Metastasis is a clinical process by which cancer spreads from a primary site where it arose to distant locations of the body. Cells that metastasize to distant sites will have the same cell characteristic as the tumor of origin. The word metastasis originates from ancient Greek language meaning “the removal from one place to another”.
Presentation
Patients with brain metastasis will present with neurologic symptoms like seizures, headache, cranial nerve deficiency, and positional vertigo. Thoracic metastasis may presentwith hemoptysis, dry cough, and dyspnea. Jaundice, hepatomegaly and nausea are usually observed in hepatic metastasis. Bone metastasis will present with the most excruciating metastasis especially those with spinal cord involvement. Regional lymph node adenopathy are typically seen in regional metastasis [8].
Workup
The following tests and work up modalities are implored in the diagnosis of metastasis:
- Tissue biopsy: Tissues taken from metastatic lesions are examined under the microscope to determine the point of origin of the tumor [9].
- Cranial CT scan: This imaging technique will demonstrate the presence and the extent of the cranial metastatic tumor.
- Chest X-ray: This imaging modality can be used to screen patients with possible chest or intrathoracic metastasis.
- Magnetic resonance imaging (MRI): This imaging scan will elucidate and define tumors intraabdominally and in the thoracic cavity.
Treatment
The management of metastasis greatly depends on the patient’s age, general health, and history of previous treatments. The treatment options for metastasis include radiosurgery, radiation therapy, debulking surgery, chemotherapy, and hormone therapy [10]. A combination therapy from among these may be implored to treat some cancer metastasis. A great majority of the cancers are hard to treat but testicular and thyroid metastasis are usually treatable.
Prognosis
The prognosis of metastastatic cancers depend on the time the disease condition is diagnosed and how aggressive the management is. The site of the metastasis also affects the relative morbidity and mortality of the patient. Brain metastasis and thoracic metastasis carries the most morbid prognosis among the other possible sites. Pain symptoms are more pronounced and debilitating in bone metastasis compared to thoracic metastasis that may sometimes remain asymptomatic. Metastasis where the tumor of origin is not identified may be difficult to treat and control which occurs in 3% of all the cases [7].
Etiology
Almost all types of cancer can metastasize including cancers of the blood and the lymphatic system. Primary tumor may metastasize to distant organs by way of the lymphatic system or the blood stream. The formation of the metastatic tumor in the recipient organ will form a clinically detectable cancer which may invade the vascular or lymphatic structures of the new site and metastasize to another site. Primary cancers can spread contiguously to another coelom or compartment which is also known as transcoelomic metastasis. Cancers can also spread to regional lymph nodes and show signs of cancer spread within a solitary or group of lymph nodes. The lymphatic spread of the cancer cells to a nearby lymph node is called transplantation and implantation metastasis [1].
Epidemiology
The actual incidence and prevalence of metastasis a disease is a reflection of the aggressiveness of a given primary cancer. Metastatic tumors to the brain are the most common type of brain tumor in adults [2]. In the case of hepatocellular carcinoma (HCC), intrathoracic metastasis is the most common site of metastasis, followed by abdominal spread, and bone metastasis accordingly [3]. As in the case of pulmonary metastasis, the incidence of its metastasis increased with increasing age. An approximate total of 6 to 10% of invasive breast cancers are initially diagnosed as metastatic or stage IV in classification.
Pathophysiology
The pathogenesis of metastasis starts with the breaking away of the cancer cells from the primary tumor that attaches to it, or degrades to the extracellular matrix (ECM) which separates the tumor from the normal apposing tissues. Recent researches on cancer have postulated that one of the most critical event involved in the development of metastasis is the development of the new blood vessel network or tumor angiogenesis [4].
In the same way, angiogenesis inhibitors has been successfully determined to prevent the progression of some metastatic processes. The endothelial progenitor cells are critical for the development of metastasis and its angiogenesis [5]. Epigenetic regulations like H3K4 methylation and H3K9 methylation in the histones allows for the proliferation of the disseminated tumor cells in distant organs [6].
Prevention
Metastasis can actively be prevented by the early diagnosis and treatment of the primary tumors. A routine annual bone scan, chest X-ray and ultrasound of the pelvic organs can prevent the progression of some primary tumors to disseminate to distant organs. Regular Pap smear and self-examination of the breast can effectively detect cancers in its very early stages. Slight neurological disturbances merit an early cranial CT scan to detect brain metastasis.
Summary
Metastasis is a medical condition where a cancer cell from a tumor of origin disseminates to another organ not directly related to it. The tumor that is formed by a metastatic cancer cell is known as a metastatic tumor or secondary tumor. The majority of metastatic tumors could not be healed by standard treatment modalities. The primary goal in the treatment of metastatic cancer is to control the neoplasm growth and control the symptoms brought about by its occurrence.
Patient Information
Definition
Metastasis is a clinical process by which cancer spreads from a primary site where it arose to distant locations of the body.
Cause
Metastasis can spread by contiguous spread, lymphatic circulation, lymph node transplantation, and hematogenous spread.
Symptoms
Symptoms largely depend on the site where metastasis has thrived. Lung metastasis presents with hemoptysis and dyspnea, brain metastasis with neurologic signs, bone metastasis with bone pain, and regional lymph node swelling.
Diagnosis
Imaging techniques for the diagnosis of metastasis include X-ray, CT scan, and MRI. Tissue biopsy of the metastasis can determine the origin and the mode of treatment.
Treatment and follow-up
Metastasis are treated with a combination of radiation therapy, chemotherapy, hormone therapy, radiosurgery and debulking surgery.
References
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- Fox BD, Cheung VJ, Patel AJ, Suki D. Epidemiology of metastatic brain tumors. Neurosurg Clin N Am. 2011 Jan; 22(1):1-6, v.
- Si MS, Amersi F, Golish SR, Ortiz JA, Zaky J, Finklestein D. Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg. 2003 Oct; 69(10):879-85.
- Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991 324 (1): 1–8. Doi: 10.1056.
- Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V. Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis. Science 2008 319 (5860): 195–198.
- Lujambio A, Esteller M. How epigenetics can explain human metastasis: a new role for microRNAs. Cell cycle 2009 (Georgetown, Tex.) 8 (3): 377–82.
- Briasoulis E, Pavlidis N. Cancer of Unknown Primary Origin. Oncologist 1997 2 (3): 142–152.
- Coghlin C, Murray GI. Current and emerging concepts in tumour metastasis. Journal of Pathology 2010; 222(1):1–15.
- Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nature Genetics 2003 33 (1): 49–54.
- Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization.Nature Reviews Cancer 2009; 9(4):274–284.