(Radiographics. 1999;19:343-356.)
© RSNA, 1999
Use of Sentinel Node Lymphoscintigraphy in Malignant Melanoma
Anthony P. Yudd, MD, PhD1,
Jeffrey S. Kempf, MD1,
James S. Goydos, MD2,
Theodore J. Stahl, MD1 and
Richard S. Feinstein, MD1
1 Department of Radiology, MEB 404, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Pl, New Brunswick, NJ 08903 (A.P.Y., J.S.K., T.J.S., R.S.F.)
2 Department of Surgery, Cancer Institute of New Jersey, New Brunswick (J.S.G.)
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Abstract
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Lymphoscintigraphy is a sensitive, inexpensive, relatively noninvasive method of identifying lymphatic drainage patterns and sentinel lymph nodes in patients with malignant melanoma. Lymphoscintigraphy with filtered technetium-99m sulfur colloid allows prompt visualization of the lymphatic system, produces high-quality images, and delivers a low radiation dose to the patient. In addition, good regional lymph node retention is seen with filtered Tc-99m sulfur colloid, improving the success rate of intraoperative gamma probe localization. In combination with surgical localization, lymphoscintigraphy allows preoperative and intraoperative identification of the sentinel node in patients with intermediate thickness melanomatous lesions, obviating radical lymph node dissection in most patients and possibly prolonging their survival. Variables such as tumor location, type and preparation of radiopharmaceutical, injection technique, imaging technique, and prior surgical intervention influence the efficacy of lymphoscintigraphy. Nevertheless, lymphoscintigraphy is recommended as a cost-effective preoperative procedure in all patients planning to undergo elective lymph node dissection. Because of the unpredictability of lymphatic drainage, preoperative scintigraphic findings may lead to changes in surgical management.
Index Terms: Lymphatic system, neoplasms, 99.8332 • Lymphatic system, radionuclide studies, 99.12974 • Melanoma, 99.8332 • Radionuclide imaging, in diagnosis of neoplasms, 99.12974 • Skin, neoplasms, 40.83
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INTRODUCTION
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Cutaneous melanoma is a malignant transformation of melanocytes that has the potential for dermal invasion and distant metastasis. There are approximately 40,000 new cases of cutaneous melanoma annually, and it has been estimated that the disease was responsible for approximately 7,300 deaths in the United States in 1998 (1). Melanoma represents 3% of all new cancers (1), and its incidence is increasing at a rate of approximately 4%–6% annually, faster than any other malignancy (2). It is estimated that in the year 2000, the chances of developing invasive melanoma during one's lifetime will be about one in 75 (2).
Primary cutaneous melanoma can be classified into five clinicohistologic groups: superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, acral-lentiginous melanoma, and subungual melanoma.
Superficial spreading melanoma is seen in younger patients. It is commonly found on the upper back in both sexes and often on the legs in females. Superficial spreading melanoma often has regular contours and ranges from tan to black, sometimes interspersed with characteristic red, white, and black hues. It represents approximately 70% of all melanomas.
Nodular melanoma manifests as a nodule or plaque without the classic radial growth pattern seen in other types of melanoma. It is always invasive from the outset, is usually 1–2 cm in diameter at presentation, and has a worse overall prognosis than the other melanoma subtypes. Nodular melanoma represents approximately 15%–30% of all melanomas.
Lentigo maligna melanoma is often seen in older patients. It begins as a small, tan, macular precancerous lesion, typically on sun-exposed skin, and usually undergoes radial growth over a 5–15-year period. Eventually the lesion enters a vertical growth phase with dermal invasion and takes on a papillonodular appearance. Lentigo maligna melanoma represents approximately 4%–10% of all melanomas, and affected patients have the highest overall survival rate.
Acral-lentiginous melanoma occurs on the palms, soles, and terminal phalanges, characteristically with a radial growth pattern with potential for invasive growth. Acral-lentiginous melanoma is usually seen in older patients and represents approximately 2%–8% of all melanomas in white patients and 35%–90% in dark-skinned patients.
Subungual melanoma involves the great toe or thumb in 75% of cases. This lesion usually manifests as a brown to black discoloration of the nail bed but may be nonpigmented. The nail plate may become detached from the nail bed. Subungual melanoma represents 2%–3% of all melanomas in white patients and has a higher prevalence in dark-skinned patients.
In this article, we discuss and illustrate the use of lymphoscintigraphy in the detection of lymphatic drainage patterns and localization of the sentinel nodes (ie, the first draining lymph nodes in each draining lymphatic basin) in patients with intermediate thickness malignant melanomatous lesions. Particular attention is given to radiopharmaceuticals and their preparation, injection techniques, and imaging guidelines, along with potential pitfalls and suggested means of avoiding them.
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STAGING AND PROGNOSTIC FACTORS
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The Breslow classification scheme for tumor staging divides lesions into four groups according to depth of tumor invasion (<0.75 mm, 0.76–1.5 mm, 1.51–2.25 mm, 2.26–3.0 mm, >3 mm) (3). A simpler but more commonly used classification scheme based on Breslow tumor depth analysis describes lesions as thin (<1 mm), intermediate thickness (1–4 mm), or thick (>4 mm) (3). The Clarke scheme (Clarke level) classifies tumors on the basis of extent of dermal invasion: level I, intraepidermal malignancy; level II, invasion of papillary dermis; level III, occupying the entire papillary dermis but not involving the reticular dermis; level IV, extending into the reticular dermis; and level V, involving the subcutaneous tissues (3).
