Results

The images are usually easy to interpret. The above-described technique depicts the lymphatic duct(s) in 80-98% of patients. In our hands, it hardly ever fails to visualize the sentinel node(s) [42,44-48]. Lymphatic drainage is complex in the neck and this is the most difficult lymphatic field for the interpretation of lymphoscintigraphy. We could not identify a sentinel node in 3 of 25 (12%) patients with a melanoma in the head and neck region [49]. O'Brien and coworkers faced this problem in 2 out of 97 patients (2%) [23], Alex and co-workers in 2 out of 22 (9%) [50]. In 34% to 84% of the patients, drainage in the neck is discordant with clinical prediction [5,23]. A lymph channel can traverse the upper neck node group and pass directly to a sentinel node in the lower neck. Bilateral drainage is seen in approximately 10% of the patients [52]. Multiple sentinel nodes are depicted in the majority of the patients, on average 2.5 per patient [23,49,53]. A total of five sentinel nodes in the neck is not rare [23,53]. The primary lesion site is often close to where one would expect the sentinel node. The bulk of the radioactive tracer stays behind at the injection site and may obscure a nearby sentinel node. In a patient with a melanoma on the cheek, for instance, a sentinel node in the underlying parotid gland is often not identifiable on the images. In this regard, lateral images may be important to maximize separation between the primary site and the sentinel node. The neck contains more than 100 lymph nodes packed in a small area. Frequently, it is difficult to distinguish first-tier nodes from secondary nodes because more than one sentinel node is often present and because nonsentinel nodes may pick up radioactivity as well (Fig. 3).

The axilla is the easiest lymphatic field for the nuclear medicine physician. Usually there is only one sentinel node [47]. Nonsentinel nodes are depicted less frequently in the axilla than in the neck and groin. When the groin receives drainage from a trunk melanoma, there is often one sentinel node above the level of the inguinal ligament. A melanoma on the leg usually drains to two superficial sentinel nodes below the inguinal ligament. Exceptions to these rules occur rather

Figure 3 Anterior (a) and right lateral (b) lymphoscintigrams of a 37-year-old man with a melanoma behind the right ear. A string of lymph nodes is visualized within 2 min. From these images, it is not clear how many sentinel nodes and how many nonsentinel nodes are depicted. The dynamic images were not helpful either. Intraoperative mapping with patent blue dye (Blue Patente V, Guerbet, Aulney-Sous-Bois, France) revealed lymphatic ducts coming from the primary lesion going to a sentinel node at the anterior margin of the sternocleidomastoid muscle, to a second sentinel node in the parotid gland, and to a third sentinel node immediately underneath the primary lesion site. The other depicted nodes were higher-echelon nodes. The second sentinel node (arrow) contained the highest level of radioactivity and was the only one with metastatic disease.

Figure 3 Anterior (a) and right lateral (b) lymphoscintigrams of a 37-year-old man with a melanoma behind the right ear. A string of lymph nodes is visualized within 2 min. From these images, it is not clear how many sentinel nodes and how many nonsentinel nodes are depicted. The dynamic images were not helpful either. Intraoperative mapping with patent blue dye (Blue Patente V, Guerbet, Aulney-Sous-Bois, France) revealed lymphatic ducts coming from the primary lesion going to a sentinel node at the anterior margin of the sternocleidomastoid muscle, to a second sentinel node in the parotid gland, and to a third sentinel node immediately underneath the primary lesion site. The other depicted nodes were higher-echelon nodes. The second sentinel node (arrow) contained the highest level of radioactivity and was the only one with metastatic disease.

frequently. We and others have seen up to five sentinel nodes in the groin [54]. Sometimes, the lymph flow goes directly to Cloquet's node, or, rarely, may bypass the superficial groin to drain directly to the hypogastric or iliac nodes. Non-sentinel nodes are often depicted in the groin and may render the images difficult to interpret.

In the neck, the skin mark can usually be placed exactly overlying the target. Occasionally, the mark is somewhat off target, presumably because the position of the head is different during the operation compared to what it was during lymphoscintigraphy. In the axilla, it is difficult to indicate the location of the sentinel node because this is much more a three-dimensional lymphatic basin than the groin or the neck. Also, the position of the arm may not be exactly the same during scintigraphy and during the operation, so layers of axillary fat containing a sentinel node may shift. What one can do is place the skin mark on the anterior chest wall and then calculate the depth on a lateral view [54]. The gamma detection probe is helpful when marking the axilla. The skin mark can always be positioned exactly overlying the target node in the groin.

Although only a small percentage of the radioactivity ends up in the sentinel node, its uptake far exceeds the uptake in the surrounding normal tissue. The accumulation of the 99mTc-nanocolloid in sentinel nodes and surrounding normal tissues was investigated in a study of 60 consecutive patients with clinically localized melanoma [42]. Sentinel nodes and nearby nonsentinel nodes were removed for examination. All excised nodes as well as small samples of skin and subcutaneous fat were measured in a gamma well counter. The uptake of the tracer as a percentage of the injected dose per gram of tissue and per node was calculated, with a correction for physical decay. The uptake in the whole sentinel node averaged 0.36% of the injected dose, with a range of 0.0013-6.8%. The average uptake per gram of tissue in the sentinel node was 1.0% of the administered dose, with a range of 0.003-17.4%. Lymph nodes are surrounded by fat, which is covered by skin. Uptake in these surrounding tissues was found to be far less than in sentinel nodes. The average uptake of radioactivity in a gram of overlying skin was 0.01% of the injected dose (range: 0.0-0.22%). In a gram of fat, the average uptake was 0.0035% (range: 0.0-0.081%). The visibility of a hot spot depends on the uptake in that location compared to the uptake in the surrounding tissues: the target-to-background ratio. Measured with a gamma detection probe in the open wound, the sentinel node-to-background ratio was calculated to be 36 on average (range: 2-722) when using the 99mTc nanocolloid [42]. In studies using the 99mTc-labeled sulfur colloid, ratios are somewhat lower, on average 8.5 with ranges of 1.0 to 65 and 30 to 300 [41,55].

