Cancer can spread to nearly any site in the body, a process known as metastasis. While organs like the liver, lungs, and bones are common sites for secondary tumors, the spread of cancer to skeletal muscle is notably rare. Skeletal muscle comprises a significant portion of the body’s mass, yet post-mortem studies suggest that metastasis to this tissue occurs in less than 1% to 17% of cancer patients, depending on the study and primary cancer type. Although the rarity of this event suggests a natural resistance, muscle metastasis is possible and does occur in specific contexts.
The General Process of Cancer Metastasis
For cancer to spread from its initial location, cells must complete a multi-step process called the metastatic cascade. This process begins with local invasion, where malignant cells detach from the primary tumor mass and break down the surrounding tissue barrier, the extracellular matrix. They then enter the bloodstream or lymphatic system (intravasation), becoming circulating tumor cells.
These circulating cells must survive the turbulent environment of the circulatory system, enduring physical stress and immune attack. The final stage involves the tumor cells adhering to the inner walls of distant blood vessels and exiting the circulation (extravasation). Once outside the vessel, the cells must colonize the new tissue and grow into a secondary tumor, a process heavily influenced by the local microenvironment, often described by the “seed and soil” concept.
Why Skeletal Muscle Resists Metastasis
Skeletal muscle, despite its high vascularity and large mass, presents an unfavorable environment for colonization by circulating tumor cells. Several factors contribute to this resistance, primarily related to the tissue’s mechanical, metabolic, and immunological characteristics. The extensive, highly organized network of muscle fibers forms a physical barrier that impedes the initial survival and subsequent growth of cancer cells after extravasation.
The high, turbulent blood flow within muscle tissue makes it difficult for circulating tumor cells to adhere to the vessel walls long enough to complete extravasation. Furthermore, the continuous mechanical forces from muscle contractions may physically dislodge any tumor cells that manage to adhere to the endothelium.
Metabolically, the muscle microenvironment is inhospitable to foreign cell growth due to the high production of lactic acid, especially during contraction. While cancer cells also produce lactic acid, the muscle tissue’s ability to tolerate or buffer higher levels of this compound may inhibit the proliferation of metastatic cells. The tissue also maintains a unique redox balance and secretes anti-tumorigenic molecules, known as myokines, which actively suppress tumor growth.
The muscle tissue benefits from robust immunosurveillance involving muscle-resident immune cells. Contractile activity mobilizes natural killer cells and increases the cytotoxic activity of anti-tumor CD8+ T-lymphocytes. This enhanced immune response, combined with the metabolic and mechanical factors, helps suppress any cancer cells that manage to reach the muscle.
When Muscle Metastasis Does Occur
While skeletal muscle is a resistant site, metastasis does occur, often in the context of advanced or widespread disease. These rare occurrences suggest that certain primary cancers possess specific characteristics that allow them to overcome the muscle’s natural defenses. The primary tumors most frequently associated with skeletal muscle metastases are lung cancer, gastrointestinal cancers, urogenital tumors, and malignant melanoma.
Lung cancer is the most common primary malignancy to spread to skeletal muscle, accounting for over 25% of cases in some reviews. These tumors often metastasize via the hematogenous route, favoring axial muscles such as the psoas, gluteal, and paravertebral muscles. Their success may involve the expression of molecular markers that facilitate adhesion to the muscle vasculature or the sheer volume of circulating tumor cells produced by a large tumor burden.
Metastasis from pelvic and abdominal malignancies may utilize the paravertebral venous plexus to spread to the nearby trunk musculature. Although rare, a specific subset of tumor cells may also gain an advantage by establishing a niche in intramuscular lymph nodes, particularly in the psoas muscle. The presence of skeletal muscle metastasis is associated with a poor prognosis and is a sign of aggressive disease.
Identification and Clinical Presentation
Skeletal muscle metastases often present a diagnostic challenge because their clinical presentation can mimic more common, benign conditions. Patients may experience localized pain, swelling, or a palpable mass, which can be mistaken for a hematoma, an abscess, or a soft tissue sarcoma. In many cases, the lesions are asymptomatic and discovered incidentally during imaging.
Due to the lack of specific symptoms, imaging modalities are relied upon for detection and characterization. Magnetic resonance imaging (MRI) is the technique of choice for its superior soft tissue contrast, although findings can be non-specific, showing hyperintensity on T2-weighted sequences. Computed tomography (CT) scans may reveal the metastasis as an intramuscular mass, often with a rim-enhancing pattern and a central area of low density.
Positron emission tomography (PET) using fluorodeoxyglucose (FDG) is highly sensitive for detecting these lesions due to the high metabolic activity of most cancers. However, a definitive diagnosis of skeletal muscle metastasis is dependent on a tissue sample. A biopsy is necessary to confirm the presence of malignant cells and to determine the cancer’s origin, guiding appropriate treatment.