Subungual Melanoma of the Hand.

BACKGROUND: The diagnosis of subungual melanoma (SUM) can be challenging and SUMs generally have a worse prognosis than melanomas arising elsewhere. Due to their rarity, the evidence to guide management is limited. This study sought to identify clinicopathological features predictive of outcome and to provide guidelines for management. METHODS: From a large, single-institution database, 103 patients with in situ (n = 9) or invasive (n = 94) SUMs of the hand treated between 1953 and 2014 were identified and their features analyzed. RESULTS: The most common site of hand SUMs was the thumb (53%). Median tumor thickness was 3.1 mm, and SUMs were commonly of the acral subtype (57%), ulcerated (58%), amelanotic (32%), and had mitoses (73%). Twenty-one patients reported prior trauma to the tumor site. Twenty-two patients were stage III at diagnosis; 7 underwent therapeutic lymph node dissection and 22 underwent elective lymph node dissection (5 positive), while 36 had sentinel node biopsy (SNB), 28% of which were positive. Forty percent of SNB-positive patients had involved non-sentinel nodes (SNs) in their completion lymph node dissection. Five-year melanoma-specific survival (MSS) and disease-free survival (DFS) rates were 70% and 52%, respectively. On multivariate analysis, regional node metastasis and right-hand tumor location were significant predictors of shorter DFS and MSS, whereas mitoses negatively impacted DFS only and increasing Breslow thickness impacted MSS only. CONCLUSIONS: This study confirms that SUMs on the hand usually present at an advanced stage. Distal amputation appears safe for invasive SUMs, and SNB should be considered as these patients have a high risk of both SN and non-SN metastasis.

Detection of unsuspected spinal cord compression in melanoma patients by 18F-fluorodeoxyglucose-positron emission tomography.

AIM: Positron emission tomography (PET) using (18)F-fluorodeoxyglucose can detect early or small metastatic deposits of melanoma and guide subsequent correlative anatomical imaging and treatment. The aim of this study was to assess the value of PET in demonstrating spinal cord compression by otherwise unsuspected metastatic disease. METHODS: Reports of 1365 PET studies performed on patients with melanoma were reviewed. Fifty patients considered to be at risk of spinal cord compression on the basis of PET were identified and 35 patients were analysed. Magnetic resonance imaging and computed tomography were used to confirm or refute the diagnosis. The symptoms and signs at the time of PET and follow-up status were compared between patients with and without confirmed spinal cord compression. RESULTS: In nine patients (26%) compression of the spinal cord or adjacent neurological structures was confirmed and eight of these patients had immediate treatment. Survival was poor in both patient groups, but three patients with confirmed compression maintained good neurological functional status following treatment. CONCLUSION: PET can detect imminent, unsuspected spinal cord compression in patients with metastatic melanoma. Immediate anatomical imaging of the spine is recommended in patients who have evidence of spinal cord compression on PET.

Sentinel node biopsy provides more accurate staging than elective lymph node dissection in patients with cutaneous melanoma.

BACKGROUND: In most major melanoma treatment centers, sentinel node biopsy (SNB), with complete regional lymph node dissection when a positive sentinel node is found, has now replaced elective lymph node dissection (ELND) for patients with primary cutaneous melanomas who are considered to be at moderate to high risk of nodal recurrence. As for ELND, however, no overall survival benefit for the SNB procedure has yet been demonstrated. The objective of this study was to compare the nodal staging accuracy and duration of survival for SNB and ELND. METHODS: A retrospective cohort study was conducted among patients with American Joint Committee on Cancer (AJCC) stage II disease treated at a single center between 1983 and 2000 with either SNB (n = 672) or ELND (n = 793). Multivariate analyses were performed using the logistic regression model for nodal staging accuracy and Cox's proportional hazards regression model for survival. RESULTS: Patient factors that influenced nodal positivity included age, Breslow thickness, ulceration, head or neck primary, and operation type (SNB or ELND). SNB was superior to ELND in the detection of micrometastases (odds ratio 1.23, 95% CI, 1.06 - 1.43) but operation type did not influence survival (P =.24). CONCLUSIONS: Sentinel node biopsy identified more nodal micrometastases than ELND but did not influence survival, although complete regional node dissection was performed in all patients who were SNB positive. This increase in staging accuracy likely results from the reliable identification of the appropriate lymph node field by preoperative lymphoscintigraphy, along with more detailed pathologic examination of the nodes removed by SNB.

