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Right arrow Nuclear Medicine
(Radiographics. 2002;22:491-502.)
© RSNA, 2002


EDUCATION EXHIBIT

Lymphoscintigraphy in Cutaneous Melanoma: A Total Body Atlas of Sentinel Node Mapping1

Charles M. Intenzo, MD, Sung M. Kim, MD, Jayant I. Patel, CNMT, Henry C. Lin, MD and John C. Kairys, MD

1 From the Division of Nuclear Medicine, Department of Radiology (C.M.I., S.M.K., J.I.P., H.C.L.), and the Department of Surgery (J.C.K.), Thomas Jefferson University Hospital, 132 S 10th St, Rm 861 Main Bldg, Philadelphia, PA 19107. Received September 4, 2001; revision requested November 16 and final revision received January 11, 2002; accepted January 14. Address correspondence to C.M.I. (e-mail: charles.intenzo@mail.tju.edu).


    Abstract
 Top
 Abstract
 Introduction
 Radiopharmaceuticals
 Imaging Considerations
 Conclusions
 References
 
Lymphoscintigraphy of malignant melanoma has been a reliable method of identifying regional lymph nodes at risk for metastases and is now considered part of the standard of care in patients with melanoma. The status of the sentinel lymph node (SLN) is predictive of the metastatic status of the corresponding regional lymph node group. Lymphatic channel mapping allows identification of the SLN, thereby making selective lymph node sampling possible. Consequently, SLN identification with lymphoscintigraphy results in both less extensive surgery and more efficient pathologic examination of the lymph node specimens. Therefore, it is imperative that radiologists and nuclear medicine physicians know which radiopharmaceuticals to use, recognize different lymphatic drainage patterns from various primary tumor sites throughout the body, use proper imaging techniques, and recognize potential pitfalls in image interpretation.

© RSNA, 2002

Index Terms: Lymphatic system, radionuclide studies, 99.12974 • Melanoma, **.83322 • Skin, neoplasms, **.8332


    Introduction
 Top
 Abstract
 Introduction
 Radiopharmaceuticals
 Imaging Considerations
 Conclusions
 References
 
In oncology, lymphoscintigraphy is a diagnostic procedure in which particulate radiopharmaceuticals are injected around a superficial tumor, with subsequent imaging of the radiopharmaceutical during its transit through lymphatic vessels into the draining lymph node basin. By definition, the sentinel lymph node (SLN) in malignant melanoma is the first node in the lymph node basin to be encountered by the lymphatic fluid draining from the tumor. The presence of metastases within the SLN allows reliable prediction of the metastatic status of the corresponding regional lymph node basin. An SLN that contains metastases indicates that there has been definite lymphatic tumor spread. Conversely, if the SLN is tumor free, the primary tumor has not spread through the lymphatic channels. Minimally invasive surgical biopsy of the SLN obviates extensive radical lymph node dissection, whose complications include chronic lymphedema, wound infection, nerve injury, and so on; therefore, accurate nodal staging of disease is essential. This has become more relevant as the prevalence of malignant melanoma has rapidly increased. In fact, the lifetime risk for melanoma in the United States will exceed 1% in the near future (1).

In this article, we discuss and illustrate typical lymph node drainage patterns from melanomas in various locations on the skin surface, including the scalp, ear, neck, shoulder, finger, back, breast, abdomen, flank, labia, thigh, calf, and great toe. The reference image (Fig 1) designates the anatomic locations of the melanomas depicted in Figures 214. We also demonstrate proper imaging techniques and discuss related pitfalls and artifacts.



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Figure 1.  Drawings illustrate the locations of the melanomas described in the subsequent figures, with the numbers 2-14 corresponding to Figures 2-14. The white arrowhead in Figures 2-14 indicates the injection sites.

 


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Figure 2a.  Stage T3 lesion in the left parietotemporal region of the scalp. (a) Anterior image obtained immediately after injection demonstrates a lymphatic channel that drains into an upper lymph node (long arrow) and a lower node (short arrow). (b) Subsequent left lateral image obtained 5 minutes later allows precise localization and identification of the lymph nodes (from top to bottom): a temporal node (upper straight arrow), preauricular node (upper black arrowhead), periparotid nodes (lower straight arrow), posterior auricular node (lower black arrowhead), and high jugular node (curved arrow). The temporal node is an SLN. (c) Anterior image of the left side of the thorax obtained 45 minutes later reveals multiple secondary lower left cervical nodes (arrow). At histologic analysis, all nodes were tumor free.

 


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Figure 2b.  Stage T3 lesion in the left parietotemporal region of the scalp. (a) Anterior image obtained immediately after injection demonstrates a lymphatic channel that drains into an upper lymph node (long arrow) and a lower node (short arrow). (b) Subsequent left lateral image obtained 5 minutes later allows precise localization and identification of the lymph nodes (from top to bottom): a temporal node (upper straight arrow), preauricular node (upper black arrowhead), periparotid nodes (lower straight arrow), posterior auricular node (lower black arrowhead), and high jugular node (curved arrow). The temporal node is an SLN. (c) Anterior image of the left side of the thorax obtained 45 minutes later reveals multiple secondary lower left cervical nodes (arrow). At histologic analysis, all nodes were tumor free.

