Meta‐analysis of sentinel lymph node positivity in thin melanoma (≤1 mm)

BACKGROUND:

Despite the lack of an established survival benefit of sentinel lymph node (SLN) biopsy, this technique has been increasingly applied in the staging of thin (≤1 mm) melanoma patients, without clear evidence to support this recommendation. The authors performed a meta‐analysis to estimate the risk, potential predictors, and outcome of SLN positivity in this group of patients.

METHODS:

MEDLINE, EMBASE, and Cochrane databases were searched for rates of SLN positivity in patients with thin melanoma. The methodologic quality of included studies was assessed using the Methodological Index for Non‐Randomized Studies criteria. Heterogeneity was assessed using the Cochran Q statistic, and publication bias was examined through funnel plot and the Begg and Mazumdar method. Overall SLN positivity in thin melanoma patients was estimated using the DerSimonial‐Laird random effect method.

RESULTS:

Thirty‐four studies comprising 3651 patients met inclusion criteria. The pooled SLN positivity rate was 5.6%. Significant heterogeneity among studies was detected (P = .005). There was no statistical evidence of publication bias (P = .21). Eighteen studies reported select clinical and histopathologic data limited to SLN‐positive patients (n = 113). Among the tumors from these patients, 6.1% were ulcerated, 31.5% demonstrated regression, and 47.5% were Clark level IV/V. Only 4 melanoma‐related deaths were reported.

CONCLUSIONS:

Relatively few patients with thin melanoma have a positive SLN. To the authors' knowledge, there are no clinical or histopathologic criteria that can reliably identify thin melanoma patients who might benefit from this intervention. Given the increasing diagnosis of thin melanoma, in addition to the cost and potential morbidity of this procedure, alternative strategies to identify patients at risk for lymph node disease are needed. Cancer 2009. © 2008 American Cancer Society.     

High nevus counts confer a favorable prognosis in melanoma patients

A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5‐ and 10‐year melanoma‐specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21–0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08–0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.     

The role of preoperative ultrasound scan in detecting lymph node metastasis before sentinel node biopsy in melanoma patients

BACKGROUND AND OBJECTIVES: To evaluate the efficacy of preoperative ultrasound (US) scanning in identifying lymph node metastasis before sentinel node biopsy (SNB), we conducted a prospective study on 125 patients with primary cutaneous melanoma (CM). METHODS: We prospectively enrolled 125 patients with >1 mm thick CM and candidate for SNB. Preoperatively, patients underwent US scanning of regional lymphatic basins and FNA of suspected lymph nodes (LN). All patients underwent lymphatic mapping and SNB. RESULTS: Combined with fine-needle aspirate (FNA) of suspect LN, US scan allowed the correct preoperative detection of 12 out of 31 histologically positive lymphatic basins, specificity and sensitivity being 100 and 39%, respectively. The false negative rate (61%) was mainly linked to tumor deposits less than 2 mm in diameter, which can be considered the current spatial resolution limit of this technique. CONCLUSIONS: Preoperative US scan could reduce the number of SNB, thus avoiding the stress of this surgical procedure in approximately 10% of patients and reducing health care costs. As a non-invasive and relatively inexpensive technique, lymph node US scan can be part of the preoperative staging process of patients' candidate for SNB in order to avoid unnecessary surgical procedures.     

Clinical and biological aspects of sentinel node biopsy in malignant melanoma — an update

The diagnostic usefulness of sentinel lymph node biopsy (SLNB) has been well established, but its therapeutic value remains unproven. First introduced by Morton and colleagues, the SLNB procedure is now widely available, and markedly enhances our ability to pathologically stage the regional nodes. Although the SLN status is acknowledged as the most powerful indicator of prognosis in melanoma, there is no evidence to-date, of survival advantage for complete lymphadenectomy in SLN-positive patients. Also, there is no effective adjuvant therapy that could benefit these sentinel node-positive patients, as yet. Additionally, new data have emerged indicating a possible increase in local/in-transit recurrence following complete lymphadenectomy in sentinel node-positive patients. To understand fully and to evaluate these observations we need information from randomized controlled trials. Major changes have occurred following the latest revision of melanoma staging system (AJCC, 6th edition). Concerning N category, these include the incorporation of the number of metastatic lymph nodes, the tumour burden of nodal metastases, and the ulceration of the primary tumour. The data obtained from the new staging system will reflect differences in prognosis that were not previously emphasized and which, we hope, will serve as a guide to more accurate analysis of metastatic pathways in cutaneous melanoma as well as a rationale for new forms of treatment.     

Sentinel lymph node biopsy in atypical Spitz nevi: Is it useful?

Aims

The aim of this study was to evaluate the incidence of lymph node metastases in patients with atypical Spitz nevi (ASN) after sentinel lymph node biopsy (SLNB) and during follow-up, and to assess the diagnostic value of the surgical procedure.

Methods

At the National Cancer Institute of Naples, Italy, 40 patients with ASN underwent SLNB between 2003 and 2011. Medical records were reviewed and all slides of the primary tumours were retrieved, rendered separately, and assessed by four experienced dermatopathologists from two different academic institutions. Each member of the review panel assessed slides separately without recourse to medical notes and blinded to each others' diagnosis. All patients were treated with wide local excision and SLN biopsy according to the standard procedure. All cases were followed up to assess outcomes.

