Causes of Lymphedema
Lymphedema results from abnormalities or damage to the lymphatic system, leading to accumulation of protein-rich interstitial fluid and fibroadipose tissue, with causes divided into primary (congenital lymphatic abnormalities) and secondary (acquired damage from surgery, radiation, infection, or malignancy). 1, 2
Primary Lymphedema
- Primary lymphedema stems from congenital lymphatic system abnormalities that impair lymphatic transport capacity from birth or develop later in life due to inherent defects in lymphatic vessels or lymph nodes. 1, 3
Secondary Lymphedema Causes
Cancer Treatment-Related (Most Common in Women)
Surgical lymph node dissection is the leading cause of secondary lymphedema, particularly:
- Axillary lymph node dissection (ALND) for breast cancer causes lymphedema in 30-50% of patients, with risk approximately four times higher than sentinel lymph node biopsy. 4, 5, 6
- Sentinel lymph node biopsy carries substantially lower risk (5.6-7.9%) compared to full ALND (13.5-28.2%). 6
- Pelvic surgery with lymph node dissection is the most common cause of unilateral lower extremity lymphedema. 7
- The extent of lymph node removal matters: removing five or more lymph nodes substantially increases lymphedema risk. 1, 2
Radiation therapy damages lymphatic channels and increases risk:
- Radiation to supraclavicular lymph nodes or axilla significantly elevates lymphedema risk, especially when combined with surgery. 8, 2
- Pelvic radiation damages lymphatic channels and increases lower extremity lymphedema risk. 7
- Combined surgery and radiation therapy creates additive risk beyond either treatment alone. 2
Malignancy-Related
- Malignancy causing lymphatic obstruction through direct tumor compression or invasion of lymphatic vessels can cause secondary lymphedema. 7
Infection-Related
- Recurrent infections (particularly cellulitis) in affected areas damage lymphatic vessels and increase lymphedema risk. 2
- Chronic venous insufficiency can contribute to lower extremity lymphedema development. 7
Major Risk Factors That Exacerbate or Trigger Lymphedema
Obesity (BMI >30 kg/m²) is a critical modifiable risk factor:
- Obesity exacerbates lymphedema severity and correlates with higher International Society of Lymphology stages. 7
- Weight loss should be mandated for overweight/obese patients to prevent or reduce lymphedema risk. 8, 7
Timeline of Development
- 70% of breast cancer-related lymphedema occurs within two years of surgery, 90% within three years, with approximately 1% annual incidence thereafter. 6
- Lymphedema may occur immediately after treatment or develop years later (up to 11-30 years post-treatment), making lifelong surveillance necessary. 8, 4
Critical Clinical Pitfall
Many patients with no traditional high-risk variables (such as mastectomy, ALND, or radiation) still develop lymphedema, indicating that risk stratification is imperfect and all patients who undergo breast surgery or radiation require monitoring. 6