predilection in men. The anterior chest wall and the abdomen are the most commonly involved sites in women. Skin metastases usually appear as non-specific groups of discrete firm painless nodules that emerge rapidly without any explanation. They vary in size from so tiny as to be of 'miliary lesions' to as large as 'Hen's egg size'. Some skin metastasis may mimic specific dermatological conditions such as cutaneous cyst, dermatofibroma, pyogenic granuloma, hemangioma, papular eruptions, herpes zoster eruptions, rapidly infiltrating plaques, alopecic patches, cellulitis and erysipelas. Histologically, the skin metastases usually show features reminiscent of the primary malignancy, but with variable degrees of differentiation. Molecularly, skin metastasis is an organized, non-random and organ-selective process orchestrated by interaction among several heterogeneous molecules, which are largely unknown. Metastasis to the skin is often a pre-terminal event that heralds poor outcome.

Tumor type-specific and skin region-selective metastasis of human cancers: another example of the “seed and soil” hypothesis

“…Perineural invasion of various cancer types (breast, colorectal, pancreatic, gastric, prostate, or head and neck cancers) is a common feature in the primary tumors with prognostic significance. Meanwhile in our cohort, we did not find perineural invasion in skin metastases [18] and earlier pathological analyses have not mentioned them either [10,11,[13][14][15], making a peripheral nerve association of skin metastasis development highly unlikely. Skin is also patterned by a developmental segmentation called Blaschko lines that do not follow nerves, blood vessels, or lymphatics, though they are similar to dermatomes [54].…”

“…Several previous reports [10,11,[13][14][15]18] indicated that significantly more skin metastases occur in the ventral skin. Furthermore, we provided new statistical evidence that some visceral cancer types gave metastases to the skin regions of the "same level," such as lung cancer mainly to supradiaphragmatic (primarily chest), colorectal cancer mainly to infradiaphragmatic (primarily abdominal), and genitourinary cancers to lower abdominal sites, as suggested by earlier observations [10,11,[13][14][15]. It is also of note that skin metastases do not respect the laterality of the primary tumor [18].…”

“…Melanoma and primary tumors in proximity to the skin (e.g., breast or head and neck cancer) preferentially produce skin metastases by locoregional spreading using mostly the lymphatic dissemination route [10,11,[13][14][15]. In contrast, the mechanism for skin metastasis tumors residing in the body cavities is far less understood.…”

“…Nevertheless, the prevalence may increase due to the longer survival of cancer patients [10][11][12]. Although skin is usually involved in a later stage of progression, it is the first sign of dissemination in a small fraction of cases [13][14][15]. However, there are two key factors that warrant special attention in skin metastasis statistics.…”

“…However, there are two key factors that warrant special attention in skin metastasis statistics. First, a significant proportion of skin metastases are derived from cancer types that are closely connected to the skin such as melanoma, breast, or head and neck cancers [13][14][15]. Second, skin metastasis statistics describe natural frequencies and do not normalize the incidence with respect to the significant differences in the prevalence of the various cancer types.…”