Results

The original diagnosis of ASN was confirmed in all 40 cases. No sentinel node positivity was recorded, and no patients developed nodal involvement during a median follow-up of 46 months (range 16–103). All patients were alive and without evidence of locoregional or distant relapse at time of review.

Conclusions

In our experience, ASN were not associated with metastatic potential. Surgical staging procedures are not justified and careful clinical surveillance is adequate.     

Real‐time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV‐1h68 in an immunocompetent animal model

There is a clinical need for improved intraoperative detection of lymph node metastases from malignant melanoma (MM). We aimed to investigate the use of recombinant vaccinia virus GLV‐1h68, expressing green fluorescent protein (GFP), for real‐time intraoperative detection of melanoma lymph node metastases in an immunocompetent animal model. Mice bearing foot pad tumors received intratumoral injections of GLV‐1h68, and 48 hr later were evaluated for popliteal lymph node metastasis using noninvasive bioluminescence imaging and fluorescence imaging. Histologic analysis of lymph nodes was performed to determine sensitivity and specificity of virus‐mediated detection. Intratumoral injection of GLV‐1h68 into primary foot pad melanoma tumors resulted in viral transmission to popliteal lymph nodes, infection of lymphatic metastases, and transgene expression that was reliably and easily detected. Histologic confirmation demonstrated favorable operating characteristics of this assay (sensitivity 80%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 91%). Detection of marker gene expression by GLV‐1h68 allowed the detection of lymphatic metastases in an immunocompetent animal model of MM. This assay is rapid, sensitive, specific and easy to perform and interpret. As a candidate gene therapy virusfor killing cancer, GLV‐1h68 may also have significant concomitant diagnostic utility in the staging of cancer patients. © 2008 Wiley‐Liss, Inc.     

New developments in melanoma: utility of ultrasound imaging (initial staging,follow-up and pre-SLNB)

Melanoma incidence is still increasing, but the mortality rate has remained unchanged. Lymph node metastases are the single most important prognostic factor for stage I/II melanoma patients. Currently, the standard of care with regard to the staging of these patients is the surgical sentinel node procedure. Ultrasound is not routine for the diagnostic work-up of primary melanomas. Some may use ultrasound for the preoperative assessment of the tumor thickness and lymphatic drainage, but this has not found wide application. For the follow-up of melanoma patients, ultrasound has been proven to be superior to physical examination for the detection of lymph node metastases. A meta-analysis has shown that ultrasound is superior to computed tomography (CT) and/or positron emission tomography (PET)-CT for the detection of lymph node metastases, whereas PET-CT was superior for the detection of distant visceral metastases. Ultrasound of regional lymph nodes has been incorporated into many national guidelines across Europe and in Australia for the follow-up of melanoma patients. A new avenue for ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is the pre-sentinel node modality. Like the situation in breast and thyroid cancer, US-FNAC, a minimally invasive procedure, may decrease the need for surgical sentinel node staging. New ultrasound morphology criteria have significantly increased the sensitivity of this technique. Peripheral perfusion is an early sign of metastases (77% sensitivity, 52% positive-predictive value), whereas balloon-shaped lymph node was a late sign of metastases (30% sensitivity, 96% positive-predictive value). Together, these new ultrasound morphology criteria were able to accurately demonstrate metastases in 65% of sentinel node-positive patients. Future perspectives of ultrasound in melanoma include the start of a large multicenter, multicountry validation study – USE-FNAC – by the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group. In light of new and promising adjuvant therapies, the need for ultrasound staging might increase rapidly.     

Previous wide local excision of primary melanoma is not a contraindication for sentinel lymph node biopsy of the trunk and extremity

BACKGROUND AND OBJECTIVES: The role of sentinel lymph node biopsy (SLNB) in patients with a previous wide local excision (WLE) was examined with case-control methodology. METHODS: A total of 168 consecutive cases of SLNB were performed in patients with truncal and extremity melanoma with tumor thickness of > or = 1 mm between October 1997 and June 2000 and were followed prospectively. For comparison, 65 of the 103 SLNB patients referred to us after their WLE (cases) were matched by tumor thickness to 65 patients who had SLNB with concurrent WLE (controls). Radiocolloid (technetium-99m sulfur colloid) was used in all cases; in addition, vital blue dye (patent blue) was used in the control group. The two groups were followed for a median of 15.4 months. RESULTS: SLNs were identified in all patients with an average of 2.1 (cases) and 2.0 (controls) SLNs excised per patient (P = 0.77). Twenty one (32.3%) of those having SLNB after previous WLE (cases) and 23 (35.4%) of those with concurrent WLE and SLNB (controls) were found to have metastatic disease in the SLN. The only false-negative in this group was detected in clinical follow-up in a patient whose truncal WLE was previously closed with a rotation flap (case). There was no significant difference in relapse-free survival (P = 0.209) and overall survival (P = 0.692) between groups. CONCLUSIONS: SLNB is feasible in patients with previous WLE for extremity and truncal melanoma. Similar rates of sentinel positivity are found when compared with those in whom their WLE was done concurrently.