The current staging system for cutaneous melanoma was put forth by the American Joint Committee on Cancer in 1988 and classifies patients according to tumor thickness (Breslow), level of dermal invasion (Clarke), and the presence of regional or distant metastases. Tumor thickness takes precedence over level of dermal invasion; however, the latter is used if tumor thickness is unknown (3). Primary tumor thickness is one of the most important prognostic factors in melanoma (Table). It is well known that patients with thin lesions (<1 mm) almost always have local disease only, whereas patients with thick lesions (>4 mm) have an approximately 60% risk for regional metastasis and a 70%–80% risk for distant metastasis within 3 years. Additional prognostic factors include the presence of regional lymph node involvement at clinical presentation. In general, truncal lesions have the worst prognosis, followed by head lesions and extremity lesions. Ulceration, high ploidy status, and male sex are additional poor prognostic factors.
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LYMPHOSCINTIGRAPHY AND THE SENTINEL NODE
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Metastatic melanoma characteristically disseminates in an orderly progression through lymphatic channels to the regional lymph node and then to more distant sites. The presence of regional lymph node involvement is the single most important prognostic factor, lowering the 5-year survival rate to approximately 50% (4). This has led to elective lymph node dissection in an effort to better classify patients for prognosis and treatment regimens. Elective lymph node dissection is not indicated in thin melanomatous lesions because local excision has a very high curative rate. Furthermore, it is generally not indicated in thick lesions due to the high prevalence of local and systemic involvement at presentation as well as high rates of regional and distant recurrence. Many groups have advocated elective lymph node dissection in patients with stage I or stage II intermediate thickness melanomatous lesions because approximately 20% of these patients will develop regional lymph node metastases. However, there are both short-term and long-term complications associated with elective lymph node dissection. In complete lymphadenectomy, short-term complications include seroma, wound infection and breakdown, lymphedema, and paresthesia; long-term complications include lymphedema, paresthesia, and hernia formation. Therefore, it would be of great benefit to find a technique that could help identify the lymph node at highest risk for metastasis, obviate radical lymph node dissection in most patients with stage I or stage II melanoma, and possibly prolong survival in such patients. It is in these patients that there has been a recent resurgence in the use of lymphoscintigraphy.
Lymphoscintigraphy was introduced in 1953 by Sherman and Ter-Pugossian (5) and has proved reliable in predicting cutaneous lymphatic flow reliably and identifying the lymphatic watershed accurately. The sentinel node (defined earlier) is the nodal site of potential micrometastasis. In 1992, Morton et al (6) validated the sentinel node concept in cutaneous melanoma with intradermal injection of blue dye and surgical-pathologic correlation. In 1993, Alex and Krag (7) performed lymphoscintigraphy with technetium-99m sulfur colloid to identify lymphatic drainage routes and sentinel nodes in combination with use of a handheld gamma probe for surgical localization. This combination technique allows preoperative and intraoperative identification of the sentinel node in patients with stage I or stage II melanoma, obviating radical lymph node dissection in most patients unless the sentinel node is positive (8–11).
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RADIOPHARMACEUTICALS
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Many radionuclides have been used to study the lymphatic system. An ideal imaging agent for cutaneous lymphoscintigraphy would have rapid clearance from the interstitial space into the lymphatic system, produce high-quality images, and deliver a low radiation dose to the patient. In addition, good retention of the radiopharmaceuticals in the regional lymph nodes is essential for successful gamma probe localization at surgery. A uniform number of small (<100-nm-diameter) particles is essential for a radiocolloid to clear from the interstitial space to the lymphatic channels and regional nodes. Larger particles (>500 nm) have been shown to remain at the injection site and to be unsatisfactory for visualization of the lymphatic system.
The lymphatic system was first studied with an imaging agent (gold-198) approximately 45 years ago. One advantage was small (2–10-nm) particle size, but this was offset by a long half-life (2.7 days), beta emission, and high-energy gamma emission of 412 keV.
Tc-99m antimony trisulfide colloid is a Tc-99m–labeled agent with favorable energy for imaging as well as size uniformity between 3 and 30 nm. However, moderate retention was found at the injection site with use of this pharmaceutical, limiting its clinical efficacy. Antimony trisulfide colloid has not been approved by the U.S. Food and Drug Administration for domestic use.
Tc-99m human serum albumin, a macromolecule approximately 4.5 nm in diameter, is one of the radiopharmaceuticals currently being used in lymphoscintigraphy. This agent clears rapidly from the interstitial space and allows prompt visualization of lymphatic channels, permitting dynamic image acquisition and good anatomic detail. However, human serum albumin has relatively poor retention in regional lymph nodes, which limits its usefulness in delayed static imaging and intraoperative gamma probe localization. We use human serum albumin in rare cases in which filtered sulfur colloid does not migrate from the injection site.
We use filtered Tc-99m sulfur colloid for lymphoscintigraphy. Tc-99m sulfur colloid is an approved agent for scintigraphy of the liver or spleen, but particle size (approximately 100–1,000 nm) is too large for lymphoscintigraphic studies, leading to marked retention at the injection site and poor visualization of the lymphatic system (12,13). Filtration of Tc-99m sulfur colloid with a 0.22-mm filter has been shown to yield smaller (10–100-nm) particles, allowing prompt visualization of the lymphatic system. In addition, there is better lymph node retention with filtered sulfur colloid than with human serum albumin. The 0.22-mm filter is available in most hospital pharmacies because it is commonly used for sterilization of hyperalimentation solutions. In our experience, filtered sulfur colloid is easily prepared and migrates rapidly to lymphatic channels, with sentinel node visualization usually occurring within 30 minutes after administration.
