eMedicine Specialties > Dermatology > Surgical
The Role of Sentinel Node Biopsy in Skin Cancer: Treatment
Updated: Mar 10, 2009
Treatment
Surgical Therapy
The use of sentinel lymph node biopsy and selective lymphadenectomy in patients with malignant melanoma with clinically negative regional lymph node basins has been widely adopted. Current NCCN guidelines recommend this as a component of treatment for clinically node-negative melanoma patients with tumors thicker than or equal to 1 mm and patients with T1b melanomas. With this approach, a complete regional lymph node dissection is performed only in patients with evidence of metastatic melanoma in the sentinel node(s). This technique is also being used for other skin cancers (eg, neuroendocrine carcinoma of the skin [Merkel cell carcinoma]) that have a propensity for regional lymphatic spread.
Despite this, current compliance with these guidelines is only approximately 50% in the United States and is lower in Europe.35,36 Single-institution overall compliance data are better (74-84%) and appear to be improving over time, but data are lowest for those patients with thicker (T2 to T4) melanomas (47-74%) who stand to benefit the most.37,38 The technical details of sentinel lymph node biopsy for malignant melanoma are described below.
Preoperative Details
Multidisciplinary approach
Sentinel lymph node biopsy with selective lymphadenectomy is a team effort and requires close collaboration by dermatologists, surgical oncologists, nuclear medicine physicians, and pathologists. Adjuvant therapy may also involve medical and radiation oncologists. A multidisciplinary programmatic approach provides optimal patient care.39
Injection technique
In the nuclear medicine department, 2-16 hours before the operation, the patient is injected intradermally around the site of the primary tumor or biopsy scar with radiocolloid, usually with a dose of 0.5-0.8 mCi. The area is massaged for 2-5 minutes.
Choice of isotope
While a variety of radiocolloids have been used successfully, unfiltered99m Tc sulfur colloid diffuses out of the sentinel lymph nodes (to second echelon lymph nodes) less rapidly than tracers with smaller particles. In the United States,99m Tc-labeled albumin colloid and human serum albumin also may be used. In Australia, colloidal antimony sulfide is used, and in Europe, human albumin nanocolloid is used.
Lymphoscintigraphy
Lymphoscintigraphy is helpful in defining at-risk nodal basins, especially for truncal melanomas and melanomas of the head and neck. Lymphoscintigraphy may help define the number of sentinel lymph nodes by showing more than one afferent lymphatic channel leading from the primary tumor site to a regional nodal basin. It can also help define the location of the sentinel lymph node within the lymphatic basin and can identify in-transit or interval lymph nodes that may contain metastatic disease.
Lymphoscintigraphy demonstrates drainage to more than one nodal basin in 10-15% of patients and drainage to interval nodes in 3-5%.33 Metastatic disease is found at the same frequency in these interval sentinel lymph nodes as within sentinel lymph nodes from conventional lymph node basins, and the status of one basin does not predict the status of the other.33,40 The sentinel node is not always found in the closest nodal basin. Accurate lymphoscintigraphy helps identify all nodes, regardless of their location, receiving direct lymphatic drainage from a primary tumor site.
Lymphoscintigram demonstrating 2 afferent lymphatics draining to 2 separate axillary sentinel lymph nodes.
While not all surgeons advocate the use of preoperative lymphoscintigraphy in all melanoma patients, most agree lymphoscintigraphy is necessary to accurately identify the sentinel node(s) in patients with head and neck melanoma. Drainage to nodal basins not predicted by standard anatomic considerations is observed with lymphoscintigraphy in as many as 60% of head and neck and 30% of truncal primary melanomas.41
Dynamic scintigraphy can be performed most conveniently immediately after injection of radiocolloid in the nuclear medicine department on the morning of the operation. Usually, the sentinel lymph node(s) is identified within 30 minutes of injection. The site of each hot sentinel lymph node is tattooed on the patient's skin for identification in the operating room. Two-view lymphoscintigrams are obtained for the surgeon. Delayed 2-hour images may be taken. Delayed images are helpful in detecting sentinel lymph nodes close to the primary site, which may be obscured on the initial views, and to detect drainage to multiple nodal basins.42
Intraoperative Details
After radioisotope is injected in the nuclear medicine suite and lymphoscintigraphy is performed, the patient is moved to the operating room. Vital blue dye (1-2 mL) is injected intradermally around the primary tumor or biopsy site after the patient is prepared and draped using sterile technique. Some clinicians use isosulfan blue dye (Lymphazurin 1%, Zenith Parenterals; Rosemont, Ill). The site is massaged gently for 5 minutes. A handheld gamma probe (eg, C-Trak probe, Care Wise Medical Products; Morgan Hill, Calif]) is used to identify hot spots in the identified regional lymph node basin or basins. If in-transit or interval nodes are identified on preoperative lymphoscintigrams, these should also be sought. Interval nodes contain metastatic disease as often as the conventional nodal basins do and may represent the only site of metastatic disease.
