- Email: [email protected]
A definitive role for sentinel lymph node mapping with biopsy for cutaneous melanoma of the head and neck
original article
J. Kelly K. Fogarty H. P. Redmond Department of Academic Surgery, Cork University, Hospital, Cork, Ireland Correspondence to: J Kelly, Department of Academic Surgery, Cork University Hospital, Cork, Ireland Tel: +353 2149 22340 Email: justinjoshkelly@ gmail.com
A DEFINITIVE ROLE FOR SENTINEL LYMPH NODE MAPPING WITH BIOPSY FOR CUTANEOUS MELANOMA OF THE HEAD AND NECK Aims: The aim of this study was to evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with cutaneous melanoma of the head and neck. Methods: Consecutive patients with cutaneous melanoma of the head and neck regions undergoing SLNM with biopsy were identied from a departmental database comprising 480 patients in total from 2000-2007. Factors examined included demographic data, histological subtype, site and depth of lesion, pre-operative lymphoscintigraphy, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, percentage of skin grafting required and follow-up. Results: The median patient age was 51 years (range 18-90 years). The mean Breslow depth was 3.25mm (range 1-19mm). Five patients presented with stage III/IV disease. A SLN was identied in 27/40 patients who underwent head and neck SLN mapping (mean two lymph nodes per patient). Of these, six (22%) patients were positive for metastatic melanoma. The false-negative rate was 9.5%. The median follow up for patients was 39.6 months (range 12-96 months). No facial nerve injury or other major morbidity occurred. Conclusions: This study indicates that SLNB is a reliable and safe technique to diagnose regional spread from head and neck cutaneous melanoma. It is more difcult than at other sites. These lesions have a higher incidence of failed SLN mapping and a higher rate of recurrence following negative SLNB, when compared to truncal and extremity lesions. Nodular melanomas are more likely to fail the sentinel lymph node mapping procedure than other histological subtypes. keywords: head and neck, melanoma, sentinel lymph node mapping, sentinel lymph node biopsy, node negative, recurrence Surgeon, 1 December 2009, pp.336-39
Introduction The incidence of cutaneous melanoma of the head and neck region has increased in recent years, along with an overall increase in the incidence of cutaneous melanoma worldwide. Primary cutaneous melanoma of the head and neck comprises 30% of all melanoma and is considered to have higher rates of local recurrence and regional nodal disease than those arising on extremity or truncal sites.1 The key to survival is early detection and treatment of micrometastatic disease as this may improve disease-free and overall survival rates.2 The status of the regional lymph node basin has been widely shown to be the most important prognostic indicator for patients diagnosed with cutaneous melanoma. Melanomas less than 1mm rarely metastasise while at least 25% of melanomas between 1.5 and 4mm and greater than 60% of melanomas greater than 4mm thick will have lymph node metastases at presentation.3 The outcome from melanoma also depends heavily on the stage at presentation. Patients with early stage disease (i.e. less than 1mm thick) achieve long-term survival in more than 90% of cases. For patients with melanomas 336
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the royal colleges of surgeons of edinburgh and ireland
greater than 1mm thickness, survival rates range from 50% to 90%.4 The introduction of the SLNB technique for the evaluation of patients with truncal and extremity melanoma by Morton et al. showed that the status of the SLN accurately represented the status of the entire nodal basin from which it was obtained. This study highlighted a novel technique of identifying patients with occult nodal metastasis who warranted therapeutic lymphadenectomy and possible adjuvant therapy, whilst also sparing the remaining 80% of patients without regional disease the morbidity associated with a formal lymphadenectomy procedure.5 The findings of the Multicentre Selective Lymphadenectomy Trial (MSLT-1) by Morton et al. confirmed that the SLN technique should be applied to melanomatous lesions greater than 1mm thick, lesions consisting solely of a shave biopsy with positive deep margins and those with adverse histological features such as significant regression or ulceration.6 While SLNB has a defined role in cutaneous melanomas of the trunk and extremities, © 2009 Surgeon 7; 6: 336-39
several questions remain unanswered with respect to its application in the head and neck region. It is limited by technical difficulties with specific concern surrounding damage to vital structures such as the facial nerve.7 There is also the distinct necessity for nuclear medicine staff as well as pathologists who specialize in SLNB technique. Furthermore, there is growing concern surrounding the reliability of the SLN to accurately predict the disease status of the entire nodal basin. In the head and neck region, the complexity and variablility of the interlacing network of cervical lymphatics was highlighted by O’Brien et al. who showed a 34% discordance rate between the clinical prediction of lymphatic drainage and lymphoscintigraphy findings in 97 cases of cutaneous melanoma of the head and neck.8 The aim of our study was to evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with cutaneous melanoma of the head and neck.
