Fine needle aspiration cytology of palpable and nonpalpable lymph nodes to detect metastatic melanoma.

BACKGROUND: Fine needle aspiration cytology (FNAC) is usually used to evaluate palpable nodes in patients with melanoma. The goal of our study is to review the sensitivity and specificity of this technique when applied to palpable but also to nonpalpable nodes. METHODS: FNAC was performed during 1984-2007 in 1279 patients with suspicious lesions and/or lymph nodes. Indications for biopsy included increased size and/or palpability of nodes or abnormal ultrasound findings such as increased perfusion or focal lesions within the lymph nodes. The sensitivity, specificity, and positive and negative predictive values of FNACs guided by palpation or ultrasound were calculated for all patients and for subgroups of patients with palpable nodes or nonpalpable but sonomorphologically suspicious nodes. RESULTS: A total of 2446 FNACs were performed in 1279 melanoma patients, of which 2011 (82.2%) FNACs had clinically or histologically confirmed results. Increased size and/or palpability of nodes was observed in 376 (29.4%) of 1279 patients, and abnormal ultrasound findings occurred for 903 (70.6%), indicating that a biopsy was needed. FNACs guided by palpation had sensitivity, specificity, and positive and negative predictive values similar to that of FNACs guided by ultrasound (sensitivity = 98.4% vs 97.2%, specificity = 100% vs 99.8%, positive predictive value = 100% vs 99.9%, and negative predictive value = 95.2% vs 96.4%, for palpation-guided FNACs vs ultrasound-guided FNACs, respectively). Results did not differ between patients with the palpable nodes and patients with nonpalpable but sonomorphologically suspicious nodes. CONCLUSIONS: Ultrasound-guided FNAC of suspicious lymph nodes and lesions in melanoma patients has a high sensitivity and specificity, and FNAC should not be limited to palpable nodes. FNAC of normal-sized nodes and/or lymph nodes with abnormal ultrasound findings can be used to identify early metastatic disease.

Multimodality approach to the sentinel node: an algorithm for the use of presentinel lymph node biopsy ultrasound (after lymphoscintigraphy) in conjunction with presentinel lymph node biopsy fine needle aspiration cytology.

In a recent article by Lam et al. describing the experience of the Sydney Melanoma Unit, a novel term called 'multimodality approach' to the sentinel node (SN) was applied. However, the timing of the use of the tools available in the presented cases should be discussed. An algorithm of which time to use, which tool to detect the correct SN by preoperative ultrasound (US) in combination with an US-guided fine needle aspiration cytology (FNAC) will be proposed and demonstrated using five clinical examples. All examples prove the advantage of a combined strategy to track down the correct and involved SN. A sensitive US power mode, for the amplification of even the slightest changes in vascularization, is the most important tool in our diagnostic preoperative approach. First, reliable US criteria, as recently published must consequently be applied. Second, a FNAC should be performed early enough, even when only early signs are visible. Third, a swift overnight cytology before sentinel lymph node biopsy should be available. US is a method for the early detection of clinically nonevident metastases. Using the proposed algorithm when to perform which part of the multimodality approach, we demonstrated the enormous information out of additionally performed US. In the case of a suspicious US finding, we always perform a FNAC of the node. In the event of a negative finding, the SLND will take place as scheduled. In the case of a positive finding, the patient can directly undergo completion lymph node dissection.

Ultrasound morphology criteria predict metastatic disease of the sentinel nodes in patients with melanoma.