Handheld gamma probe for radioguided sentinel lymph node biopsy.
Using the gamma probe to detect a hot spot in the inguinal area.
The blue dye may also be seen coursing through the dermal lymphatics en route to the regional lymph node basin(s).
Blue dye seen traveling along afferent lymphatics of the leg after injection of isosulfan blue dye around a nodular melanoma of the dorsum of the foot.
A small incision is made over the hot spot. A blue-stained afferent lymphatic vessel is sought, and a combination of this visual cue and the gamma probe leads to the identification of a hot and/or blue sentinel lymph node or nodes. Care should be taken to minimize flap placement because this may interrupt the afferent lymphatics and make sentinel node identification more difficult. More than one sentinel lymph node (with a separate draining afferent lymphatic vessel) is identified in more than 50% of patients.
Blue-stained afferent lymphatic leading to blue-stained inguinal lymph node.
After the sentinel lymph nodes are removed, the lymph node basin is scanned with the gamma probe for residual activity. Absent–to–low-level radioactivity confirms that the sentinel nodes have been removed. The ratio of activity of the sentinel lymph node to nonsentinel lymph nodes should be at least 3:1 in vivo. Generally, the ratio of activity of the ex vivo sentinel lymph node to nonsentinel lymph nodes should be greater than 10:1. At operation, a sentinel lymph node is any blue-stained node, any node with a blue-stained afferent lymphatic, or any node with greater than 10% of the radioactivity ex vivo of the hottest node.
The "10% rule" was generated from the Sunbelt Melanoma Trial experience and suggests that any lymph node with greater than 10% of the ex vivo radioactivity of the hottest lymph node should be removed.33 Ex vivo counts eliminate the contribution of shine-through from the primary site or from sentinel nodes remaining in the lymph node basin. This method is reportedly associated with a detection failure rate of approximately 2%. Any clinically suspicious, enlarged, firm, or pigmented lymph nodes should also be removed because tumor cells blocking afferent lymphatics may prevent uptake of radioactive tracer and/or blue dye into a tumor-containing sentinel lymph node.
If, despite these techniques, no sentinel lymph node is identified, either dissection of the lymph node basin or termination of the procedure and close clinical follow-up of the patient may be chosen. This decision should be based on a preoperative discussion with the patient and the metastatic risk associated with the primary tumor. Sentinel node identification rates can approach 99% when the procedure is performed by a trained multidisciplinary team.
Postoperative Details
Histopathology
Processing the sentinel lymph node involves taking step-sections at multiple levels and performing immunohistochemical staining with S-100 protein and homatropine methylbromide (HMB-45) to identify micrometastatic disease.10 If any question exists about abnormal cells on these first sections, additional sections of the lymph node are taken. Immunohistochemistry identifies an additional 10-20% of patients with positive sentinel lymph nodes, in whom micrometastases are not seen on routine sections stained with hematoxylin and eosin (H&E). Melanoma antigen–recognizing T cells 1 (MART-1 or Melan A) antibody staining also may be performed to help identify occult micrometastatic disease in a sentinel lymph node. At least some of the increased rate of detection of micrometastatic disease is attributable to step-sectioning at multiple levels.
A small focus of subcapsular metastatic melanoma in a lymph node (hematoxylin and eosin, original magnification X200).
An international consensus group advocates a more formal and detailed sampling of the sentinel lymph node.39 Their approach involves bivalving the lymph node, fixing the 2 halves face down, and subsequently sectioning each half into 10 sections, which alternately are used for H&E staining, immunohistochemistry, and molecular staging. The Sydney Melanoma Unit performs 2 H&E sections (1 and 4) and 2 with S-100 and HMB-45 immunohistochemistry (2 and 3) on 4 sequential 5-mm thick sections taken from each block of 3-mm longitudinal slices of the sentinel lymph node. They cite a detection failure rate of less than 1% and an acceptable cost-to-benefit ratio with this method. Recommendations for optimal enhanced pathologic analysis vary, but all include step-sectioning and immunohistochemistry.10
Another technique described to increase the accuracy of pathologic examination of the sentinel lymph node is carbon dye mapping of the microanatomy of the lymph node to direct the pathologist to the portion of the node most likely to contain metastatic disease.43 The sensitivity of intraoperative frozen-section examination of the sentinel lymph node is disappointingly low (<50%), although false-positive results are almost never reported. Because of the risk of tissue loss and damage during the frozen-section procedure, most melanoma centers eschew frozen sectioning and rely on permanent sections, except to confirm grossly suggestive metastatic disease.10,39
The potential for understaging patients because of tissue loss after frozen sectioning is underscored by reports of lower than expected rates of sentinel node metastases from institutions where frozen section examinations are routinely performed. Intraoperative imprint cytology has been reported to have a sensitivity of approximately 40% for melanoma patients and better preserves the lymph node for permanent section evaluation.44
Similar protocols are followed for the evaluation of sentinel lymph nodes from other skin cancers. For neuroendocrine carcinoma of the skin, the pancytokeratin antibody AE1/AE3, cytokeratin 20, and chromogranin A immunostaining on permanent sections helps identify micrometastatic disease in the sentinel lymph node.
