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Using Lymphoscintigraphy to Evaluate Suspected Lymphedema of the Extremities

¹ Department of Radiology, Winthrop University Hospital, 259 First St., Mineola, NY 11501.
² Lymphedema Therapy, 77 Froehlich Farm Blvd., Woodbury, NY 11797.

Received June 15, 2001; accepted after revision July 30, 2001.

Presented at the annual meeting of the American Roentgen Ray Society, Seattle, April 2001.

Address correspondence to D. S. Katz.

Lymphedema is the painless progressive accumulation of protein-rich fluid in the interstitial spaces of the skin, resulting from an anatomic or functional obstruction of the lymphatic system [1]. Lymphedema of the lower or upper extremities is typically a chronic condition that has several possible causes and that presents considerable physical as well as psychological difficulties for patients [2]. Patients with lymphedema experience extremity swelling, decreased coordination and mobility, and secondary infections [2]. The disorder typically affects the dermis and spares the deeper compartments [3]. At the initial medical evaluation of patients with suspected extremity lymphedema, it is highly desirable for physicians to define the abnormality; to determine whether the suspected abnormality is, in fact, a lymphatic one (Figs. 1A,1B and 2A,2B) before instituting a therapeutic plan; and to establish an objective baseline [3]. The differential diagnosis of suspected extremity lymphedema includes obesity, venous disease, and systemic disease (e.g., hypoalbuminemia) [2]. Lymphoscintigraphy is now the primary imaging modality used in determining a diagnosis in patients with suspected extremity lymphedema. The technique has been refined over the past few decades and has proved reliable and reproducible [2]. The study is noninvasive with no known adverse effects. In addition, the radiation dose received during the examination is low, and the study can be repeated after therapy [3].

View larger version (47K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —37-year-old man who presented with bilateral leg edema for several years after bicycle crash but had normal findings on lymphoscintigraphy. Anterior lymphoscintigrams obtained 1 hr (A) and 3 hr (B) after injection of radionuclide show no abnormalities. Note that two main lymphatic trunks (closed arrows, A) in both calves and both thighs and ilioinguinal lymph nodes are symmetric. Artifacts (open arrows, A) related to scatter at injection sites in both feet are present. Cardiac, renal, and bladder uptake seen on B is due to free pertechnetate.

View larger version (32K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —37-year-old man who presented with bilateral leg edema for several years after bicycle crash but had normal findings on lymphoscintigraphy. Anterior lymphoscintigrams obtained 1 hr (A) and 3 hr (B) after injection of radionuclide show no abnormalities. Note that two main lymphatic trunks (closed arrows, A) in both calves and both thighs and ilioinguinal lymph nodes are symmetric. Artifacts (open arrows, A) related to scatter at injection sites in both feet are present. Cardiac, renal, and bladder uptake seen on B is due to free pertechnetate.

View larger version (10K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —55-year-old woman with clinically suspected lymphocele in right axilla and edema in right upper extremity but with normal findings on lymphoscintigraphy. Early lymphoscintigram of upper extremities obtained 10 min after injection of radionuclide, with patient's shoulders at top of image, shows rapid lymphatic drainage. A = level of axillae, E = level of elbows, RT = right side, LT = left side.

View larger version (45K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —55-year-old woman with clinically suspected lymphocele in right axilla and edema in right upper extremity but with normal findings on lymphoscintigraphy. Delayed lymphoscintigram of both axillary regions and upper thorax shows normal bilateral axillary lymph nodes (arrows). Note absence of lymphocele or any other abnormality.

Classification of Lymphedema

Various clinical classification systems have been developed to describe the severity of extremity lymphedema [2]. One system [4] classifies lymphedema as stage 1, 2, or 3. Stage 1 is reversible lymphedema, with pitting edema and swelling that decreases when the limb is elevated, and stage 2 is nonpitting edema that does not decrease when the limb is elevated. Stage 3 is lymphostatic elephantiasis, with a huge increase in size of the limb and hardened skin.

Primary lymphedema (Figs. 3,4A,4B,5A,5B,5C,5D,5E) can be a nonhereditary or a genetic condition; can be unilateral or bilateral; and may present at birth, at puberty, or in adulthood [3]. The onset of edema is usually spontaneous—without a history of trauma, surgery, or radiation therapy [2]—and most often occurs in patients before the ages 30 or 35 years; the lower limbs are more often and more severely affected than the upper extremities [2, 3]. The nonfamilial form is much more common than the familial form. Secondary lymphedema (Figs. 6,7,8,9A,9B,10,11), which is much more common than primary lymphedema, may be caused by therapy for cancer, particularly axillary lymph node dissection and radiation therapy for breast cancer, as well as regional lymph node dissection for melanoma and pelvic lymph node dissection [2, 3]. The disorder can present months or years after the initial injury, and its origin is complex [3]. In the developing world, filariasis and other infections are common causes of secondary lymphedema [3]. In some cases, it may not be possible to categorize patients as having either primary or secondary lymphedema, either by history or by lymphoscintigraphy (Figs. 12A,12B,13,14A,14B,14C,14D). Both primary and secondary lymphedema can progress to chronic inflammation and irreversible perilymphatic fibrosis [1].

