The role of ultrasound in detection and management of regional disease in melanoma patients.

Melanoma follow-up programs are directed towards early detection of tumor recurrence. Because the majority of first relapses occur in the regional lymph node area, special focus is placed on this region using various techniques in addition to physical examination. During the last several years, particularly ultrasound B-scan has evolved as a technique of major importance for detection of such regional melanoma recurrences. The technique shows high sensitivity and specificity, discriminating regional or subcutaneous melanoma metastases from nonspecific nodes. Furthermore, suspicious findings can be evaluated quickly and reliably by the minimally invasive technique of ultrasound-guided fine-needle aspiration cytology (FNAC). For regional metastases located deeply or close to vulnerable structures, the new method of ultrasound-guided anchor-wire-marking facilitates subsequent surgery. In summary, ultrasound B-scan has become an essential technique in the follow-up of melanoma patients.

Ultrasound-guided fine needle aspiration cytology as an addendum to sentinel lymph node biopsy can perfect the staging strategy in melanoma patients.

BACKGROUND: Ultrasound guided fine needle aspiration cytology (US-guided FNAC) can identify microscopic involvement of lymph nodes as in breast cancer and avoid surgical sentinel node (SN). Its utility in melanoma patients is controversial and subject of this study. METHODS: Between 2001 and 2010 over 1000 stage I/II consecutive melanoma patients prospectively underwent US-FNAC prior to SN biopsy. All patients underwent lymphoscintigraphy prior to US-FNAC. The Berlin US morphology criteria: Peripheral perfusion (PP), loss of central echoes (LCE) and balloon shaped (BS) were registered. FNAC was performed in case of presence of any of these factors. SN tumour burden was measured according to the Rotterdam criteria. All patients underwent SN or lymph node dissection (LND) in case of positive FNAC. FINDINGS: Mean/median Breslow thickness was 2.58/1.57 mm. Mean/median follow-up was 56/53 months (1-132). SN positivity rate was 21%. US-FNAC Sensitivity was 71% (US only) and 51% (US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). PP, LCE and BS had sensitivity of 69%, 24% and 24% respectively. Sensitivity of US-FNAC increased with increasing SN tumour burden. PP was an early sign of metastasis (58% in <0.1mm metastases). Threshold size of a metastasis for FNAC was 0.3mm. Five-year survival correlated to US-FNAC status (95% in negative and 59% in positive). INTERPRETATION: Ultrasound guided FNAC (US-FNAC) according to the Berlin morphology criteria could correctly identify at least half of all tumour positive sentinel nodes, prior to the surgical SN procedure. Peripheral perfusion is an early sign of metastasis, which is very sensitive, but with lower positive predictive value (PPV). It is responsible for the sensitivity of the procedure. Balloon shape is a sign of advanced metastases, with lower sensitivity, but high PPV. US-FNAC sensitivity correlated with increasing T-stage, ulceration of the primary and increasing SN tumour burden. US-FNAC status accurately predicts survival.

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.

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.

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.

Ultrasound-guided fine needle aspiration cytology prior to sentinel lymph node biopsy in melanoma patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) allows early detection of metastases, thereby enabling early treatment in melanoma patients likely to benefit from adjuvant therapies. This prospective study analyzes the possible benefits of additional ultrasound (US) and fine needle aspiration cytology (FNAC) of sentinel nodes (SN) prior to SLNB. METHOD: Over a 2-year period 127 melanoma patients with 151 SN were scheduled for SLNB. All SN were initially identified with lymphoscintigraphy, then identified and evaluated by US and the cells aspirated for cytology (FNAC). US findings and FNAC results were compared to surgical findings. RESULTS: Of 127 patients, 114 had one SN each, 12 had two, and one had three. In vivo US achieved a sensitivity of 79% (95% CI: 62-91%) and a specificity of 72% (95% CI: 62-81%). FNAC showed a sensitivity of 59% (95% CI: 41-76%) and a specificity of 100% (95% CI: 95-100%). The combination of these two in vivo methods achieved an overall sensitivity of 82% (95% CI: 65-93%) and an overall specificity of 72% [95% CI: 62-81%]. CONCLUSION: Combined US and FNAC provides important information prior to SLNB in that both procedures identify metastases in the lymph nodes (sensitivity > 80%). Patients with positive FNAC may proceed directly to complete lymph node dissection (cLND) instead of having initial SLNB. Thus, combined US and FNAC may prevent unnecessary anesthesia and surgical management as well reduce costs. In our study 16% (19/121) fewer SLNB procedures were carried out, subsequently replaced by cLND. For patients with a negative combination of in vivo US and FNAC, SLNB remains the best diagnostic option.