Determinants of outcome in melanoma patients with cerebral metastases.

PURPOSE: To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. PATIENTS AND METHODS: All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. RESULTS: A total of 1137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 patients; and supportive care alone, 210 patients. Median survival according to treatment received for these four groups was 8.9, 8.7, 3.4, and 2.1 months, respectively; the differences between surgery and nonsurgery groups were statistically significant. On multivariate analysis, significant factors associated with improved survival were surgical treatment (P <.0001), no concurrent extracerebral metastases (P <.0001), younger age (P =.0007), and longer disease-free interval (P =.036). Prognostic factors analysis confirmed the important influence of patient selection on treatment received. CONCLUSION: This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

Short-term digital surface microscopic monitoring of atypical or changing melanocytic lesions.

OBJECTIVE: To examine the outcome of short-term digital surface microscopic monitoring of suspicious or changing atypical melanocytic lesions. DESIGN: Digital surface microscopic (oil epiluminescence microscopy, and dermoscopy) images of clinically melanocytic lesions were taken with a color calibrated 3 CCD video instrument. In general, lesions were moderately atypical, flat or only slightly raised, without a history of change or surface microscopic evidence of melanoma, or were mildly atypical lesions with a history of change. Lesions were monitored during a 2.5- to 4.5-month period (median, 3.0 months). With the exception of overall change in pigmentation consistent with that seen in surrounding skin (solar exposure changes), any morphologic change after monitoring was considered an indication to excise. SETTING: Sydney Melanoma Unit, Sydney, Australia (a referral center). PATIENTS: A consecutive sample of 318 lesions from 245 patients (aged 4-81 years). MAIN OUTCOME MEASURE: Specificity for the diagnosis of melanoma. RESULTS: Of the 318 lesions, 81% remained unchanged. Of the 61 lesions that showed morphologic changes, 7 (11% of changed and 2% of total lesions) were found to be early melanoma (5 in situ and 2 invasive with a Breslow thickness of 0.25 mm and 0.28 mm, respectively). None of these melanomas developed any classic surface microscopic features of melanoma and therefore could be identified only by morphologic change. The specificity for the diagnosis of melanoma by means of short-term digital monitoring was 83%. CONCLUSION: On the assumption that all melanoma will change during the monitored period, surface microscopy digital monitoring is a useful adjunct for the management of melanocytic lesions.

Do nodal metastases from cutaneous melanoma of the head and neck follow a clinically predictable pattern?

BACKGROUND: Potential lymphatic drainage patterns from cutaneous melanomas of the head and neck are said to be variable and frequently unpredictable. The aim of this article is to correlate the anatomic distribution of pathologically involved lymph nodes with primary melanoma sites and to compare these findings with clinically predicted patterns of metastatic spread. METHODS: A prospectively documented series of 169 patients with pathologically proven metastatic melanoma was reviewed by analyzing the clinical, operative, and pathologic records. Clinically, it was predicted that melanomas of the anterior scalp, forehead, and face could metastasize to the parotid and neck levels I-III; the coronal scalp, ear, and neck to the parotid and levels I-V; the posterior scalp to occipital nodes and levels II-V; and the lower neck to levels III-V. Minimum follow up was 2 years. RESULTS: There were 141 therapeutic (97 comprehensive, 44 selective) and 28 elective lymphadenectomies (4 comprehensive dissections, 21 selective neck dissections, and 3 cases in which parotidectomy alone was performed). Overall, there were 112 parotidectomies, 44 of which were therapeutic and 68 elective. Pathologically positive nodes involved clinically predicted nodal groups in 156 of 169 cases (92.3%). The incidence of postauricular node involvement was only 1.5% (3 cases). No patient was initially seen with contralateral metastatic disease; however, 5 patients (2.9%) failed in the contralateral neck after therapeutic dissection. In 68% of patients, metastatic disease involved the nearest nodal group, and in 59% only a single node was involved. CONCLUSIONS: Cutaneous malignant melanomas of the head and neck metastasized to clinically predicted nodal groups in 92% of patients in this series. Postauricular and contralateral metastatic node involvement was uncommon.