 


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Figure 2c.  Stage T3 lesion in the left parietotemporal region of the scalp. (a) Anterior image obtained immediately after injection demonstrates a lymphatic channel that drains into an upper lymph node (long arrow) and a lower node (short arrow). (b) Subsequent left lateral image obtained 5 minutes later allows precise localization and identification of the lymph nodes (from top to bottom): a temporal node (upper straight arrow), preauricular node (upper black arrowhead), periparotid nodes (lower straight arrow), posterior auricular node (lower black arrowhead), and high jugular node (curved arrow). The temporal node is an SLN. (c) Anterior image of the left side of the thorax obtained 45 minutes later reveals multiple secondary lower left cervical nodes (arrow). At histologic analysis, all nodes were tumor free.

 


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Figure 3a.  Stage T4 melanoma of the left ear. (a, b) Left lateral images obtained immediately after injection (a) and 5 minutes later with a Co-57 flood source behind the patient (b) demonstrate at least two nodes at the distal aspect of the lymphatic channel (straight arrow), followed by two nodes more inferolaterally (curved arrow). The second image indicates that the former nodes are most likely periparotid and superior jugular nodes, whereas the latter are supraclavicular nodes. (c) Anterior image obtained 30 minutes after injection with the patient’s left arm elevated shows the periparotid and superior jugular nodes (straight arrow) and supraclavicular nodes (curved arrow). Prophylactic neck dissection was performed because of the large size of the tumor (4.8 mm), but all nodes were tumor free.

 


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Figure 3b.  Stage T4 melanoma of the left ear. (a, b) Left lateral images obtained immediately after injection (a) and 5 minutes later with a Co-57 flood source behind the patient (b) demonstrate at least two nodes at the distal aspect of the lymphatic channel (straight arrow), followed by two nodes more inferolaterally (curved arrow). The second image indicates that the former nodes are most likely periparotid and superior jugular nodes, whereas the latter are supraclavicular nodes. (c) Anterior image obtained 30 minutes after injection with the patient’s left arm elevated shows the periparotid and superior jugular nodes (straight arrow) and supraclavicular nodes (curved arrow). Prophylactic neck dissection was performed because of the large size of the tumor (4.8 mm), but all nodes were tumor free.

 


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Figure 3c.  Stage T4 melanoma of the left ear. (a, b) Left lateral images obtained immediately after injection (a) and 5 minutes later with a Co-57 flood source behind the patient (b) demonstrate at least two nodes at the distal aspect of the lymphatic channel (straight arrow), followed by two nodes more inferolaterally (curved arrow). The second image indicates that the former nodes are most likely periparotid and superior jugular nodes, whereas the latter are supraclavicular nodes. (c) Anterior image obtained 30 minutes after injection with the patient’s left arm elevated shows the periparotid and superior jugular nodes (straight arrow) and supraclavicular nodes (curved arrow). Prophylactic neck dissection was performed because of the large size of the tumor (4.8 mm), but all nodes were tumor free.

 


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Figure 4a.  Stage T3 lesion of the posterior neck. (a) Initial anterior image of the neck and chest reveals a lymph node in the left cervical region (arrow). (b) Anterior image obtained 20 minutes later shows the original node (long arrow) with a faint second node inferiorly and a third node inferomedial to the other two nodes (short arrow). Because the melanoma was in the midline, it was important to inspect both sides of the body. About 40 minutes after injection, we noticed a small spot in the right axilla on the persistence scope. (c) Anterior image obtained over the right hemithorax reveals a right axillary node (arrow). At surgery, findings obtained with a gamma probe indicated that the left-sided nodes were more posterior than anterior and were spinal accessory nodes. At histologic analysis, only the first node (arrow in a, long arrow in b) contained tumor cells.

 


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Figure 4b.  Stage T3 lesion of the posterior neck. (a) Initial anterior image of the neck and chest reveals a lymph node in the left cervical region (arrow). (b) Anterior image obtained 20 minutes later shows the original node (long arrow) with a faint second node inferiorly and a third node inferomedial to the other two nodes (short arrow). Because the melanoma was in the midline, it was important to inspect both sides of the body. About 40 minutes after injection, we noticed a small spot in the right axilla on the persistence scope. (c) Anterior image obtained over the right hemithorax reveals a right axillary node (arrow). At surgery, findings obtained with a gamma probe indicated that the left-sided nodes were more posterior than anterior and were spinal accessory nodes. At histologic analysis, only the first node (arrow in a, long arrow in b) contained tumor cells.

 


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Figure 4c.  Stage T3 lesion of the posterior neck. (a) Initial anterior image of the neck and chest reveals a lymph node in the left cervical region (arrow). (b) Anterior image obtained 20 minutes later shows the original node (long arrow) with a faint second node inferiorly and a third node inferomedial to the other two nodes (short arrow). Because the melanoma was in the midline, it was important to inspect both sides of the body. About 40 minutes after injection, we noticed a small spot in the right axilla on the persistence scope. (c) Anterior image obtained over the right hemithorax reveals a right axillary node (arrow). At surgery, findings obtained with a gamma probe indicated that the left-sided nodes were more posterior than anterior and were spinal accessory nodes. At histologic analysis, only the first node (arrow in a, long arrow in b) contained tumor cells.