table 1. Distribution of cutaneous head and neck melanoma Site
No. of cases (%) N=40
Regions of false negatives
Temple
11
27.5
Yes (2)
Cheek
10
25
Yes (1)
Post scalp/ occiput
4
10
Ant neck triangle
3
7.5
Mandible
3
7.5
Ear
3
7.5
Forehead
2
5
Methods
Nose
1
2.5
Consecutive patients with cutaneous melanoma of the head and neck regions undergoing SLNM with biopsy were evaluated. This subgroup of patients was identified from a prospectively maintained departmental database comprising 480 patients in total from 20002007. To ensure patient confidentiality, access to this database was limited to one person. Factors examined included demographic data, histological subtype, site and depth of lesion, pre-operative lymphoscintigraphy, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, percentage of skin grafting required and follow-up. The SLNB technique performed adhered to internationally recognised guidelines.9 All patients underwent pre-operative lymphoscintigraphy to ascertain the number and location of regional nodal basins at risk for metastatic disease. The lymphoscintigraphy was performed on the morning of the patients’ surgery using a standard dose of technetium injected intradermally into the four quadrants surrounding the primary melanoma lesion. Planar and dynamic phase imaging were performed two hours following injection. The SLN was then indentified by a combination of the lymphoscintigraphy and peri-operative gamma probe. Occasionally, we do not use intra-operative blue dye particularly for melanomas affecting the face for two reasons. We feel that injection of the blue dye itself around the lesion can lead to further aesthetic disturbance and that it also remains around the injection site for a considerable amount of time. Even though this is not standard practice we did not use this technique in five patients, in only one of whom we failed to identify a sentinel node. The procedure was complete when all nodal basins had minimal background radioactivity relative to the primary lesion and sentinel nodes. All SLNs retrieved were sent for histological evaluation using serial permanent sectioning. Evaluation included staining with haematoxylin-eosin (H&E). If the SLNs were negative with H&E staining, further evaluation was performed using immunohistochemical staining for S100, melan-A and HMB-45. Patients who had a positive SLN result were offered further completion lymphadenectomy within three weeks of their SLNM procedure. All patients were followed-up as per Cork University Hospital cancer guidelines.10 No patients were lost to follow-up.
Scalp
1
2.5
Lip
1
2.5
Eyelid
1
2.5
Results Sixty patients with cutaneous melanoma of the head and neck region were initially identified from the database. Fifteen (25%) patients had either melanoma in situ or lesions <1mm without adverse histo© 2009 Surgeon 7; 6: 336-39
logical features; all had histologically confirmed complete excision. Another five (8.3%) patients presented with stage III/IV disease. Forty patients were thus enrolled in the study proper. Of the remaining 40 evaluable patients who underwent primary excision and SLNM, 15 (37.5%) were women and 25 (62.5%) were men. The median patient age was 51 years (range 18-90 years). The mean Breslow depth was 3.25 mm (range 1-19mm). Melanoma subtypes included nodular (52.5%), superficial spreading (20%), lentigo (17.5%), spindle cell/ spitzoid (5%) and histology unavailable (5%). Three lesions (7.5%) were ulcerated. The distributions of the 40 applicable primary melanoma lesions are listed in Table 1. Using a combination of pre-operative lymphoscintigraphy, intraoperative gamma probe and isosolfan blue dye, a SLN was found in 27/40 cases (67.5%) performed. The average number of lymph nodes retrieved per patient was two (range 1-3). The majority of the sentinel nodes removed were taken from the cervical chain (13), pre-auricular (10), occipital (2), post-auricular (1) and buccal (1). There was no morbidity associated with the procedure. No adverse reactions with the blue dye were encountered and, specifically, there was no reported damage to any cranial nerve function or vital neck structures. Twenty (50%) patients underwent skin grafting at the time of their SLNM to ensure adequacy of margins. Of the 27 patients, 6 (22%) had metastatic melanoma identified using SLNB. A further breakdown of these patients according to Breslow depth is shown in Table 2. All these patients underwent further lymphadenectomy. The median follow-up for patients was 39.6 months (range 12-96 months). Of the patients who had a failed SLNM procedure (13) or a histologically negative SLN (21), three patients had a regional nodal recurrence. This occurred in a median of 11 months (range 2-18 months). Hence our false negative result is 2/21 (9.5%) on an intention to treat analysis with a regional recurrence rate of 7.7%. Two patients had a successful SLNM procedure but no evidence of lymph node metastatic spread. The third patient failed the SLNM procedure. All three patients recurred to the regional lymph node basin. The reasons for a failed mapping procedure included a failure of the technetium to spread radiographically to the regional nodes or a failure to locate any hot nodes during surgery. No blind exploratory dissection was undertaken. Of the 13 patients who had a failed SLNM procedure 10 (77%) had nodular melanomas.