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LYMPHOSCINTIGRAPHIC TECHNIQUE
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Lymphoscintigraphy for evaluation of sentinel nodes in combination with surgical intervention can be performed in 1 day (diagnostic lymphoscintigraphy followed by gamma probe–aided lymphadenectomy) or over 2 days. The 2-day procedure requires two separate injections: one injection for diagnostic lymphoscintigraphy and the other for surgery. The surgeons at our institution prefer the 2-day protocol.
Fifteen to 20 mCi (555–740 MBq) of Tc-99m sulfur colloid in approximately 1 mL of dispersion medium is obtained from a central radiopharmacy and is filtered through a 0.22-mm filter. The technologist or physician replaces the needle on the original syringe with a new needle and a filter. The radiopharmaceutical is pushed slowly through the filter and is collected in the barrel of a 1-mL syringe. The filter is then washed with additional saline solution, so that approximately 0.1 mL of filtrate is collected in three 1-mL syringes. After the activity is assayed, it is diluted to a final concentration of approximately 0.1 mCi (3.7 MBq)/0.1 mL for the diagnostic study and 0.025–0.050 mCi (0.925–1.85 MBq)/0.1 mL for the surgical localization. With this technique, approximately 10%–20% of the original activity is recovered. We filter the sulfur colloid just prior to patient injection.
The injection site is prepared with povidone-iodine (Betadine; Purdue Frederick, Norwalk, Conn) and alcohol, and the patient is draped to limit surface contamination during injection of the Tc-99m sulfur colloid. The radiopharmaceutical is administered intradermally at four to eight points about the lesion or scar. It has been suggested that, because head melanomas drain inferiorly, the inferior injection of radiopharmaceutical should not be administered in such cases because it may obscure an adjacent lymph node (12). Each injection has a volume of 0.1 mL. Intradermal injection will produce a wheal that is frequently painful to the patient. It is important that all air be removed from the syringe because intradermal injection gives rise to a slight amount of back pressure and compression of the air bubble. During withdrawal of the needle, the resulting reexpansion of air will cause aerosolization of the radiopharmaceutical and surface contamination (Fig 1). To control contamination, a sterile gauze pad is placed over the injection site during needle withdrawal (14). After the radiopharmaceutical has been administered, the patient is immediately positioned beneath the gamma camera and 30 sets of dynamic images are obtained at 30 seconds per frame. Typically, two to three sets of dynamic images are acquired. The study is monitored closely by the technologist and physician. Occasionally, the dynamic images are reframed to longer time intervals (eg, 3 minutes per frame) to better delineate lymph node channels. Typically, after approximately 30 minutes of imaging, the physician will further localize the lymph nodes with anatomic landmarks (eg, a mark is made 2 cm inferior and medial to the palpable femoral artery). Static images of 3–5 minutes duration along with cobalt-57 flood source transmission images in various projections are obtained for better lymph node localization. The final set of images is obtained approximately 1
–2 hours after initial administration of the radiopharmaceutical. In cases of truncal melanoma, it is necessary to image both axillary and inguinal regions to exclude unanticipated drainage routes. Summed images produced by combining the static emission and transmission images can be useful for surgical localization. Scaling of the emission and transmission images prior to their summation is necessary to obtain the desired contrast between the visualized lymph node and the body contour lines.
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Figure 1xy. Surface contamination. Images from a lymphedema study of the anterior thigh (left) and calf (right) regions demonstrate surface contamination of the right lower extremity compared with normal draining lymph channels in the left lower extremity. The surface contamination is due to aerosolization of the radiopharmaceutical caused by air in the syringe and inadequate draping of the patient at the time of injection.
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EXPERIENCE
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We have performed over 70 lymphoscintigraphic studies in patients with stage I or stage II melanoma and have reviewed the results in the first 50 patients. Head and neck lesions were seen in eight cases, truncal lesions in 30 cases, and extremity lesions in 12 cases. In two cases, drainage tracks were not visualized; in one of these cases, however, the draining nodes were located directly beneath the lesion. An average of 1.8 sentinel nodes were identified in each case. In seven patients, positive nodes were seen at pathologic examination. In six of these seven patients, the sentinel node was the only positive node; in the seventh patient, both the sentinel node and an adjacent node were positive.
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USEFULNESS OF LYMPHOSCINTIGRAPHY
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If sentinel node biopsy is to be useful in the evaluation and treatment of patients with melanoma, a reliable method for localizing these nodes is needed. Lymphoscintigraphy is highly sensitive (>95%) in the localization of sentinel nodes and their lymph node basins. The location of these basins cannot necessarily be predicted from the site of the primary lesion. Discordance between drainage patterns identified at lymphoscintigraphy and those predicted on the basis of classic anatomic drainage patterns has been reported in 32%–62% of truncal lesions (12,14) and 63%–84% of head and neck melanomas (15,16). The number of sentinel nodes also varies by location. The upper extremity averages slightly more than one sentinel node, and the lower extremity averages 1.8 sentinel nodes (Figs 2–5) (17). The trunk and the head and neck average 1.7 and 2.7 sentinel nodes, respectively (Figs 6–11) (14–17). Use of an intraoperative gamma probe can help localize and identify radiolabeled lymph nodes but may not help distinguish sentinel nodes from secondary nodes. The intraoperative blue dye technique, which involves intralesional injection of a blue dye with subsequent visualization of lymphatic channels and lymph nodes, can help confirm the identity of the sentinel node and has been reported to be successful in 80% of cases (18). Thus, lymphoscintigraphy with use of an intraoperative probe and the blue dye technique are complementary rather than competing procedures.
