Pearls and pitfalls of radionuclide imaging of the lymphatic system. Part 1: sentinel node lymphoscintigraphy in malignant melanoma

Radionuclide imaging of the lymphatic system has a major role in the management of two main patient groups. First, pre-operative lymphoscintigraphy is a highly accurate method of sentinel node localization and can help guide minimally invasive surgery in a variety of tumour groups. Second, lymphoscintigraphy can play a pivotal role in assessing the cause of extremity swelling. This is the first of two pictorial essays on radionuclide imaging of the lymphatic system and will focus on sentinel node imaging in malignant melanoma. Regional nodal sampling is routinely performed in an increasing number of tumour groups and is well established in malignant melanoma and breast carcinoma. Careful attention to technical performance and image interpretation is essential to maximize the clinical utility of the test. This article provides a pictorial review of the interpretative pearls and pitfalls of sentinel node lymphoscintigraphy in malignant melanoma patients.     

Nondetection of sentinel lymph node with lymphoscintigraphy as a result of massive malignant invasion shown by positron emission tomography.

PURPOSE: The authors report the complementary roles of lymphoscintigraphy in sentinel node mapping and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in a massively invaded sentinel node. MATERIALS AND METHODS: A 49-year-old woman was referred to the authors' institution after the resection of a malignant melanoma (Clark IV, Breslow 5.25) of the right buttock. No evidence of regional or distant organ metastases was observed on bone scintigraphy or thoracoabdominal or cerebral computed tomographs. Preoperative lymphoscintigraphy showed drainage around a circular structure, without any node detected. F-18 FDG PET imaging detected an area of focal, markedly hypermetabolic activity at the same location. RESULTS: The focal, markedly hypermetabolic activity detected by F-18 FDG PET corresponded to a massively invaded sentinel node not shown by lymphoscintigraphy but found and removed at the time of surgery. Radical regional lymphadenectomy showed only one small additional lymph node micrometastasis detected after immunohistochemical staining for S-100 protein and HMB45 antigen. CONCLUSIONS: This case emphasizes the complementary roles of lymphoscintigraphy sentinel node mapping and F-18 FDG PET. Indeed, a massively invaded sentinel node may be detected by PET but missed by lymphoscintigraphy.     

Technical aspects of performing lymphoscintigraphy: optimization of methods used to obtain images

Sentinel node detection is an important part of the clinical management of newly diagnosed melanoma. Now there is a similar or even greater enthusiasm for sentinel node evaluation in patients with breast carcinoma. However, controversies exist regarding the dose, volume, and route of administration. Even the role of lymphoscintigraphy itself, in contrast to using only a hand-held gamma probe during surgery for sentinel node detection, is being debated. Nevertheless, many centers and surgeons find that lymphoscintigraphy images are valuable in the treatment of patients and they use lymphoscintigraphy as a guide during surgery and to confirm the results obtained with the hand-held probe. Centers just beginning to use lymphoscintigraphy may find the images especially useful. Given this fact, the authors wanted to define the practical and technical aspects of performing lymphoscintigraphy in patients with breast cancer and examined various methods for the optimization of the technique of image acquisition. The suggested technique is generally free of the controversies noted above and applies to most patients. It includes various maneuvers that aim to improve the rate of sentinel node visualization using the gamma camera and the accuracy of node detection. The recommendations presented here should prove useful for both those experienced and for those centers just beginning to use the technique of lymphoscintigraphy.     

Alternative lymphatic pathway after previous axillary node dissection in recurrent/primary breast cancer