Increase in the sensitivity for melanoma diagnosis by primary care physicians using skin surface microscopy.

BACKGROUND: Skin surface microscopy (oil epiluminescence microscopy, dermoscopy, dermatoscopy) has been shown to increase the diagnostic accuracy of melanoma. However, all studies to date have been in an expert setting. OBJECTIVES: To determine whether primary care physicians (PCP) (general practitioners) could improve their melanoma diagnosis using surface microscopy after a short education intervention. METHODS: Seventy-four practising PCP completed a pretest of 50 melanomas and 50 atypical non-melanoma pigmented skin lesions (PSL) containing matched clinical and surface microscopy photographs. PCP were randomized between a surface microscopy education intervention or control group, followed by an identical post-test. RESULTS: Following training there was a significant improvement in the post-test vs. pretest in both clinical melanoma diagnosis (62.7% vs. 54.6%; P = 0.007) and surface microscopy melanoma diagnosis (75.9% vs. 57.8%; P = 0.000007). No difference was found in the control group between the post-test vs. pretest clinical melanoma diagnosis (53.7% vs. 50.6%; P = 0.21) or the surface microscopy melanoma diagnosis (54.8% vs. 52.9%; P = 0.56). Following training there was a significant improvement in the diagnosis of melanoma using surface microscopy vs. clinical diagnosis (75.9% vs. 62.7%; P = 0.000007), which was absent in the control group (54.8% vs. 53.7%; P = 0.59). No significant difference was found in clinical vs. surface microscopy post-test results for non-melanoma PSL in either the intervention group or control group. Improvement in the sensitivity for the diagnosis of melanoma with surface microscopy was seen without a decrease in specificity; this indicated that the effect should occur without increasing the number of needless excisions. CONCLUSIONS: All PCP in countries where melanoma leads to significant mortality should be trained in skin surface microscopy.

Interval nodes: the forgotten sentinel nodes in patients with melanoma.

BACKGROUND: Any sentinel lymph node that receives lymph drainage directly from a primary melanoma site, regardless of its location, may contain metastatic disease. This is true even if the sentinel node does not lie in a recognized node field. Interval (in-transit) nodes that lie along the course of a lymphatic vessel between a primary melanoma site and a recognized node field are sometimes seen during lymphatic mapping for sentinel node biopsy. If drainage to such interval nodes is ignored by the surgeon during sentinel node biopsy, metastatic melanoma will be missed in some patients. HYPOTHESIS: When lymph drains directly from a cutaneous melanoma site to an interval node, that sentinel node has the same chance of harboring micrometastatic disease as a sentinel node in a recognized node field. DESIGN: Preoperative lymphoscintigraphy with technetiumTc 99m antimony trisulfide colloid was performed to define lymphatic drainage patterns and, since 1992, to locate the sentinel lymph nodes for surgical biopsy or for permanent skin marking of their location with point tattoos. SETTING: Melanoma unit of a university teaching hospital. PATIENTS: A total of 2045 patients with cutaneous melanoma were studied in 13 years. RESULTS: Interval nodes were found in 148 patients (7.2%). The incidence of interval nodes varied with the site of the primary melanoma. Interval nodes were more common with melanomas on the trunk than with those on the lower limbs. Micrometastatic disease was found in 14% of interval nodes that underwent biopsy as sentinel nodes. This incidence is similar to that found in sentinel nodes located in recognized node fields, confirming the potential clinical importance of interval nodes. CONCLUSIONS: Interval nodes should be removed surgically along with any additional sentinel nodes in standard node fields if the sentinel node biopsy procedure is to be complete. In some patients, an interval node will be the only lymph node that contains metastatic disease.

Surface microscopy of pigmented basal cell carcinoma.