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Figure 2a. Figures 2, 3. (2) Left lower extremity melanoma. (a) Dynamic images demonstrate sequential filling of two sentinel lymph nodes (arrow and arrowhead) in the left groin via a single lymphatic channel. (b) Delayed anterior transmission (top) and emission (bottom) images with body contour lines demonstrate clearance of the filtered Tc-99m sulfur colloid from the lymph channel and depict more centrally located lymph nodes. The inferior node (arrow) is the sentinel node; the superior nodes are secondary nodes. (3) Right thigh melanoma. (a) Dynamic images demonstrate two sentinel lymph nodes (arrows) and their drainage tracts to the inguinal region. The large lower area of activity (arrowhead) corresponds to the tumor injection site. (b) Delayed anterior emission and transmission (top left and right) images and lateral emission and transmission (bottom left and right) images with body contour lines reveal the anterior location of the two inguinal node groups.
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Figure 2bxy. Figures 2, 3. (2) Left lower extremity melanoma. (a) Dynamic images demonstrate sequential filling of two sentinel lymph nodes (arrow and arrowhead) in the left groin via a single lymphatic channel. (b) Delayed anterior transmission (top) and emission (bottom) images with body contour lines demonstrate clearance of the filtered Tc-99m sulfur colloid from the lymph channel and depict more centrally located lymph nodes. The inferior node (arrow) is the sentinel node; the superior nodes are secondary nodes. (3) Right thigh melanoma. (a) Dynamic images demonstrate two sentinel lymph nodes (arrows) and their drainage tracts to the inguinal region. The large lower area of activity (arrowhead) corresponds to the tumor injection site. (b) Delayed anterior emission and transmission (top left and right) images and lateral emission and transmission (bottom left and right) images with body contour lines reveal the anterior location of the two inguinal node groups.
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Figure 5axy. Right forearm melanoma. (a) Initial anterior dynamic images obtained with the patient's arm next to the head demonstrate rapid drainage to lymph nodes about the elbow (arrows) and delayed tract drainage to the axillary region (arrowhead). (b) Anterior emission and transmission (top left and right) images and lateral emission and transmission (bottom left and right) images with body contour lines further delineate the nodes about the elbow (arrow) and in the axillary region (arrowhead). Note that the patient's arm is now elevated.
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Figure 5bxy. Right forearm melanoma. (a) Initial anterior dynamic images obtained with the patient's arm next to the head demonstrate rapid drainage to lymph nodes about the elbow (arrows) and delayed tract drainage to the axillary region (arrowhead). (b) Anterior emission and transmission (top left and right) images and lateral emission and transmission (bottom left and right) images with body contour lines further delineate the nodes about the elbow (arrow) and in the axillary region (arrowhead). Note that the patient's arm is now elevated.
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Figure 6axy. Melanoma of the left scapula. (a) Initial and 30-minute-delayed posterior (top left and right) and anterior (bottom left and right) dynamic images demonstrate no apparent drainage of the radiopharmaceutical. Arrow indicates a mild increase in activity in the lower most lateral "injection site" on the anterior images. (b) Delayed anterior emission and transmission images (top left and right) with body contour lines demonstrate drainage to the axillary region (arrow). Right anterior oblique emission and transmission images (bottom left and right) with body contour lines further demonstrate the sentinel node (arrow) and secondary central drainage (arrowhead). Note that the patient's arm position has changed (cf Fig 5b).
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Figure 6bxy. Melanoma of the left scapula. (a) Initial and 30-minute-delayed posterior (top left and right) and anterior (bottom left and right) dynamic images demonstrate no apparent drainage of the radiopharmaceutical. Arrow indicates a mild increase in activity in the lower most lateral "injection site" on the anterior images. (b) Delayed anterior emission and transmission images (top left and right) with body contour lines demonstrate drainage to the axillary region (arrow). Right anterior oblique emission and transmission images (bottom left and right) with body contour lines further demonstrate the sentinel node (arrow) and secondary central drainage (arrowhead). Note that the patient's arm position has changed (cf Fig 5b).
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Figure 11a. Melanoma of the left side of the scalp. (a) Left lateral dynamic images reveal an anterior lymphatic channel with immediate drainage to an anterior superior cervical lymph node (arrowhead) and a posterior lymphatic channel with immediate drainage to a postauricular sentinel node (arrow). (b) Delayed lateral emission (top) and transmission (bottom) images with body contour lines demonstrate the two sentinel lymph nodes and additional cervical nodes.
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Figure 11b. Melanoma of the left side of the scalp. (a) Left lateral dynamic images reveal an anterior lymphatic channel with immediate drainage to an anterior superior cervical lymph node (arrowhead) and a posterior lymphatic channel with immediate drainage to a postauricular sentinel node (arrow). (b) Delayed lateral emission (top) and transmission (bottom) images with body contour lines demonstrate the two sentinel lymph nodes and additional cervical nodes.
