This study was designed to examine the feasibility of combining lymphoscintigraphy and intraoperative sentinel node identification in patients with head and neck melanoma by using a hybrid protein colloid that is both radioactive and fluorescent.
Eleven patients scheduled for sentinel node biopsy in the head and neck region were studied. Approximately 5 h before surgery, the hybrid nanocolloid labeled with indocyanine green (ICG) and technetium-99m (99mTc) was injected intradermally in four deposits around the scar of the primary melanoma excision. Subsequent lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) were performed to identify the sentinel nodes preoperatively. In the operating room, patent blue dye was injected in 7 of the 11 patients. Intraoperatively, sentinel nodes were acoustically localized with a gamma ray detection probe and visualized by using patent blue dye and/or fluorescence-based tracing with a dedicated near-infrared light camera. A portable gamma camera was used before and after sentinel node excision to confirm excision of all sentinel nodes.
A total of 27 sentinel nodes were preoperatively identified on the lymphoscintigraphy and SPECT/CT images. All sentinel nodes could be localized intraoperatively. In the seven patients in whom blue dye was used, 43% of the sentinel nodes stained blue, whereas all were fluorescent. The portable gamma camera identified additional sentinel nodes in two patients. Ex vivo, all radioactive lymph nodes were fluorescent and vice versa, indicating the stability of the hybrid tracer.
ICG–99mTc-nanocolloid allows for preoperative sentinel node visualization and concomitant intraoperative radio- and fluorescence guidance to the same sentinel nodes in head and neck melanoma patients.
Electronic supplementary material
The online version of this article (doi:10.1245/s10434-011-2180-7) contains supplementary material, which is available to authorized users.
Neck lymph node status is the most important factor for prognosis in head and neck squamous cell carcinoma. Sentinel node detection reliably predicts the lymph node status in melanoma and breast cancer patients. This study evaluates the predictive value of sentinel node detection in 50 patients suffering from pharyngeal and laryngeal carcinomas with a N0 neck as assessed by ultrasound imaging. Following 99m-Technetium nanocolloid injection in the perimeter of the tumour intraoperative sentinel node detection was performed during lymph node dissection. Postoperatively the histological results of the sentinel nodes were compared with the excised neck dissection specimen. Identification of sentinel nodes was successful in all 50 patients with a sensitivity of 89%. In eight cases the sentinel node showed nodal disease (pN1). In 41 patients the sentinel node was tumour negative reflecting the correct neck lymph node status (pN0). We observed one false-negative result. In this case the sentinel node was free of tumour, whereas a neighbouring lymph node contained a lymph node metastasis (pN1). Although we have shown, that skipping of nodal basins can occur, this technique still reliably identifies the sentinel nodes of patients with squamous cell carcinoma of the pharynx and larynx. Future studies must show, if sentinel node detection is suitable to limit the extent of lymph node dissection in clinically N0 necks of patients suffering from pharyngeal and laryngeal squamous cell carcinoma.
British Journal of Cancer (2002) 87, 711–715. doi:10.1038/sj.bjc.6600445 www.bjcancer.com
© 2002 Cancer Research UK
sentinel node; N0 neck; squamous cell carcinoma; larynx; pharynx; occult metastases
Adequate staging and treatment of the neck in squamous cell carcinoma of the oral cavity and oropharynx (OSCC) is of paramount importance. Elective neck dissection (END) of the clinical N0-neck is widely advocated as neck treatment. With regard to the prevalence of 20–40% of occult neck metastases found in the ND specimens, the majority of patients undergo surgery of the lymphatic drainage basin without therapeutic benefit. Sentinel node biopsy (SNB) has been shown to be a safe, reliable and accurate alternative treatment modality for selected patients. Using this technique, lymphatic mapping is crucial. Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. SPECT/CT allows the surgeon for better topographical orientation and delineation of sentinel lymph nodes (SLN's) against surrounding structures. Additionally, SPECT/CT has the potential to detect more SLN's which might harbour occult disease, than LS. SPECT/CT is recommended to be used routinely, although SPECT/CT is not indispensable for successful SNB.
Objective: To evaluate the performance and feasibility of sentinel lymph node biopsy in breast cancer patients using technetium-99m (99mTc) sulphur colloid and gamma probe.