View larger version (29K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3. —34-year-old man with recurrent left foot and leg swelling and multiple episodes of left leg cellulitis. Anterior lymphoscintigram obtained 3 hr after injection of radionuclide reveals markedly delayed and diminished flow in left leg, with no lymphatic trunks or clinically relevant collaterals visualized. Note absence of radionuclide uptake in expected location of left ilioinguinal lymph nodes (thick arrow), compared with uptake on right side (thin arrow). Findings are consistent with aplasia of lymphatic vessels in left leg and primary lymphedema. LT = left side of body.

View larger version (29K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A. —64-year-old woman who has had bilateral lower extremity swelling for 42 years (worse on left), consistent with primary lymphedema. Anterior lymphoscintigram of lower extremities obtained 1 hr after injection of radionuclide shows little lymphatic drainage. Upper marker indicates location of groin, and lower marker indicates knee.

View larger version (27K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B. —64-year-old woman who has had bilateral lower extremity swelling for 42 years (worse on left), consistent with primary lymphedema. Lymphoscintigram obtained 3.5 hr after injection of radionuclide reveals few lymphatic channels bilaterally and marked dermal backflow (arrows) in lower calves.

View larger version (39K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A. —30-year-old man with primary lower extremity lymphedema and Prader-Willi syndrome. Lymphoscintigram obtained 45 min after injection of radionuclide shows multiple large and tortuous lymphatic channels with multiple additional lymphatic vessels in thighs and calves. Increased numbers of bilateral ilioinguinal lymph nodes (small arrows) as well as megalymphatics (large arrows) in right calf both medially and laterally are visible.

View larger version (33K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B. —30-year-old man with primary lower extremity lymphedema and Prader-Willi syndrome. Anterior lymphoscintigram obtained 2.5 hr after injection of radionuclide shows prominent number of fine collateral lymphatic channels (open arrow) and left dermal backflow (solid arrow).

View larger version (34K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5C. —30-year-old man with primary lower extremity lymphedema and Prader-Willi syndrome. Spot posterior lymphoscintigram obtained 3.5 hr after injection of radionuclide shows improved visualization of right collateral channels and subtle left dermal backflow (arrows). Dermal backflow is secondary effect of poor lymphatic transport. Round marker in left upper corner of image indicates level of knees. RT = right side, LT = left side.

View larger version (146K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5D. —30-year-old man with primary lower extremity lymphedema and Prader-Willi syndrome. Photographs of legs before (D) and after (E) complex lymphedema therapy. Note improvement, particularly at ankles.

View larger version (147K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5E. —30-year-old man with primary lower extremity lymphedema and Prader-Willi syndrome. Photographs of legs before (D) and after (E) complex lymphedema therapy. Note improvement, particularly at ankles.

View larger version (55K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6. —58-year-old man with left leg edema after prostate and bilateral pelvic lymph node resection. Anterior lymphoscintigram obtained 95 min after injection of radionuclide shows delayed left lower extremity lymphatic drainage with decreased left ilioinguinal lymph nodes (large arrow). Collateral lymphatic trunks are seen in left thigh and calf (small arrows). Same findings were present on image obtained 4 hr after injection (not shown).

View larger version (109K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7. —72-year-old man with secondary lymphedema in left leg after fall that injured leg several months earlier. Anterior spot lymphoscintigram of both calves obtained 3.5 hr after injection of radionuclide shows decreased number of lymphatic channels in left calf (large arrows), with associated dermal backflow (small arrows). K = level of knees, A = level of ankles, RT = right side, LT = left side.

View larger version (41K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8. —53-year-old man who fractured right ankle 1 year earlier presented with right leg swelling. Anterior lymphoscintigram obtained 3.25 hr after injection of radionuclide shows normal left lower extremity but dermal backflow (solid arrows) in right calf. Note increased number of right-sided ilioinguinal lymph nodes (open arrows) of uncertain importance.

View larger version (130K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9A. —71-year-old woman with right lower extremity edema and history of substantial injury to right knee. Anterior lymphoscintigram (composite transmission and emission image) of both calves obtained 25 min after injection of radionuclide reveals normal left leg and focal collection (arrow) in right medial calf representing lymphocele.