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Lymphoscintigraphy is not a perfect technique: In two reproducibility studies, agreement in sentinel node identification at repeat lymphoscintigraphy was 83% and 88%, respectively (17,19). This is important because, in several studies, 10%–25% of patients had positive lymph nodes, and in 67%–83% of these patients, only the sentinel node was positive. Failure to identify any drainage pattern or lymph nodes at lymphoscintigraphy has been reported in up to 10% of cases; however, a better general estimate would be less than 1% of cases (20). Factors accounting for the variability of lymphoscintigraphy include tumor location, radiopharmaceutical and its preparation, injection technique, imaging technique, and prior surgical intervention.
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CONCLUSIONS
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Cutaneous lymphoscintigraphy is a sensitive, inexpensive, relatively noninvasive method of identifying draining lymphatic channels and primary sentinel nodes in patients with intermediate thickness malignant melanomatous lesions. Filtered Tc-99m sulfur colloid is easily prepared, migrates rapidly to lymphatic channels, and allows prompt localization of sentinel nodes. Lymphoscintigraphy is recommended as a cost-effective preoperative procedure in all patients planning to undergo elective lymph node dissection. Because of the unpredictability of lymphatic drainage, preoperative scintigraphic findings may lead to changes in surgical management.
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Figure 3a. Figures 2, 3. (2) Left lower extremity melanoma. (a) Dynamic images demonstrate sequential filling of two sentinel lymph nodes (arrow and arrowhead) in the left groin via a single lymphatic channel. (b) Delayed anterior transmission (top) and emission (bottom) images with body contour lines demonstrate clearance of the filtered Tc-99m sulfur colloid from the lymph channel and depict more centrally located lymph nodes. The inferior node (arrow) is the sentinel node; the superior nodes are secondary nodes. (3) Right thigh melanoma. (a) Dynamic images demonstrate two sentinel lymph nodes (arrows) and their drainage tracts to the inguinal region. The large lower area of activity (arrowhead) corresponds to the tumor injection site. (b) Delayed anterior emission and transmission (top left and right) images and lateral emission and transmission (bottom left and right) images with body contour lines reveal the anterior location of the two inguinal node groups.
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Figure 3b. Figures 2, 3. (2) Left lower extremity melanoma. (a) Dynamic images demonstrate sequential filling of two sentinel lymph nodes (arrow and arrowhead) in the left groin via a single lymphatic channel. (b) Delayed anterior transmission (top) and emission (bottom) images with body contour lines demonstrate clearance of the filtered Tc-99m sulfur colloid from the lymph channel and depict more centrally located lymph nodes. The inferior node (arrow) is the sentinel node; the superior nodes are secondary nodes. (3) Right thigh melanoma. (a) Dynamic images demonstrate two sentinel lymph nodes (arrows) and their drainage tracts to the inguinal region. The large lower area of activity (arrowhead) corresponds to the tumor injection site. (b) Delayed anterior emission and transmission (top left and right) images and lateral emission and transmission (bottom left and right) images with body contour lines reveal the anterior location of the two inguinal node groups.
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Figure 4a. Right lower extremity melanoma. (a) Dynamic images demonstrate prompt appearance of two sentinel lymph nodes (arrows) as well as independent lymph channels. (b) Reframed 3-minute dynamic images better demonstrate the independent draining lymph channels. (c) On delayed transmission (left) and emission (right) images with body contour lines, lymph nodes appear similar to the single sentinel node in
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Figure 4b. Right lower extremity melanoma. (a) Dynamic images demonstrate prompt appearance of two sentinel lymph nodes (arrows) as well as independent lymph channels. (b) Reframed 3-minute dynamic images better demonstrate the independent draining lymph channels. (c) On delayed transmission (left) and emission (right) images with body contour lines, lymph nodes appear similar to the single sentinel node in
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Figure 4cd. Right lower extremity melanoma. (a) Dynamic images demonstrate prompt appearance of two sentinel lymph nodes (arrows) as well as independent lymph channels. (b) Reframed 3-minute dynamic images better demonstrate the independent draining lymph channels. (c) On delayed transmission (left) and emission (right) images with body contour lines, lymph nodes appear similar to the single sentinel node in
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Figure 7axyz. Melanoma of the left side of the upper back. (a) Dynamic posterior images demonstrate bilateral lymphatic channels draining to the right (arrowhead) and especially the left (arrow) axilla. (b) Delayed posterior emission and transmission (top left and right) images and delayed anterior transmission (bottom left and right) images with body contour lines demonstrate sentinel lymph nodes on both the left (arrow) and right (arrowhead) sides. (c) Delayed left lateral emission and transmission (top left and right) images and right lateral emission and transmission (bottom left and right) images with body contour lines help confirm the anteriorly located lymph nodes.
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Figure 7bxy. Melanoma of the left side of the upper back. (a) Dynamic posterior images demonstrate bilateral lymphatic channels draining to the right (arrowhead) and especially the left (arrow) axilla. (b) Delayed posterior emission and transmission (top left and right) images and delayed anterior transmission (bottom left and right) images with body contour lines demonstrate sentinel lymph nodes on both the left (arrow) and right (arrowhead) sides. (c) Delayed left lateral emission and transmission (top left and right) images and right lateral emission and transmission (bottom left and right) images with body contour lines help confirm the anteriorly located lymph nodes.