Reverse-transcriptase polymerase chain reaction
Currently, in clinical studies, molecular staging is being applied to sentinel lymph nodes removed from melanoma patients in an effort to improve the sensitivity of detecting occult metastatic disease. This method uses reverse-transcriptase polymerase chain reaction (RT-PCR) to detect messenger RNA for markers frequently expressed by melanoma cells. The sensitivity of RT-PCR is estimated to be an order of magnitude greater than that of immunohistochemistry. The marker used most commonly is tyrosinase, the enzyme that governs tyrosine metabolism in pigment cells. RT-PCR can also be used to detect other melanoma surface antigens such as Gp-100, MART-1, melanoma-associated antigen 3, and melanoma inhibitory activity.
Studies suggest that the 2-year recurrence rate for patients with a histologically (including immunohistochemistry) negative and PCR-negative sentinel lymph node is 2-9%. The 2-year recurrence rate is 13-30% for patients with a histologically negative yet PCR-positive lymph node and 60-67% for patients with lymph nodes positive by both methods.45,46 These data suggest that lymph node metastases missed by pathologic assessment are clinically relevant. Other studies have not found molecular staging of sentinel lymph nodes to have prognostic significance.47 The ongoing Sunbelt Melanoma Trial and Florida Melanoma Trial both use this technology and should provide useful information on the clinical relevance of molecular staging.
Completion regional lymphadenectomy
Complete regional lymphadenectomy should be performed in all patients with positive sentinel lymph node results, even when the volume of disease is quite small, in the absence of participation in a randomized clinical trial. As yet, no method reliably predicts which patients will have residual metastatic disease in other nonsentinel lymph nodes in the regional basin. While, in most series, 70-80% of patients (range 58-92%) have no further disease identified, the pathologic examination after regional lymph node dissection is, of necessity, less rigorous than that used for evaluation of the sentinel lymph node; therefore, these numbers probably underestimate the true incidence of additional nodal disease.
Several investigators have identified some correlation between various assessments of tumor burden (size, number, and/or location) within the sentinel lymph node or nodes and the likelihood of nonsentinel lymph node metastases on completion lymph node dissection.10,48,49 Others studies have not found such an association,50,51 and numerous studies have failed to show any reliable and reproducible way of prospectively identifying those patients at an acceptably low risk of harboring residual disease in the nodal basin so as to forgo completion lymphadenectomy.10
One population-based data analysis (National Cancer Institute's Surveillance, Epidemiology and End Results [SEER] database 1998 to 2001) showed that less than 70% of US melanoma patients with a positive sentinel lymph node receive a completion lymph node dissection.35 Another, using National Cancer Data Base data from 2004-2005, found that only 50% of melanoma patients with a positive sentinel lymph node biopsy underwent completion lymph node dissection.52 Because melanoma remains a disease in which appropriate surgical treatment is of paramount importance (ie, because of the paucity of highly effective systemic therapy options), the consequences of inadequate treatment may be grave.
A complete axillary lymph node dissection should include all level I, II, and III nodes and should remove all lymph nodes and fatty and areolar tissue from within the anatomic boundaries of the axilla. Usually, these specimens include a minimum of 15-20 lymph nodes. This is not the operation commonly performed for breast cancer staging and underscores the importance of including a trained surgical oncologist with experience in the treatment of melanoma as a member of the multidisciplinary team.
The appropriate extent of groin dissection remains controversial. Isolated pelvic, obturator, or iliac nodal disease may be seen without involvement of (superficial) inguinal nodes, but this is uncommon. After a positive inguinal sentinel lymph biopsy result, the approach may be to perform only a superficial groin dissection at all times, a radical groin dissection at all times, or the deep groin dissection selectively, depending on the number of involved superficial nodes, the status of the node of Cloquet, or the site of the primary tumor (extremity vs trunk).