the royal colleges of surgeons of edinburgh and ireland | 337
table 2. Distribution of sentinel lymph node biopsy (slnb) according to Breslow depth <1mm
1-2mm
2-4mm
>4mm
Total
15
14
15
11
Positive SLNB (%)
-
3 (50%)
1 (16%)
2 (33%)
Discussion The incidence of cutaneous melanoma in Ireland has risen by 3% between 1997 and 2001 with more than 400 reported new cases per year. This represents 2% of all new invasive cancer cases in Ireland and 1% of all cancer deaths annually (n=64).11 The advantages of SLNB are numerous. It improves the accuracy of staging and provides valuable prognostic information to guide subsequent treatment decisions. It allows early therapeutic lymph node dissection for patients with nodal metastases and determines those who may benefit from adjuvant therapy with interferon D2b or those suitable to enter into appropriate clinical trials. While SLNB has a defined role in cutaneous melanomas of the trunk and extremities, several questions remain unanswered with respect to its application in the head and neck region. It is limited by technical difficulties with specific concern surrounding damage to vital structures such as the facial nerve. There is also growing concern surrounding the reliability of the SLN to accurately predict the disease status of the entire nodal basin. In the head and neck region, studies have shown the complex and variable distribution of cervical lymphatics by highlighting a significant discordance between clinically predicted lymphatic drainage patterns and actual lymphoscintigraphy findings.8 Regional nodal failures in all melanoma patients following a negative SLNB are uncommon and some studies have previously suggested that this was most commonly because conventional histological evaluation was unable to identify occult metastatic disease.12 Sentinel lymph node mapping with subsequent biopsy for cutaneous melanoma of the head and neck is technically challenging for today’s surgeon. In our study SLNB succeeded in 27/40 cases (67.5%) Our SNB identification failure rate is high (32.5%) compared to >5-10% for truncal and extremity melanoma. Various reasons have been suggested as to why SLNM fails. These include (1) when the primary lesion is overlying the draining lymph node basin, (2) learning curve of the performing surgeon/pathologist/nuclear medicine staff, (3) inappropriately high radioactivity level, (4) movement of the dye into the second or nonsentinel lymph node and (5) incorrect injection technique of the dye. The performing surgeon has successfully identified the sentinel node in >350 patients with truncal and extremity melanoma. Patients undergoing SLNM for cutaneous melanoma should be managed via a multidisciplinary team and the overall success rate of the procedure may be attributable in some part to this. It has been suggested that a 30-person learning curve be recommended for a surgeon performing these cases.9 Experienced nuclear medicine staff are imperative as inappropriate administration of the radio-labelled isotope can directly affect the outcome of the procedure. Interpretation by a pathologist experienced in the technique of SLNB is imperative as a more thorough and detailed analysis of the SLNs is required than when examining a formal lymphadenectomy sample.13 338
|
table 3. Review of other centres’ experience with slnb for cutaneous head and neck melanoma Number
Positive SLNB (%)
False negative rate (%)
Modalities used
2002
56
7.1
1.9
DE±J
2001
12
0
8.3
DE
Rasgon16 2001
24
20.8
10
DEJ
Carlson17 2000 58
17.5
21.3
DE±J
2000 30
26.7
9.1
DEJ
1998
23
14
5
DE±J
1997
58
11
0
DEJ
1995
20
20
25
DEJ
Author
Year
Patel14 Jacobs15
Jansen
18
19
Alex
Wells
20
O’Brien8