OBJECTIVES: To describe the relevant morphologic features and to create a simple diagnostic method for pigmented basal cell carcinoma (BCC) using in vivo cutaneous surface microscopy (ie, dermoscopy, dermatoscopy, or oil epiluminescence microscopy). DESIGN: Pigmented skin lesions were photographed in vivo using immersion oil (surface microscopy). All pigmented skin lesions were excised and reviewed for histological diagnosis. Photographs of 142 pigmented BCCs, 142 invasive melanomas, and 142 benign pigmented skin lesions were randomly divided into 2 equally sized training and test sets. Images from the training set were scored for 45 surface microscopy features. From this a model was derived and tested on the independent test set. SETTING: All patients were recruited from the primary case and referral centers of the Sydney Melanoma Unit, Sydney, Australia, and the Skin and Cancer Unit, Skin and Cancer Associates, Plantation, Fla. PATIENTS: A random sample (selected from a larger database) of patients whose lesions were excised. MAIN OUTCOME MEASURES: Sensitivity and specificity of the model for diagnosis of pigmented BCCs. RESULTS: The following model was created. For a pigmented BCC to be diagnosed it must not have the negative feature of a pigment network and must have 1 or more of the following 6 positive features: large gray-blue ovoid nests, multiple gray-blue globules, maple leaflike areas, spoke wheel areas, ulceration, and arborizing "treelike" telangiectasia. On an independent test set the model had a sensitivity of 97% for the diagnosis of pigmented BCCs and a specificity of 93% for the invasive melanoma set and 92% for the benign pigmented skin lesion set. CONCLUSION: A robust surface microscopy method is described that allows the diagnosis of pigmented BCCs from invasive melanomas and benign pigmented skin lesions. Arch Dermatol. 2000;136:1012-1016

Locally advanced melanoma: results of postoperative hypofractionated radiation therapy.

BACKGROUND: High rates of locoregional recurrence have been reported from surgical series of locally advanced melanoma. In this study, the outcomes of patients treated with surgery and postoperative hypofractionated radiation therapy were reviewed to assess local recurrence and survival. METHODS: From 1989 to 1998, 174 patients with International Union Against Cancer Stage I-III melanoma received postoperative radiation therapy, either as a component of their initial management or following surgery for recurrence. Radiation was delivered to the primary site in 35 cases and involved regional lymph nodes in 139. The indications for irradiation included microscopically positive surgical margins or other adverse pathologic features. All patients received a hypofractionated schedule of 30-36 grays (Gy) in 5-7 fractions over 2.5 weeks. RESULTS: Recurrence within the radiation fields was identified in 20 patients (11%) at a median time of 6 months. There was no difference in recurrence rates for patients with microscopically positive margins compared with other indications for adjuvant treatment. The main complication of treatment was symptomatic arm lymphedema in 58% of patients following axillary dissection and postoperative irradiation. The median disease specific survival for the entire group was 25 months from radiation therapy, and the 5-year survival was 41%. The only factor that predicted significantly for decreased survival was infield recurrence (the median survival periods were 13 months and 35 months for those with and without infield recurrence, P < 0.0001). The median time to the development of distant metastasis was 19 months. CONCLUSIONS: Despite the high incidence of distant metastasis, locoregional control remains an important goal in the management of melanoma. Compared with published surgical data, postoperative adjuvant radiation therapy given according to a hypofractionated schedule was effective in reducing local recurrence in patients at high risk of locoregional failure.

Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy.

BACKGROUND: Accurate staging of melanoma patients by sentinel node (SN) biopsy can be achieved only if all SNs draining a given melanoma site are identified and removed for detailed histologic examination. Lymphoscintigraphy with a radiolabeled colloid provides an objective and reliable method of locating SNs and demonstrates that confident prediction of their location is not possible on clinical grounds. STUDY DESIGN: Lymphatic drainage pathways demonstrated by preoperative lymphoscintigraphy for 1,759 patients with primary cutaneous melanomas were reviewed, and locations of SNs in these patients were documented. An SN was defined as any node receiving direct lymphatic drainage from a primary melanoma site. RESULTS: In many instances the cutaneous lymphatic drainage pathways were found to be at variance with longheld concepts of lymphatic anatomy. Several new pathways were identified, draining to SNs in unexpected sites. These included triangular intermuscular space SNs (from upper back and, rarely, upper limb primaries), paraaortic and retroperitoneal SNs (from upper and lower back primaries), and costal margin SNs with onward drainage to internal mammary nodes (from periumbilical primaries). Occasional drainage to node fields on the opposite side of the body was noted from head, neck, and trunk primaries, and drainage to interval nodes (by definition, SNs) outside recognized lymph node fields was also observed. CONCLUSIONS: Knowledge of the possibility of these unusual lymphatic drainage patterns and SN sites should help to ensure the accuracy and completeness of SN identification. Preoperative lymphoscintigraphy to definitively locate SNs is recommended for every patient undergoing an SN biopsy procedure.