OBJECTIVES: The sentinel lymph node approach has almost become the standard procedure of choice in the management of patients with early breast cancer. The status of sentinel nodes, whether or not pathologically involved by cancer cells, represents those of the axillary nodes with a negative predictive value of almost 100%. If the axillary lymphatic nodal drainage is altered, alternative lymphatic pathways and accordingly sentinel node location will be changed. METHODS: In this article, 4 patients are presented, 3 with recurrent breast cancer who had already undergone lumpectomy, axillary node dissection, and radiotherapy in the past and 1 with primary breast cancer after surgical removal of a malignant melanoma on her back and had axillary node dissection on the same side as the breast cancer. These patients underwent lymphoscintigraphy followed by sentinel node localization using the gamma probe and also blue dye injection during surgery. RESULTS: All patients showed alternate lymphatic pathways, 1 had an ipsilateral internal mammary node and crossed lymphatics to a contralateral axillary node, 2 had intramammary sentinel nodes, and 1 had an internal mammary on the same side. Pathologic examination of the intramammary and contralateral sentinel nodes were negative for metastases. Internal mammary sentinel nodes were not biopsied. CONCLUSION: We feel that sentinel node lymphoscintigraphy should be done even in patients who have altered lymphatic pathways resulting from previous axillary node dissection. It allows identifying and biopsy of the sentinel node at its new unpredicted location.     

Sentinel node detection and definition may depend on the imaging agent and timing.

PURPOSE: Two cases of sentinel lymph node imaging are presented in which the results are exceptions to what the literature generally defines as sentinel lymph nodes. In one case, Tc-99m antimony trisulfide colloid produced significantly different results than did Tc-99m tin colloid. In the second case, the results bring into question the definition of a sentinel node as the first in a lymphatic drainage pathway. MATERIALS AND METHODS: In one patient, lymphoscintigraphy was performed initially using Tc-99m antimony trisulfide colloid injected intradermally around a melanoma excision site. Repeated lymphoscintigraphy 1 month later, 1 hour before sentinel node excision, was done using Tc-99m tin colloid, a larger particle than antimony trisulfide colloid. The second patient, with a melanoma biopsied only, had sentinel node imaging performed using Tc-99m sulfide colloid, a particulate also larger than antimony trisulfide colloid and also 1 hour before sentinel node excision. RESULTS: In the first patient, imaging with the smaller antimony trisulfide colloid showed more lymphatic pathways and more sentinel nodes than with tin colloid. In the second patient, the first focus of retention of the imaging agent in the lymphatic pathway seen showed less intense accumulation than the next focus in the pathway, contrary to published reports that the sentinel node shows more intense accumulation than do nodes further downstream in a lymphatic pathway. CONCLUSIONS: There are exceptions to published characteristics of sentinel node lymphoscintigraphy, so care must be exercised in localizing sentinel nodes.     

Biopsy of sentinel lymph nodes guided by lymphoscintigraphic mapping in patients with breast cancer

OBJECTIVE. The purpose of this study was to determine the technical success rate of sentinel node biopsy with lymphoscintigraphy in women with breast cancer and the frequency with which sentinel node biopsy obviated axillary dissection. Factors affecting the success rate of sentinel node biopsy and lymphoscintigraphy were also evaluated. MATERIALS AND METHODS. Retrospective review revealed 119 women with breast cancer who underwent lymphoscintigraphy and sentinel node biopsy at our institution during the study period. A planned axillary dissection was performed in 13 of the first 16 patients; otherwise, axillary dissection was only performed if tumor was present in sentinel nodes or if the sentinel node biopsy was unsuccessful. RESULTS. Sentinel node biopsy was successful in 96% of patients, and sentinel node metastases were found in 20%. In 78% of patients, a negative sentinel node biopsy obviated axillary dissection. Prior excisional biopsy was not associated with a failed sentinel node biopsy (p = 0.750) but was associated with failed lymphoscintigraphy (p = 0.01). Successful lymphoscintigraphy was associated with successful sentinel node biopsy (p < 0.0001). No association was found between the histology or size of the tumor and a failed sentinel node biopsy (p = 0.46 and p = 0.1, respectively) or failed lymphoscintigraphy (p = 0.36 and p = 0.47, respectively). CONCLUSION. Sentinel node biopsy guided by lymphoscintigraphy, intraoperative gamma probe, and isosulfan blue dye is an effective alternative to axillary dissection in patients with breast cancer. Lymphoscintigraphy improved the success rate of sentinel node biopsy. Large tumor size or prior excisional biopsy should not prevent patients from having sentinel node biopsy.     

Identification of bilateral breast sentinel lymph nodes draining primary melanoma of the back by preoperative lymphoscintigraphy and intraoperative mapping.