It is also important to accurately select patients who are suitable to undergo SLNB. We excluded patients with in situ lesion, lesions <1mm without adverse histological features on stage III/IV disease and also patients who had previous surgery to the predicted draining lymphatic tissue (two patients). A review of data currently available in the literature concerning other institutions’ experience with SLNB in cutaneous melanoma of the head and neck is presented in Table 3.14-20 The 22% rate of SLN positivity and the 9.5% false negative rate from our own study compare favourably with those in Table 3. However, the false negative rates quoted were quite variable ranging from 0 to 25%. There are likely numerous causes as to the discordance between studies. Some studies used numbers as low as 12 patients. Some studies used only T1 and T2 lesions. Variation in the time allowed for follow-up period is also an important factor to consider. The median range of followup periods here was 11-30 months. Our own median follow-up for patients was 39.6 months (range 12-96 months). Not all studies used the combined modalities of SLN detection: D=lymphoscintigraphy, E= gamma-probe and J= blue dye. To date there have been surprisingly few studies that have formally characterised the basis for false negative SLNB in melanoma and other cancers, the exception being a recent study from the John Wayne Cancer Institute which categorised some of the risk factors for recurrence in node negative patients. This study reported a ‘false negative’ rate of 8.9%, identifying increasing tumour thickness, the presence of ulceration and head/neck primary tumours as risk factors for the development of recurrence in the presence of a negative node. In a commentary following presentation of their findings, the authors also referred to an increased incidence of nodular melanoma in their patients with node negative recurrence.21 This study indicates that SLNB is a reliable and safe technique to diagnose regional spread from head and neck cutaneous melanoma. It is more difficult than at other sites. These lesions have a higher incidence of failed SLN mapping and a higher rate of recurrence following negative SLNB, when compared to trunk and extremity lesions. Nodular melanomas are more likely to fail the sentinel lymph node mapping procedure than other histological subtypes.
Copyright © 3 December 2008
the royal colleges of surgeons of edinburgh and ireland
© 2009 Surgeon 7; 6: 336-39
REFERENCES 1. Daryanani D, Plukker JTh, Jong de MA et al. Increased incidence of brain metastases in cutaneous head and neck melanoma. Melanoma Res 2005; 15: 119–24 2. Pacico MD, Grover R, Sanders R. Use of an earlydetection strategy to improve disease control in melanoma patients. Br J Plast Surg 2004; 57(2): 105-11 3. Balch CM, Buzaid AC, Soong SJ et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 3635-48 4. Greene FL, Page DL, Fleming ID et al. AJCC Cancer Staging Manual 6th ed. New York: Springer Verlag, 2002 5. Morton DL, Wen DR, Wong JH et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 392-99 6. Morton DL, Cochran AJ, Thompson JF et al. Multicentre Selective Lymphadenectomy Trial Group. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicentre trial. Ann Surg 2005; 242: 302-11 7. Eicher SA, Clayman GL, Myers JN et al. A prospective study of intraoperative lymphatic mapping for head and neck cutaneous melanoma. Arch Otolaryngol Head Neck Surg 2002; 128: 241-46 8. O’Brien CJ, Uren RF, Thompson JF et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg 1995; 170: 461-66 9. 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. Annals of Surgery 1999; 230(4): 453-65 10. Clinical Guidelines for Melanoma, Cork University Hospital, Melanoma Steering group committee, Redmond HP, O’Shaughnessy M, Andrews E, Breathnach O, O’Reilly S, Fogarty K 11. http://www.ncri.ie/ncri/index.shtml. National Cancer Registry of Ireland 12. Gershenwald JE, Colome MI, Lee JE et al. Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 1998 16(6); 2253-60 13. Cascinelli N, Belli F, Santinami M et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO Melanoma Program experience. Ann Surg Oncol 2000; 7: 469-74 14. Patel SG, Coit DG, Shaha AR et al. Sentinel lymph node biopsy for cutaneous head and neck melanomas. Arch Otolaryngol Head Neck Surg 2002; 128: 285- 291 15. Jacobs IA, Chevinsky AH, Swayne LC et al. Gamma probe-directed lymphatic mapping and sentinel lymphadenectomy in primary melanoma: reliability of the procedure and analysis of failures after longterm follow up. J Surg Oncol 2001; 77: 157-64 16. Rasgon BM. Use of low-dose technetium Tc 99m sulfur colloid to locate sentinel lymph nodes in melanoma of the head and neck: preliminary study. Laryngoscope 2001; 111: 1366-72
© 2009 Surgeon 7; 6: 336-39