Methods: From May 2000 to March 2001, 70 patients with a tumour less than 5 cm with clinically negative axillary lymph nodes underwent sentinel node biopsy followed by standard axillary dissection. 99mTc sulphur colloid was injected around the primary tumour the day before surgery and a gamma probe was used to detect the sentinel lymph node during the surgical procedure. Sentinel lymph node biopsy was compared with standard axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes.
Results: The sentinel lymph node was successfully identified in 67 of 70 patients (95.71%). The number of sentinel lymph nodes ranged from 1–5 (mean 1.5) and non-sentinel nodes ranged from 5–22 (mean 13.3). Of the 67 patients with successfully identified sentinel lymph nodes, 43.28% (29/67) were histologically positive. Sensitivity of the sentinel lymph node to predict axilla was 82.75%; specificity was 100%. Positive and negative predictive values were 100% and 88.3% respectively. The sentinel lymph node was falsely negative in five patients, yielding an accuracy of 92.53%. Sentinel lymph node biopsy was more accurate for T1 tumours than for T2 tumours.
Conclusions: The gamma probe guided method after overnight migration of 99mTc sulphur colloid is technically feasible for detecting sentinel lymph nodes in most breast cancer patients, accurately predicting the axillary lymph node status, and appears more accurate for T1 lesions than for larger lesions. This minimally invasive axillary staging procedure represents a major advance in the surgical treatment of breast cancer.
The purpose of this study was to investigate the feasibility of sentinel node frozen biopsy to minimize the extensive pelvic lymph nodes dissection in early stage cervical cancer patients on the basis that the risk of skip metastasis to the paraaortic area is negligible. Twenty-six patients with early stage cervical cancer were enrolled in this study. Technetium-99m colloid albumin (Tc(99m)) was injected intradermally around the tumor for allowing preoperative lymphoscintigraphy and intraoperative hand-held gama probe detection of seninel nodes. For visual detection, isosulfan blue dye was injected into the peritumoral sites before peritoneal opening. Postoperative morbidity and negative predictive value were the endpoints of this study. The 26 patients, ranging in age from 32 to 71 yr, underwent intraoperative sentinel nodes mapping. All the patients underwent complete pelvic lymph nodes dissection including para-aortic nodes. There was one case with positive non-sentinel nodes despite the negative sentinel node by frozen biopsy (negative predictive value, 95.2%). This new technique of sentinel node mapping is safe and simple to perform. Further clinical trials using the combination of Tc(99m) and isosulfan blue dye are warranted and this technique will make a true advance for less aggressive management of patients with early stage cervical cancer.
Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1–T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node as positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer. © 2000 Cancer Research Campaign
vulvar cancer; lymph node; lymphoscintigraphy; sentinel node; lymphadenectomy
Preoperative lymphoscintigraphy is one of the three methods of evaluating sentinel nodes in patients with breast cancer; however, it has been reported to have a high false negative rate.
We report here two cases where the preoperative lymphoscintigraphy was found to be fallacious. A 44-year-old female with T2N0 breast cancer underwent preoperative lymphoscintigraphy with Tc99 sulfur colloid which failed to show any uptake in axilla or internal mammary chain. Intraoperative scintigraphy with blue dye and hand held gamma probe identified sentinel lymph node in axilla. Another patient with T2N0 lesion underwent preoperative lymphoscintigraphy which showed a sentinel lymph node in axilla and another in supraclevicular fossa. Intraoperative scintigraphy failed to show supraclevicular node however axillary node was correctly identified.
These two cases further strengthen the need to carry out triple test in identification of sentinel lymph node in patients with breast cancer. It also demonstrates the fallacies of preoperative lymphoscintigraphy.
To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer.
Patients and Methods
Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed.
In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%).
Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.
Lymphoscintigraphy is an important part of sentinel node mapping in breast cancer patients. Sometimes star shaped artefacts due to septal penetration can be problematic during imaging. In the current study, we evaluated the possibility of high energy (HE) collimators use for lymphoscintigraphy.
Patients and methods
Twenty patients with early breast carcinoma were included. Thirty minutes after radiotracer injection (99mTc-antimony sulphide colloid), anterior and lateral images were acquired using a dual head gamma camera equipped with a parallel hole low energy high resolution (LEHR) collimator on one head and HE collimator on another head. All images were reviewed by two nuclear medicine specialists regarding detectability and number of axillary sentinel nodes and presence of star artefact.
All images taken by LEHR collimators showed star artefact of the injection site. No image taken by HE collimator showed this effect. In two patients the sentinel node was visible only by HE collimator. Tumour location in both of these patients was in the upper lateral quadrant and both had history of excisional biopsy. In two patients additional sentinel node was visible adjacent to the first one only on the LEHR images.