Two studies, the Multicenter Sentinel Lymphadenectomy Trial (MSLT) II and part II of the Florida Melanoma Trial are currently enrolling subjects after a positive sentinel lymph node biopsy result to be randomized to completion lymphadenectomy or no further surgical treatment. The MSLT-II aims to accrue 4200 subjects with primary melanomas greater or equal to 1.2 mm (or Clark level IV/V or ulceration) to undergo lymphatic mapping (with blue dye, carbon dye, and radiocolloid) with sentinel lymphadenectomy. Those with a positive sentinel lymph node (by H&E, immunohistochemistry, or RT-PCR) will be randomized to completion lymph node dissection or observation (including follow-up nodal ultrasonography) with therapeutic lymph node dissection for relapse.
Part II of the Florida Melanoma Trial seeks to randomize subjects with positive sentinel nodes by H&E histology, immunohistochemistry, or PCR to completion lymph node dissection plus adjuvant therapy with interferon alfa-2b or interferon alfa-2b alone. The study will obtain candidates for randomization from a planned accrual of 3200 clinical stage I and II patients with melanomas thicker than 0.75 mm undergoing lymphoscintigraphy, lymphatic mapping, and sentinel lymph node biopsy from 10 institutions (part I of the study).
Whether or not small foci of disease in a sentinel lymph node (variably defined as <0.2 mm, <0.1 mm, or isolated tumor cells) is clinically significant and should be treated the same as other positive sentinel lymph nodes is a subject of great current interest. In some studies, isolated tumor cells in a sentinel lymph node have prognostic significance and are associated with additional melanoma-positive lymph nodes upon completion lymph node dissection in greater than 10% of patients, while other investigations have found no prognostic benefit for sentinel lymph node evaluation beyond routine H & E techniques.47,53 A European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group trial scheduled to be activated in 2009, the MINITUB trial, will evaluate the role of completion lymph node dissection for melanoma patients with "sub-micrometastatic" disease (defined as <0.1 mm) in the sentinel lymph node.
Postoperative care
In general, patients who undergo sentinel lymph node biopsy alone require no special postoperative care. They may be discharged the day of the procedure, depending on the nature of the treatment of the primary melanoma. Instructions and written materials on lymphedema prevention and precautions should be provided to patients. Extremity elevation and ACE bandage wraps may be used to prevent lymphedema in the initial treatment of patients who undergo lower extremity sentinel lymph node biopsy. These patients are usually fitted with a compression stocking 4-6 weeks postoperatively.
Adjuvant therapy
Systemic treatment with high-dose interferon alfa-2b or participation in a clinical trial is generally offered to stage III patients. Adjuvant radiotherapy is recommended for most patients with multiple cervical lymph node metastases and for those patients with bulky nodal metastases or extracapsular extension at any site.
Follow-up
Appropriate follow-up monitoring of patients with intermediate-thickness and deep primary cutaneous melanoma after sentinel lymph node biopsy, and treatment in general, remains controversial. Advantages to a regular follow-up program include a detailed history and physical examination (with total skin and regional lymph node examinations), with particular focus on the site of the primary melanoma and regional lymph node basin(s). Follow-up monitoring may detect second primary melanomas (approximately 5% of patients at 5 y) and recurrent disease at an early stage, when it may be treated more easily. Follow-up care also may include psychosocial support, identification of familial melanoma, and ongoing patient education.
Typically, examinations are performed at 3- to 6-month intervals for 5 years and annually thereafter. Usually, chest radiography and liver function tests with a lactate dehydrogenase level are performed annually, although most clinicians recognize that these tests are insensitive. Lifelong surveillance is recommended, not only to detect new primary skin cancers, but also to detect late recurrences (>10 y post diagnosis). These recommendations are typical for stage I or II melanomas thicker than 1 mm or for Clark level IV or V melanomas and for patients with stage III melanoma. Similar guidelines are used for follow-up monitoring of patients with neuroendocrine carcinoma of the skin and other types of skin cancer with some propensity for local, regional, and distant recurrence.
For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Skin Cancer and Skin Biopsy.
Complications
Although sentinel lymph node dissection with selective lymphadenectomy is less morbid than elective lymph node dissection, as with any invasive procedure, complications do occur. In the Sunbelt Melanoma Trial, the overall complication rate was less than 5% for sentinel lymph node biopsy alone and 23% for sentinel lymph node biopsy with completion lymph node dissection for metastatic disease. The mortality rate was 0% for both procedures.33 Complications occur more frequently in patients with comorbid habits or illness, such as cardiac disease, obesity, diabetes mellitus, and cigarette smoking. The complication rate has also been reported to increase with the number of sentinel nodes removed.
