Joint Program in Nuclear Medicine

Lymphedema

Jac D. Scheiner, MD
Annick Van den Abbeele, MD

February 21, 1996

Presentation

A 47 y.o. female, status post radiation therapy for pelvic tumor, presented with left lower extremity swelling.

Imaging Technique

Imaging technique depends upon the study indication.

Evaluation of extremity lymphedema -
- 0.05 cc injections of Tc-99m Sulfur Colloid (0.22 micrometer filtered, 0.5 mCi per injection) are performed intradermally. 2 injections are performed on the dorsum of the foot or hand. Injection of the contralateral extremity provides a useful comparison.
- Patient ambulates (~ 2 flights of stairs) to aid lymphatic return.
- For lower extremity lymphoscintigraphy, sweeps are performed, leaving the injection sites just out of the field of view, up through the chest, in anterior and posterior projections, at a rate of 8 cm per minute.
- Full body sweep images are obtained every 30 minutes x three, followed by another set of images at three hours, and then as needed.
- The end point of a normal exam occurs when the clinical question is answered and the liver is visualized.
Evaluation of lymphatic spread from truncal melanoma or breast cancer-
- 0.05 cc injections of Tc-99m Sulfur Colloid (total dose = 1 - 4 mCi) are performed intradermally. 4-8 injections are made around the melanoma site.
- Image field includes all possible drainage pathways. Acquire dynamic images at 1 minute per frame until lymph nodes in the drainage area are visualized. Static images are then performed until changes in the lymphatic drainage pattern are no longer seen.
Internal Mammary Lymphoscintigraphy (IMLS) (8):
- 0.5 to 1.0 mCi of Tc-99m SC is injected in a volume of 0.1 to 0.2 cc. Injection is performed with patient supine, ~3 cm inferior to xiphoid process and 1-2 cm medial to the mid-clavicular line on the relevant side. A 1.0 cc tuberculin syringe is used, with a 22 gauge, 1.5 inch needle. The injection should be deposited just anterior to the posterior rectus sheath (depth of ~ 2 cm).
- Imaging is performed with the patient supine, after a 3 hour delay. Using a parallel hole, low energy, all purpose collimator, the following 100,000 count images of the chest are obtained:
  - Sternal notch is delineated by a cobalt-57 (Co-57) marker, and the most superior aspect of the injection site is at the inferior edge of the image.
  - Sternal notch, mid-sternum, and xiphoid are delineated by Co-57 markers.
  - The costochondral junctions of the first five ribs are delineated by Co-57 markers.
- For 3-dimensional imaging (to determine lymph node depth), a 30 degree slant hole collimator is used, positioned horizontally above the patient. The field of view includes the internal mammary lymph nodes (IMLNs), as well as Co-57 markers delineating the sternal notch, mid-sternum, and xiphoid.
  - Two 100,000 count images are obtained with the collimator rotated 180 degrees between images.
  - Distance scaling from the resulting image to a digitizer tablet is provided via an image obtained with four Co-57 markers placed at the corners of a 10-cm square.
  - IMLS images are digitized and the three dimensional coordinates are obtained. The depth of a visualized lymph node from the camera face = R/tan (30 degrees), where R = one half the distance between the same node on the two images.

Imaging Findings

A cutaneous 'flare' of tracer activity ascends the left lower extremity (shown by arrows: large arrow = femoral lymph node, small arrows = cutaneous flare). Tracer was not visualized superior to the inguinal region. A single femoral lymph node is identified, although the major pelvic lymph nodes are not seen. Other images (not provided) failed to visualize the liver.

Differential Diagnosis

The cutaneous flare is diagnostic of lymphedema on lymphoscintigraphy. The most likely etiology in this case is a band of fibrosis in the pelvis/inguinal region (induced by the radiation therapy) which occludes lymphatic return. Other etiologies of lymphedema include intralumenal causes, such as lymphadenopathy secondary to tumor or infection, extralumenal causes, such as extrinsic compression of lymphatic vessels by surrounding edema and other masses, and states in which there is a paucity of lymphatic vessels (either congenital or due to surgical resection).

Diagnosis

Lymphedema secondary to obstruction by radiation induced fibrosis.

Discussion

Lymphoscintigraphy (LS) provides a relatively noninvasive, cost effective, highly sensitive method to assess abnormalities of lymphatic drainage and lymphatic drainage patterns of tumors. Among the most common indications of lymphoscintigraphy are the evaluation of lymphedema (1,2) and mapping lymphatic spread of truncal melanoma (3) and breast cancer (4). Lymphoscintigraphy has also been used in the work-up of lymphangiomas, lymphoceles (5), chylous ascites (6), and other chylous leaks. It has also been useful in assessing lymphatic drainage before and after reconstructive and plastic surgery(7 ).