PURPOSE We have shown that ultrasound (US) -guided fine needle aspiration cytology (FNAC) can accurately identify the sentinel node (SN). Moreover, US-guided FNAC before the surgical SN procedure could identify up to 65% of all SN metastases. Herein we analyzed in detail the different US morphologic patterns of SN metastases. PATIENTS AND METHODS From July 2001 to December 2007, a total of 650 patients with melanoma scheduled for sentinel lymph node dissection were examined. We present the first 400 with sufficient follow-up (mean 40, median 39 months). Several morphologic characteristics were scored. In case of suspicious/clearly malignant US patterns a FNAC was performed. The final histology was considered the gold standard. Results Median Breslow was 1.8 mm. The sensitivity and positive predictive value of the most important factors were: peripheral perfusion (PP) present (77% and 52%, respectively), loss of central echoes (LCE; 60% and 65% respectively), and balloon shape (BS; 30% and 96% respectively). Together these factors have a sensitivity of 82% and PPV of 52% (P < .001). PP identified more patients with lower volume disease. PP and combined BS and LCE were independent prognostic factors for survival (hazard ratio, 2.19; P < .015; and hazard ratio, 5.50; P < .001, respectively). CONCLUSION Preoperative US and FNAC can identify 65% of SN metastases and thus reduce the need for surgical SN procedures. Peripheral perfusion is an early sign of involvement and of crucial importance to achieve a high identification rate. Balloon shape and loss of central echoes are late signs of metastases. We recommend US evaluation to identify those patients, who can directly proceed to a complete lymph node dissection after a positive US-guided FNAC of the SN.

Rotterdam Criteria for sentinel node (SN) tumor burden and the accuracy of ultrasound (US)-guided fine-needle aspiration cytology (FNAC): can US-guided FNAC replace SN staging in patients with melanoma?

PURPOSE: Sentinel node (SN) status is the most important prognostic factor for overall survival (OS) for patients with stage I/II melanoma, and the role of the SN procedure as a staging procedure has long been established. However, a less invasive procedure, such as ultrasound (US) -guided fine-needle aspiration cytology (FNAC), would be preferred. The aim of this study was to evaluate the accuracy of US-guided FNAC and compare the results with histology after SN surgery was performed in all patients. PATIENTS AND METHODS: Four hundred consecutive patients who underwent lymphoscintigraphy subsequently underwent a US examination before the SN procedure. When the US examination showed a suspicious or malignant pattern, patients underwent an FNAC. Median Breslow thickness was 1.8 mm; mean follow-up was 42 months (range, 4 to 82 months). We considered the US-guided FNAC positive if either US and/or FNAC were positive. If US was suggestive of abnormality, but FNAC was negative, the US-guided FNAC was considered negative. RESULTS: US-guided FNAC identified 51 (65%) of 79 SN metastases. Specificity was 99% (317 of 321), with a positive predictive value of 93% and negative predictive value of 92%. SN-positive identification rate by US-guided FNAC increased from 40% in stage pT1a/b disease to 79% in stage pT4a/b disease. US-guided FNAC detected SN tumors more than 1.0 mm in 86% of cases, SN tumors of 0.1 to 1.0 mm in 46% of cases, and SN tumors less than 0.1 mm in 23% of cases. Estimated 5-year OS rates were 92% for patients with negative US-guided FNAC results and 51% for patients with positive results. CONCLUSION: US-guided FNAC of SNs is highly accurate. Up to 65% of the patients with SN-positive results in our institution could have been spared an SN procedure.

Cutaneous lycopene and beta-carotene levels measured by resonance Raman spectroscopy: high reliability and sensitivity to oral lactolycopene deprivation and supplementation.

Carotenoids, naturally occurring lipophilic micronutrients, possess an antioxidant activity associated with protection from damage induced by free radicals. The present study investigated an innovative non-invasive method to measure cutaneous levels of lycopene and beta-carotene and to monitor the distribution of orally administered lactolycopene in human skin and plasma. A double-blind placebo-controlled randomized study was performed in 25 volunteers, who were under a lycopene-deprived diet (4 weeks prior to study until end of the study) and orally received either lactolycopene or placebo for 12 weeks. Skin and plasma levels of lycopene and beta-carotene were monitored monthly using Raman spectroscopy and HPLC, respectively. Cutaneous levels of lycopene and beta-carotene monitored by resonance Raman spectroscopy showed high reliability. Irrespective of the investigated area, cutaneous levels were sensitive to lycopene deprivation and to oral supplementation; the forehead showed the closest correlation to lycopene variation in plasma. Plasma and skin levels of lycopene were both sensitive to oral intake of lactolycopene and, interestingly, also skin levels of beta-carotene. Thus, oral supplementation with lycopene led to an enrichment of beta-carotene in human skin, possibly due to the fact that carotenoids act in the skin as protection chains, with a natural protection against free radicals.

Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes.

SUMMARY BACKGROUND DATA: The more intensive sentinel node (SN) pathologic workup, the higher the SN-positivity rate. This is characterized by an increased detection of cases with minimal tumor burden (SUB-micrometastasis <0.1 mm), which represents different biology. METHODS: The slides of positive SN from 3 major centers within the European Organization of Research and Treatment of Cancer (EORTC) Melanoma Group were reviewed and classified according to the Rotterdam Classification of SN Tumor Burden (<0.1 mm; 0.1-1 mm; >1 mm) maximum diameter of the largest metastasis. The predictive value for additional nodal metastases in the completion lymph node dissection (CLND) and disease outcome as disease-free survival (DFS) and overall survival (OS) was calculated. RESULTS: In 388 SN positive patients, with primary melanoma, median Breslow thickness was 4.00 mm; ulceration was present in 56%. Forty patients (10%) had metastases <0.1 mm. Additional nodal positivity was found in only 1 of 40 patients (3%). At a mean follow-up of 41 months, estimated OS at 5 years was 91% for metastasis <0.1 mm, 61% for 0.1 to 1.0 mm, and 51% for >1.0 mm (P < 0.001). SN tumor burden increased significantly with tumor thickness. When the cut-off value for SUB-micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was 89%, and 10% had additional non-SN nodal positivity. CONCLUSION: This large multicenter dataset establishes that patients with SUB-micrometastases <0.1 mm have the same prognosis as SN negative patients and can be spared a CLND. A <0.2 mm cut-off for SUB-micrometastases does not seem correct for melanoma, as 10% additional nodal positivity is found.

Impact of molecular staging methods in primary melanoma: reverse-transcriptase polymerase chain reaction (RT-PCR) of ultrasound-guided aspirate of the sentinel node does not improve diagnostic accuracy, but RT-PCR of peripheral blood does predict survival.

PURPOSE: This study analyzes (1) the value of tyrosinase reverse-transcriptase polymerase chain reaction (RT-PCR) of aspirates obtained by ultrasound-guided fine-needle aspiration cytology (US-FNAC) of sentinel nodes (SNs) in patients with melanoma before sentinel lymph node biopsy (SLNB) and (2) the value of RT-PCR of blood samples of all SLNB patients. PATIENTS AND METHODS: Between 2001 and 2003, 127 patients with melanoma (median Breslow depth, 2.1 mm) underwent SLNB. FNAC was performed in all SNs of all patients pre- and post-SLNB. The aspirates were partly shock-frozen for RT-PCR and were partly used for standard cytology. Peripheral blood was collected at the time of SLNB and at every outpatient visit thereafter. RESULTS: Thirty-four (23%) of 120 SNs were positive for melanoma. SN involvement was predicted by US-FNAC with a sensitivity of 82% and a specificity of 72%. Additional tyrosinase RT-PCR revealed the same sensitivity of 82% and a specificity of 72%. At a median follow-up time of 40 months from first blood sample, peripheral-blood RT-PCR was a significant independent predictor of disease-free survival (DFS) and overall survival (OS; P < .001). CONCLUSION: US-FNAC is highly accurate and eliminates the need for SLNB in 16% of all SLNB patients. RT-PCR of the aspirate or excised SN does not improve sensitivity or specificity. RT-PCR of blood samples predicts DFS and OS.

Use of ultrasound to early identify, diagnose and localize metastases in melanoma patients.

Specialized medical centers perform high-resolution ultrasound of lymph nodes in melanoma patients to detect metastases early. Ultrasound represents a highly effective method for the discrimination of lymph node and soft-tissue metastases from other space-occupying lesions. Frequent follow-up examinations with ultrasound provide early detection of tumor recurrences and seem to lead to a prolonged overall survival. The ultrasound findings are validated by fine-needle aspiration cytology. Depicted and verified metastases should be removed as soon as possible. The authors recommend the performance of ultrasound before every sentinel lymph node dissection to avoid unnecessary operations.