Primary Lymphedema: Prodigal Son of Lymphatic Malformation

49

B. B. (Byung-Boong) Lee, MD, PhD, FACS

Professor of Surgery and Director, Center for Vein, Lymphatics and Vascular Malformations,

George Washington University, Washington DC, USA

 

Through many decades, no one paid enough attention on the obscure but unique origin of the primary lymphedema but considered harmless to deal as one of chronic lymphedema (1, 2).

Indeed, through the last century our knowledge on primary lymphedema has been so limited that we did not know the full nature of the primary lymphedema as a tip of the iceberg of the lymphatic malformation (LM); it is still considered not much serious issue to the clinicians (3, 4).

On the contrary, the secondary lymphedema, mostly involved to the cancer management in the developed countries, has been well investigated for advanced management to reduce if not prevent the condition by appropriate measurement (5, 6).

Nevertheless, the efforts to define the relationship of the primary lymphedema with the rest of lymphatic malformation for more than two decades began to deliver substantial new information to help us to understand this neglected condition better.  Recently published “IUP Consensus on Primary Lymphedema-2009” is one of these contribution (7).

This consensus group, however, decided to limit its scope strictly to the subject linked to the clinical aspect of  primary lymphedema as the most crucial message to be delivered at this time;  the other side of the coin from the LM’s point of view as one of vast groups of the congenital vascular malformations (CVMs) was intentionally left to avoid unnecessary confusion (8).

Regardless, conventional concept defines primary lymphedema based on this anatomical defect on the lymph transporting system, classified to the LM even though some of the primary lymphedema by definition has a limited pathology in the functional level with no morphological/ anatomical defect involved (7).

Therefore, additional knowledge on the LM side view will be certainly helpful to understand the nature of the primary lymphedema as one of the LM, and subsequently for improved management  as one of the LM with a bird eye’s view, which we can no longer afford to ignore.

The LM is the outcome of defective development of the lymphatic system  during various stages of the lymphangiogenesis either alone or combined with other vascular defects affecting the capillary, arterial, and venous system. Such combined condition with other CVMs is distinctively different from independent condition on its clinical behavior so that it is now separately classified as ‘hemolymphatic malformation’  to improve its management (9, 10).  (Table 1)

Therefore, thoughtful consideration on this risk combined with other CVMs (e.g. Klippel-Trenaunay Syndrome) is mandated on every primary lymphedema even if the condition is clinically obvious as a solitary LM lesion (11).

The majority of primary lymphedema represent the clinical manifestation of this LM developed during the ‘later’ stage of the lymphangiogenesis, which is grouped as the ‘truncular’ lesions. Such embryological subclassification is extremely important  because the ‘extratruncular’ lesion from the ‘early’ stage keeps its evolutional potential originated from the mesenchymal cells while the truncular lesion from the ‘later’ stage does not (12, 13).

Another words, the ‘truncular’ LM lesion to cause primary lymphedema  is a ‘stable’ lesion involved to fully matured lymphatic vessel trunk/system in general as defective conditions of hypoplasia, aplasia, numerical hyperplasia, or dilation (lymphangiectasia) with valvular incompetence. But the ‘extratruncular’ LM lesion, often known as ‘lymphangioma’, is such ‘unstable’ condition to grow when stimulated (e.g. female hormone, menarche, pregnancy, trauma, surgery) (14, 15).

Infrequently, we clinicians encounter the primary lymphedema/truncular LM coexisting with the extratruncular LM (e.g. capillary/cavernous lymphangioma) often in a hidden condition; a fair portion of such condition is further combined with additional CVM lesions (e.g. truncular & extratruncular venous malformation) to make its clinical management much complicated.

Without proper management of coexisting extratruncular LM lesions with priority, the truncular LM as primary lymphedema would not respond to DLT (decongestive lymphatic therapy) -oriented conservative care effectively (16) and often deteriorate fast following increased frequency of the local-regional-systemic infection with/without lymphatic leakage from the extratruncular LM lesions.

When the primary lymphedema is further combined with venous malformation (VM) (17, 18), the VM lesion should have a priority to any of coexisting extratruncular LM lesions except life-threatening lymphangioma (e.g. infected cystic hygroma affecting the upper airway).

By timely care on coexisting VM- truncular and/or extratruncular – lesions (e.g. Klippel-Trenaunay Syndrome), the DLT-based primary lymphedema care will be more effective with much better long term prognosis.

When the arterio-venous malformation (AVM) (19, 20) is further combined with the VM to the LM, known as Parkes-Weber Syndrome, the AVM lesion should be controlled with priority whenever feasible with no delay.  Otherwise, the lymphedema will progress rapidly resisting to the conventional DLT.

Conclusion

Primary lymphedema is mostly clinical manifestation of the truncular LM lesion; it should be managed with full consideration on closely existing extratruncular LM as well as other CVM lesions for fail-proof management.