17. Carlson GW, Murray DR, Greenlee R et al. Management of malignant melanoma of the head and neck using dynamic lymphoscintigraphy and gamma probeguided sentinel lymph node biopsy. Arch Otolaryngol Head Neck Surg 2000; 126:433-37 18. Jansen L, Koops HS, Nieweg OE et al. Sentinel node biopsy for melanoma in the head and neck region. Head Neck 2000; 22: 27-33 19. Alex JC, Krag DN, Harlow SP et al. Localization of regional lymph nodes in melanomas of the head and neck. Arch Otolaryngol Head Neck Surg 1998; 124: 135- 40 20. Wells KE, Rapaport DP, Cruse CW et al. Sentinel lymph node biopsy in melanoma of the head and neck. Plast Reconstr Surg 1997; 100: 591-94 21. Zogakis T, Essner R, Wang H et al. Melanoma recurrence patterns after negative sentinel lymphadenectomy Arch Surg 2005; 140: 865-72
the royal colleges of surgeons of edinburgh and ireland | 339
J. Kelly K. Fogarty H. P. Redmond Department of Academic Surgery, Cork University, Hospital, Cork, Ireland Correspondence to: J Kelly, Department of Academic Surgery, Cork University Hospital, Cork, Ireland Tel: +353 2149 22340 Email: justinjoshkelly@ gmail.com
A DEFINITIVE ROLE FOR SENTINEL LYMPH NODE MAPPING WITH BIOPSY FOR CUTANEOUS MELANOMA OF THE HEAD AND NECK Aims: The aim of this study was to evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with cutaneous melanoma of the head and neck. Methods: Consecutive patients with cutaneous melanoma of the head and neck regions undergoing SLNM with biopsy were identied from a departmental database comprising 480 patients in total from 2000-2007. Factors examined included demographic data, histological subtype, site and depth of lesion, pre-operative lymphoscintigraphy, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, percentage of skin grafting required and follow-up. Results: The median patient age was 51 years (range 18-90 years). The mean Breslow depth was 3.25mm (range 1-19mm). Five patients presented with stage III/IV disease. A SLN was identied in 27/40 patients who underwent head and neck SLN mapping (mean two lymph nodes per patient). Of these, six (22%) patients were positive for metastatic melanoma. The false-negative rate was 9.5%. The median follow up for patients was 39.6 months (range 12-96 months). No facial nerve injury or other major morbidity occurred. Conclusions: This study indicates that SLNB is a reliable and safe technique to diagnose regional spread from head and neck cutaneous melanoma. It is more difcult than at other sites. These lesions have a higher incidence of failed SLN mapping and a higher rate of recurrence following negative SLNB, when compared to truncal and extremity lesions. Nodular melanomas are more likely to fail the sentinel lymph node mapping procedure than other histological subtypes. keywords: head and neck, melanoma, sentinel lymph node mapping, sentinel lymph node biopsy, node negative, recurrence Surgeon, 1 December 2009, pp.336-39
Introduction The incidence of cutaneous melanoma of the head and neck region has increased in recent years, along with an overall increase in the incidence of cutaneous melanoma worldwide. Primary cutaneous melanoma of the head and neck comprises 30% of all melanoma and is considered to have higher rates of local recurrence and regional nodal disease than those arising on extremity or truncal sites.1 The key to survival is early detection and treatment of micrometastatic disease as this may improve disease-free and overall survival rates.2 The status of the regional lymph node basin has been widely shown to be the most important prognostic indicator for patients diagnosed with cutaneous melanoma. Melanomas less than 1mm rarely metastasise while at least 25% of melanomas between 1.5 and 4mm and greater than 60% of melanomas greater than 4mm thick will have lymph node metastases at presentation.3 The outcome from melanoma also depends heavily on the stage at presentation. Patients with early stage disease (i.e. less than 1mm thick) achieve long-term survival in more than 90% of cases. For patients with melanomas 336
|
the royal colleges of surgeons of edinburgh and ireland