Interpretation:

A normal study should demonstrate the expected major lymphatic vessels and lymph node groups draining the injected site, followed by visualization of the liver (annotated). Lymphatic vessels drain into the thoracic duct, which drains into the left subclavian vein. Visualization of the liver confirms patent communication of the lymphatic system with the venous system.

Lymphedema typically manifests as a 'veil' of tracer activity1 on delayed views which ascends the injected extremity. It may be accompanied by a paucity of visualized draining lymph nodes. If it appears that tracer has failed to migrate from the injection site, the dermal layer (which contains the majority of the lymphatic tissue) may not have been injected. If an epidermal or subdermal injection is suspected, the exam should be repeated.

Etiology:

Generally, extremity edema has three main etiologies:

low plasma osmotic pressure (usually seen in cases of kidney or liver failure, but also seen associated with inflammation and associated increased vascular permeability),
obstruction of venous return (with etiologies ranging from heart failure to venous thrombus), and
obstruction of lymphatic return (9).

Some of the more commonly encountered causes of impaired lymphatic return include congenital deficiency of lymphatic vessels, luminal obstruction by lymphadenopathy (due to tumor or infection), and compression of the lymphatic vessel lumen via fibrosis (i.e. radiation therapy) or edema (often venous in etiology) in the surrounding tissues (10).

Indications:

Lymphedema:

Lymphoscintigraphy has emerged as the diagnostic study of choice to evaluate for the presence of lymphedema. Whereas conventional lymphangiography better demonstrates lymph vessel morphology, lymphoscintigraphy can readily demonstrate the presence of lymphedema, the location of major nodal groups, and lymphatic drainage patterns at a lower price and with less toxicity and radiation exposure to the patient. Also, lymphangiography is technically more difficult to perform, provides little functional information, and may have significant side effects (including local tissue necrosis, contrast reaction, and exacerbation of lymphedema) (1,2).

A study of 17 patients (20 extremities) referred for lymphedema resulted in 8 true positive, 9 true negative, 0 false positive, and 3 false negative extremity images; the 3 false negatives were not imaged within the first hour, decreasing the sensitivity for detecting subtle pedal lymphedema and cross-over filling of major lymph nodes (1). Another study, of 115 patients (190 extremities) referred for the evaluation of extremity edema, showed lymphoscintigraphy to be 92% sensitive and 100% specific for the diagnosis of lymphedema (11). The treatment of lymphedema includes encouraging high quality skin hygiene and prophylactic antibiotics (these limbs are at higher risk for infection), along with physical activity, extremity elevation, and compressive hose to enhance lymphatic return. If these efforts fail to alleviate the symptoms, and the underlying etiology of the impaired lymphatic drainage is not readily correctable, microsurgical anastomosis of lymphatic vessels to veins can be performed to aid lymphatic return (12).

Lymphatic Drainage of Tumors:

Another important use of lymphoscintigraphy is to access the lymphatic drainage patterns of tumors. When combined with a blue dye solution or an intraoperative gamma probe (13), the vascular surgeon is aided in resecting the pertinent draining lymph nodes, while sparing the patient unnecessary lymphatic dissection and its associated morbidity. It is not uncommon for lymph node drainage to occur in unexpected patterns. In a study in which lymphoscintigraphy was performed in 212 patients with primary cutaneous melanoma of the head, neck, or trunk, showed drainage patterns which were not expected by historical anatomic guidelines in 63% of patients with head and neck melanoma, and 32% of patients with truncal melanoma (14). This changed operative intervention in 47% of patients. Also, as a result of the lymphoscintigraphy findings, 28% did not undergo node dissection. No recurrence has been noted in lymph nodes not positive by LS during a 2.8 year follow-up. In another study, in which LS was performed on 34 patients with suspected breast cancer, lymphatic drainage from the tumor region crossed the center line of the breast in 32% (15). As a result of these and other studies, lymphoscintigraphy has proven to be an extremely useful imaging modality in the work-up of patients being considered for lymph node dissection.

