1. Cystic Hygroma and its management
- Honestly, an out-dated term as it does not apply to the morphology and distribution of most lymphatic malformations. (This term typically indicates macrocystic malformations of the neck and axilla that present in the perinatal period.)
- Cystic hygroma is characterized by large, multilocular macrocysts, filled with a straw-colored, watery, protein-rich fluid.
- Other ways of characterizing lymphangioma are either by the size of the cystic components (i.e. larger or smaller than 2 cm cubed, macro vs micro-cystic), by the size of the lymphatic channels on microscopy (i.e. capillary-sized or dilated, capillary lymphangioma vs cavernous lymphangioma) and whether there is a vascular component to the mass (i.e. hemangiolymphangioma).

2. What are they?
Benign maldevelopment of lymphaticovenous sacs with sequestration of lymphatic tissue
No longer communicates with the normal lymph system and accumulation of fluid leads to cystic enlargement
Appear early in life, generally posterior triangle (6% of all benign lesions of infancy and childhood)
6th week gestation, failure of cervical mesenchyme (future lymph channels and jugular nodes) to form communications w/ the internal jugular venous system.
50-65% present at birth, 90% present by 2nd year of life
75% are located in the posterior triangle of the neck, 20% axilla, 5% mediastinum, retroperitoneum, pelvis and groin. (rarely may communicate with axilla or mediastinum under the clavicle)

3. Lay of the land (typically)
healthtap.com
medkaau.com

4. Histology Gut 2009;58:1184 doi:10.1136/gut.2008.166769
● Large, irregular vascular spaces filled w/ a watery, protein-rich fluid and lined by flattened, bland epithelial cells with fibroblastic or collagenous stroma
● Stroma may contain lymphocytes
● Occasionally inflammation can obscure lymphatic origin
● Not encapsulated, so removal without cyst rupture can be difficult
Truly not much different from cavernous lymphangiomas except they tend to be softer and, the term cystic hygroma is typically assigned to those lymphangiomas that develop in fetuses.
Gut 2009;58:1184 doi: /gut

5. Growth Pattern No skin involvement with cystic hygroma
Grow along fascial planes and around neurovascular structures
Largely asymptomatic (depending on size/location)
Involvement of neurovascular structures within these masses can make complete excision nearly impossible.

6. Potential Complications
Hemorrhage within the mass
Infection
Visual, auditory, oral or esophageal obstruction
Airway obstruction
Hemorrhage can lead to rapid enlargement of the mass
Infection can lead to cellulitis or a frank abscess
Large neck lymphangiomas may invade floor of mouth, leading to dysphagia or may obstruct the ear canal or visual field.
Life threatening complications arise from airway obstruction either from blocking the nose and/or mouth or from tracheal compression.
Usually painless unless hemorrhagic or infected

7. Methods of Treatment Drainage Surgical Excision Sclerotherapy
Radiofrequency ablation and laser excision (used for microcystic lymphatic malformations)
Combination therapy
Spontaneous regression is uncommon but has been known to occur after acute inflammation. The mechanism of this is thought to be similar to that of the sclerosing agents. (i.e. cytokine activation and damage to the endothelial lining)

8. Drainage
Needle aspiration alone is not indicated for definitive treatment
Useful for emergent decompression of a cyst to relieve airway obstruction or to facilitate delivery
Needle aspiration fails to remove the cystic lining so recurrence is almost guaranteed.

9. Excision Long been the preferred method of treatment
Downside is incomplete excision due to involvement of vital structures
CT or MRI is indicated to evaluate the full extent of the lesion for surgical planning.
Complete excision of the cystic mass is the gold standard treatment but, sometimes part of the mass must be left due to encasement of vital structures such as nerves and blood vessels. It is not worth the sacrifice or potential damage of these structures to have a benign mass removed. (i.e. an unacceptably high complication rate for the treatment of a benign condition)
Prenatal diagnosis by ultrasound of an anterior or posterior cervical lymphatic malformation has significant implications.
EXIT (ex utero intrapartum treatment, where the baby’s airway is managed prior to coming off placental oxygenation) procedures can be done to obtain a surgical airway if it seems the mass would compromise this.
Posterior lesions have been associated with Turner syndrome, as well as other congenital anomalies. They carry a high prenatal mortality rate, particularly with hydrops and diffuse lymphedema, and thus require that amniocentesis with chromosomal analysis be performed and genetic and family counseling be provided.

10. Excision cont. Traditional approach is an incision overlying the mass
Neck scars are very cosmetically unpleasing in various cultures.
More recently, some have used an endoscopic approach through the anterior chest. (Han, et al.)
- Traditional incision can leave an aesthetically unappealing scar.
- Anterior chest approach via laparoscopy study involved 6 infants and children (June 2005 through October 2010) and had no conversions to open, no post-op complications and had a good cosmetic outcome.

11. Recurrence
If the entire cyst can be resected, recurrence is practically zero.
Subtotal resection leads to recurrence about 56%
Partial resection has 86% recurrence
Drainage only leads to nearly 100% recurrence.
These recurrence rates are for approximately five years post-op.
Sometimes, microvesicles can appears around the scar years after excision.