greater than 1mm thickness, survival rates range from 50% to 90%.4 The introduction of the SLNB technique for the evaluation of patients with truncal and extremity melanoma by Morton et al. showed that the status of the SLN accurately represented the status of the entire nodal basin from which it was obtained. This study highlighted a novel technique of identifying patients with occult nodal metastasis who warranted therapeutic lymphadenectomy and possible adjuvant therapy, whilst also sparing the remaining 80% of patients without regional disease the morbidity associated with a formal lymphadenectomy procedure.5 The findings of the Multicentre Selective Lymphadenectomy Trial (MSLT-1) by Morton et al. confirmed that the SLN technique should be applied to melanomatous lesions greater than 1mm thick, lesions consisting solely of a shave biopsy with positive deep margins and those with adverse histological features such as significant regression or ulceration.6 While SLNB has a defined role in cutaneous melanomas of the trunk and extremities, © 2009 Surgeon 7; 6: 336-39
several questions remain unanswered with respect to its application in the head and neck region. It is limited by technical difficulties with specific concern surrounding damage to vital structures such as the facial nerve.7 There is also the distinct necessity for nuclear medicine staff as well as pathologists who specialize in SLNB technique. Furthermore, there is growing concern surrounding the reliability of the SLN to accurately predict the disease status of the entire nodal basin. In the head and neck region, the complexity and variablility of the interlacing network of cervical lymphatics was highlighted by O’Brien et al. who showed a 34% discordance rate between the clinical prediction of lymphatic drainage and lymphoscintigraphy findings in 97 cases of cutaneous melanoma of the head and neck.8 The aim of our study was to evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with cutaneous melanoma of the head and neck.
table 1. Distribution of cutaneous head and neck melanoma Site
No. of cases (%) N=40
Regions of false negatives
Temple
11
27.5
Yes (2)
Cheek
10
25
Yes (1)
Post scalp/ occiput
4
10
Ant neck triangle
3
7.5
Mandible
3
7.5
Ear
3
7.5
Forehead
2
5
Methods
Nose
1
2.5
Consecutive patients with cutaneous melanoma of the head and neck regions undergoing SLNM with biopsy were evaluated. This subgroup of patients was identified from a prospectively maintained departmental database comprising 480 patients in total from 20002007. To ensure patient confidentiality, access to this database was limited to one person. Factors examined included demographic data, histological subtype, site and depth of lesion, pre-operative lymphoscintigraphy, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, percentage of skin grafting required and follow-up. The SLNB technique performed adhered to internationally recognised guidelines.9 All patients underwent pre-operative lymphoscintigraphy to ascertain the number and location of regional nodal basins at risk for metastatic disease. The lymphoscintigraphy was performed on the morning of the patients’ surgery using a standard dose of technetium injected intradermally into the four quadrants surrounding the primary melanoma lesion. Planar and dynamic phase imaging were performed two hours following injection. The SLN was then indentified by a combination of the lymphoscintigraphy and peri-operative gamma probe. Occasionally, we do not use intra-operative blue dye particularly for melanomas affecting the face for two reasons. We feel that injection of the blue dye itself around the lesion can lead to further aesthetic disturbance and that it also remains around the injection site for a considerable amount of time. Even though this is not standard practice we did not use this technique in five patients, in only one of whom we failed to identify a sentinel node. The procedure was complete when all nodal basins had minimal background radioactivity relative to the primary lesion and sentinel nodes. All SLNs retrieved were sent for histological evaluation using serial permanent sectioning. Evaluation included staining with haematoxylin-eosin (H&E). If the SLNs were negative with H&E staining, further evaluation was performed using immunohistochemical staining for S100, melan-A and HMB-45. Patients who had a positive SLN result were offered further completion lymphadenectomy within three weeks of their SLNM procedure. All patients were followed-up as per Cork University Hospital cancer guidelines.10 No patients were lost to follow-up.