Immediate complications of the procedure include failure to identify a sentinel lymph node (generally, <5%), anaphylaxis or other allergic reactions to the intradermal injection of blue dye (<1%), and bleeding. The immediate false-negative rate is defined as the proportion of nodal basins with positive nonsentinel lymph node results after negative results are obtained from sentinel lymph node biopsy immediately followed by elective completion lymph node dissection. In published series that include initial cases early on in the learning curve, the immediate false-negative rate ranged from 4.7-8.3%, with an associated accuracy of 98-99%.14,54,55 Further studies of this nature are unlikely, given the acceptance of sentinel lymph node biopsy with selective lymph node dissection.
Short-term postoperative complications of the procedure include hematoma, wound infection, seroma, and flap necrosis. In the Sunbelt Melanoma Trial, hematoma or seroma (2%) and wound infection (1%) were the most common complications of sentinel lymph node biopsy.
Long-term postoperative sequelae may include persistent blue discoloration of the skin at the injection site (for >30 d in <10% of patients), lymphatic fistulae, lymphocele, lymphedema (generally <2% and 0.66% in 1 large trial), and neurologic complications, including transient or persistent neurapraxia, cutaneous anesthesia, paresthesias, and neuropathy. Sentinel lymph node biopsy does not increase the risk of in-transit metastases.
Reports on the risk of locoregional recurrence with follow-up ranging from 13-60 months in 14 published series show that the risk of isolated nodal relapse in the mapped basin after a negative sentinel lymph node biopsy is 1-6%, while the locoregional relapse rate ranges from 5-10%. These data include varying numbers of patients with thin or otherwise low-risk melanomas expected to have minimal risk of relapse. A 2008 study found that the rate of locoregional disease alone as the first site of relapse was 33% in patients treated in a lymph node–noncompliant fashion versus 6% in patients who appropriately underwent sentinel lymph node biopsy followed by completion lymph node dissection for a positive sentinel lymph node.37 Historic (presentinel lymph node biopsy era) rates of melanoma relapse in a previously dissected nodal basin (including cases with clinically apparent lymph node metastases) are in the range of 3-5%.56
Contemporary series of sentinel lymph node–negative melanoma patients with greater than or equal to 500 such patients followed for a median of 16-60 months report a failure rate (nodal recurrence in previously mapped basin in the absence of new in-transit or systemic disease or first recurrence in any regional nodal basin) of 1.5-6%. This corresponds to a false-negative rate (false-negative cases divided by true-positive plus false-negative cases) of 7-24%.7,9,57,43,58,59,60,61 Data from the MSLT I trial suggest that the false-negative rate declines after 25 cases at an institution.62
Potential technical reasons for failure include errors in surgical technique; failure of nuclear medicine mapping; alterations in lymphatic drainage by inflammation, infection, or previous surgery; and errors in the pathologic examination of a correctly identified true sentinel node.63 Reexamination of negative findings from sentinel lymph nodes from patients with regional nodal relapse using careful step-sectioning and immunohistochemistry has been demonstrated to detect micrometastatic disease in 40-80% of patients. Conversely, nodal relapse may result from newly developed nodal metastases arising from clinically occult or newly apparent local or in-transit disease. Most (30-60%) relapses in sentinel node–negative patients are distant metastasis without any evidence of local, in-transit, or regional disease.
More on The Role of Sentinel Node Biopsy in Skin Cancer |
| Overview: The Role of Sentinel Node Biopsy in Skin Cancer |
 Treatment: The Role of Sentinel Node Biopsy in Skin Cancer |
| Follow-up: The Role of Sentinel Node Biopsy in Skin Cancer |
| Multimedia: The Role of Sentinel Node Biopsy in Skin Cancer |
| References |
| « Previous Page | Next Page » |
References
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. Mar-Apr 2008;58(2):71-96. [Medline].
LeJeune FJ, Das Gupta TK, Chaudhuri PK, eds. Malignant Melanoma, Medical and Surgical Management. New York: McGraw-Hill; 1994.
Hieken TJ, Ronan SG, Farolan M, Shilkaitis AL, Kim DK, Das Gupta TK. Beta 1 integrin expression in malignant melanoma predicts occult lymph node metastases. Surgery. Oct 1995;118(4):669-73; discussion 673-5. [Medline].
Hieken TJ, Ronan SG, Farolan M, Shilkaitis AL, Das Gupta TK. Molecular prognostic markers in intermediate-thickness cutaneous malignant melanoma. Cancer. Jan 15 1999;85(2):375-82. [Medline].
Voit C, Kron M, Rademaker J, et al. Molecular staging in stage II and III melanoma patients and its effect on long-term survival. J Clin Oncol. Feb 20 2005;23(6):1218-27. [Medline].