A 30-year-old white woman with a primary malignant melanoma of her right back at the Sappey line, 4 cm from the midline at the L2 level, underwent preoperative lymphoscintigraphy and intraoperative mapping of the sentinel lymph node using lymphazurin injection at the primary site and a hand-held gamma probe. Lymphoscintigraphy showed one sentinel lymph node in each breast and another one in the right axilla. These three sentinel lymph nodes were accurately identified using a hand-held gamma probe during operation. An additional sentinel and one nonsentinel lymph node from the right axilla were harvested. All four sentinel lymph nodes were blue and showed significantly elevated radioactivity compared with background. Histologic analysis showed that all these lymph nodes were negative for metastatic melanoma. She has been followed for a period of 26.7 months since her selective sentinel lymphadenectomy and has been free of disease to date. This case illustrates the importance of preoperative lymphoscintigraphy in identifying in-transit sentinel lymph nodes in both breasts in addition to the clinically predictable sentinel lymph node(s) in the right axilla.     

Preoperative radionuclide lymphangiography and sentinel node localization with radionuclide techniques. Advantages and ambiguous aspects

Axillary lymph node status is one of the most important prognostic factors for patients with melanoma and early breast cancer. Axillary lymph node dissection is an important part of the surgical treatment of breast cancer. As an alternative to axillary node dissection was proposed the sentinel lymph node detection (SLND). This technique was initially described for detecting occult lymph node metastasis in patients with melanoma and recently is used for breast cancer patients. Nowadays the radioisotopique techniques, including the lymphoscintigraphy and the intraoperative detection of SN, have received attention as a possible alternative to axillary lymph nodes dissection because of the clinical value of SN in malignancies and the development of technical equipment. We review the different techniques of preoperative lymphoscintigraphy and intraoperative detection of SN, including the radioisotopique tracers, timing and site of injection and the clinical value of both methods in patients with early breast cancer.     

Preoperative evaluation of sentinel lymph node status in melanoma by means of (99m)Tc-MIBI and lymphoscintigraphy: a case report

Previous reports have shown that (99m)Tc-sestamibi (MIBI) could detect clinically occult metastatic melanoma lesions. This article reports on a patient with invasive melanoma of the right heel in whom the sentinel node status was preoperatively evaluated with this tracer. Although regional lymph nodes were clinically negative, (99m)Tc-MIBI scintigraphy showed focal increased tracer uptake in the right groin that corresponded to the location of 2 sentinel nodes visualized by lymphoscintigraphy with (99m)Tc-colloidal rhenium sulfide performed the same day. A gamma-probe was used intraoperatively to guide the excision of the sentinel nodes that were further classified as metastatic by histopathology. This double-technique approach is technically feasible and has the potential of selecting a group of patients who might benefit from a selective complete lymphadenectomy.     

Preliminary experiences with sentinel lymph node detection in cases of vulvar malignancy

Lymph node status is the most important prognostic factor in vulvar malignancy. The aim of this pilot study was to explore the clinical significance of radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight patients with squamous cell carcinoma and two patients with malignant melanoma of the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint, OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node was checked by a single-head gamma camera-computer system (MB 9200, Mediso, Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed in each case. At lymphadenectomy, the sentinel lymph node was separately removed and histologically studied. Three of the ten patients had positive sentinel lymph nodes (micrometastasis). Five months later one of them had local recurrence of the vulvar cancer, and another had inguinal recurrence of the tumour 6 months postoperatively; the third patient was operated on only recently. Our preliminary results are impressive and suggest that lymphoscintigraphy is an easy and reliable method for detection of the sentinel lymph node in vulvar malignancy.     

Intramammary sentinel lymph node preoperative identification with SPECT/CT in a patient with breast cancer. Clinical meaning and relevance

We present the case of a patient with breast cancer who underwent selective sentinel lymph node biopsy. An intramammary sentinel lymph node was identified with SPECT/CT in the preoperative lymphoscintigraphy. We describe our diagnostic and therapeutic procedure regarding this finding and the literature review to evaluate the clinical significance of their identification and metastases, especially in regards to more appropriate axillary management. Further studies with more statistical significance are necessary to elucidate the most suitable attitude when an intramammary sentinel lymph node is identified with the lymphoscintigraphy.     

