Received 19 November 2015; accepted 4 March 2016; published 7 March 2016
The Sentinel Lymph Node Biopsy (SLNB) in melanoma is an important tool of staging. AJCC  and National Comprehensive Cancer Network (NCCN)  - guidelines describe the factors that affect staging. However these are constantly reviewed and modified. Ulceration and mitotic rate are considered as factors that affect the staging of thin melanoma (AJCC T1a to T1b). Until 2013, the NCCN 2011  guidelines recommended the following factors as “adverse features”: Breslow ≥ 0.75 mm, positive deep margins, Lymphovascular Invasion (LVI), and Clark level IV. From 2013, the NCCN 2013  and NCCN 2016  guidelines for SLNB with Breslow up to 1 mm take into account the “high-risk features”: Ulceration, High mitotic rate and Lymphovascular Invasion (LVI). The purpose of this study is to evaluate the role of SLNB in thin melanomas, with Breslow thickness ≤ 0.75 mm and 0.76 - 1.0 mm respectively.
2. Patients and Methods
From 2010 to 2015, 104 patients with thin melanoma Stage IA with presence of “adverse” or “high-risk features” and from Stage IB only TIb, N0, M0 (AJCC) were included and divided in 2 groups:
・ Group A: 68 patients with Breslow ≤ 0.75 mm.
・ Group B: 36 patients with Breslow 0.76 - 1.0 mm.
All patients had signed the appropriate consent form and assured that the ethical and moral issues were respected. Initially all patients underwent excision of the primary site and the histopathology report confirmed the presence of melanoma as well as the important associated histopathologic features. Subsequently the patients underwent wide local excision and SLNB under general anesthesia preferably, or even local anesthesia in some cases, if the SLNB concerned the groin or axillary area. At the day of surgery all patients underwent lymphoscintigraphy and the position of SLN was found with the γ-camera and marked at the skin. At the operating room we injected the patent blue at the pre-existing scar intradermally for lymphatic mapping. Intraoperatively we used the gamma probe in order to find the SLN, which was dyed blue in most of the cases. Then we excised the SLN and sent it to histopathology department.
We retrospectively reviewed and analyzed the histopathology reports of SLNB procedures in both groups. Demographic characteristics (Gender and Age) are shown in Table 1.
In Group A, there was no positive SLN (0/68 patients with positive SLN 0%).
In Group B, 4 out of 36 (4/36) patients were found with positive SLN (11.1%) and underwent completion lymph node dissection (CLND).
In both Groups, 4 out of 104 (4/104) patients had positive SLN (3.8%) (Table 2).
The accuracy and the true positive rate of SLNB in the detection of thin melanomas were estimated by measuring the Sensitivity and the Positive Predictive Value. All of our positive cases (100%) were true positives (TP) and therefore we had no false positive (FP) results (0%).
The sensitivity was measured using the formula:
Table 1. Demographic characteristics of 104 patients.
Table 2. Positive sentinel lymph nodes results in relation to depth of primary thin melanoma in our department.
(FN: False Negative)
Therefore the Sensitivity was 100%.
The Positive Predicting Value (PPV) was measured using the formula:
Therefore the PPV was also 100%.
As such in our study the true positive rate of SLNB was 100%.
The demographic and clinical data as well as the histopathologic features of the patients with thin melanoma and positive SLNs are described in Table 3. Furthermore the CLND histopathology report of the patient 2 revealed 1 positive lymph node.
Sentinel Lymph Node Biopsy (SLNB) in melanoma is an important tool of staging. The impact on overall survival still remains unclear. The guidelines in regard to Breslow thickness, taking in mind where SLNB staging benefits do not outweigh the risks of the procedure, are constantly reviewed and modified. Factors associated with increased incidence of positive SLNs in melanoma patients have been thoroughly studied and reported in the literature and include tumor thickness  - , ulceration  -  , mitotic rate      , lymphovascular invasion   , Clark level   , microsatellites  , presence of vertical growth phase  , anatomical location  and age    -  .
Currently the NCCN recommendations for SLNB in melanomas with Breslow thickness ≤ 1 mm, apart from the primary tumour thickness take into account the “high-risk features”: Ulceration, High Mitotic Rate and Lymphovascular Invasion. Microsatellitosis when present in the initial biopsy or wide excision specimen defines at least N2c and at least Stage IIIB disease   . From 2013 the NCCN guidelines divide further the Stage IA and Stage IB in to two more subcategories considering as threshold value the Breslow thickness of 0.75 mm and recommend that melanoma patients with Breslow thickness ≤ 0.75 mm with any features should be considered for wide excision. This recommendation is followed by the footnote: “In general, SLNB is not recommended for primary melanomas ≤ 0.75 mm thick, unless there is significant uncertainty about the adequacy of microstaging. For melanomas 0.76 to 1.0 mm thick, SLNB may be considered in the appropriate clinical context. In patients with thin melanomas (≤1.0 mm), apart from primary tumor thickness, there is little consensus as to what should be considered ‘high-risk features’ for a positive SLN. Conventional risk factors for a positive SLN, such as ulceration, high mitotic rate, and lymphovascular invasion (LVI), are very uncommon in melanomas ≤ 0.75 mm thick. When present, SLNB may be considered on an individual basis”   .
In our study (Table 1) there was no positive SLN in any patient of the ≤0.75 mm group (group A). Same results in the ≤0.75 mm group (group A) were also reported in the literature by Wong et al. 2006  , Vermeeren et al. 2009  and Hinz et al. 2012  (Table 4). However other studies by Bedrosian et al. 2000  , Bleicher et al. 2003  , Kesmodel et al. 2005  , Ranieri et al. 2006  , Wright et al. 2008  , Murali et al. 2012  and Han et al. 2012  reported positive SLN in the ≤0.75 mm group (group A), ranging from 1.7% to 6% (Table 4). In our study (Table 1) in the 0.76 - 1.00 mm group (group B) the percentage of positive SLNs was 11.1%, whereas in the above-mentioned studies  -  it was ranging from 3.9% to 12.8%. Because of the existence of the above studies with positive SLNs in the Breslow thickness ≤ 0.75 mm group (group A), the SLNB procedure in melanoma patients with Breslow thickness ≤ 0.75 mm should be considered on an individual basis when “high-risk features” are present.
Table 3. Demographic and clinical data and features of histopathology results of the patients with primary thin melanoma and positive sentinel lymph node.
aSSM: Superficial Spreading Melanoma; bNM: Nodular Melanoma; cM.D: Maximum Diameter.
Table 4. Studies with positive SLN in patients with thin melanoma.
Our findings justify the SLNB procedure in thin melanomas of 0.76 - 1.0 mm. In melanomas ≤ 0.75 mm, SLNB should be considered on an individual basis when “high-risk features” are present. More comparable studies should be evaluated in order to accurately define the threshold value of Breslow thickness where SLNB is safely deemed unnecessary.
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