Boone B, Blokx W, De Bacquer D, Lambert J, Ruiter D, Brochez L. The role of VEGF-C staining in predicting regional metastasis in melanoma. Virchows Arch. Sep 2008;453(3):257-65. [Medline].
Cascinelli N, Belli F, Santinami M, et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO Melanoma Program experience. Ann Surg Oncol. Jul 2000;7(6):469-74. [Medline].
Jansen L, Nieweg OE, Peterse JL, Hoefnagel CA, Olmos RA, Kroon BB. Reliability of sentinel lymph node biopsy for staging melanoma. Br J Surg. Apr 2000;87(4):484-9. [Medline].
[Best Evidence] Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. Sep 28 2006;355(13):1307-17. [Medline].
Scolyer RA, Murali R, Satzger I, Thompson JF. The detection and significance of melanoma micrometastases in sentinel nodes. Surg Oncol. Sep 2008;17(3):165-74. [Medline].
Balch CM, Soong SJ, Atkins MB, et al. An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin. May-Jun 2004;54(3):131-49; quiz 182-4. [Medline].
Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet. Mar 14 1998;351(9105):793-6. [Medline].
Balch CM, Soong S, Ross MI, et al. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol. Mar 2000;7(2):87-97. [Medline].
Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. Apr 1992;127(4):392-9. [Medline].
Alex JC, Krag DN. Gamma-probe guided localization of lymph nodes. Surg Oncol. 1993;2(3):137-43. [Medline].
Albertini JJ, Cruse CW, Rapaport D, et al. Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma. Ann Surg. Feb 1996;223(2):217-24. [Medline].
Morton DL, Thompson JF, Essner R, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg. Oct 1999;230(4):453-63; discussion 463-5. [Medline].
Jacobs IA, Chang CK, DasGupta TK, Salti GI. Role of sentinel lymph node biopsy in patients with thin (<1 mm) primary melanoma. Ann Surg Oncol. Jun 2003;10(5):558-61. [Medline].
Ranieri JM, Wagner JD, Wenck S, Johnson CS, Coleman JJ 3rd. The prognostic importance of sentinel lymph node biopsy in thin melanoma. Ann Surg Oncol. Jul 2006;13(7):927-32. [Medline].
Wong SL, Brady MS, Busam KJ, Coit DG. Results of sentinel lymph node biopsy in patients with thin melanoma. Ann Surg Oncol. Mar 2006;13(3):302-9. [Medline].
Corsetti RL, Allen HM, Wanebo HJ. Thin < or = 1 mm level III and IV melanomas are higher risk lesions for regional failure and warrant sentinel lymph node biopsy. Ann Surg Oncol. Jul 2000;7(6):456-60. [Medline].
Karakousis GC, Gimotty PA, Botbyl JD, et al. Predictors of regional nodal disease in patients with thin melanomas. Ann Surg Oncol. Apr 2006;13(4):533-41. [Medline].
Gimotty PA, Botbyl J, Soong SJ, Guerry D. A population-based validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. Nov 1 2005;23(31):8065-75. [Medline].
Puleo CA, Messina JL, Riker AI, et al. Sentinel node biopsy for thin melanomas: which patients should be considered?. Cancer Control. Oct 2005;12(4):230-5. [Medline].
Wright BE, Scheri RP, Ye X, et al. Importance of sentinel lymph node biopsy in patients with thin melanoma. Arch Surg. Sep 2008;143(9):892-9; discussion 899-900. [Medline].
Yao KA, Hsueh EC, Essner R, Foshag LJ, Wanek LA, Morton DL. Is sentinel lymph node mapping indicated for isolated local and in-transit recurrent melanoma?. Ann Surg. Nov 2003;238(5):743-7. [Medline].
Su LD, Fullen DR, Sondak VK, Johnson TM, Lowe L. Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients. Cancer. Jan 15 2003;97(2):499-507. [Medline].
Urso C, Borgognoni L, Saieva C, et al. Sentinel lymph node biopsy in patients with "atypical Spitz tumors." A report on 12 cases. Hum Pathol. Jul 2006;37(7):816-23. [Medline].
Murali R, Sharma RN, Thompson JF, et al. Sentinel lymph node biopsy in histologically ambiguous melanocytic tumors with spitzoid features (so-called atypical spitzoid tumors). Ann Surg Oncol. Jan 2008;15(1):302-9. [Medline].
Mehrany K, Otley CC, Weenig RH, Phillips PK, Roenigk RK, Nguyen TH. A meta-analysis of the prognostic significance of sentinel lymph node status in Merkel cell carcinoma. Dermatol Surg. Feb 2002;28(2):113-7; discussion 117. [Medline].