 


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Figure 5a.  Stage T3 lesion of the right shoulder. (a) Immediate anterior image shows a right supraclavicular lymph node (arrow). (b) Posterior image obtained 20 minutes later again shows the right supraclavicular lymph node (long arrow) and also reveals a right axillary node (short arrow). Subsequent images obtained during the next 30 minutes (not shown) demonstrated no additional nodes. Only the supraclavicular node contained tumor cells at histologic analysis.

 


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Figure 5b.  Stage T3 lesion of the right shoulder. (a) Immediate anterior image shows a right supraclavicular lymph node (arrow). (b) Posterior image obtained 20 minutes later again shows the right supraclavicular lymph node (long arrow) and also reveals a right axillary node (short arrow). Subsequent images obtained during the next 30 minutes (not shown) demonstrated no additional nodes. Only the supraclavicular node contained tumor cells at histologic analysis.

 


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Figure 6a.  Stage T3 lesion of the back. (a) Immediate posterior image shows only the injection site. (b) Left lateral image obtained 5 minutes later reveals a cluster of three left axillary nodes (arrow). No other nodes were visualized on delayed images (not shown). At histologic analysis, all nodes were tumor free. This case demonstrates the importance of lateral views: The injection site and lymph nodes could be superimposed on frontal views.

 


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Figure 6b.  Stage T3 lesion of the back. (a) Immediate posterior image shows only the injection site. (b) Left lateral image obtained 5 minutes later reveals a cluster of three left axillary nodes (arrow). No other nodes were visualized on delayed images (not shown). At histologic analysis, all nodes were tumor free. This case demonstrates the importance of lateral views: The injection site and lymph nodes could be superimposed on frontal views.

 


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Figure 7a.  Stage T2 lesion of the left breast in a 43-year-old woman. (a) Immediate anterior image obtained with the patient’s left arm elevated shows formation of a lymphatic channel (arrow). (b) Repeat anterior image obtained 5 minutes later reveals an axillary node (arrow). (c) Delayed left lateral image obtained 20 minutes later shows the original node (long arrow) and two additional axillary nodes (short arrows). A scan of the abdomen (not shown) revealed no abdominal or pelvic nodes. None of the axillary lymph nodes contained tumor cells at histologic analysis.

 


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Figure 7b.  Stage T2 lesion of the left breast in a 43-year-old woman. (a) Immediate anterior image obtained with the patient’s left arm elevated shows formation of a lymphatic channel (arrow). (b) Repeat anterior image obtained 5 minutes later reveals an axillary node (arrow). (c) Delayed left lateral image obtained 20 minutes later shows the original node (long arrow) and two additional axillary nodes (short arrows). A scan of the abdomen (not shown) revealed no abdominal or pelvic nodes. None of the axillary lymph nodes contained tumor cells at histologic analysis.

 


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Figure 7c.  Stage T2 lesion of the left breast in a 43-year-old woman. (a) Immediate anterior image obtained with the patient’s left arm elevated shows formation of a lymphatic channel (arrow). (b) Repeat anterior image obtained 5 minutes later reveals an axillary node (arrow). (c) Delayed left lateral image obtained 20 minutes later shows the original node (long arrow) and two additional axillary nodes (short arrows). A scan of the abdomen (not shown) revealed no abdominal or pelvic nodes. None of the axillary lymph nodes contained tumor cells at histologic analysis.

 


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Figure 8a.  Stage T2 melanoma of the right third finger. (a) Immediate anterior image of the right arm demonstrates a Tc-99m marker placed lateral to the patient’s elbow (long arrow) and an epitrochlear lymph node (short arrow). The patient’s shoulder is out of the field of view at the upper right, and the patient’s right hand is out of the field of view at the lower left. (b) Anterior image of the right shoulder obtained 5 minutes later reveals two axillary nodes (arrow). At histologic analysis, all nodes were tumor free.

 


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Figure 8b.  Stage T2 melanoma of the right third finger. (a) Immediate anterior image of the right arm demonstrates a Tc-99m marker placed lateral to the patient’s elbow (long arrow) and an epitrochlear lymph node (short arrow). The patient’s shoulder is out of the field of view at the upper right, and the patient’s right hand is out of the field of view at the lower left. (b) Anterior image of the right shoulder obtained 5 minutes later reveals two axillary nodes (arrow). At histologic analysis, all nodes were tumor free.

 


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Figure 9.  Stage T2 lesion overlying the abdominal wall above the umbilicus. Anterior image of the chest and abdomen obtained 5 minutes after injection reveals substernal lymph nodes (curved arrow) as well as bilateral axillary nodes (straight arrows). Delayed images of the chest and abdomen obtained 20 minutes later (not shown) demonstrated no changes. A delayed image of the anterior pelvis obtained 30 minutes after injection (also not shown) revealed no pelvic or inguinal lymph nodes. At histologic analysis, all lymph nodes were tumor free.

 


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Figure 10a.  Stage T3 lesion of the right lower flank. An image of the pelvis obtained immediately after injection (not shown) revealed no lymphatic channels or nodes. (a) Anterior image of the pelvis obtained 30 minutes later still shows no nodes. The site of injection is out of the field of view to the patient’s right. (b) Anterior image obtained 10 minutes later with the camera placed over the chest reveals two axillary lymph nodes (arrow). A delayed image of the pelvis obtained 20 minutes later (not shown) demonstrated no changes. Both axillary lymph nodes contained tumor cells at histologic analysis.