Scalp
1
2.5
Lip
1
2.5
Eyelid
1
2.5
Results Sixty patients with cutaneous melanoma of the head and neck region were initially identified from the database. Fifteen (25%) patients had either melanoma in situ or lesions <1mm without adverse histo© 2009 Surgeon 7; 6: 336-39
logical features; all had histologically confirmed complete excision. Another five (8.3%) patients presented with stage III/IV disease. Forty patients were thus enrolled in the study proper. Of the remaining 40 evaluable patients who underwent primary excision and SLNM, 15 (37.5%) were women and 25 (62.5%) were men. The median patient age was 51 years (range 18-90 years). The mean Breslow depth was 3.25 mm (range 1-19mm). Melanoma subtypes included nodular (52.5%), superficial spreading (20%), lentigo (17.5%), spindle cell/ spitzoid (5%) and histology unavailable (5%). Three lesions (7.5%) were ulcerated. The distributions of the 40 applicable primary melanoma lesions are listed in Table 1. Using a combination of pre-operative lymphoscintigraphy, intraoperative gamma probe and isosolfan blue dye, a SLN was found in 27/40 cases (67.5%) performed. The average number of lymph nodes retrieved per patient was two (range 1-3). The majority of the sentinel nodes removed were taken from the cervical chain (13), pre-auricular (10), occipital (2), post-auricular (1) and buccal (1). There was no morbidity associated with the procedure. No adverse reactions with the blue dye were encountered and, specifically, there was no reported damage to any cranial nerve function or vital neck structures. Twenty (50%) patients underwent skin grafting at the time of their SLNM to ensure adequacy of margins. Of the 27 patients, 6 (22%) had metastatic melanoma identified using SLNB. A further breakdown of these patients according to Breslow depth is shown in Table 2. All these patients underwent further lymphadenectomy. The median follow-up for patients was 39.6 months (range 12-96 months). Of the patients who had a failed SLNM procedure (13) or a histologically negative SLN (21), three patients had a regional nodal recurrence. This occurred in a median of 11 months (range 2-18 months). Hence our false negative result is 2/21 (9.5%) on an intention to treat analysis with a regional recurrence rate of 7.7%. Two patients had a successful SLNM procedure but no evidence of lymph node metastatic spread. The third patient failed the SLNM procedure. All three patients recurred to the regional lymph node basin. The reasons for a failed mapping procedure included a failure of the technetium to spread radiographically to the regional nodes or a failure to locate any hot nodes during surgery. No blind exploratory dissection was undertaken. Of the 13 patients who had a failed SLNM procedure 10 (77%) had nodular melanomas.