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Figure 7cxy. Melanoma of the left side of the upper back. (a) Dynamic posterior images demonstrate bilateral lymphatic channels draining to the right (arrowhead) and especially the left (arrow) axilla. (b) Delayed posterior emission and transmission (top left and right) images and delayed anterior transmission (bottom left and right) images with body contour lines demonstrate sentinel lymph nodes on both the left (arrow) and right (arrowhead) sides. (c) Delayed left lateral emission and transmission (top left and right) images and right lateral emission and transmission (bottom left and right) images with body contour lines help confirm the anteriorly located lymph nodes.
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Figure 8a. Melanoma of the left side of the upper back. (a) Posterior dynamic image (top) demonstrates prompt appearance of an "axillary node" (arrow) and a posterior cervical node (arrowhead) at the base of the neck. Posterior transmission image (bottom) reveals that anatomic landmarks with body contour lines fail to demonstrate lymph node localization due to their anterior location. Delayed anterior emission is seen at lower left. (b) Anterior static image fails to demonstrate the "axillary node." (c) Delayed left lateral emission (top) and transmission (bottom) images with body contour lines show that the "axillary node" (arrow) is actually located posteriorly in the triangular space of the scapula (18).
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Figure 8b. Melanoma of the left side of the upper back. (a) Posterior dynamic image (top) demonstrates prompt appearance of an "axillary node" (arrow) and a posterior cervical node (arrowhead) at the base of the neck. Posterior transmission image (bottom) reveals that anatomic landmarks with body contour lines fail to demonstrate lymph node localization due to their anterior location. Delayed anterior emission is seen at lower left. (b) Anterior static image fails to demonstrate the "axillary node." (c) Delayed left lateral emission (top) and transmission (bottom) images with body contour lines show that the "axillary node" (arrow) is actually located posteriorly in the triangular space of the scapula (18).
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Figure 8c. Melanoma of the left side of the upper back. (a) Posterior dynamic image (top) demonstrates prompt appearance of an "axillary node" (arrow) and a posterior cervical node (arrowhead) at the base of the neck. Posterior transmission image (bottom) reveals that anatomic landmarks with body contour lines fail to demonstrate lymph node localization due to their anterior location. Delayed anterior emission is seen at lower left. (b) Anterior static image fails to demonstrate the "axillary node." (c) Delayed left lateral emission (top) and transmission (bottom) images with body contour lines show that the "axillary node" (arrow) is actually located posteriorly in the triangular space of the scapula (18).
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Figure 9a. Melanoma of the left side of the scalp. (a) Left lateral dynamic images reveal an anterior lymphatic channel with immediate drainage to a preauricular sentinel node (arrow) and a posterior lymphatic channel with drainage to a superior cervical sentinel node (arrowhead). (b) Delayed lateral emission (top) and transmission (bottom) images with body contour lines better delineate the position of the two sentinel lymph nodes.
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Figure 9b. Melanoma of the left side of the scalp. (a) Left lateral dynamic images reveal an anterior lymphatic channel with immediate drainage to a preauricular sentinel node (arrow) and a posterior lymphatic channel with drainage to a superior cervical sentinel node (arrowhead). (b) Delayed lateral emission (top) and transmission (bottom) images with body contour lines better delineate the position of the two sentinel lymph nodes.
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Figure 10a. Melanoma of the left side of the scalp. (a) Left lateral dynamic images demonstrate anterior and posterior lymphatic channels with drainage to anterior (arrow) and posterior (arrowhead) superior cervical sentinel lymph nodes. (b) Delayed lateral emission (top) and transmission (bottom) images with body contour lines obtained with lead over the primary lesion show the two sentinel nodes and an additional secondary draining node inferior to the anterior cervical node.
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Figure 10b. Melanoma of the left side of the scalp. (a) Left lateral dynamic images demonstrate anterior and posterior lymphatic channels with drainage to anterior (arrow) and posterior (arrowhead) superior cervical sentinel lymph nodes. (b) Delayed lateral emission (top) and transmission (bottom) images with body contour lines obtained with lead over the primary lesion show the two sentinel nodes and an additional secondary draining node inferior to the anterior cervical node.
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Footnotes
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Address reprint requests to A.P.Y.
See the commentary by Baxter following this article.
Received for publication February 25, 1998.
Revision received March 23, 1998. June 26, 1998.
Accepted for publication June 29, 1998.
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O'Brien CJ, Uren RF, Thompson JF, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg 1995; 170:461-466.[Medline]
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Kapteijn BAE, Nieweg OE, Olmos V, et al. Reproducibility of lymphoscintigraphy for lymphatic mapping in cutaneous melanoma. J Nucl Med 1996; 37:972-974.[Abstract/Free Full Text]
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Uren RF, Howman-Giles RB, Thompson JF, et al. Lymphatic drainage to triangular intermuscular space lymph nodes in melanoma on the back. J Nucl Med 1996; 37:964-966.[Abstract/Free Full Text]
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Mudun A, Murray DR, Herda SC, et al. Early stage melanoma: lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intraoperative gamma probe. Radiology 1996; 199:171-175.[Abstract/Free Full Text]
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Invited Commentary
Kirkman G. Baxter, MD
Department of Radiology and Nuclear Medicine, University of Kansas Medical Center, Kansas City, Kansas
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Introduction
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Lymphoscintigraphy has been a part of nuclear medicine for over 40 years. However, the procedure has been revitalized with its expanding use for sentinel node localization. In 1992, Morton et al (1) described the intraoperative use of blue dye for localization of the sentinel node in malignant melanoma, thereby increasing the use of sentinel node localization in this disease.