 


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Figure 10b.  Stage T3 lesion of the right lower flank. An image of the pelvis obtained immediately after injection (not shown) revealed no lymphatic channels or nodes. (a) Anterior image of the pelvis obtained 30 minutes later still shows no nodes. The site of injection is out of the field of view to the patient’s right. (b) Anterior image obtained 10 minutes later with the camera placed over the chest reveals two axillary lymph nodes (arrow). A delayed image of the pelvis obtained 20 minutes later (not shown) demonstrated no changes. Both axillary lymph nodes contained tumor cells at histologic analysis.

 


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Figure 11a.  Stage T2 melanoma of the right labium minus. (a) Immediate anterior image of the pelvis reveals a right inguinal lymph node (arrow). (b) On an image obtained 20 minutes later, the node is more prominent (long arrow), and at least two additional right inguinal nodes are seen (short arrow). A delayed anterior image of the abdomen and pelvis obtained 50 minutes after injection (not shown) revealed no additional pelvic nodes and no lymph nodes in the abdomen. At histologic analysis, all nodes were tumor free.

 


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Figure 11b.  Stage T2 melanoma of the right labium minus. (a) Immediate anterior image of the pelvis reveals a right inguinal lymph node (arrow). (b) On an image obtained 20 minutes later, the node is more prominent (long arrow), and at least two additional right inguinal nodes are seen (short arrow). A delayed anterior image of the abdomen and pelvis obtained 50 minutes after injection (not shown) revealed no additional pelvic nodes and no lymph nodes in the abdomen. At histologic analysis, all nodes were tumor free.

 


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Figure 12a.  Stage T2 lesion of the anterior distal right thigh. (a) Immediate anterior image of the lower extremities shows the injection site above the right knee. (b, c) Anterior (b) and right lateral (c) images of the pelvis obtained 23 minutes later reveal two right inguinal lymph nodes (straight arrow). Note that each node has its own lymphatic channel (curved arrows). This indicates that both nodes are SLNs: If there were only one channel, the more inferior node would be an SLN and the more superior node would be a secondary node. (d) Delayed anterior pelvic image obtained 5 minutes later reveals a right external iliac node (short arrow) superior to the inguinal nodes (long arrow). Because the former did not have its own lymphatic channel, it is a secondary node. Subsequent delayed images of the pelvis and abdomen (not shown) revealed no additional nodes. At histologic analysis, all nodes were tumor free.

 


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Figure 12b.  Stage T2 lesion of the anterior distal right thigh. (a) Immediate anterior image of the lower extremities shows the injection site above the right knee. (b, c) Anterior (b) and right lateral (c) images of the pelvis obtained 23 minutes later reveal two right inguinal lymph nodes (straight arrow). Note that each node has its own lymphatic channel (curved arrows). This indicates that both nodes are SLNs: If there were only one channel, the more inferior node would be an SLN and the more superior node would be a secondary node. (d) Delayed anterior pelvic image obtained 5 minutes later reveals a right external iliac node (short arrow) superior to the inguinal nodes (long arrow). Because the former did not have its own lymphatic channel, it is a secondary node. Subsequent delayed images of the pelvis and abdomen (not shown) revealed no additional nodes. At histologic analysis, all nodes were tumor free.

 


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Figure 12c.  Stage T2 lesion of the anterior distal right thigh. (a) Immediate anterior image of the lower extremities shows the injection site above the right knee. (b, c) Anterior (b) and right lateral (c) images of the pelvis obtained 23 minutes later reveal two right inguinal lymph nodes (straight arrow). Note that each node has its own lymphatic channel (curved arrows). This indicates that both nodes are SLNs: If there were only one channel, the more inferior node would be an SLN and the more superior node would be a secondary node. (d) Delayed anterior pelvic image obtained 5 minutes later reveals a right external iliac node (short arrow) superior to the inguinal nodes (long arrow). Because the former did not have its own lymphatic channel, it is a secondary node. Subsequent delayed images of the pelvis and abdomen (not shown) revealed no additional nodes. At histologic analysis, all nodes were tumor free.

 


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Figure 12d.  Stage T2 lesion of the anterior distal right thigh. (a) Immediate anterior image of the lower extremities shows the injection site above the right knee. (b, c) Anterior (b) and right lateral (c) images of the pelvis obtained 23 minutes later reveal two right inguinal lymph nodes (straight arrow). Note that each node has its own lymphatic channel (curved arrows). This indicates that both nodes are SLNs: If there were only one channel, the more inferior node would be an SLN and the more superior node would be a secondary node. (d) Delayed anterior pelvic image obtained 5 minutes later reveals a right external iliac node (short arrow) superior to the inguinal nodes (long arrow). Because the former did not have its own lymphatic channel, it is a secondary node. Subsequent delayed images of the pelvis and abdomen (not shown) revealed no additional nodes. At histologic analysis, all nodes were tumor free.

 


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Figure 13a.  Stage T2 melanoma of the anterior left calf inferior to the knee. (a) Immediate anterior image of the left leg demonstrates a lymphatic channel efferent from the injection site. (b) Anterior image of the lower pelvis and proximal thighs obtained 10 minutes later reveals a chain of left inguinal nodes (arrow). An anterior abdominal image obtained 30 minutes after injection (not shown) failed to reveal radiotracer uptake in any iliac or periaortic nodes. At histologic analysis, all nodes were tumor free.