HE collimators can be used for sentinel lymph node mapping and lymphoscintigraphy of the breast cancer patients. This collimator can almost eliminate star-shaped artefacts due to septal penetration which can be advantageous in some cases. However, to separate two adjacent sentinel nodes from each other LEHR collimators perform better.
sentinel node; lymphoscintigraphy; collimator; HEAP; high energy all purpose; low energy high resolution; LEHR
To evaluate the accuracy of sentinel lymph node biopsy in breast cancer patients at this institution, using combined technetium-99m (99mTc) sulphur colloid and patent blue vital dye.
From March 2007 to July 2008, 50 patients with a tumour of less than 3 cm and with clinically negative axillary lymph nodes underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection (ALND). Sub-areolar 99mTc sulphur colloid injection was performed the day before surgery, and patent blue vital dye was also injected sub-areolarly at least 5 minutes before surgery. Sentinel lymph node was identified during the surgical procedure, using a gamma probe and direct vision. All sentinel nodes underwent frozen section analysis. Later haematoxylin and eosin staining and immunohistochemical analysis were performed. Finally, SLNB was compared with standard ALND for its ability to accurately reflect the final pathological status of the axillary nodes.
The sentinel lymph node (SLN) was identified in 48 of 50 patients (96%). The number of sentinel lymph nodes ranged from one to four (mean 1.48) and non-sentinel nodes ranged from seven to 27 (mean 14.33). Of the 48 patients with successfully identified SLNs, 29.17% (14/48) were histologically positive. Sensivity of the SLN to predict axilla was 93.75%; accuracy was 97.96%. The SLN was falsely negative in one patient—6.25% (1/16).
The SLNB represents a major advance in the surgical treatment of breast cancer as a minimally invasive procedure predicting the axillary lymph node status. This validation study demonstrates the accuracy of the SLNB and its reasonable false negative rate when performed in our institute. It can now be used as the standard method of staging in patients with early breast cancer at this institution.
Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area.
The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described.
The sentinel lymph node was defined as the first lymph node to receive drainage from a primary cancer. The aims of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of the hand-held gamma probe procedure for sentinel lymph node biopsy in papillary thyroid carcinoma and to evaluate these results in clinical staging. A total of 99 consecutive papillary thyroid carcinoma patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intra-operative sentinel lymph node localization was performed using a hand-held gamma probe. Patients were observed at follow-up at 2 and 6 months and, thereafter, yearly. Sequential lymphoscintigraphy was able to identify at least one sentinel lymph node in 98/99 cases (99%), using intra-operative hand-held gamma probe, the surgeon was able to detect at least one sentinel lymph node in all cases. Sentinel lymph node metastases were diagnosed in 49%. Overall, 79 patients underwent ablative 131I therapy. The median value of thyroglobulin in N0 vs. N1 patients was 1 ng/ml vs. 1.9 ng/ml (p = 0.03) and 0.2 ng/ml vs. 1 ng/ml (p = 0.001) before and after 131I therapy, respectively. The pre-operative lymphoscintigraphy and the intra-operative gamma probe offer significant advantages over the vital dye technique, described in our previous experience. The rate of nodal involvement (49%) is very high considering that no patients had clinically palpable nodes or suspected at echography. 131I whole body scan and thyroglobulin measurements confirmed sentinel lymph node in papillary thyroid carcinoma as a reliable procedure. In patients classified N0, by sentinel lymph node biopsy, ablative 131I therapy could be avoided.
Thyroid; Cancer; Node metastases; Sentinel lymph node; Radiocolloid lymphoscintigraphy
For accurate nodal staging, all blue and radioactive lymph nodes should be sampled during the sentinel lymph node biopsy for breast cancer. We report a case of anomalous drainage in which one of the sentinel lymph nodes was unexpectedly found in the level III axillary space.
A 40-year-old female underwent mastectomy for extensive high-grade ductal carcinoma in-situ (DCIS) with micro-invasion. The index lesion was located in the right upper inner quadrant. Lymphoscintigraphy was performed on the morning of surgery. Two sentinel lymph nodes were identified. At operation, 5 mls of isosulfan blue dye was injected at the same site of the radio-colloid injection. The first sentinel lymph node was found at level I and was blue and radioactive. The second sentinel node was detected in an unexpected anomalous location at level III, medial to the pectoralis minor. Both sentinel nodes were negative.