the royal colleges of surgeons of edinburgh and ireland | 337
table 2. Distribution of sentinel lymph node biopsy (slnb) according to Breslow depth <1mm
1-2mm
2-4mm
>4mm
Total
15
14
15
11
Positive SLNB (%)
-
3 (50%)
1 (16%)
2 (33%)
Discussion The incidence of cutaneous melanoma in Ireland has risen by 3% between 1997 and 2001 with more than 400 reported new cases per year. This represents 2% of all new invasive cancer cases in Ireland and 1% of all cancer deaths annually (n=64).11 The advantages of SLNB are numerous. It improves the accuracy of staging and provides valuable prognostic information to guide subsequent treatment decisions. It allows early therapeutic lymph node dissection for patients with nodal metastases and determines those who may benefit from adjuvant therapy with interferon D2b or those suitable to enter into appropriate clinical trials. While SLNB has a defined role in cutaneous melanomas of the trunk and extremities, several questions remain unanswered with respect to its application in the head and neck region. It is limited by technical difficulties with specific concern surrounding damage to vital structures such as the facial nerve. There is also growing concern surrounding the reliability of the SLN to accurately predict the disease status of the entire nodal basin. In the head and neck region, studies have shown the complex and variable distribution of cervical lymphatics by highlighting a significant discordance between clinically predicted lymphatic drainage patterns and actual lymphoscintigraphy findings.8 Regional nodal failures in all melanoma patients following a negative SLNB are uncommon and some studies have previously suggested that this was most commonly because conventional histological evaluation was unable to identify occult metastatic disease.12 Sentinel lymph node mapping with subsequent biopsy for cutaneous melanoma of the head and neck is technically challenging for today’s surgeon. In our study SLNB succeeded in 27/40 cases (67.5%) Our SNB identification failure rate is high (32.5%) compared to >5-10% for truncal and extremity melanoma. Various reasons have been suggested as to why SLNM fails. These include (1) when the primary lesion is overlying the draining lymph node basin, (2) learning curve of the performing surgeon/pathologist/nuclear medicine staff, (3) inappropriately high radioactivity level, (4) movement of the dye into the second or nonsentinel lymph node and (5) incorrect injection technique of the dye. The performing surgeon has successfully identified the sentinel node in >350 patients with truncal and extremity melanoma. Patients undergoing SLNM for cutaneous melanoma should be managed via a multidisciplinary team and the overall success rate of the procedure may be attributable in some part to this. It has been suggested that a 30-person learning curve be recommended for a surgeon performing these cases.9 Experienced nuclear medicine staff are imperative as inappropriate administration of the radio-labelled isotope can directly affect the outcome of the procedure. Interpretation by a pathologist experienced in the technique of SLNB is imperative as a more thorough and detailed analysis of the SLNs is required than when examining a formal lymphadenectomy sample.13 338
|
table 3. Review of other centres’ experience with slnb for cutaneous head and neck melanoma Number
Positive SLNB (%)
False negative rate (%)
Modalities used
2002
56
7.1
1.9
DE±J
2001
12
0
8.3
DE
Rasgon16 2001
24
20.8
10
DEJ
Carlson17 2000 58
17.5
21.3
DE±J
2000 30
26.7
9.1
DEJ
1998
23
14
5
DE±J
1997
58
11
0
DEJ
1995
20
20
25
DEJ
Author
Year
Patel14 Jacobs15
Jansen
18
19
Alex
Wells
20
O’Brien8
It is also important to accurately select patients who are suitable to undergo SLNB. We excluded patients with in situ lesion, lesions <1mm without adverse histological features on stage III/IV disease and also patients who had previous surgery to the predicted draining lymphatic tissue (two patients). A review of data currently available in the literature concerning other institutions’ experience with SLNB in cutaneous melanoma of the head and neck is presented in Table 3.14-20 The 22% rate of SLN positivity and the 9.5% false negative rate from our own study compare favourably with those in Table 3. However, the false negative rates quoted were quite variable ranging from 0 to 25%. There are likely numerous causes as to the discordance between studies. Some studies used numbers as low as 12 patients. Some studies used only T1 and T2 lesions. Variation in the time allowed for follow-up period is also an important factor to consider. The median range of followup periods here was 11-30 months. Our own median follow-up for patients was 39.6 months (range 12-96 months). Not all studies used the combined modalities of SLN detection: D=lymphoscintigraphy, E= gamma-probe and J= blue dye. To date there have been surprisingly few studies that have formally characterised the basis for false negative SLNB in melanoma and other cancers, the exception being a recent study from the John Wayne Cancer Institute which categorised some of the risk factors for recurrence in node negative patients. This study reported a ‘false negative’ rate of 8.9%, identifying increasing tumour thickness, the presence of ulceration and head/neck primary tumours as risk factors for the development of recurrence in the presence of a negative node. In a commentary following presentation of their findings, the authors also referred to an increased incidence of nodular melanoma in their patients with node negative recurrence.21 This study indicates that SLNB is a reliable and safe technique to diagnose regional spread from head and neck cutaneous melanoma. It is more difficult than at other sites. These lesions have a higher incidence of failed SLN mapping and a higher rate of recurrence following negative SLNB, when compared to trunk and extremity lesions. Nodular melanomas are more likely to fail the sentinel lymph node mapping procedure than other histological subtypes.
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© 2009 Surgeon 7; 6: 336-39
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