 


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Figure 13b.  Stage T2 melanoma of the anterior left calf inferior to the knee. (a) Immediate anterior image of the left leg demonstrates a lymphatic channel efferent from the injection site. (b) Anterior image of the lower pelvis and proximal thighs obtained 10 minutes later reveals a chain of left inguinal nodes (arrow). An anterior abdominal image obtained 30 minutes after injection (not shown) failed to reveal radiotracer uptake in any iliac or periaortic nodes. At histologic analysis, all nodes were tumor free.

 


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Figure 14a.  Stage T4 lesion of the left great toe. (a) Dorsal (anterior) view of the left foot obtained immediately after injection reveals a lymphatic channel (arrow) efferent from the injection site. (b) Subsequent anterior image of the left leg shows no lymph nodes at this level (the lymphatic channel runs anteromedially and is not well visualized). (c) Anterior image of the pelvis obtained 5 minutes later reveals prominent radiotracer uptake in a left inguinal node (arrow) as well as two smaller nodes superolaterally. A delayed image of the abdomen and pelvis obtained 30 minutes later (not shown) revealed no additional nodes. At histologic analysis, only the single node with the more prominent uptake contained metastases, and this node is the SLN.

 


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Figure 14b.  Stage T4 lesion of the left great toe. (a) Dorsal (anterior) view of the left foot obtained immediately after injection reveals a lymphatic channel (arrow) efferent from the injection site. (b) Subsequent anterior image of the left leg shows no lymph nodes at this level (the lymphatic channel runs anteromedially and is not well visualized). (c) Anterior image of the pelvis obtained 5 minutes later reveals prominent radiotracer uptake in a left inguinal node (arrow) as well as two smaller nodes superolaterally. A delayed image of the abdomen and pelvis obtained 30 minutes later (not shown) revealed no additional nodes. At histologic analysis, only the single node with the more prominent uptake contained metastases, and this node is the SLN.

 


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Figure 14c.  Stage T4 lesion of the left great toe. (a) Dorsal (anterior) view of the left foot obtained immediately after injection reveals a lymphatic channel (arrow) efferent from the injection site. (b) Subsequent anterior image of the left leg shows no lymph nodes at this level (the lymphatic channel runs anteromedially and is not well visualized). (c) Anterior image of the pelvis obtained 5 minutes later reveals prominent radiotracer uptake in a left inguinal node (arrow) as well as two smaller nodes superolaterally. A delayed image of the abdomen and pelvis obtained 30 minutes later (not shown) revealed no additional nodes. At histologic analysis, only the single node with the more prominent uptake contained metastases, and this node is the SLN.

 

    Radiopharmaceuticals
 Top
 Abstract
 Introduction
 Radiopharmaceuticals
 Imaging Considerations
 Conclusions
 References
 
In scintigraphy of malignant melanoma, technetium-99m–labeled colloids (eg, filtered and unfiltered Tc-99m sulfur colloid, Tc-99m antimony trisulfide colloid) as well as Tc-99m–labeled albumin (eg, Tc-99m human serum albumin [HSA]) are generally used. The difference in the movement of these agents through lymphatic channels and lymph nodes is attributable to differences in particle size. The particles must be small enough to enter the lymphatic vessels, yet large enough not to leak from these lymphatic vessels and diffuse into the capillary membranes. However, if the particles are too large, they will migrate too slowly through the lymphatic vessels, thereby preventing sufficient accumulation in a lymph node prior to imaging or mapping. Given these requirements, the optimum particle size ranges from 30 to 100 nm (2).

Glass et al (3) evaluated Tc-99m sulfur colloid, Tc-99m antimony trisulfide colloid, and Tc-99m HSA in a comparison study, which demonstrated that the three pharmaceuticals had similar distribution patterns. However, differences were evident in terms of extent of lymph node radiotracer uptake and total number of lymph nodes visualized. HSA, both colloidal and noncolloidal, demonstrated rapid clearance from the injection site and allowed good lymphatic channel visualization. However, because of its small particle size (<10 nm), it passes through the lymph nodes too rapidly and migrates to numerous non-SLNs, thereby making SLN identification difficult if not impossible. Furthermore, in the United States, HSA is not approved by the Food and Drug Administration (FDA) for use in lymphoscintigraphy. Tc-99m antimony trisulfide colloid, whose particle size ranges from 30 to 50 nm, is an excellent agent for lymphoscintigraphy. Unfortunately, it is available only in Europe, Australia, and Canada, but not in the United States (1).

In the United States today, Tc-99m sulfur colloid is the only FDA-approved agent for lymphoscintigraphy. However, its large particle size (100–1,000 nm) makes it less than ideal for lymphoscintigraphy. Many investigators have found that filtering the sulfur colloid into smaller particles makes it comparable to Tc-99m antimony trisulfide colloid (2,46). By passing the sulfur colloid through a 0.2-µm filter, the particles are filtered to a maximum size of 100 nm, with the vast majority of particles being 15–50 nm. In our laboratory, a 0.2-µm filter is used, as recommended and used by the H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida in Tampa (1).