Mondi MM, Cuenca RE, Ollila DW, Stewart JH 4th, Levine EA. Sentinel lymph node biopsy during pregnancy: initial clinical experience. Ann Surg Oncol. Jan 2007;14(1):218-21. [Medline].
Khera SY, Kiluk JV, Hasson DM, et al. Pregnancy-associated breast cancer patients can safely undergo lymphatic mapping. Breast J. May-Jun 2008;14(3):250-4. [Medline].
McMasters KM, Noyes RD, Reintgen DS, et al. Lessons learned from the Sunbelt Melanoma Trial. J Surg Oncol. Jul 1 2004;86(4):212-23. [Medline].
Gomez-Rivera F, Santillan A, McMurphey AB, et al. Sentinel node biopsy in patients with cutaneous melanoma of the head and neck: recurrence and survival study. Head Neck. Oct 2008;30(10):1284-94. [Medline].
Cormier JN, Xing Y, Ding M, et al. Population-based assessment of surgical treatment trends for patients with melanoma in the era of sentinel lymph node biopsy. J Clin Oncol. Sep 1 2005;23(25):6054-62. [Medline].
Grange F, Vitry F, Granel-Brocard F, et al. Variations in management of stage I to stage III cutaneous melanoma: a population-based study of clinical practices in France. Arch Dermatol. May 2008;144(5):629-36. [Medline].
Erickson Foster J, Velasco JM, Hieken TJ. Adverse outcomes associated with noncompliance with melanoma treatment guidelines. Ann Surg Oncol. Sep 2008;15(9):2395-402. [Medline].
Erickson JL, Velasco JM, Hieken TJ. Compliance with melanoma treatment guidelines in a community teaching hospital: time trends and other variables. Ann Surg Oncol. Apr 2008;15(4):1211-7. [Medline].
Cochran AJ, Balda BR, Starz H, et al. The Augsburg Consensus. Techniques of lymphatic mapping, sentinel lymphadenectomy, and completion lymphadenectomy in cutaneous malignancies. Cancer. Jul 15 2000;89(2):236-41. [Medline].
Carling T, Pan D, Ariyan S, Narayan D, Truini C. Diagnosis and treatment of interval sentinel lymph nodes in patients with cutaneous melanoma. Plast Reconstr Surg. Mar 2007;119(3):907-13. [Medline].
Thompson JF, Uren RF, Shaw HM, et al. Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg. Aug 1999;189(2):195-204. [Medline].
Scarsbrook AF, Ganeshan A, Bradley KM. Pearls and pitfalls of radionuclide imaging of the lymphatic system. Part 1: sentinel node lymphoscintigraphy in malignant melanoma. Br J Radiol. Feb 2007;80(950):132-9. [Medline].
Morton DL, Hoon DS, Cochran AJ, et al. Lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: therapeutic utility and implications of nodal microanatomy and molecular staging for improving the accuracy of detection of nodal micrometastases. Ann Surg. Oct 2003;238(4):538-49; discussion 549-50. [Medline].
Creager AJ, Shiver SA, Shen P, Geisinger KR, Levine EA. Intraoperative evaluation of sentinel lymph nodes for metastatic melanoma by imprint cytology. Cancer. Jun 1 2002;94(11):3016-22. [Medline].
Shivers SC, Wang X, Li W, et al. Molecular staging of malignant melanoma: correlation with clinical outcome. JAMA. Oct 28 1998;280(16):1410-5. [Medline].
Romanini A, Manca G, Pellegrino D, et al. Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome. Ann Oncol. Nov 2005;16(11):1832-40. [Medline].
Scoggins CR, Ross MI, Reintgen DS, et al. Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma. J Clin Oncol. Jun 20 2006;24(18):2849-57. [Medline].
Frankel TL, Griffith KA, Lowe L, et al. Do micromorphometric features of metastatic deposits within sentinel nodes predict nonsentinel lymph node involvement in melanoma?. Ann Surg Oncol. Sep 2008;15(9):2403-11. [Medline].
Gershenwald JE, Andtbacka RH, Prieto VG, et al. Microscopic tumor burden in sentinel lymph nodes predicts synchronous nonsentinel lymph node involvement in patients with melanoma. J Clin Oncol. Sep 10 2008;26(26):4296-303. [Medline].
Guggenheim M, Dummer R, Jung FJ, et al. The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma--a retrospective analysis of 392 cases. Br J Cancer. Jun 17 2008;98(12):1922-8. [Medline].
Roka F, Mastan P, Binder M, et al. Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients. Eur J Surg Oncol. Jan 2008;34(1):82-8. [Medline].
Bilimoria KY, Balch CM, Bentrem DJ, et al. Complete lymph node dissection for sentinel node-positive melanoma: assessment of practice patterns in the United States. Ann Surg Oncol. Jun 2008;15(6):1566-76. [Medline].