Breast cancer with metastatic invasion of the sentinel lymph node in an internal mammary chain and with axillary chains free of tumor lesionS

The lymphoscintigraphy is a widely accepted procedure to detect the sentinel node in breast cancer. This is a case report of a 45 year old woman diagnosed of breast cancer who was referred to the nuclear medicine facility to perform the sentinel node detection procedure. The lymphoscintigraphy prior to surgery shows a double pathway in the tracer migration: one going to the axillary area and the second to the internal mammary chain and shows hot spots that represent the sentinel nodes. After surgical removal of those nodes, the pathological analysis report indicated tumor infiltration in the internal mammary chain sentinel node with all axillary nodes free of malignant cells. The aim of this report is to emphasize the importance of performing a pathological analysis of all the sentinel nodes detected in lymphoscintigraphy.     

Radioguided sentinel lymph node biopsy in malignant cutaneous melanoma.

The procedure of sentinel lymph node biopsy in patients with malignant cutaneous melanoma has evolved from the notion that the tumor drains in a logical way through the lymphatic system, from the first to subsequent levels. As a consequence, the first lymph node encountered (the sentinel node) will most likely be the first affected by metastasis; therefore, a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Although the long-term therapeutic benefit of the sentinel lymph node biopsy per se has not yet been ascertained, this procedure distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, from those with metastatic involvement, who may benefit from additional therapy. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that an average of only 20% of melanoma patients with a Breslow thickness between 1.5 and 4 mm harbor metastasis in their sentinel node and are therefore candidates for elective lymph node dissection. Furthermore, histologic sampling errors (amounting to approximately 12% of lymph nodes in the conventional routine) can be reduced if one assesses a single (sentinel) node extensively rather than assessing the standard few histologic sections in a high number of lymph nodes per patient. The cells from which cutaneous melanomas originate are located between the dermis and the epidermis, a zone that drains to the inner lymphatic network in the reticular dermis and, in turn, to larger collecting lymphatics in the subcutis. Therefore, the optimal route for interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is intradermal or subdermal injection. (99m)Tc-Labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas along the midline of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the nodes. The sentinel lymph node should have a significantly higher count than that of the background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. Virtually the entire sentinel lymph node should be processed for histopathology, including both conventional hematoxylin-eosin staining and immune staining with antibodies to the S-100 and HMB-45 antigens. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is approximately 98% in institutions that perform a high number of procedures and approaches 99% when combined with the vital blue-dye technique. Growing evidence of the high correlation between a sentinel lymph node biopsy negative for cancer and a negative status for the lymphatic basin-evidence, therefore, of the high prognostic value of sentinel node biopsy-has led to the procedure's being included in the most recent version of the TNM staging system and starting to become the standard of care for patients with cutaneous melanoma.     

Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study

The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation 20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity.     

Feasibility of sentinel node lymphoscintigraphy in stage I testicular cancer

The aim of this study was to investigate the feasibility of lymphoscintigraphy for sentinel node identification in testicular cancer. Five patients with clinical stage I testicular cancer were prospectively included. A single dose of technetium-99m nanocolloid (mean dose 99 MBq, volume 0.2 ml) was injected into the funiculus in the first patient and into the testicular parenchyma in the following four patients. Dynamic lymphoscintigraphy was performed over 10 min, followed by early and late static images after 15 min and 2 to 24 h, respectively. Lymphoscintigraphy was followed by laparoscopic sentinel node biopsy on the same day in the last two patients using patent blue dye and an endoscopic gamma probe. The funicular administration route showed five hot spots in the right inguinal region after 2 h. Intratesticular administration resulted in sentinel node visualisation in three of the four patients. Dynamic images showed afferent lymphatic vessels to one sentinel node in the left para-aortic region in two patients and two sentinel nodes in the left para-aortic region in another patient. Sentinel nodes were intraoperatively identified in one of two patients who underwent laparoscopic exploration. It is concluded that lymphoscintigraphy for sentinel node identification is feasible in stage I testicular cancer using intratesticular radiocolloid administration.     

Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics

Detection of the "true" sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the skin leads to an improvement in the accuracy of identification and localisation of sentinel lymph nodes by lymphoscintigraphy.     

Use of lymphoscintigraphy with SPECT/CT for sentinel node localization in a case of vaginal melanoma

A 45-year-old woman with vaginal melanoma underwent Tc-99m sulfur colloid (filtered) lymphoscintigraphy with the acquisition of planar and SPECT/CT images for localization of a sentinel node before surgery. The study identified both inguinal and perirectal sentinel nodes, which proved beneficial in mapping potential anatomic spread of disease for staging and therapy planning. These results provide evidence for the use of routine SPECT/CT imaging for pelvic lymphoscintigraphic studies or as an adjunct tool for localizing sentinel nodes in cases that would not be demonstrated with planar imaging alone.     

乳腺癌前哨淋巴结核素显像新进展

乳腺癌是全球女性发病率最高的恶性肿瘤, 为保证患者的生存率、减少术后并发症, 20世纪90年代用"腋窝前哨淋巴结活检术取代腋窝淋巴结清扫"的观点被提出并逐渐发展成为乳腺癌患者保乳术的常规方法。除腋窝前哨淋巴结外, 内乳前哨淋巴结的重要性同样不容忽视, 但是否将其作为前哨淋巴结活检的对象仍存在争议。面对目前形势, 核医学工作者做了大量研究, 在保证腋窝前哨淋巴结高显示率的同时尽可能提高内乳前哨淋巴结的显示率。笔者对近十年来国内外研究者在乳腺癌前哨淋巴结核素显像中的核素示踪剂、注射技术、显像仪器等方面的最新进展进行综述。     

Vital dyes in sentinel node localization

Vital blue dyes were used to show the feasibility and accuracy of intraoperative lymphatic mapping of the sentinel node (SN) in patients with melanoma, breast cancer, and other solid tumors. Surgeons who have successfully completed an adequate number of cases of intraoperative mapping and sentinel lymph node dissection (SLND) can use blue dye alone to localize the SN. However, radiopharmaceutical agents can facilitate intraoperative mapping; preoperative lymphoscintigraphy can identify the location of the SN, and intraoperative mapping with the gamma probe can provide an auditory signal that complements the visual guide provided by the blue dye. Studies are required to establish more clearly the intralymphatic kinetics of the various radiopharmaceutical agents. An ongoing international Phase III trial in melanoma, the 2 upcoming trials in breast cancer, and similar trials for other solid tumors will further clarify the future role of SLND.     

Timing of sentinel lymphadenectomy in cutaneous melanoma

PURPOSE: The conduct of sentinel lymphadenectomy for cutaneous melanoma varies substantially among the medical disciplines. The authors sought to characterize the number of hot spots identified during preoperative lymphoscintigraphy for cutaneous melanoma and to determine its relation to the harvesting of sentinel lymph nodes. METHODS: Sixty-nine patients with cutaneous melanoma underwent lymphoscintigraphy with filtered Tc-99m sulfur colloid before sentinel lymphadenectomy. The lymphoscintigrams were reviewed and the number of hot spots visualized over time and the number of sentinel nodes harvested were determined. RESULTS: Lymphoscintigraphy identified 79 patients with 87 lymphatic basins at risk for metastatic disease. Lymphoscintigraphy was performed in a mean time of 30 minutes (range, 15 to 40 minutes). The mean number of hot spots increased from 0.2 to 2.0 hot spots 40 minutes after the initial static image, but the number of hot spots stabilized between 20 and 40 minutes. The same number of sentinel nodes as hot spots visualized were harvested in 58% of patients. Fewer sentinel nodes were identified at the time of surgery than were visualized by lymphoscintigrams in 39% of patients. CONCLUSIONS: More hot spots were identified up to 40 minutes after the initiation of lymphoscintigraphy. Sentinel lymphadenectomy can be performed as near to 40 minutes after the initiation of lymphoscintigraphy as is logistically reasonable. However, there may be substantial latitude in delayed performance of sentinel lymphadenectomy.