Consistent with the protocol of the Moffitt Center, 600 µCi (1.67 x 107 Bq) of filtered Tc-99m sulfur colloid is drawn up in 1 mL of saline solution. This is then divided into four equal doses of 150 µCi each and injected intradermally around the lesion with tuberculin syringes. Each injection site is about 1 cm from the lesion.


    Imaging Considerations
 Top
 Abstract
 Introduction
 Radiopharmaceuticals
 Imaging Considerations
 Conclusions
 References
 
Imaging Protocol
Imaging is started immediately after injection because cutaneous lymphatic flow is quite rapid. For lymphoscintigraphy, we use a large-field-of-view detector with a parallel-hole collimator, an energy setting of 140 keV for Tc-99m, and a 10% window. For the first image, the patient is positioned with the injection site in the field of view to assess radiotracer contamination. If such contamination is present, whether on the skin surface or on cloth, it must be removed. Before subsequent imaging is performed, it is desirable to obtain an outline of the patient’s body for image orientation purposes. This outline is obtained with use of a radioactive flood source (eg, cobalt-57) inserted between the patient and the detector surface. On the resulting transmission image, the flood source background appears black, whereas the patient’s body is outlined as a "cold" area, which will facilitate image interpretation. Subsequent imaging involves positioning the detector over the region of the lymph nodes that drain the lesion. Digital images are acquired sequentially on a computer every 60 seconds. This rapid-sequence imaging is necessary to follow the lymphatic channels because they are seen only transiently. Analog film images are acquired sequentially for 5 minutes. The lymphatic channel draining the lesion is afferent to the SLN. If more than one channel is identified, there is more than one SLN. This helps in distinguishing SLNs from non-SLNs. At times during the imaging sequence, the patient is repositioned in an oblique or lateral plane to visualize lymph nodes that are projected over the injection site or superimposed on other lymph nodes. When the region of interest is the axillary node basin, the arm is extended and placed behind the patient’s head. Initially in our series, the skin overlying the lymph nodes was marked with either gentian violet stain or a marking pen with indelible ink. The surgeon preferred to inspect the scan himself rather than rely on marking of the skin surface. If one prefers to mark the skin surface rather than send the scans to the operating room, it is important to mark the skin with the patient in the same relative position as that anticipated for surgical biopsy.

After the imaging is completed, the patient is taken to the operating room and examined by the surgeon with an intraoperative nuclear probe prior to lymph node removal. This device is a handheld gamma ray–detecting probe (Neoprobe, Columbus, Ohio) that detects the radioactivity of the draining lymph nodes, thereby directing the surgeon to the optimal incision site (7). Some surgeons may also use blue dye at the time of surgery to help further delineate the lymphatic drainage patterns and lymph nodes.

Typical Lymphatic Drainage Patterns and Key Points
Figure 2 demonstrates a stage T3 lesion in the left parietotemporal region of the scalp. On an anterior image obtained immediately after the intradermal injection of four doses of radiotracer around the lesion, a draining lymphatic channel is visualized, followed by at least two lymph nodes along the channel (Fig 2a). (In this and all subsequent figures, the injection sites are designated by a white arrowhead.) For better delineation and localization of these nodes, a left lateral image was obtained 5 minutes later (Fig 2b). This image reveals more lymph nodes than were appreciated on the anterior projection. In fact, the first lymph node drained by the lymphatic channel, a temporal node, could not be seen clearly on the anterior image. Immediately inferior to the temporal node is a preauricular node, followed by two periparotid nodes and a posterior auricular node located inferior to the periparotid nodes. The lymphatic channel then drains caudally and anteriorly into a high jugular node. Because the temporal node was the first node that appeared along the lymphatic tract, it is by definition an SLN. The remaining nodes may be nonsentinel (secondary) nodes. Additional secondary nodes are visualized in the left cervical region on a delayed image (Fig 2c).

Figure 3 demonstrates how obtaining a transmission image allows more precise anatomic localization of lymph nodes. The first image obtained after injection of radiotracer around a T4 melanoma of the left ear is a left lateral image obtained without the Co-57 flood source behind the patient (Fig 3a). Immediately afterward, the flood source was applied and a repeat left lateral image was acquired (Fig 3b). The latter image allowed proper orientation for image interpretation; it is evident that the lymphatic channel drains into several lymph nodes in the periparotid and superior jugular region and that there are two lymph nodes in the supraclavicular chain. Such anatomic detail and localization is more difficult (if not impossible) by inspecting the nontransmission image alone.

Figure 4 demonstrates the importance of scanning both sides of the body whenever the primary lesion is midline in location. Initial anterior images of the neck obtained over an interval of about 20 minutes in a patient with stage T3 melanoma of the posterior neck demonstrate three left cervical lymph nodes (Fig 4a, Fig 4b). Approximately 20 minutes later, we noticed a small area of activity in the right axilla on the persistence scope. An image obtained over the right hemithorax reveals a right axillary lymph node (Fig 4c). By subsequently using the gamma probe in the operating room, the surgeon determined that the three left-sided nodes were located along the spinal accessory chain and within the supraclavicular fossa.