Sentinel node studies have also been used to identify the sentinel draining node or nodes in malignant melanoma and breast cancer and in squamous cell carcinoma of the genitalia and head and neck. The preceding article by Yudd et al adds to the growing literature on the usefulness of sentinel lymph node studies in patients with malignant melanoma. The topic has become very popular on the lecture circuit and in the scientific literature. A MedLine search for recent entries on radionuclide imaging of lymph nodes produced 97 entries for the past 18 months alone. Most of these articles have appeared in the nonradiology literature.
Successful lymphoscintigraphy requires appropriate selection of a radiotracer, proper injection of the tracer, and proper imaging with subsequent marking of the identified sentinel lymph nodes. An intraoperative gamma probe has also become standard in the operating room as a useful adjuvant to imaging for lymph node localization. Many controversies concerning proper lymphoscintigraphic technique have appeared in the literature and have generated added confusion.
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SELECTION OF TRACER MATERIAL
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Vera et al (2) have provided an excellent historical review of the use of different radiolabeled particles and macromolecules in lymphoscintigraphy. The ideal agent for lymphoscintigraphy would have nearly complete uptake at the site of the sentinel lymph node, little retention at the site of injection, and little distribution to secondary lymph nodes. Although Tc-99m sulfur colloid does not meet all these criteria, it is the most commonly used imaging agent at most institutions. Sulfur colloid has become the agent of choice in the United States; however, not all preparations of sulfur colloid are equal. Eshina et al (3) described the effects of different preparation techniques on particle size. The duration of the boiling and cooling of the sulfur colloid preparation as well as the time elapsed since the last elution of the molybdenum-99 generator affected particle size. Eshina et al achieved their best overall results in lymphoscintigraphy with particles they generated by heating the product for 3 minutes, letting it cool for 2 minutes, and using the highest amount of ingrowth of Tc-99m. The colloidal particles varied from less than 30 nm to more than 10 m in diameter. Paganelli et al (4) used three different-sized colloidal particles (<50 nm, 50–80 nm, 200–1,000 nm) to localize sentinel nodes in breast cancer patients. Their best results were obtained with the larger colloidal particles. The sentinel node could be identified most clearly with these larger particles, even after 14–16 hours, allowing more accurate surgical localization. It seems apparent that the best lymphoscintigraphic results will be produced with use of a standard-sized sulfur colloid.
In their review of lymphoscintigraphic agents, Glass et al (5) compared Tc-99m sulfur colloid with Tc-99m human serum albumin and Tc-99m albumin colloid. They showed that Tc-99m human serum albumin had faster washout from injection sites and provided better definition of lymph node channels. They also suggested that Tc-99m human serum albumin could permit faster preoperative or intraoperative node localization. However, as Yudd et al comment, nodal retention is lower with human serum albumin, making localization of the sentinel node more difficult.
Although many surgeons use an isosulfan blue dye (Lymphazurin; United States Surgical, Norwalk, Conn) for intraoperative localization of sentinel nodes, this method has its limitations. The use of dye allows visualization of draining nodes but assumes prior knowledge of the site of lymphatic drainage. Also, a lymph node that is demonstrated with blue dye may not be the only node or the sentinel node of drainage. Vera et al (2) developed a nonparticulate receptor-binding radiotracer for lymphoscintigraphy that would have the advantages of prompt clearance (similar to blue dye) and prolonged nodal retention (similar to a colloid). They used a Tc-99m–labeled polydiethylenetriamine pentaacetic acid polymannosyl polylysine (Tc-99m DTPA-man-PL) tracer that would target a receptor in lymphoid tissue. Such a product would allow high specific activities that would have a better chance of demonstrating nodes with a large tumor burden. In lymphoscintigraphy, it has always been a theoretic concern that nodes largely replaced by tumor might not have sufficient uptake with a colloid. In addition, it has been postulated that this type of agent would allow better visualization of the sentinel node with less uptake in secondary nodes. This radiopharmaceutical approach makes sense compared with the nontargeted approach using sulfur colloid. It will be interesting to follow the development of specific targeted agents such as Tc-99m DTPA-man-PL for lymphoscintigraphy.
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INJECTION OF TRACER MATERIAL
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Injected volume and level of radioactivity need to be standardized for reproducible lymph node localization. Yudd et al made four to eight injections around the site of the melanoma, each injection having a volume of 0.1 mL and containing 100 mCi (3.7 MBq) of radioactivity. We use this same technique at our institution. Larger injected volumes would tend to be more painful for the patient and would not necessarily produce better results. In patients who have undergone substantial surgery, injection is best performed away from sites of scar tissue: Lymphatic drainage would be disrupted if a study were performed in a patient who had undergone extensive lesion resection. Injection is best performed intradermally, where lymphatic drainage is the most abundant. Injection into the subcutaneous tissue could lead to incorrect identification of a sentinel lymph node or technical failure (6), whereas injection deeper into the subcutaneous fat where lymphatic vessels are sparse could lead to very slow migration of tracer material.
