Metastatic carcinoma - Definition

Background: Cutaneous metastases from carcinoma are relatively uncommon in clinical practice, but they are very important to recognize. Cutaneous metastasis may herald the diagnosis of internal malignancy. Early recognition can lead to accurate and prompt diagnosis and timely treatment. The recognition of cutaneous metastases often dramatically alters therapeutic plans, especially when metastases signify persistence of cancer originally thought to be cured. Some tumors metastasize with predilection to specific areas. Recognition of these patterns can be useful in directing the search for an underlying tumor.

Pathophysiology: The breasts, the stomach, the lungs, the uterus, the large intestine, and the kidneys are the most frequent organs to produce cutaneous metastasis. Cancers that have the highest propensity to metastasize to the skin include melanoma (45% of cutaneous metastasis cases), breast (30%), nasal sinuses (20%), larynx (16%), and oral cavity (12%). Because breast cancer is so common, cutaneous metastasis of breast cancer is most often encountered. Although some tumors are very common, they may not necessarily eventuate in metastasis in a manner that parallels their incidence in the overall population. For example, prostate cancer is very common, but cutaneous metastasis from prostate carcinoma is relatively uncommon.

Frequency: Mortality/Morbidity: The mortality rate is high in patients with cutaneous metastases. The appearance of cutaneous metastases signals widespread metastatic disease, resulting in a poor diagnosis. Patients usually survive for a short period of time (about 1 y), depending on the type of carcinoma.

Sex: The most common sources of cutaneous metastases in woman are the breasts (69%), the colon (9%), melanoma (5%), the ovaries (4%), and the lungs (4%). In men, they are the lungs (24%), the colon (19%), melanoma (13%), and the oral cavity (12%).

Age: Cutaneous metastases are very rare in children. Rhabdomyosarcoma, leukemia, and neuroblastoma are the most frequent causes in children.

In men younger than 40 years, the most common sources of cutaneous metastases (in decreasing order of frequency) are melanoma, colon cancer, and lung cancer. In men older than 40 years, the most common sources of cutaneous metastases (in decreasing order of frequency) are lung cancer, colon cancer, squamous cell carcinoma in the oral cavity, and melanoma.

In women younger than 40 years, the most common sources of cutaneous metastases are breast cancer, colon carcinoma, and ovarian carcinoma. In women older than 40 years, they are breast carcinoma, colon carcinoma, lung cancer, ovarian carcinoma, and melanoma.

History:

In most cases, cutaneous metastases develop after the initial diagnosis of the primary malignancy (eg, metastases of breast carcinoma involving the chest wall several years after a mastectomy). In a very small percentage of patients, metastases may be discovered at the same time or prior to the diagnosis of a primary tumor (eg, lung and renal cell carcinoma presenting as scalp metastases in a man who otherwise appears well and gives no history of prior malignancy).

Patients may present with rapidly developing nodules or tumors. Although asymptomatic in most instances, pain and tenderness may be noted. Any rapidly developing or eruptive lesions should warrant careful consideration of the possibility of metastasis. The term carcinoma of unknown primary site (CUPS) is used when dealing with a metastasis that occurs before primary tumor diagnosis. In dealing with cutaneous CUPS, the age, the sex, and the affected skin region of the patient as well as the histology of the lesion are important clues that are useful in determining a likely primary tumor.

Physical:

Most cutaneous metastases occur in a body region near the primary tumor. The most common presentation of cutaneous metastases is nodules. The nodules are often nonpainful, round or oval, firm, mobile, and rubbery in texture. The nodules are usually flesh colored, although they may also be other colors (eg, from flesh colored to brown or blue-black). Often, the nodules from the metastases of renal cell carcinoma and occasionally thyroid carcinoma are red and purple. They vary in size from barely perceptible lesions to large tumors. Multiple nodules appear rapidly before growth slows down.