Figure 5 shows a fairly typical drainage pattern for a melanoma within the upper aspect of the shoulder. This stage T3 lesion of the right shoulder initially drains into a supraclavicular lymph node (Fig 5a). A subsequent image obtained 20 minutes later also reveals a right axillary lymph node (Fig 5b). The lymphatic drainage in this area is quite variable and may drain to one or both of these nodal basins. In this case, both nodes are SLNs because they have separate drainage from the primary tumor.

Figure 6 illustrates the need for lateral projections when the axilla is involved, due to possible superimposition of the injection site over the draining lymph nodes on the frontal projection. The patient presented with a T3 melanoma on the skin overlying the left scapula. An immediate anterior image demonstrates only the injection site (Fig 6a). However, a left lateral view obtained 5 minutes later demonstrates three left axillary lymph nodes (Fig 6b). A subsequent left lateral view obtained 10 minutes later (not shown) revealed no additional nodes, and a repeat anterior image obtained 10 minutes later (also not shown) again depicted only the injection site. Because the lymph nodes and the injection site were superimposed over each other in the same anteroposterior horizontal plane, had we not performed left lateral imaging, the lymph nodes would not have been observed, yielding false-negative results.

Lateral projections are also very useful when the melanoma is on the skin surface overlying the breast, as in Figure 7. The patient is a woman with a T2 melanoma of the left breast. An anterior image obtained immediately after radiotracer injection reveals a lymphatic channel (Fig 7a). As in lymphoscintigraphy of primary breast tumors, the patient’s ipsilateral arm was elevated. A repeat anterior image obtained 5 minutes later demonstrates a single left axillary lymph node (Fig 7b). A subsequent left lateral view (Fig 7c) reveals two additional nodes that were not evident on the repeat anterior projection: Because all three axillary lymph nodes were superimposed over one an-other on the anterior projection, there appeared to be only one lymph node.

Figure 8 depicts lymph node drainage patterns involving a melanoma of the upper extremity—in this case, a stage T2 melanoma of the right third finger. An image obtained immediately after injection reveals a right epitrochlear lymph node (Fig 8a), whereas a subsequent image of the right arm and shoulder reveals two axillary nodes (Fig 8b). This demonstrates the importance of imaging the entire extremity when the melanoma is located on the distal aspect of the extremity. Clearly, if only the axillary image had been obtained, the epitrochlear node would have gone undetected. Previous reports have shown that epitrochlear nodes are found in 18% of patients with melanoma in this distribution (8).

Midline melanomas of the abdomen, like those of the neck, also require imaging of both sides of the body. Pelvic imaging is equally important in the event that the tumor drains into inguinal lymph nodes instead of or in addition to axillary nodes. For example, Figure 9 demonstrates a stage T2 melanoma located superior to the umbilicus. An anterior projection of the chest and abdomen obtained immediately after injection demonstrates substernal nodes as well as bilateral axillary nodes. Images of the pelvis (not shown) demonstrated no additional nodes. A large-field-of-view gamma camera facilitates imaging of the abdomen and both axillae.

On occasion, the SLN is not within the lymph node basin that is closest to the primary tumor. This is exemplified in Figure 10, in which a T3 lesion of the lower right flank drains only into two right axillary lymph nodes. The initial images (not shown) were obtained over the abdomen and pelvis in anticipation of finding lymph nodes in one of these locations. Because none was observed by 30 minutes after injection (Fig 10a), we scanned the chest and detected the two right axillary nodes (Fig 10b).

Figure 11 demonstrates a melanoma in a quite unusual location: the right labium minus. A right inguinal node is visualized on an anterior image obtained immediately after injection, along with a faint lymphatic channel draining to the node (Fig 11a). On a subsequent image obtained 20 minutes later, this node is better visualized, along with an adjacent node paradoxically located inferior to it (Fig 11b). Lymph nodes were also visualized more superiorly. At surgery performed in conjunction with the use of blue dye, the lymphatic anatomy was clearly defined. The lymphatic drainage passed through the first visualized node to a node located slightly inferior to it and adjacent to the femoral vein at the level of the inguinal ligament. Drainage then flowed cephalad to the external iliac nodal chain beneath the inguinal ligament. For a primary tumor in a location such as this, it is important to obtain delayed images of the abdomen in the event that abdominal lymph nodes might be seen. In this case, abdominal images were negative.

Because the SLN is the first node in a group to be encountered by lymphatic flow through the lymphatic channel, visualization of the lymphatic channel to the first node will help correctly identify the true SLN. Continuous dynamic or rapid-sequence imaging is extremely useful because lymphatic channels appear only transiently. This point is illustrated in Figure 12, which demonstrates a T2 melanoma of the distal right thigh. Two right inguinal lymph nodes were seen on a static image obtained 25 minutes after injection (not shown). However, inspection of the dynamic image acquired 23 minutes after injection reveals two lymphatic channels, both draining into the two inguinal lymph nodes (Fig 12b, Fig 12c). This indicates that both nodes are SLNs because each has its own lymphatic channel. Dynamic images are needed to help identify lymphatic channels that might not be observed on static images.

Figure 13 depicts a stage T2 melanoma of the anterior left calf. An anterior view of the lower extremities obtained immediately after injection reveals a lymphatic channel draining from the primary tumor anteromedially along the left thigh (Fig 13a). A subsequent anterior view of the pelvis and upper left thigh reveals a chain of left in-guinal nodes, as one would anticipate (Fig 13b). Subsequent images of the abdomen (not shown) revealed no additional nodes. All of the inguinal nodes were tumor free.

