Edema by definition is increased fluid in the interstitial space of the tissue.  All edema results from dysfunction of the lymphatic system.  The increase in fluid in the interstitial space of the tissue results from either too much fluid entering the tissue from the blood vessels overwhelming lymphatic function, failure of the lymphatic system to function properly in many cases due to the presence of inflammation, or damage or maldevelopment of the lymphatic system.  Many diseases can cause lymphedema including heart failure,(1) liver disease(2) and infection.(3)

Lymphedema can be primary or secondary.  Primary lymphedema is rare and caused by genetic mutations many of which have been identified.(4)  Secondary lymphedema means that the lymphatic system is not functioning due to damage to the lymphatic system from surgery, usually for cancer treatment, cancer therapies including chemotherapy or radiation, or from immune dysfunction from obesity or other inflammatory processes resulting in the deposition of fibrotic adipose tissue (fibroadipose), impaired lymphangiogenesis, and dysfunctional lymphatic pumping.(5)  Certain genes can also predispose a person to the development of lymphedema after cancer therapy.(6)  Oftentimes people may present with a combination of primary and secondary lymphedema.

As lymphedema accumulates in tissue, the fluid rich in proteins causes fat to grow.(7, 8)  This fat becomes very fibrotic and can grow in localized areas in massive amounts inhibiting mobility.(9)  Compression garments and manual therapy help to prevent the accumulation of fat.  Once the fibroadipose tissue has developed, it does not respond well to compression or manual therapies.  The fat in lymphedema can be removed by liposuction which is also called suction assisted protein lipectomy (SAPL).(10)

References

1. Aspelund A, Robciuc MR, Karaman S, Makinen T, Alitalo K. Lymphatic System in Cardiovascular Medicine. Circ Res. 2016;118(3):515-30. Epub 2016/02/06 06:00. PubMed PMID: 26846644.

2. Ludwig J, Linhart P, Baggenstoss AH. Hepatic lymph drainage in cirrhosis and congestive heart failure. A postmortem lymphangiographic study. Arch Pathol. 1968;86(5):551-62.

3. Mendoza N, Li A, Gill A, Tyring S. Filariasis: diagnosis and treatment. Dermatol Ther. 2009;22(6):475-90. Epub 2009/11/06 06:00. PubMed PMID: 19889133.

4. Blatt J, Powell CM, Burkhart CN, Stavas J, Aylsworth AS. Genetics of hemangiomas, vascular malformations, and primary lymphedema. J Pediatr Hematol Oncol. 2014;36(8):587-93. Epub 2014/09/16 06:00. PubMed PMID: 25222064.

5. Dayan JH, Ly CL, Kataru RP, Mehrara BJ. Lymphedema: Pathogenesis and Novel Therapies. Annu Rev Med. 2018;69:263-76. Epub 2017/09/07 06:00. PubMed PMID: 28877002.

6. Rockson SG. The Genetic Predisposition to Breast Cancer-Associated Lymphedema. Lymphat Res Biol. 2019;17(3):287. Epub 2019/06/14 06:00. PubMed PMID: 31194621.

7. Schneider M, Conway EM, Carmeliet P. Lymph makes you fat. Nat Genet. 2005;37(10):1023-4.

8. Zampell JC, Aschen S, Weitman ES, Yan A, Elhadad S, De Brot M, et al. Regulation of adipogenesis by lymphatic fluid stasis: part I. Adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg. 2012;129(4):825-34. doi: 10.1097/PRS.0b013e3182450b2d.

9. Bogusz AM, Hussey SM, Kapur P, Peng Y, Gokaslan ST. Massive localized lymphedema with unusual presentations: report of 2 cases and review of the literature. Int J Surg Pathol. 2011;19(2):212-6. doi: 10.1177/1066896908320833. Epub 2008 Jul 8.

10. Schaverien MV, Munnoch DA, Brorson H. Liposuction Treatment of Lymphedema. Semin Plast Surg. 2018;32(1):42-7. Epub 2018/04/11 06:00. PubMed PMID: 29636653.