12. Sclerotherapy Agents include: OK – 432 Bleomycin – toxicity limits use
Doxycycline
Ethanol – widely used in the US due to its availability
Sodium Tetradeyl Sulfate
Fibrin glue

13. Sclerotherapy cont.
OK – 432 (Picibanil) : Freeze-dried, heat and penicillin-killed, mixture of group A Streptococcus pyogenes
Shown to cause either total or marked shrinkage of cystic lesions without scarring of the overlying skin.
Found to be superior to bleomycin therapy with less toxicity.
Better for macrocystic lesions than for microcystic.
OK – 432 had emerged as one of the best primary agents for sclerotherapy. Originally approved in Japan in 1975 as an anticancer agent, currently still expensive and not approved for use in the United States.
Works by inducing cystokines. Found to be a potent multicytokine inducer, specifically a strong inducer of IL-12, and it may exert its antitumor effect by promoting a Th1-dominant state (cytotoxic T-cells).
Initial trials for use in lymphatic malformations included 64 pts and used OK – 432 either primarily (group A, n=46) or as secondary treatment in patients who had recurrence after surgical excision (group B, n=14) or after bleomycin treatment failure (group C, n=4).
With OK-432 injection, if shrinkage was not seen 3-6 post-treatment, a second injection was done and injections were repeated every 4-6 weeks with increasing concentrations if satisfactory results were not seen.
Group A: 67% has either complete or marked shrinkage BUT, for cystic lesions, 92% (22/24 pts with cystic lesions) had either complete or marked shrinkage.
Group B: 36% had total or marked shrinkage
Group C: 50% had total or marked shrinkage
If initial shrinkage of the lesion occurred, recurrence even years later was not seen.
Macrocystic lesions are thought to have better, larger intercystic communications than microcystic, allowing better distribution of the sclerosing agent and hence, better results.
Worse results in groups B & C thought to be due to scarring from prior treatments causing blockage of intercystic communications.
Post-injection fevers are extremely common but are short-lived and able to be treated with antipyretics.
Extensive swelling after injection is not very common but is a dangerous side-effect of sclerotherapy and pts may need to stay intubated in the ICU with pressure dressings on for a few days post-injection.
Pt’s who failed primary OK-432 injection and had to have surgery were found not to have fibrosis that hindered surgical excision and were actually noted to have less post-operative lymphorrhea.

14. Radiotherapy and Laser excision
Radiofrequency ablation involves either a high (deep) or low (superficial) radiofrequency to destroy tissue.
Temperatures reached are less than with traditional cautery so surrounding tissue thermal damage is lessened.
Mainly useful with microcystic lesions as macrocystic lesions are too large to be dealt with in this way.
- These methods are mainly used for other lymphatic malformations, such as microcystic malformations involving the oral cavity or larynx.
- They are nice techniques in that they provide pin-point destruction of the lesion with minimal damage to the surrounding tissue and the depth of the tissue destruction can be altered.
- These methods have not really been applied to the larger, generally more external lesions of cystic hygromas.

15. Combination Therapy
A combination of cyst aspiration and injection of OK – 432 has been shown to markedly reduce the mass size.
Recurrence did not occur with any of the patients in the study
Complications from combination aspiration and sclerotherapy were minimal.
Combination of cyst rupture/aspiration with OK – 432 sclerotherapy has been studied (Mitsukawa & Satoh), showing good results (but only 5 patient study)

16. Proposed Algorithm for LMs at large
From “Lymphatic malformations: A proposed management algorithm” by Osthuizen and Russell, out of Our Lady’s Hospital for Sick Children in Dublin. Studied 14 patients over a period of 10 years.

17. Continued
It is preferred first to observe a cystic hygroma. Then, if there is no significant regression and the pt feels they want treatment of the mass, sclerotherapy is the first treatment of choice. If repeated rounds of sclerotherapy fail to achieve a desirable result, or if there is concern for airway compromise at any point, the pt must be reassessed and an operative plan can be made.

18. References
S. Ogita, T. Tsuto, K. Nakamura, E. Deguchi, N. Iwai, OK-432 Therapy in 64 Patients With Lymphangioma, Journal of Pediatric Surgery. 29 (1994) N. Mitsukawa, K. Satoh, New Treatment for Cystic Lymphangiomas of the Face and Neck: Cyst Wall Rupture and Cyst Aspiration Combined With Sclerotherapy, The Journal of Craniofacial Surgery. 23 (2012) J. Oosthuizen, P. Burns, J. Russell Lymphatic malformations: A proposed management algorithn, International Journal of Pediatric Otorhinolaryngology. 74 (2010) S. Kim, K. Kauvanough, D. Orbach, A. Alomari, J. Mulliken, R. Rahbar, Long-term Outcomes of Radiofrequency Ablation for Intraoral Microcystic Lymphatic Malformation, Archives of Otolaryngology Head and Neck Surgery. 137 (2011) L. Nielsen, B. Charabi, F. Jensen, G. Claesson, P. Bretlau, Cystic hygroma: OK-432 is superior to surgery, International Congress Series (2003)