REFERENCES

  1. Lee BB: Lymphedema-Angiodysplasia Syndrome: a Prodigal form of Lymphatic Malformation (LM). Phlebolymphology, 47:324-332, 2005.
  2. Lee BB, Kim YW, Seo JM, Hwang JH, Do YS, Kim DI, Byun HS, Lee SK, Huh SH, Hyun WS: Current concepts in lymphatic malformation (LM). J Vasc Endovasc Surg 39(1) 67-81, 2005.
  3. Lee BB: Current issue in management of chronic lymphedema: Personal Reflection on an Experience with 1065 Patients. Commentary, Lymphology 38 (2005): 28 -31.
  4. Lee BB: Chronic lymphedema, no more stepchild to modern medicine! Eur J Lymphol, 14 (42):6-12, 2004.
  5. Lee BB: Lymphatic Malformation, Pages 31-42, Chapter 4, Lymphedema-Diagnosis and Treatment. Tredbar, Morgan, Lee, Simonian, Blondeau (eds). Springer-Verlag London Limited 2008.
  6. Lee BB: Lymphoedeme post-chirurgical: un terme frappe d’interdiction pour les chirurgiens. Angeiologie 56(4): 7 – 8, 2004.
  7. Lee BB, Andrade M, Bergan J, Boccardo F, Campisi C, Damstra R, Flour M, Gloviczki P, Laredo J, Piller N, Michelini S, Mortimer P, Villavicencio JL : Diagnosis and treatment of Primary Lymphedema – Consensus Document of the International Union of Phlebology (IUP)-2009. International Angiology 2010 Oct;29(5):454-70.
  8. Lee BB, Villavicencio JL: Primary Lymphedema and Lymphatic Malformation:  are they the two sides of the same coin? Eur J Vasc Endovasc Surg (2010) 39:646-653
  9. Lee BB, Kim HH, Mattassi R, Yakes W, Loose D, G. Tasnadi. A new approach to the congenital vascular malformation with a new concept: how the pioneer Prof. Stefan Belov enlightened us through the Seoul consensus. Int J Angiol 12:248-251, 2003.

10.  Lee BB, Mattassi R, Loose D, Yakes W, Tasnadi G, Kim HH: Consensus on Controversial Issues in Contemporary Diagnosis and Management of Congenital Vascular Malformation– Seoul Communication –. Int J Angiol, 2004 ; 13(4): 182-192

11.  Lee BB, Laredo J, Seo JM, Neville R: Hemangiomas and Vascular Malformations. Mattassi, Loose, Vaghi (eds) Chapter 29, Treatment of Lymphatic Malformations. Pages 231-250. Springer-Verlag Italia, 2009, Milan, Italy.

12.  Lee BB, Laredo J, Lee TS, Huh S, Neville R. Terminology and classification of congenital vascular malformations. Phlebology. 2007; 22(6):249-52.

13.  Lee BB, Villavicencio L: Chapter 68. General Considerations. Congenital Vascular Malformations. Section 9. Arteriovenous Anomalies. Pages 1046-1064. Rutherford’s Vascular Surgery. 7th Edition. Cronenwett JL and Johnston KW, Eds. Saunders Elsevier, Philadelphia, PA, USA. 2010

14.  Lee, BB, Kim, YW, Kim, DI, Hwang JH, Laredo, J and Neville, R: Supplemental surgical treatment to end stage (stage IV –V) of chronic lymphedema. Int Angiol. 2008 Oct; 27(5):389-95.

15.  Lee BB: Surgical Management of Lymphedema, Pages 55-63, Chapter 6, Lymphedema-Diagnosis and Treatment. Tredbar, Morgan, Lee, Simonian, Blondeau (eds) Springer-Verlag London Limited 2008.

16.  Lee BB, Bergan, JJ: New Clinical and Laboratory Staging Systems to Improve Management of Chronic Lymphedema. Lymphology 38 (3):122-129, 2005.

17.  Lee BB. Do YS, Byun HS, Choo IW, Kim DI, Huh SH: Advanced management of venous malformation (VM) with ethanol sclerotherapy: mid-term results. J Vasc Surg 37(3):533-8, 2003.

18.  Lee BB, Bergan J. Gloviczki P, Laredo J, Loose DA, Mattassi R, Parsi K, Villavicencio JL, Zamboni P: Diagnosis and treatment of venous malformations – Consensus Document of the International Union of Phlebology (IUP)-2009. International Angiology 2009 December; 28(6):434-51.

19.  Lee, B.B., Laredo, J., Deaton, D.H., and Neville, R.F. Arteriovenous malformations:  evaluation and treatment. Pages 583-593, Chapter 53, Handbook of Venous Disorders:  Guidelines of the American Venous Forum, 3rd Edition; Gloviczki, P., Ed; A Hodder Arnold: London, UK. 2009.

20.  Lee BB, Lardeo J, Neville R. Arterio-venous malformation: how much do we know? Phlebology 2009; 24:193-200

Table 1. Hamburg Classification of Congenital Vascular Malformation (CVM), modified*

Main classification based on its predominant vascular component:

Arterial  malformation

Venous malformation

AV (arteriovenous) shunting malformation

Lymphatic  malformation

Capillary malformation

Combined vascular malformation

Embryological subclassification:

Extratruncular forms – developmental arrest at the earlier stages of embryonal life:

Diffuse, infiltrating

Limited, localized

Truncular forms – developmental arrest at the later stages of embryonal life:

Obstruction & Stenosis

Hypoplasia; Aplasia; Hyperplasia

Membrane; Congenital spur; Web

Dilatation

Localized (aneurysm)

Diffuse (ectasia)

* Both extratruncular and truncular forms may exist together in same vascular malformation; may be combined with other various malformations (e.g. capillary, arterial, AV shunting, venous, hemolymphatic and/or lymphatic); and/or may exist with hemangioma.

* Based on the consensus on the CVM classification through the international workshop in Hamburg, Germany, 1988, which was upheld by subsequently founded ISSVA (International Society for Vascular Anomaly).