Sentinel node staging can lead to unexpected patterns of lymphatic drainage. For accurate staging, it is important to survey all potential sites of nodal metastasis either with preoperative lymphoscintigraphy and/or rigorous examination of regional nodal basins with the intra-operative gamma probe.
The objective of the study was to evaluate the long term results of the sentinel node (SN) biopsy technique in the management of the clinically negative (N0) neck in patients with early oral squamous cell carcinoma (T1–T2). Patients with positive SN underwent neck dissection. A sentinel lymph node (SLN) biopsy was performed on 31 consecutive patients. Six of the 31 patients were upstaged by the results of the SLN biopsy. The SLN biopsy allowed the identification of node metastasis in 100% of the cases with a sensitivity of 100%, specificity of 100%, and negative predictive value of 100%. There was a mean follow-up of 59 months. The neck control rate was 100% in the SLN negative group and two SLN positive patients developed subsequent neck disease (neck control rate of 88%). One SLN patient presented at the follow-up with a second primary tumor, 18 months later treated successfully by chemoradiotherapy. The overall survival rate was 100% in both groups. The promising reported short-term results have been sustained by long term follow-up. Patients with negative SLN achieved an excellent neck control rate. The neck control rate in SN negative patients was superior to that in SLN positive patients, but not statistically different.
sentinel lymph node; characteristics of patients; head and neck cancer
Sentinel node biopsy is an alternative to elective neck dissection for the management of T1/T2 oral and oro-pharyngeal squamous cell carcinomas and is also finding application to head and neck cancer at other sites. The main clinical aim of sentinel node biopsy is to achieve better staging and there is now evidence that the procedure reduces morbidity. Reported detection rates for sentinel neck nodes are greater than 95% and there is also a negative predictive value of 95% for negative sentinel nodes. Current histopathological protocols have been developed for use in the research setting and are designed to identify all micrometastatic disease. However the use of step serial sectioning at 150 micron intervals with pan-cytokeratin immunohistochemistry is currently advised and appears to upstage nodes by approximately 20% over the initial single routine stained section. Adoption of the UICC/TNM definitions is recommended for future sentinel node studies, but further refinements and descriptions are required. The SENT trial has recruited over 300 cases from 10 European centres and a quality control study of the pathological material is in progress. At the first consensus meeting of the SENT pathology group there were excellent levels of agreement on the diagnosis of positive and negative nodes, and a number of potential pitfalls such as non-malignant inclusions and staining artefacts were identified.
Oral cancer; Head and neck cancer; Sentinel node; Neck dissection; Histopathology; SENT trial; Lymphoscintigraphy; Guidelines; Pan-cytokeratin; Benign lymph node inclusion
The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection.
This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with 99mTc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB.
In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%.
For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).
The management of regional lymphatics in patients with melanoma has evolved over the past several decades from delayed lymphadenectomy, to elective resection, to the current approach which utilizes sentinel lymph node mapping to accomplish a selective approach to performing lymphadenectomy. Sentinel lymphatic mapping allows for an opportunity to demonstrate regional lymphatic disease prior to the development of lymphadenopathy. Complete resection of a nodal basin can be reserved for patients with documented disease in a sentinel node while patients with a negative sentinel node can avoid an unnecessary and potentially morbid surgery. The preliminary results of sentinel node mapping at Ochsner Medical Institutions reflect an outstanding ability to demonstrate the sentinel node in patients with trunk and extremity melanoma when radioactive colloid is used in combination with a vital blue dye. The results of sentinel node mapping in patients with head and neck melanoma have not been as reliable and require additional refinements of technique.
The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of 99mTc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy.
British Journal of Cancer (2002) 87, 705–710. doi:10.1038/sj.bjc.6600359 www.bjcancer.com
© 2002 Cancer Research UK
breast cancer; lymphoscintigraphy; sentinel node; staging
The purpose of this study was to describe the use of lymphoscintigraphy and sentinel lymph node biopsy for the management of children with melanoma and sarcomas. We report the experience of two children’s hospitals that utilize this technique to identify sentinel lymph nodes for lymph node biopsy and dissection.
We identified 56 patients (median age 10.8 years) who underwent 58 lymphoscintigraphy procedures. There were 33 patients with melanoma and melanocytic lesions, and 23 with sarcomas.