View larger version (52K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9B. —71-year-old woman with right lower extremity edema and history of substantial injury to right knee. Lymphoscintigram obtained 4.5 hr after injection of radionuclide reveals marked dermal backflow (arrow) in right calf, which hides focal collection visible on earlier image. Note markedly delayed lymphatic drainage in right calf.

View larger version (63K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10. —55-year-old woman who has experienced right arm edema for 1 year after removal of recurrent right axillary cysts and abscesses. Image was acquired with patient's outstretched arms placed on rectangular view camera. Early lymphoscintigram of arms shows delayed lymphatic drainage in right arm, with fewer lymph nodes in right (open arrow) than in left axilla (solid arrow) and collateral channels at level of right elbow, consistent with secondary lymphedema. Dashed arrows indicate elbow markers.

View larger version (102K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11. —66-year-old man with history of swelling in left arm after removal of left forearm melanoma and left axillary lymph node dissection. Lymphoscintigram of arms obtained 50 min after injection of radionuclide shows rapid lymphatic drainage of both forearms but decreased number of left axillary lymph nodes (small arrow) and multiple focal collections (large arrow) in left upper arm, consistent with dilated lymphatics. Findings are consistent with left axillary level obstruction from previous lymph node dissection. H = level of hands, E = level of elbows, A = level of axillae, RT = right side, LT = left side.

View larger version (98K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 12A. —43-year-old woman with history of extensive travel to numerous developing countries evaluated for suspected lymphedema. Results of multiple examinations for infection—including filarial disease—were negative. Photograph of patient shows massive swelling in both thighs.

View larger version (68K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 12B. —43-year-old woman with history of extensive travel to numerous developing countries evaluated for suspected lymphedema. Results of multiple examinations for infection—including filarial disease—were negative. Lymphoscintigram of lower extremities shows dermal backflow (arrow) in right calf, with otherwise prompt lymphatic drainage in both legs. No right lymphocele or other right thigh lymphatic abnormality is revealed. Left leg is unremarkable. Findings are consistent with obesity ("lipedema") with relatively minor lymphatic abnormality in right calf unrelated to obesity.

View larger version (56K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 13. —41-year-old woman who had lymphangioma removed from left thigh at birth and who presented with new soft-tissue mass in left anterior thigh and edema of left lower extremity. Delayed lymphoscintigram of lower extremities reveals no lymphocele or dermal backflow but does show fewer ilioinguinal lymph nodes (arrow) on left side than on right. Latter finding may be residual effect of prior surgery, normal variant, or related to low flow obstruction.

View larger version (116K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 14A. —44-year-old man who had bilateral lower extremity edema below the waist for 1 year without history of surgery or trauma. Abdominal and pelvic lymphadenopathy identified on CT was biopsied and was negative for malignancy. Cause of findings is unknown. Early anterior lymphoscintigrams of calves (A) and knees (B) show fine lymphatic collaterals (arrows), especially in left leg. R = right side, L = left side.

View larger version (105K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 14B. —44-year-old man who had bilateral lower extremity edema below the waist for 1 year without history of surgery or trauma. Abdominal and pelvic lymphadenopathy identified on CT was biopsied and was negative for malignancy. Cause of findings is unknown. Early anterior lymphoscintigrams of calves (A) and knees (B) show fine lymphatic collaterals (arrows), especially in left leg. R = right side, L = left side.

View larger version (59K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 14C. —44-year-old man who had bilateral lower extremity edema below the waist for 1 year without history of surgery or trauma. Abdominal and pelvic lymphadenopathy identified on CT was biopsied and was negative for malignancy. Cause of findings is unknown. Lymphoscintigram obtained 45 min after injection of radionuclide shows lymphocele or megalymphatic vessel (large arrow) in right calf, diffuse bilateral dermal backflow (small arrows), and early filling (open arrow) of abnormal structures in abdomen and pelvis, consistent with small lymph nodes and abnormal lymph vessels in mesentery.

View larger version (50K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 14D. —44-year-old man who had bilateral lower extremity edema below the waist for 1 year without history of surgery or trauma. Abdominal and pelvic lymphadenopathy identified on CT was biopsied and was negative for malignancy. Cause of findings is unknown. Lymphoscintigram obtained 3.5 hr after injection of radionuclide shows diffuse bilateral dermal backflow and extravasation (small arrows) from lymphatic channels. Abnormal structures (large arrows) in abdomen and pelvis are accentuated and are also seen in thorax (open arrow).