If lymphoscintigraphy were to be repeated, would it show the same drainage pattern? Its reproducibility was the subject of two studies. The first study was performed at our institution and concerned 25 patients with clinically localized melanoma [40]. The same investigator performed two scintigraphic studies in an identical fashion in each patient with a 2-4-week interval. The 99mTc-nanocolloid was the tracer used. Both dynamic and static imaging were performed. Both scintigraphy series showed drainage to the same lymphatic fields in all patients. However, a difference in number of sentinel nodes depicted on the first and second study was noted in three patients (12%). So, the reproducibility was 88%. Otherwise, the images were identical for number and location of nodes. In the second study, the 99mTc sulfur colloid was used [55]. The result was similar with a repro-ducibility of 85%. The reason for this limited reproducibility is unknown, but a number of causes can be considered either related to the tracer, to the technique, or to the patient. Unnoticed variations in the technique of injection or the site of injection and variations in the composition of the radiopharmaceutical are possible explanations. Perhaps lymphatic drainage may vary in time within an individual. Factors like previous exertion, body hydration, variation in tissue oncotic, and hydrostatic pressure of blood may play a role [56]. Lymphoscintigraphy reflects drainage and may show such a variability in the physiologic process. In most patients in our own study, the first scintigraphy study was done a few weeks after the primary lesion had been excised [40]. All patients underwent their second preoperative scan a maximum of 4 weeks after the first scan. During the wound-healing process, granulation tissue is gradually replaced by more dense and compact fibrous tissue. It is conceivable that such alterations influence to some extent the lymphatic drainage of the area concerned. No matter what the reasons for the discrepancies are, the limited reproducibility is a matter of concern. This variability may explain some of the false-negative sentinel node procedures that have been reported.

The reproducibility of the reporting of lymphoscintigraphy studies has also been investigated [44]. There is a concordance rate of 98% when different nuclear medicine physicians interpret the lymphoscintigraphy images of the same patient.

Despite paying attention to every detail of the lymphoscintigraphy, there is sometimes a discrepancy between the number of sentinel nodes that is indicated by lymphoscintigraphy and the number of sentinel nodes found during the operation. This observation prompted us to review the nuclear medicine reports and operative notes of our first 150 patients [57]. The primary lesion was situated in the head and neck region in 13 patients, on the trunk in 52, on the arm in 23, and on a lower extremity in 62 patients. Dynamic and static lymphoscintigraphy were performed as described earlier in this chapter.

Compared to lymphoscintigraphy, a different number of sentinel nodes was found during the operation in 33 of the 189 lymphatic fields (17%). Scintigraphy suggested too few nodes in 26 basins and too many in 6. Only one of the discrepancies was felt to be due to inadequate surgical exploration. The majority of discrepancies in the number of sentinel nodes was apparently caused by the limited resolution of the gamma camera (i.e., its limited discriminating power). A typical scenario was the failure of flow images to distinguish two parallel lym phatic channels that were running to two separate nodes. Occasionally, a single hot spot on the static images proved on exploration to be, in fact, made up by two adjacent sentinel nodes, each with a separate blue lymphatic duct leading to it (Fig. 4). In a few patients, two separate lymphatic channels drained to opposite ends of a single elongated lymph node, giving the false impression that two sentinel nodes were present.

99mtc Nanocolloid

Figure 4 Lymphoscintigraphy of a 48-year-old woman with a melanoma on the right forearm. (a) Anterior view 30 min;(b) right lateral view 30 min;(c) anterior view 2 h;(d) right lateral view 2 h. To the casual observer, the late images (c, d) may show one hot spot. With careful observation of the early lateral view (b), however, there may be two adjoining sentinel nodes. During the operation, we identified two lymphatic ducts and removed two sentinel nodes adjacent to each other. Both were radioactive. Subsequent scanning of the wound for residual radioactivity revealed a definite hot focus right underneath the site where the two sentinel nodes had been removed. Exploring deeper down, a third blue lymphatic channel was found, coming from the direction of the arm, leading to a third node that was both blue and radioactive. The limited resolution of the gamma camera made it impossible to identify the third sentinel node on the images.

Figure 4 Lymphoscintigraphy of a 48-year-old woman with a melanoma on the right forearm. (a) Anterior view 30 min;(b) right lateral view 30 min;(c) anterior view 2 h;(d) right lateral view 2 h. To the casual observer, the late images (c, d) may show one hot spot. With careful observation of the early lateral view (b), however, there may be two adjoining sentinel nodes. During the operation, we identified two lymphatic ducts and removed two sentinel nodes adjacent to each other. Both were radioactive. Subsequent scanning of the wound for residual radioactivity revealed a definite hot focus right underneath the site where the two sentinel nodes had been removed. Exploring deeper down, a third blue lymphatic channel was found, coming from the direction of the arm, leading to a third node that was both blue and radioactive. The limited resolution of the gamma camera made it impossible to identify the third sentinel node on the images.

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