Primary mucosal and glans penis melanomas: the Sydney Melanoma Unit experience.

BACKGROUND: Melanomas that arise on mucosal surfaces and the glans penis are rare. METHODS: A retrospective study of the Sydney Melanoma Unit experience with 69 patients treated since 1956 for these types of melanomas was undertaken to determine primary lesion site, sex, age at diagnosis, symptoms, clinical stage at first presentation. histopathology, treatment and outcome. RESULTS: Primary lesion sites were: nasal cavity (n = 9), oral cavity (n = 16), vulva/vagina (n = 25), anus/rectum (n = 13) and glans penis (n = 6). At diagnosis, 55 patients had local disease only, eight had regional lymph node metastases and six had widespread disease. Local recurrence as the first sign of relapse developed in 15 of the 55 stage I patients (three-stage system). Prognosis for the entire group was poor, only 10% being disease free 3 years after diagnosis and overall 3- and 5-year actuarial survival being 40% and 23%. respectively. The only statistically significant factor influencing survival was stage of disease at diagnosis (P = 0.002). CONCLUSIONS: Possible reasons for poor survival include: (i) non-specific symptoms resulting in late presentation; (ii) locally advanced disease not being recognized by a clinician as a rare form of melanoma, resulting in a delay in treatment; (iii) anatomical constraints precluding surgery with generous margins and consequently resulting in a high incidence of local recurrence. Also, rich vascularity and multiple lymphatic drainage pathways may mean a predisposition to early dissemination. Prompt diagnosis and referral to a specialist unit for treatment and follow up are essential. Adequate surgery remains the cornerstone of treatment for these types of melanoma until more effective systemic therapies become available.

High-resolution ultrasound to diagnose melanoma metastases in patients with clinically palpable lymph nodes.

High-resolution ultrasound was used to determine if it could predict the presence of metastatic disease in 52 patients with melanoma who had developed newly palpable lymph nodes during clinical follow-up. Ultrasound proved accurate in diagnosing the presence of nodal metastases; it had a sensitivity of 94%, a specificity of 87% and an accuracy of 89%. The ultrasound features which together were diagnostic of the presence of nodal metastases were a node thickness greater than two-thirds of the node length and the presence of low-level echoes in the node. When these two features were both present on ultrasound, node metastases were present in every case. Ultrasound can be used to evaluate newly palpable lymph nodes in patients with melanoma. A normal ultrasound finding does not exclude micrometastases, but a lymph node showing the two key ultrasound features aforementioned is highly likely to contain metastatic disease and should be treated accordingly.

Treatment of large, persistent lymphocoeles using an argon beam coagulator and talc.

BACKGROUND: Lymphocoele formation can be a troublesome surgical complication after lymph node dissection and mobilization of large skin flaps. Occasionally, lymphocoeles persist for prolonged periods despite repeated aspiration. Treatment by sclerotherapy has been recommended, but this requires a prolonged treatment time and often causes intense pain. METHODS: The technique used to treat large, persistent lymphocoeles involved 'painting' the lymphocoele wall with an argon beam coagulator after evacuating its contents. Sterile talc was then distributed liberally through the cavity, a closed suction drain placed and the wound closed. RESULTS: The procedure was completely successful in each of the four patients treated. After a mean follow-up period of 11 months (range 6-15 months) no lymphocoele recurrence has occurred. CONCLUSIONS: Use of an argon beam coagulator and talc reliably achieves rapid, definitive obliteration of large, persistent lymphocoeles.

Clinical outcomes of localized melanoma of the foot: a case-control study.

