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Reconstructive RECONSTRUCTIVE Differential Diagnosis of Lower Extremity Enlargement in Pediatric Patients Referred with a Diagnosis of Lymphedema Carolyn C. Schook, B.A. Background: There are many causes for a large lower limb in the pediatric age John B. Mulliken, M.D. group. These children are often mislabeled as having lymphedema, and incor- Steven J. Fishman, M.D. rect diagnosis can lead to improper treatment. The purpose of this study was to Ahmad I. Alomari, M.D. determine the differential diagnosis in pediatric patients referred for lower Frederick D. Grant, M.D. extremity “lymphedema” and to clarify management. Arin K. Greene, M.D., Methods: The authors’ Vascular Anomalies Center database was reviewed be- M.M.Sc. tween 1999 and 2010 for patients referred with a diagnosis of lymphedema of Boston, Mass. the lower extremity. Records were studied to determine the correct cause for the enlarged extremity. Alternative diagnoses, sex, age of onset, and imaging studies were also analyzed. Results: A referral diagnosis of lower extremity lymphedema was given to 170 children; however, the condition was confirmed in only 72.9 percent of patients. Forty-six children (27.1 percent) had another disorder: microcystic/macrocystic lymphatic malformation (19.6 percent), noneponymous combined vascular malformation (13.0 percent), capillary malformation (10.9 percent), Klippel- Trenaunay syndrome (10.9 percent), hemihypertrophy (8.7 percent), posttrau- matic swelling (8.7 percent), Parkes Weber syndrome (6.5 percent), lipedema (6.5 percent), venous malformation (4.3 percent), rheumatologic disorder (4.3 percent), infantile hemangioma (2.2 percent), kaposiform hemangioendothe- lioma (2.2 percent), or lipofibromatosis (2.2 percent). Age of onset in children with lymphedema was older than in patients with another diagnosis (p ϭ 0.027). Conclusions: “Lymphedema” is not a generic term. Approximately one-fourth of pediatric patients with a large lower extremity are misdiagnosed as having lymphedema; the most commonly confused causes are other types of vascular anomalies. History, physical examination, and often radiographic studies are required to differentiate lymphedema from other conditions to ensure the child is managed appropriately. (Plast. Reconstr. Surg. 127: 1571, 2011.) ymphedema is the chronic, progressive swell- tial causes of congenital lower extremity over- ing of tissue caused by inadequate lymphatic growth, referring physicians likely are most Lfunction. Lymphedema may result from familiar with the term “lymphedema.” anomalous development (primary) or injury (sec- Lymphedema, however, is typically an adult dis- ondary) to lymph nodes or lymphatic vessels. Al- ease caused by lymphadenectomy and/or irradi- though lymphedema is a specific condition, chil- ation to the axilla or groin. Primary pediatric dren with a large lower limb are often labeled as lymphedema is rare; a child erroneously diag- having lymphedema, regardless of the underlying nosed with lymphedema may undergo unneces- cause. Because lymphedema is much more prev- sary tests and be given incorrect treatment. The alent in the general population than other poten- purposes of this study were to determine the ac- curacy of the term “lymphedema” for pediatric lower limb enlargement and to document other From the Departments of Plastic and Oral Surgery, Surgery, and Radiology, Vascular Anomalies Center, Children’s Hos- causes with which it is frequently confused. pital Boston, Harvard Medical School. Received for publication July 22, 2010; accepted October 11, 2010. Disclosure: The authors have no financial interest Copyright ©2011 by the American Society of Plastic Surgeons to declare in relation to the content of this article. DOI: 10.1097/PRS.0b013e31820a64f3 www.PRSJournal.com 1571 Plastic and Reconstructive Surgery • April 2011 PATIENTS AND METHODS Weber syndrome (6.5 percent), venous malforma- After approval from the Committee on Clini- tion (4.3 percent), infantile hemangioma (2.2 per- cal Investigation at Children’s Hospital Boston, cent), or kaposiform hemangioendothelioma (2.2 our Vascular Anomalies Center database was re- percent). Other conditions confused with viewed for patients sent between 1999 and 2010 lymphedema were hemihypertrophy (8.7 percent), labeled with lower extremity “lymphedema.” In- posttraumatic swelling (8.7 percent), lipedema (6.5 dividuals with disease onset after 21 years of age percent), rheumatologic disease (4.3 percent), and were excluded to ensure that only a pediatric co- lipofibromatosis (2.2 percent). hort was studied. The correct diagnosis was deter- Female patients constituted 62.1 percent of mined by history, physical examination, photo- patients (77 of 124) with lymphedema and 58.7 graphs, imaging studies, and/or