Carcinoma may engender a brisk inflammatory response mimicking cellulitis. This pattern is referred to as inflammatory breast carcinoma. When many telangiectatic blood vessels are encountered, the pattern is referred to as carcinoma telangiectodes. Occasionally, the skin may have an orange peel–like appearance (peau d'orange), and/or changes in the local blood flow may occur. In other cases, the skin may feel firm and have a breastplatelike appearance, which is referred to as carcinoma en cuirasse.

Breast cancer is one of the most common malignancies to spread to the skin. The most likely site for cutaneous metastases in women is the chest; less common sites include the scalp, the neck, the upper extremities, the abdomen, and the back. Occasionally, patients with metastatic breast cancer may have a firm, scarlike area in the skin. When this occurs on the scalp, hair may be lost, and the clinical appearance may mimic alopecia areata, except that the skin exhibits marked induration on palpation. This condition is known as alopecia neoplastica

Lung cancer is the most frequently encountered metastasis in men. The most common site for cutaneous metastases in men is the chest, followed by the abdomen and the back. Other areas (in decreasing order of frequency) include the scalp, the neck, the face, the extremities, and the pelvis. For women, the most common areas (in decreasing order of frequency) are the chest, the abdomen, the back, and the upper extremities.

Gastrointestinal cancers (usually colon and stomach cancer) often metastasize to the abdomen and the pelvis. Gastrointestinal carcinomas may spread along the urachus and produce nodules at the umbilicus. The presentation of nodules at the umbilicus has been referred to as a Sister Mary Joseph nodule. Sister Mary Joseph was a nurse at the Mayo Clinic who helped prepare patients prior to operation for gastrointestinal surgery. She noted that the nodules at the umbilicus were an ominous sign of extensive involvement of colorectal carcinoma.

About 60,000 Americans develop malignant melanoma each year, but only 9,000 deaths are attributed to malignant melanoma annually in the United States. When malignant melanoma metastasizes, the skin is commonly involved. In men, melanomas are likely to metastasize to the chest, the extremities, and the back. A large portion of female patients have metastases to the lower extremities. Metastases of melanoma may simulate blue nevi and may be epidermotropic or simulate primary cutaneous melanoma.

Cutaneous metastases from squamous cell carcinoma in the oral cavity usually remain in the local area, most often affecting the neck and the face.

Renal cell carcinoma may metastasize to the scalp, to operative scars, or on many other surfaces. Because of the prominent vascular supply of renal cell carcinoma, lesions may mimic a hemangioma or a pyogenic granuloma.

Metastases from the ovary and the uterus are seen in the skin of the lower abdomen, the groin, or the upper thigh.

Causes:

Metastases arise as disconnected extensions of a primary tumor. This occurs when cancerous cells break away from a primary tumor and spread elsewhere. By definition, this makes the primary tumor malignant. Determining whether a primary neoplasm will metastasize is difficult because of many factors, but, generally, the larger and faster a neoplasm grows, the more likely it will metastasize.

Cells may have a predictable metastatic spread, but unusual sites of metastasis may be encountered. The use of sentinel lymph node studies is an attempt to define likely paths of metastasis to identify whether metastasis has occurred. Unfortunately, for some tumors like melanoma, there is as of yet no clear evidence that lymphatic spread is the predominant mode of metastasis.

Many steps have to be met for metastasis to occur. The primary tumor has to be large enough to release a sufficient amount of neoplastic cells into the circulatory or lymphatic system. These cells need certain properties, such as cell suspension and mitotic rate, to survive while in circulation. Most single neoplastic cells released are destroyed by the immune system, whereas clusters of 6 or 7 cells have a better chance of metastases. To establish metastases once the neoplastic cells are in the circulation system, the neoplastic cells need to attach and penetrate vessel walls. The most common attachment sites are based on the circulatory path, but the neoplastic cells also have affinities to certain target tissues. Once attachment occurs, a thrombus forms around the neoplastic cells through endothelial cell injury. This thrombus serves as protection for the neoplastic cells. The new metastasis establishes itself and obtains nutrition initially through diffusion and then it forms its own vessels.