The controversy over whether melanoma of the foot has a poorer prognosis than melanoma of the leg remains unresolved. This investigation used a case-control design to address this issue. This design consisted of a survival analysis of 119 cases with localized melanoma of the foot and 238 controls with localized melanoma of the leg that were matched on prognostic factors including tumor thickness, ulceration, surgical treatment, gender, year of diagnosis, and age. There was a statistically significant difference between the survival rates of cases and controls. The 5-year survival rate for cases was 74.3% compared to 85.2% for controls. At 10 years, the survival rate was 63.6% for cases and 77.2% for controls. Cases experienced a higher percentage of distant recurrences than controls. These results imply that patients with melanoma of the foot have a poorer survival than patients with melanoma of the leg after controlling for prognostic factors.

The surgical treatment of primary melanoma.

Local control is paramount to the clinical management of melanoma. A general consensus has been reached regarding the surgical treatment of primary malignant melanoma. By means of well-designed, multi-institutional, prospective, and randomized trials, the margins of excising the primary melanoma have been reduced considerably since the initial guidelines set out by W. S. Handley in 1907. The margins of excision now recommended are designed to limit the risk of local recurrence with its potential effect on survival and achieve the optimal cosmetic outcome. These margins are modified according to particular anatomic site constraints.

Desmoplastic and desmoplastic neurotropic melanoma: experience with 280 patients.

BACKGROUND: It has been suggested that desmoplastic melanoma (DM) and desmoplastic neurotropic melanoma (DNM) are associated with worse prognoses and higher local recurrence rates than other forms of melanoma. In the current study, a large series of patients with DM and DNM treated at a tertiary referral center was reviewed. METHODS: For 190 patients with DM and 90 patients with DNM accrued over a 10-year period, clinical features were recorded and all available histopathology was reviewed. The associations between clinical and pathologic variables, biologic behavior, and eventual outcome were analyzed. RESULTS: The male-to-female ratio was 1.75:1 and the median patient age 61 years. The median tumor thickness was 2.5 mm, and 44% of cases were amelanotic. Five-year survival was 75%. Significant predictors of overall survival were a high mitotic rate (P=0.003) and tumor thickness (P=0.011). All the DNMs exceeded 1.5 mm in thickness and were graded as Clark's level IV or V. There was a significant increase in local recurrence when neurotropism was present (P < 0.001). The rate of local recurrence was not higher for DM than for other cutaneous melanomas. CONCLUSIONS: There was no statistically significant difference in survival for patients with DM and those with DNM, and overall survival for both was similar to that for patients with other cutaneous melanomas. However, there was a lower rate of regional lymph node metastasis at initial presentation and as the first recurrence for both DM and DNM. The local recurrence rate was higher when the surgical clearance margin was <1 cm and when neurotropism was present.

Factors affecting survival following local, regional, or distant recurrence from localized melanoma.

BACKGROUND AND OBJECTIVES: Approximately one third of all melanoma patients will experience disease recurrence. Factors that affect patient survival following local, regional, or distant first recurrences of localized melanoma are the subject of this investigation. METHODS: Survival times for a total of 1,085 first recurrences from 4,568 localized melanoma patients were examined in relationship to patient and disease factors by Cox regression. Nearly half (48.8%) of all first recurrences were regional, 21.8% were local, and 29.4% were distant recurrences. RESULTS: Survival following recurrence differed significantly by site of recurrence (local, regional, or distant; P < 0.0001). Within each site, the median survival time did not differ by time of recurrence following diagnosis. Significant tumor factors for survival following local recurrence included tumor thickness (P = 0.0263) and lesion location (P < 0.0001). For regional recurrences, survival was significantly related to ulceration (P = 0.0105) and whether the recurrence was combined with a local recurrence (P = 0.0429). Survival following distant metastasis was related to number of distant sites (P < 0.0001) and whether a visceral site was involved (P < 0.0001). CONCLUSIONS: Patient and tumor characteristics predict survival following recurrence. Regardless of disease-free interval, long-term follow-up of melanoma patients is necessary. Patients experiencing distant metastasis have the shortest median survival time compared to patients experiencing local or regional recurrences.