Another melanoma of the lower extremities is shown in Figure 14—in this case, a stage T4 lesion of the left great toe. A dorsal (anterior) view of the left foot obtained immediately after injection reveals a lymphatic channel arising from the injection site (Fig 14a). No popliteal nodes are visualized (Fig 14b). An anterior view of the pelvis demonstrates the lymphatic channel draining into multiple left inguinal nodes, the most prominent of which contained metastases (Fig 14c). The other nodes were tumor free.


    Conclusions
 Top
 Abstract
 Introduction
 Radiopharmaceuticals
 Imaging Considerations
 Conclusions
 References
 
SLN mapping with lymphoscintigraphy is a valuable diagnostic tool used by the surgeon for accurate localization of the SLN. Morton et al (9) were the first to advocate use of the SLN concept for the staging of early melanoma, and lymphoscintigraphy is now considered part of the standard of care in this patient population (10). Therefore, it is imperative that the radiologist or nuclear medicine physician know which radiopharmaceuticals to use, recognize different lymphatic drainage patterns from various primary tumor sites throughout the body, use proper imaging techniques, and be aware of potential pitfalls in image interpretation. These pitfalls are discussed in the following paragraphs.

First, there may be more than one SLN because multiple lymphatic channels can drain lymphatic fluid from a given tumor site to more than one lymph node group in multiple anatomic locations. This is exemplified in Figure 12, in which two SLNs are identified by the fact that each node has its own lymphatic channel with direct flow of lymphatic fluid from the tumor.

Second, proper patient positioning and imaging in the lateral or oblique projection will allow detection of a node or nodes not seen on a frontal view, which would otherwise lead to false-negative results. For example, in Figure 6, axillary lymph nodes are seen on the lateral projection only, due to superimposition of these nodes over the injection site on the frontal projections.

Third, the SLN may not necessarily be anatomically close to the primary tumor, so that imaging (or at least surveying with the gamma camera) of unsuspected sites for the SLN should be performed, particularly if no nodes are observed near the primary lesion. This is illustrated in Figure 10, in which a melanoma of the right flank region drains into two right axillary lymph nodes. Intuitively, one would have anticipated lymph node visualization in the abdomen or pelvis. Had we not imaged the chest, these nodes would have gone undetected. Similarly, when lymphoscintigraphy is performed for a primary tumor located in a lower extremity, abdominal imaging should also be performed to ascertain the presence of periaortic or other abdominal lymph nodes.

Fourth, the location of the SLN can vary from one patient to another, even if the primary lesions are in similar locations (11). The patterns and sites of lymphatic drainage we have observed and have presented in this article serve as examples but may differ somewhat from those observed by others.

Finally, not only is proper imaging technique important, but it is essential that radiologists and nuclear medicine physicians communicate effectively with the surgeon. Moreover, the departments of nuclear medicine, surgery, and even pathology must work as a team to coordinate imaging, surgical procedures, and handling of the pathologic specimens.


    Footnotes
 
** indicates entire organ system. Back

Abbreviations: HSA = human serum albumin, SLN = sentinel lymph node


    References
 Top
 Abstract
 Introduction
 Radiopharmaceuticals
 Imaging Considerations
 Conclusions
 References
 

  1. Berman CG, Choi J, Hersh MR, Clark RA. Melanoma lymphoscintigraphy and lymphatic mapping. Semin Nucl Med 2000; 30:49-55.[CrossRef][Medline]
  2. Hung JC, Wiseman GA, Wahner HW, et al. Filtered Tc-99m sulfur colloid evaluated for lymphoscintigraphy. J Nucl Med 1995; 36:1895-1901.[Abstract/Free Full Text]
  3. Glass EC, 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]
  4. Mudun A, Murray DR, Herda SC, et al. Early stage melanoma: lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intra-operative gamma probe. Radiology 1996; 199:171-175.[Abstract/Free Full Text]
  5. Goldfarb LR, Alazraki NP, Eshima D, et al. Lymphoscintigraphic identification of sentinel lymph nodes: clinical evaluation of 0.22-micron filtration of Tc-99m sulfur colloid. Radiology 1998; 208:505-509.[Abstract/Free Full Text]
  6. Eshima D, Eshima L, Botti N, et al. Tc-99m sulfur colloid for lymphoscintigraphy: effects of preparation parameters. J Nucl Med 1996; 37:1575-1578.[Abstract/Free Full Text]
  7. Jacobs IA, Chevinsky AH, Swayne LC, et al. Gamma-probe directed lymphatic mapping and sentinel lymphadenectomy in primary melanoma: reliability of the procedure and analysis of failures after long-term follow-up. J Surg Oncol 2001; 77:157-164.[CrossRef][Medline]
  8. Tanabe KK. Lymphatic mapping and epitrochlear lymph node dissection for melanoma. Surgery 1997; 121:102-104.[CrossRef][Medline]
  9. Morton DL, Wen D, Wong JH, et al. Technical details of intra-operative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127:392-399.[Abstract/Free Full Text]
  10. Morton DL, Chan AD. Current status of intra-operative lymphatic mapping and sentinel lymphadenectomy for melanoma: is it standard of care? J Am Coll Surg 1999; 189:214-223.[CrossRef][Medline]
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