Of 58 lymphoscintigraphy procedures, sentinel lymph nodes were identified in 52 (90% success rate). Using the combination of intraoperative blue dye injection and lymphoscintigraphy, the success rate was 95% (55/58). Metastatic disease was found in 14 sentinel lymph nodes (13 patients with melanoma and melanocytic lesions, and 1 patient with rhabdomyosarcoma).
We have found that lymphoscintigraphy with sentinel lymph node biopsy is an effective method to identify patients who may benefit from more extensive lymph node dissection and to identify those patients who are unlikely to benefit from further lymph node exploration.
lymphoscintigraphy; sentinel node; melanoma; sarcoma; pediatric
The aim of this pilot trial was to study the feasibility of sentinel node percutaneous preoperative gamma probe-guided biopsy as a valid preoperative method of assessment of nodal status compared to surgical sentinel lymph node biopsy.
This prospective study enrolled 10 consecutive patients without evidence of axillary lymph node metastases at preoperative imaging. All patients underwent sentinel node occult lesion localization (SNOLL) using radiotracer intradermic injection that detected a “hot spot” corresponding to the sentinel node in all cases. Gamma probe over the skin detection with subsequent ultrasonographically guided needle biopsy of the sentinel node were performed. The percutaneous needle core histopathological diagnosis was compared to the results of the surgical biopsy.
Preoperative sentinel node identification was successful in all patients.
The combination of preoperative gamma probe sentinel node detection and ultrasound-guided biopsy could represent a valid alternative to intraoperative sentinel node biopsy in clinically and ultrasonographically negative axillary nodes, resulting in shorter duration of surgery and lower intraoperative risks.
Sentinel Lymph Node Biopsy (SLNB); Sentinel Node Occult Lesion Localization (SNOLL); preoperative axillary node core needle biopsy
To document experience with sentinel lymph-node biopsy in patients who have already undergone a wide local excision for melanoma because in many centres previous wide excision has been a contraindication for sentinel lymph-node biopsy.
A prospective cohort study.
A tertiary care academic cancer centre.
One hundred patients who presented with cutaneous melanoma (depth >1 mm or Clark level IV) after having undergone wide local excision of the primary lesion that was not situated in the head or neck. The follow-up was 3 years.
Sentinel lymph-node biopsy. Patients with truncal melanoma had preoperative lymphoscintigraphy to document the nodal basins at risk. Technetium-99m sulfur colloid (0.5–1 mCi in 0.5 mL) was injected intradermally around the scar, and the sentinel lymph node was excised with the aid of a hand-held gamma detector.
Accuracy of the biopsy and false-negative rates in this setting.
Of the 100 patients, 44 had truncal and 56 had extremity lesions. The average tumour depth was 3.47 mm and 3.07 mm respectively. Thirty-one patients had a sentinel lymph node positive for melanoma metastasis. Biopsies were positive for melanoma in 18 (41%) truncal lesions and 13 (23%) extremity lesions. There were 3 (9%) false-negative sentinel lymph-node biopsies as diagnosed by clinically evident nodal disease subsequently appearing in the nodal basin subjected to biopsy. Two occurred in patients after large rotation flap closures of truncal lesions. The third patient had a subungual melanoma of the great toe. No disease was found in the 2 nodes dissected. Two of the 3 false-negative biopsy results were obtained before serial sections and immunohistochemical staining were used to examine the sentinel lymph nodes.
Sentinel lymph-node biopsies can successfully identify clinically occult nodal metastases in patients who have had previous wide local excision of a melanoma, but the false-negative rate in patients with rotation flap closures should be taken into consideration.
The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid (99 mTc-Sb2S3) particles are used to perform preoperative lymphoscintigraphy for SLN identification, they are retained in the SLN but are absent or present in only tiny amounts in non-SLNs. The present study investigated the potential for a novel means of assessing the accuracy of surgical identification of SLNs. This involved the use of inductively coupled plasma–mass spectrometry (ICP-MS) to analyze antimony concentrations in fine-needle biopsy (FNB) samples from surgically procured lymph nodes.
A total of 47 FNB samples from surgically excised lymph nodes (32 SLNs and 15 non-SLNs) were collected. The SLNs were localized by preoperative lymphoscintigraphy that used 99 mTc-Sb2S3, blue dye, and gamma probe techniques. The concentrations of antimony were measured in the FNB samples by ICP-MS.