Technique of Lymphoscintigraphy

In the most common method used to perform lymphoscintigraphy of the extremities, 74-296 MBq of millipore-filtered ^99mTc sulfur colloid suspended in 0.10 mL of saline is injected into the interdigital web spaces between the first and second digits on the patient's right and left lower (or upper) extremities, creating a wheal. Both of the feet (or hands) are massaged for 2 min immediately after the injection. A high-resolution collimator is always used, the camera speed is set at 8 cm/min, and images of at least 300,000 counts are acquired. A flow study is performed, and the arrival of radionuclide delivery to the knees and groin (or to the elbows and axillary regions for the arms) is timed. Spot and whole-body images are obtained for up to 3-4 hr; the study is also tailored to the need for individual findings.

Findings on Lymphoscintigraphy

In patients with normal lymphatic anatomy and function (Figs. 1A,1B and 2A,2B), a predictable sequence should be seen on lymphoscintigraphy. In the lower extremities, symmetric migration of the radionuclide should be seen through discrete lymph vessels (three to five lymph vessels per calf and one to two per thigh). Then bilateral visualization of ilioinguinal lymph nodes should occur within 1 hr, as should visualization of the liver because of the systemic circulation of the radiocolloid [1]. Typically, approximately one to three popliteal nodes and two to 10 ilioinguinal nodes are visualized [5]. A parallel sequence should be seen in the upper extremities.

On lymphoscintigrams with abnormal findings, a variety of findings can be identified (Figs. 3,4A,4B,5A,5B,5C,5D,5E,6,7,8,9A,9B,10,11,12A,12B,13,14A,14B,14C,14D), including interruption of lymphatic flow, collateral lymph vessels, dermal backflow, delayed flow, delayed visualization or nonvisualization of lymph nodes, a reduced number of lymph nodes, dilated lymphatics, and in severe cases, no visualization of the lymphatic system at all [1, 5]. Purely qualitative analysis has been reported to be very accurate for confirming or excluding the diagnosis of lymphedema, with a sensitivity as high as 92% and a specificity as high as 100% [1].

Despite earlier reports, most authorities believe that primary lymphedema cannot be reliably differentiated from secondary lymphedema on the basis of lymphoscintigraphic findings alone [1, 5]. Some authors have reported that lymphoscintigrams of patients with primary lymphedema tend to show a lack of lymphatic vessels and absent or delayed transport, whereas those of patients with secondary lymphedema tend to show obstruction with visualization of discrete lymphatic trunks and slow transport [3]. In both primary and secondary lymphedema, however, both dermal backflow and a decreased number of lymph nodes can be identified [3].

Therapy for Lymphedema and Role of Scintigraphic Follow-Up

Lymphedema is a chronic condition that is notoriously difficult to treat and that has no known curative therapy. Surgical procedures have been attempted, but none have proven to be particularly successful [2]. At present, the most successful conservative therapy is a 4-6 week regime known as complex lymphedema therapy [6,7,8]. This labor-intensive therapy requires as many as 4 hr per day [4, 6, 7] (Figs. 5D and 5E). In a report by Boris et al. [7], 30 patients whose progress was followed up for as long as 1 year after complex lymphedema therapy had an average 86% decrease in their initial extremity volume. Lymphoscintigraphy can be repeated after therapy to provide an objective measure of the disease status in patients [3, 4, 8].

References

1. Ter SE, Alavi A, Kim CK, Merli G. Lymphoscintigraphy: a reliable test for the diagnosis of lymphedema. Clin Nucl Med 1993;18:646 -654[Medline]
2. Szuba A, Rockson SG. Lymphedema: classification, diagnosis, and therapy. Vasc Med 1998;3:145 -156[Abstract/Free Full Text]
3. Williams WH, Witte CL, Witte MH, McNeill GC. Radionuclide lymphangioscintigraphy in the evaluation of peripheral lymphedema. Clin Nucl Med 2000;25:451 -464[Medline]
4. Foldi E, Foldi M, Weissleder H. Conservative therapy of lymphedema of the limbs. Angiology 1985;36:171 -180
5. Weissleder H, Weissleder R. Lymphedema: evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients. Radiology 1988;167:729 -735[Abstract/Free Full Text]
6. Casley-Smith JR, Foldi M, Ryan TJ, et al. Summary of the 10th International Congress of Lymphology: working group discussions and recommendations. Lymphology 1985;18:175 -180
7. Boris M, Weindorf S, Lasinski B, Boris G. Lymphedema reduction by noninvasive complexlymphedema therapy. Oncology 1994;8:95 -106[Medline]
8. Hwang JH, Kwon JY, Lee KW, et al. Changes in lymphatic function after complex physical therapy for lymphedema. Lymphology 1999;32:15 -21[Medline]

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This Article Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moshiri, M. Articles by Yung, E. Search for Related Content PubMed PubMed Citation Articles by Moshiri, M. Articles by Yung, E. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?