Scheri RP, Essner R, Turner RR, Ye X, Morton DL. Isolated tumor cells in the sentinel node affect long-term prognosis of patients with melanoma. Ann Surg Oncol. Oct 2007;14(10):2861-6. [Medline].
Thompson JF, McCarthy WH, Bosch CM, et al. Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res. Aug 1995;5(4):255-60. [Medline].
Reintgen DS, Brobeil A. Lymphatic mapping and selective lymphadenectomy as an alternative to elective lymph node dissection in patients with malignant melanoma. Hematol Oncol Clin North Am. Aug 1998;12(4):807-21, vii. [Medline].
Warso MA, Das Gupta TK. Melanoma recurrence in a previously dissected lymph node basin. Arch Surg. Mar 1994;129(3):252-5. [Medline].
Chao C, Wong SL, Ross MI, et al. Patterns of early recurrence after sentinel lymph node biopsy for melanoma. Am J Surg. Dec 2002;184(6):520-4; discussion 525. [Medline].
Nowecki ZI, Rutkowski P, Nasierowska-Guttmejer A, Ruka W. Sentinel lymph node biopsy in melanoma patients with clinically negative regional lymph nodes--one institution's experience. Melanoma Res. Feb 2003;13(1):35-43. [Medline].
Yee VS, Thompson JF, McKinnon JG, et al. Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy. Ann Surg Oncol. Jun 2005;12(6):429-39. [Medline].
Caraco C, Marone U, Celentano E, Botti G, Mozzillo N. Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma. Ann Surg Oncol. Sep 2007;14(9):2662-7. [Medline].
Carlson GW, Page AJ, Cohen C, et al. Regional recurrence after negative sentinel lymph node biopsy for melanoma. Ann Surg. Sep 2008;248(3):378-86. [Medline].
Morton DL, Cochran AJ, Thompson JF, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. Sep 2005;242(3):302-11; discussion 311-3. [Medline].
Karim RZ, Scolyer RA, Li W, et al. False negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology. Ann Surg. Jun 2008;247(6):1003-10. [Medline].
Chan AD, Essner R, Wanek LA, Morton DL. Judging the therapeutic value of lymph node dissections for melanoma. J Am Coll Surg. Jul 2000;191(1):16-22; discussion 22-3. [Medline].
Koh HK, Sober AJ, Day CL Jr, et al. Prognosis of clinical stage I melanoma patients with positive elective regional node dissection. J Clin Oncol. Aug 1986;4(8):1238-44. [Medline].
Kirkwood JM. Building upon the standard of care in adjuvant therapy of high-risk melanoma. J Clin Oncol. Dec 1 2005;23(34):8559-63. [Medline].
Eggermont AM, Suciu S, Santinami M, et al. EORTC 18991: Long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma: final results of a randomized phase III trial. J Clin Oncol. 2007;25(18 suppl):8504.
Testori A, Lazzaro G, Baldini F, et al. The role of ultrasound of sentinel nodes in the pre- and post-operative evaluation of stage I melanoma patients. Melanoma Res. Jun 2005;15(3):191-8. [Medline].
Stretch JR, Somorjai R, Bourne R, et al. Melanoma metastases in regional lymph nodes are accurately detected by proton magnetic resonance spectroscopy of fine-needle aspirate biopsy samples. Ann Surg Oncol. Nov 2005;12(11):943-9. [Medline].
Gadd MA, Cosimi AB, Yu J, et al. Outcome of patients with melanoma and histologically negative sentinel lymph nodes. Arch Surg. Apr 1999;134(4):381-7. [Medline].
Gannon CJ, Rousseau DL Jr, Ross MI, et al. Accuracy of lymphatic mapping and sentinel lymph node biopsy after previous wide local excision in patients with primary melanoma. Cancer. Dec 1 2006;107(11):2647-52. [Medline].
Hochwald SN, Coit DG. Role of elective lymph node dissection in melanoma. Semin Surg Oncol. Jun 1998;14(4):276-82. [Medline].
Shen P, Guenther JM, Wanek LA, Morton DL. Can elective lymph node dissection decrease the frequency and mortality rate of late melanoma recurrences?. Ann Surg Oncol. Mar 2000;7(2):114-9. [Medline].
Further Reading
Keywords
sentinel node biopsy, sentinel lymphadenectomy, skin cancer biopsy, selective lymphadenectomy, melanoma surgery, skin cancer, melanoma, skin cancer surgery, malignant melanoma, lymph node metastasis, sentinel lymph node biopsy, melanoma staging, melanoma treatment, melanoma prognosis