histopathology. percent (27 of 46) of children without the disor- Alternative conditions, sex, and age-of-onset were der (p ϭ 0.68). Median age of onset in children recorded. The Mann-Whitney U test was used to with lymphedema was older [4 years (range, 0 to differentiate age of onset between patients with 12 years)] than in patients with another diagnosis lymphedema and children with other disorders. [0 years (range, 0 to 4 years)] (p ϭ 0.027). At least Age of onset was defined in years and, if present one imaging study was obtained in 84.7 percent before 12 months of age, was recorded as 0. Results (144 of 170) of children: magnetic resonance im- are presented as median with interquartile range aging in 93 (54.1 percent), ultrasonography in 78 (25th to 75th percentile). A two-tailed value of p (45.9 percent), plain film radiography in 53 (31.2 Ͻ 0.05 was considered significant. Statistical anal- percent), lymphoscintigraphy in 35 (20.6 per- ysis was performed using the SPSS software pack- cent), computed tomography in 27 (15.9 per- age (version 16.0; SPSS, Inc., Chicago, Ill.). cent), echocardiography in 13 (7.6 percent), and/or angiography in 12 patients (7.1 percent). RESULTS A referral diagnosis of lower extremity DISCUSSION lymphedema was identified in 170 children of Lymphedema is an often loosely used label for 9477 patients in the database (1.8 percent). an enlarged lower extremity in children, regard- Lymphedema was confirmed in 124 patients (72.9 less of the cause. Lymphedema is a precise term percent). The remaining 27.1 percent (46 of 170) that defines chronic, progressive swelling of sub- of patients referred with lymphedema had a dif- cutaneous tissue caused by abnormal develop- ferent diagnosis (Table 1). Seventy percent (32 of ment or injury to the lymphatic vasculature. Pri- 46) had another type of vascular anomaly: micro- mary lymphedema most commonly affects the cystic/macrocystic lymphatic malformation (19.6 lower extremity (Fig. 1). Patients have a significant percent), noneponymous combined vascular mal- risk of infection, and limb enlargement occurs formation (13.0 percent), diffuse capillary mal- over time from adipose deposition and fibrosis. formation with overgrowth (10.9 percent), Klip- Lymphedema can be differentiated from other pel-Trenaunay syndrome (10.9 percent), Parkes causes of extremity overgrowth by history and physical examination in approximately 90 percent of patients. The foot is always involved and swell- Table 1. Causes of an Enlarged Lower Extremity ing proceeds proximally. Edema becomes less pit- Referred with an Incorrect Diagnosis of Lymphedema ting over time as adipose and fibrous tissue are 1 No. (%) deposited. Definitive diagnosis of lymphedema Microcystic/macrocystic lymphatic requires lymphoscintigraphy, which is 92 percent malformation 9 (19.6) sensitive and 100 percent specific for the Noneponymous combined vascular disorder.2 Compromised lymphatic function is il- malformation 6 (13.0) Klippel-Trenaunay syndrome 5 (10.9) lustrated by delayed transit and/or cutaneous ac- Capillary malformation 5 (10.9) cumulation (dermal backflow) of radiolabeled Hemihypertrophy 4 (8.7) colloid injected into the feet. Posttraumatic swelling 4 (8.7) Parkes Weber syndrome 3 (6.5) Management of lymphedema requires daily Lipedema 3 (6.5) washing and moisturizing of the extremity to min- Venous malformation 2 (4.3) imize desiccation, skin breakdown, and subse- Rheumatologic disease 2 (4.3) Infantile hemangioma 1 (2.2) quent cellulitis. Patients should wear protective Kaposiform hemangioendothelioma 1 (2.2) clothing to prevent incidental trauma, which also Lipofibromatosis 1 (2.2) can lead to infection. Compression therapy using Total 46 (100) a custom-fitted garment and a pneumatic pump 1572 Volume 127, Number 4 • Pediatric Lower Limb Enlargement Fig. 1. Images demonstrating primary lymphedema in a 2-year-old boy with left lower extremity swelling that had been present since birth (left). (Above, right) Lymphoscintig- raphy demonstrates dermal backflow and absent inguinal node drainage 21⁄2 hours after injection.(Below,right)AxialT2-weightedmagneticresonanceimagingwithfatsaturation shows a hyperintense reticular network of dilated subcutaneous channels between the dermis and fascial plane. helps to reduce the volume of the extremity and not more likely to have lymphedema than boys; slow progression. Patients with significant mor- therefore, sex should not be considered when dif- bidity who have failed conservative treatment ferentiating lymphedema from other conditions. may be considered for contour resection. We If the diagnosis remains equivocal following his- prefer suction-assisted lipectomy for moderately tory and physical examination, lymphoscintigra- enlarged extremities and staged skin/subcuta-
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