The mean and median antimony concentrations (in parts per billion) were .898 and .451 in the SLNs, and .015 and .068 in the non-SLNs, the differences being highly statistically significant (P < .00005).
Our results show that ICP-MS analysis of antimony concentrations in FNB specimens from lymph nodes can accurately confirm the identity of SLNs. Used in conjunction with techniques such as proton magnetic resonance spectroscopy for the nonsurgical evaluation of SLNs, ICP-MS analysis of antimony concentrations in FNB samples could potentially serve as a minimally invasive alternative to surgery and histopathologic evaluation to objectively classify a given node as sentinel or nonsentinel and determine its tumor-harboring status.
Clinical; Fine-needle biopsy; Melanoma; Pathology; Sentinel lymph node
Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma.
A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation.
The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients.
Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.
Melanoma; Sentinel lymph node
Several 99mTc-labeled agents that are not approved by the U.S. Food and Drug Administration are used for lymphatic mapping. A new low-molecular-weight mannose receptor–based, reticuloendothelial cell-directed, 99mTc-labeled lymphatic imaging agent, 99mTc-tilmano-cept, was used for lymphatic mapping of sentinel lymph nodes (SLNs) from patients with primary breast cancer or melanoma malignancies. This novel molecular species provides the basis for potentially enhanced SLN mapping reliability.
In a prospectively planned, open-label phase 2 clinical study, 99mTc-tilmanocept was injected into breast cancer and cutaneous melanoma patients before intraoperative lymphatic mapping. Injection technique, preoperative lymphoscintigraphy (LS), and intraoperative lymphatic mapping with a handheld gamma detection probe were performed by investigators per standard practice.
Seventy-eight patients underwent 99mTc-tilma-nocept injection and were evaluated (47 melanoma, 31 breast cancer). For those whom LS was performed (55 patients, 70.5%), a 99mTc-tilmanocept hot spot was identified in 94.5% of LS patients before surgery. Intraoperatively, 99mTc-tilmanocept identified at least one regional SLN in 75 (96.2%) of 78 patients: 46 (97.9%) of 47 in melanoma and 29 (93.5%) of 31 in breast cancer cases. Tissue specificity of 99mTc-tilmanocept for lymph nodes was 100%, displaying 95.1% mapping sensitivity by localizing in 173 of 182 nodes removed during surgery. The overall proportion of 99mTc-tilmanocept-identified nodes that contained metastatic disease was 13.7%. Five procedure-related serious adverse events occurred, none related to 99mTc-tilmanocept.
Our results demonstrate the safety and efficacy of 99mTc-tilmanocept for use in intraoperative lymphatic mapping. The high intraoperative localization and lymph node specificity of 99mTc-tilmanocept and the identification of metastatic disease within the nodes suggest SLNs are effectively identified by this novel mannose receptor–targeted molecule.
Objective To establish the prognostic value of knowledge of sentinel node status in melanoma.
Design Single centre prospective observational study, with sentinel nodes identified by lymphoscintigraphy, γ probe, and intraoperative blue dye and examined by both conventional histopathology and immunopathology.
Setting Specialist surgical service in west of Scotland.
Participants 482 patients with melanoma who consented to sentinel node biopsy in 1996-2003.
Main outcome measure Time to recurrence of or death from melanoma.
Results Of 472 patients who consented to sentinel node biopsy and in whom at least one sentinel node was identified, 367 (78%) had no tumour in the sentinel node. At mean follow-up of 42 months, 299 (82%) of this group were alive and free from disease, 24 were alive with melanoma recurrence, and 31 had died of melanoma. Of 105 patients with a positive sentinel node biopsy, 44 (42%) were alive and disease free, 12 were alive with recurrence, and 46 had died of melanoma. The survival difference between patients who were negative and those who were positive for tumour in the sentinel node was highly significant at all thickness levels over 1.0 mm (P < 0.001). Multivariate analysis showed that sentinel node status was independent of tumour thickness and ulceration. 71/105 (68%) patients with a positive sentinel node had a negative completion lymphadenectomy, and 44/71 (62%) were alive and disease free at follow-up; 34 patients with a positive sentinel node had further nodes involved, and only 4 (12%) were disease free (P < 0.001). 16 patients (13 sentinel node biopsy positive; 3 negative) died of other causes.
Conclusion Sentinel node status is a highly significant predictor of prognosis in melanoma and should be considered in adjuvant studies. However, it should not be regarded as a standard of care until mature data from ongoing randomised trials are available.