Primary Lymphedema of the Upper Extremities: Clinical and Lymphoscintigraphic Features in 23 Patients

Jeremy A. Goss, MD, Reid A. Maclellan, MD, MMSc, and Arin K. Greene, MD, MMSc. Lymphatic Research Biology 2018

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Primary Lymphedema of the Upper Extremities: Clinical and Lymphoscintigraphic Features in 23 Patients

Jeremy A. Goss, MD, Reid A. Maclellan, MD, MMSc, and Arin K. Greene, MD, MMSc. Lymphatic Research Biology 2018

Background: Primary idiopathic lymphedema is an uncommon condition that typically affects the lower extremities. Patients have a malformed lymphatic system that causes subcutaneous fluid and adipose deposition. Rarely, the disease also has been described in the upper extremities. The purpose of this study was to investigate a cohort of patients with primary arm lymphedema to better understand the disease.

Methods: Patients evaluated in our Lymphedema Program between 2008 and 2018 were reviewed for individuals with upper extremity primary lymphedema. Gender, age of onset, morbidity, associated features, and management were identified. Transit of radio labeled tracer and dermal backflow on lymphoscintigraphy were recorded.

Results: Twenty-three patients of 234 individuals with primary lymphedema had upper extremity disease (9.8%). Eleven subjects were male. Age of onset was infancy (n=15), adolescence (n=5), or adulthood (n=3). The disease affected the left arm (n=11), right arm (n=9), or both upper extremities (n=3). Lymphoscintigraphy in 15 patients exhibited delayed transit of tracer and 2 illustrated dermal backflow. One-half of individuals also had primary lower extremity lymphedema (six unilateral and six bilateral). None of the patients in the cohort exhibited a family history of lymphedema. Two individuals had Turner syndrome. Morbidity included infection (n=5), other lymphatic anomalies (n=6), and lymphangiosarcoma (n=1).

Conclusions: The upper extremities are a rare location for primary lymphedema and patients often also have lymphedema of the legs. Compared with that of the lower extremities, primary disease of the arm is more likely to be associated with systemic lymphatic dysfunction and has a lower risk of familial transmission.

Main findings

  • Eleven subjects were male. Age of onsetwas infancy (n=15), adolescence (n=5), or adulthood (n=3). The disease affected the left arm (n=11), right arm (n=9), or both upper extremities (n=3).
  • Increased volume was mild (n=10), moderate (n=4), and severe (n=9).
  • Twelve subjects did not have tracer uptake into the axillary nodes at the completion of the study 4 hours after injection of the radiolabeled colloid into the hands. Twelve individuals exhibited primary lower extremity lymphedema (6 unilateral, 6 bilateral), and 2 of these had Turner syndrome . None of the patients in the study had a family history of lymphedema. Six individuals (26%) exhibited systemic lymphatic anomalies that included gastrointestinal lymphangiectasia, pleural effusions, chylous ascities, microcystic lymphatic malformation of the face, and/or bone and spleen lesions. Five patients experienced an infection and one developed lymphangiosarcoma.
  • The risk of lymphangiosarcoma might be greater in primary upper extremity lymphedema compared with lower extremity lymphedema.
  • Thirteen percent of our cohort exhibited dermal backflow by lymphoscintigraphy compared with 31% of patients with primary lower extremity lymphedema.
  • Patients with primary arm lymphedema might have a different pattern of underlying lymphatic structural anomalies. Proximal transit of lymphatic fluid against less gravitational force compared with the leg also might influence the presence of dermal backflow.
  • Two mutations have been associated with primary arm lymphedema in combination with lower extremity disease and other abnormalities (GJC2 and CCBE1). Patients with Turner syndrome have an *50% risk of lymphedema that typically presents in infancy and usually involves all four limbs.
  • Because primary upper extremity lymphedema is so rare, we advocate for lymphoscintigraphy to confirm the disease.
  • A patient with a high suspicion of arm lymphedema who has a normal lymphoscintigram should have the test repeated 1 year later because a latency period can exist until the study shows abnormalities.