Even greater controversy exists concerning optimal injection technique for lymphoscintigraphy in breast carcinoma. Intratumoral, peritumoral, and intradermal injections have all been used in various studies. Paganelli et al (4) achieved a 98% success rate with subdermal injections for breast lymphoscintigraphy. This technique provided faster draining and better results than peritumoral injections. However, controversy remains as to whether subdermal and peritumoral injections yield identical results. Both Cox et al (7) and Borgstein et al (8) used peritumoral injections. Injected volumes were also typically larger in breast imaging studies (4–6 mL) when injection was performed about the tumor site. These differences in injection technique for malignant melanoma and breast cancer need to be understood by the nuclear physician performing lymphoscintigraphy.
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PATIENT IMAGING
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There is little dispute about the need for immediate imaging of the patient following injection of tracer material. By obtaining only delayed images, one runs the risk of missing the sentinel lymph node because multiple nodes may be visualized or the tracer material may have cleared from the sentinel node. Dynamic imaging allows visualization of the lymphatic vessels over time, which can improve tracking of drainage patterns. Use of a transmission image to provide some anatomic landmarks is also helpful to the surgeon needing to see the body outline. A simple anteroposterior view of the axilla may not be sufficient; lateral or oblique views may be necessary to document the depth of a node. Once the sentinel node or nodes have been identified, an indelible ink mark is placed on the skin and covered with a water-resistant covering to protect it for surgery, which is usually performed the following day. Delayed images obtained up to 2 hours after initial imaging may demonstrate additional nodal drainage groups.
Identification of the sentinel lymph node has been shown to be reproducible. Mudun et al (9) demonstrated that in 85% of cases, the same lymph node could be identified at repeat lymphoscintigraphy. In the remaining cases, inconsistent results were believed to be secondary to the numerous variables in the study, including injection technique, injected dose and volume, lesion site, and previous surgical intervention. This raises the issue of whether the 2-day study technique might potentially produce incongruent findings when the surgeon looks for the sentinel node in the operating room during the second day.
The use of a gamma probe is becoming a standard part of lymphoscintigraphy at many institutions. Although use of blue dye allows the surgeon to visualize a node, localization may be difficult if the sentinel node is deep. In addition, blue dye passes rapidly out of the node. A probe provides the surgeon with an additional localization tool. Albertini et al (10) showed that the sentinel node was localized in 96% of cases when blue dye and an intraoperative gamma probe were both used, compared with 69.5% of cases when blue dye alone was used and 83.5% of cases when the probe alone was used. However, there are several manufacturers of gamma probes, and parameters such as energy window, sensitivity, collimation, shielding, and detector type have not yet been standardized. These parameters affect the quality of the probe and its usefulness in the operating room. Tiourina et al (11) reviewed some of the operating characteristics of four available gamma probes and subjected the probes to laboratory testing. Each probe performed differently, and Tiourina et al described how various characteristics influenced the test results. Clearly, the probe must be appropriate for the desired procedure, whether it be lymph node localization with technetium or localization of other isotopes in immunoscintigraphy. As Tiourina et al suggested, the surgeon, nuclear medicine physician, and physicist must all work together to choose the proper probe.
Many questions exist regarding the handling of radioactive tissues. Proper radiation monitoring with ring badges would seem appropriate for the surgeon involved in sentinel node localization. Cox et al (7) routinely quarantined specimens for 48 hours before processing them for permanent section analysis. In a study of patients who underwent lymphoscintigraphy with Tc-99m carcinoembryonic antigen, Bares et al (12) found dose rates ranging from 0.2 to 1.6 rem/h at a distance of .05 meters from the patient. They concluded that for a surgeon performing 50 operations per year at 4 hours of radiation exposure per surgery, the annual radiation dose would be about twice that which natural background exposure would produce. Measurements like these will need to be obtained in individuals performing lymphoscintigraphy to assess low-level radiation exposure.
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SUMMARY
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Lymphoscintigraphy for sentinel node localization has entered the mainstream of nuclear medicine. Adherence to proper technique and high imaging standards will ensure good results and increase acceptance of this procedure among our clinical colleagues. It will be crucial to establish the best technique for each of the various types of sentinel node localization procedures.
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References
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Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127:392-399.
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Paganelli G, deCicco C, Cremonesi M, et al. Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer (abstr). Eur J Nucl Med 1998; 25:838.
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Glass ED, Essner R, Morton DL. Kinetics of three lymphoscintigraphic agents in patients with cutaneous melanoma. J Nucl Med 1998; 39:1185-1190.[Abstract/Free Full Text]
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Tanabe KK, Reintgen D. The rule of sentinel lymph node mapping for melanoma. Adv Surg 1998; 31:79-103.
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Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998; 227:645-653.[Medline]
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Borgstein PJ, Pijpers R, Comans EF, et al. Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg 1998; 186:275-283.[Medline]
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Mudun A, Murray DR, Herda SC, et al. Early stage melanoma: lymphoscintigraphy reproducibility of sentinel node detection and effectiveness of the intraoperative gamma probe. Radiology 1996; 199:171-175.
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Albertini JJ, Cruse CW, Rapaport D, et al. Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma. Ann Surg 1996; 223:217-224.[Medline]
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Tiourina T, Arends B, Huysmans D, et al. Evaluation of surgical gamma probes for radioguided sentinel node localization. Eur J Nucl Med 1998; 25:1224-1231.[Medline]
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Bares R, Muller B, Jass J, et al. The radiation dose to surgical personnel during intraoperative radioimmunoscintimetry. Eur J Nucl Med 1992; 19:110-112.[Medline]
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Abstract
INTRODUCTION