Placement of Radiation Ports:

Lymphoscintigraphy has also been used to guide radiation oncologists in the placement of radiation ports. As a result of autopsy measurements, radiation therapists had often assumed that IMLNs are located, at most, 3 cm deep and 3 cm lateral to the midline (16). However, a prospective study examining normal IMLS performed in 167 patients (768 nodes) showed that 14% of IMLN chains cross-communicated with the IMLN on the other side, and approximately 4% of IMLNs were deeper than 3 cm (8). A conventional tangential field would have missed at least one IMLN in 16% of patients. By mapping the IMLN chain with LS, only the pertinent lymphatic vessels are included in the field, and tissue that does not contain pertinent lymphatic vessels may be excluded.

Involvement with Tumor:

Lymphoscintigraphy has also proven to be one of the most sensitive methods of detecting lymph node involvement with tumor, even before the intralymphatic tumor has grown to demonstrate a significant size on CT or MRI. A study in which lymphoscintigraphy was performed in 209 patients with high-risk truncal melanoma showed lymphoscintigraphy to be 94% sensitive in detecting draining sites which contained metastases (3). When taking into account node palpability, the sensitivity rose to 98%. The extremely high sensitivity of LS for lymphadenopathy makes this test extremely useful in cancer staging, especially in light of a recent study of 40 women with breast cancer which showed 22 cases of ipsilateral internal mammary lymph node involvement in which there was not significant (diameter greater than 1 cm) lymph node enlargement on CT or MRI (4).

In summary, lymphoscintigraphy provides a sensitive method of investigating many disease processes.

References

1. Ter Se, Alavi A, Kim CK, Merli G. Lymphoscintigraphy. A reliable test for the diagnosis of lymphedema. Clinical Nuclear Medicine 1993;18:646-654.

2. Golueke PJ, Montgomery RA, Minken SL, Perler BA, Williams GM. Lymphoscintigraphy to confirm the clinical diagnosis of lymphedema. J Vasc Surg 1989;10:306-312.

3. Uren RF, Howman-Giles RB, Shaw HM, Thompson JF, McCarthy WH. Lymphoscintigraphy in high risk melanoma of the trunk: predicting draining node groups, defining lymphatic channels and locating the sentinel node. J Nucl Med 1993;34:1435-1440.

4. Turoglu HT, Janjan NA, Thorsen MK, et al. Imaging of regional spread of breast cancer by internal mammary lymphoscintigraphy, CT, and MRI. Clinical Nuclear Medicine 1992;17:482-484.

5. Wells RG, Ruskin JA, Sty JR. Lymphoscintigraphy Lower Extremity Lymphangioma. Clin Nucl Med 1986;11:523.

6. Gregg DC, Wells RG, Sty JR. Lymphoscintigraphy Chylous Ascites and Lymphocele Demonstration. Clin Nucl Med 1988;13: 300.

7. Slavin SA, Upton J, Kaplan WD, Van den Abbeele A. An investigation of lymphatic function following free tissue transfer. (in press)

8. Kaplan WD, Andersen JW, Siddon RL, et al. The Three-Dimensional Localization of Internal Mammary Lymph Nodes by Radionuclide Lymphoscintigraphy. J Nucl Med 1988;29:473-478.

9. Robbins SL, Cotran RS: Pathologic Basis of Disease. Philadelphia, W.B. Saunders Company,1979, pp.109-110.

10. Bull RH, Gane JN, Evans JE, Joseph AE, Mortimer PS. Abnormal lymph drainage in patients with chronic venous leg ulcers. Journal of the American Academy of Dermatology 1993;28:585-590.

11. Gloviczki P, Calcagno D, Schirger A, et al. Noninvasive evaluation of the swollen extremity: experiences with 190 lymphoscintigraphy examinations. J Vasc Surg 1989;9:683-689.

12. Browse NL. The diagnosis and management of primary lymphedema. J Vasc Surg 1986;3:181.

13. Alazraki N. Lymphoscintigraphy and the Intraoperative Gamma Probe. J Nucl Med 1995;36:1780-1783 [editorial].

14. Norman J, Wells K, Kearny R, Cruse CW, Berman C, Reintgen D. Identification of lymphatic drainage basins in patients with cutaneous melanoma. Seminars in Surgical Oncology 1993;9:224-227.

15. Uren RF, Howman-Giles RB, Thompson JF, et al. Mammary Lymphoscintigraphy in Breast Cancer. J Nucl Med 1995;36:1775-1780.

16. Lindskoug B, Hultborn A. Tissue heterogeneity in the anterior chest wall and its influence on radiation therapy of the internal mammary lymph nodes. Acta Radiol Ther 1976;15:97-116.

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J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu