Localized Melanoma Research Articles

Lymphoscintigraphy in clinical routine practice: Reproducibility and accuracy in melanoma patients with a long-term follow-up

The sentinel node status is the most important single factor determining overall survival for patients with localized melanoma. Preoperative lymphoscintigraphy (LS) is essential in locating the correct sentinel lymph node (SN) and the reproducibility of the method determines the accuracy of the sentinel node biopsy (SNB). This study aims at determining the reproducibility and accuracy of LS in routine clinical practice after long-term follow-up. One hundred and eight melanoma patients with clinically unpredictable lymphatic drainage were prospectively enrolled to undergo two LS. The first LS was performed to determine the site and number of the lymphatic basins to plan SNB anesthesia and the second preoperative LS was to allow SN localization intra-operatively. Lymphatic drainage was demonstrated in all patients. In 84 of 108 cases, both LSs were concordant in terms of site and number of nodal basins visualized. After a median follow-up of 80 months, no nodal recurrence was observed in the five patients with a decreased number of lymph node basins. In the group with increased number of lymph node basins, one patient developed nodal metastases in the same regional lymph node basin visualized by both LS studies. LS is an accurate and reproducible method to determine the localization of the sentinel node in the day-to-day routine to clinical practice when primary melanoma is also located in body sites with variable lymphatic drainage.

Primary Melanoma of the Right Colon Presenting With Gastrointestinal Bleeding

A 73 year old female presented with painless fresh rectal bleeding and anaemia. At colonoscopy, a large mass arising from the right colon was visualised and biopsied. Histological evaluation established a diagnosis of melanoma. Thorough clinical examination confirmed the presence of primary localised melanoma which was amenable to resection. At laparotomy, right hemicolectomy and lymphadenectomy were performed. Two years after her surgery, our patient is well without any evidence of disease recurrence. Primary melanoma of the colon is a very rare clinical entity and limited data are available regarding its pathogenesis, treatment and outcome. Primary surgical resection in localised disease appears to be the mainstay of treatment, although the role of adjuvant therapy is still to be established.

Quality of Life in Women with Localised Breast Cancer or Malignant Melanoma 2 Years After Initial Treatment: a Comparison

Two thirds of female breast cancer patients and more than 80 % of malignant melanoma patients are diagnosed with localised disease and good prognosis with a 5-year relative survival of more than 90 % in Germany. This study was conducted to present quality of life (QoL) data from a German population-based cohort of female breast cancer and melanoma patients without recurrence for approximately 2 years after initial diagnosis. In 2003-2004, patients with localised breast cancer and melanoma were recruited from the Munich Cancer Registry (Upper Bavaria, Germany) to answer QoL questionnaires. Differences between breast cancer and melanoma patients were investigated with regard to age and aspects of communication with their medical caregivers. One thousand three hundred and four breast cancer and 348 melanoma patients were included. Breast cancer patients were about 7 years older and had significantly lower QoL and higher symptom scores than melanoma patients. Communication needs were generally similar in both groups; however, breast cancer patients experienced more empathy from their medical caregivers. In breast cancer patients, communication was an independent factor for all QoL functioning scores. Even when faced with a similarly good prognosis, breast cancer patients have a worse QoL than melanoma patients 2 years after diagnosis. An explanation may be more distinctive surgery and systemic therapy, older patients with comorbidities and misunderstood risk communication in breast cancer patients that may stoke anxiety and fears. Further reasons could be unceasing public discussion about breast cancer and its instrumentalisation for political purposes.

Age as a Prognostic Factor in Patients with Localized Melanoma and Regional Metastases

We postulated that the worse prognosis of melanoma with advancing age reflected more aggressive tumor biology and that in younger patients the prognosis would be more favorable. The expanded AJCC melanoma staging database contained 11,088 patients with complete data for analysis, including mitotic rate. With increasing age by decade, primary melanomas were thicker, exhibited higher mitotic rates, and were more likely to be ulcerated. In a multivariate analysis of patients with localized melanoma, thickness and ulceration were highly significant predictors of outcome at all decades of life (except for patients younger than 20 years). Mitotic rate was significantly predictive in all age groups except patients <20 and >80 years. For patients with stage III melanoma, there were four independent variables associated with patient survival: number of nodal metastases, patient age, ulceration, and mitotic rate. Patients younger than 20 years of age had primary tumors with slightly more aggressive features, a higher incidence of sentinel lymph node metastasis, but, paradoxically, more favorable survival than all other age groups. In contrast, patients >70 years old had primary melanomas with the most aggressive prognostic features, were more likely to be head and neck primaries, and were associated with a higher mortality rate than the other age groups. Surprisingly, however, these patients had a lower rate of sentinel lymph node metastasis per T stage. Among patients between the two age extremes, clinicopathologic features and survival tended to be more homogeneous. Melanomas in patients at the extremes of age have a distinct natural history.

Abstract 4483: Preclinical study of Dbait, an inhibitor of three DNA repair pathways, in breast cancer treatment.

Abstract Background: Five main types of therapies are available for the treatment of Breast Cancer (BC): surgery, radiation therapy, chemotherapy, hormone therapy, and most recently, targeted therapy. Most patients are treated with surgery in combination with one or more additional therapies for optimal cancer management. The limit of targeted therapy is that they are usually directed at specific targets in the body (extracellular receptors, kinases and enzymes) and therefore apply for limited number of patients. Herceptin and more recently trastuzumab have been shown to increase survival of patients over-expressing the HER2/neu receptor (20-30% of BC). PARP inhibitors that act as synthetic lethal with BRCA deficiency have shown promising results. These inhibitors that target the PARP-dependent DNA repair pathway seem however less efficient in patient with active homologous recombination repair. We have recently developed a new strategy (DNA repair bait, Dbait in short) that inhibits three central repair pathways (Homologous Recombination, Non Homologous End Joining and Single Strand Break Repair). DT01 is the 1st drug candidate of this family of DNA repair inhibitor already in a phase 1 trial in local metastatic melanoma. This study demonstrates the efficiency of DT01 in BC treatment. Materials and methods: Twelve BC cell lines were characterized for DNA repair gene expression and activation of the DNA damage response DDR (pH2AX and PAR detection) by western blot analysis of the proteins and classified according to their BRCA status. Clonal survival to Dbait (the DT01 in vitro variant) was analyzed 10 days after treatment. Four xenografted models derived from cell lines or patient samples were assayed for sensitivity to DT01. DT01 (5mg) was subcutaneousely administered every day for a week (5 sessions) or four days per week for three weeks (12 sessions of 2mg). In parallel, the PARP inhibitor ABT-888 was orally administered at the dose of 25 mg/day/kg during one week to compare efficiencies. Tumor growth and survival of untreated and treated animals were monitored during 150 days. Tumors were analyzed for different repair and stress markers by immunocytology. Results: This study provides the evidences that: i) Dbait induces death in vitro in BRCA-/- cells but also in BRCA+/+ cells having a high level of spontaneous DDR; ii) DT01 controls tumor growth in all the model tested with or without BRCA mutation; iii) DT01 cured 30% BRCA-/- tumors; iv) DT01 was more efficient that ABT-888 which did not allow any cure and showed a 73% increase of survival. At the end of the study 80% of the animals treated by DT01 were still alive. Conclusion: DT01 is a promising investigational medicinal product to treat Breast Cancer. Its association with radiotherapy is under investigation. Citation Format: Marie Dutreix, Youlia M. Kirova, Amelie Croset, Flavien Devun, Jian-Sheng Sun. Preclinical study of Dbait, an inhibitor of three DNA repair pathways, in breast cancer treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4483. doi:10.1158/1538-7445.AM2013-4483

Vinblastine-induced apoptosis of melanoma cells is mediated by Ras homologous A protein (Rho A) via mitochondrial and non-mitochondrial-dependent mechanisms

Despite the availability of melanoma treatment at the primary site, the recurrence of local melanoma can metastasize to any distant organ. Currently, the available therapies for the treatment of metastatic melanoma are of limited benefit. Thus, the functional analysis of conventional therapies may help to improve their efficiency in the treatment of metastatic melanoma. In the present study, the exposure of melanoma cells to vinblastine was found to trigger apoptosis as evidenced by the loss of mitochondrial membrane potential, the release of both cytochrome c and apoptosis inducing factor, activation of caspase-9 and 3, and cleavage of Poly (ADP-ribose)-Polymerase. Also, vinblastine enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. In addition, vinblastine induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins. Moreover, inhibitory experiments addressed a central role for Rho A in the regulation of vinblastine-induced apoptosis of melanoma cells via mitochondrial and non-mitochondrial-dependent mechanisms. In conclusion, the present study addresses for the first time a central role for Rho A in the modulation of vinblastine-induced apoptosis of melanoma cells and thereby provides an insight into the molecular action of vinblastine in melanoma treatment.

PM.86 Melanoma in Pregnancy: A Case Report

A 36 year old presented at 20 weeks gestation with an abnormal mole. Biopsy revealed a non-ulcerated Stage 1B malignant melanoma with 1.3 mm Breslow thickness and 3.5 mitosis/mm2 (T2a)....

Quality of life and comorbidity in localized malignant melanoma: results of a German population‐based cohort study

Incidences of malignant melanoma continue to increase in fair-skinned populations. At least 80% of patients are diagnosed with localized disease and can expect a 5-year relative survival rate of >90%. Given that the median age at diagnosis of malignant melanoma is 59 years, many patients already suffer chronic diseases when they are confronted with cancer. The aim of this study was to analyze the effect of additional chronic diseases on health-related quality of life (QoL) in a population-based cohort of melanoma patients two years after presumably curative treatment. In 2003-2004, 1085 patients with localized malignant melanoma were recruited from the population-based Munich Cancer Registry to answer validated QoL questionnaires. Information about comorbidities was also obtained. Factors predicting QoL were analyzed using multivariate logistic regression models. A total of 781 patients (72%) returned completed questionnaires, of which 664 (61%) could be included in the analyses. Quality of life scores and differences in subgroups (e.g., sex and age) were essentially similar to those in the general population. Age, number of comorbidities, and several chronic diseases (e.g. heart and kidney disease, diabetes, former depression) were the strongest predicting factors and influenced almost every aspect of QoL. Localized malignant melanoma does not worsen QoL per se, compared with QoL in the general population. Comorbidities have similar effects on QoL in malignant melanoma patients as they do in the general population. Therefore, cohorts of patients with localized malignant melanoma can represent a basis for comparisons with other cohorts of cancer patients to determine the respective impacts of cancer-related and non-cancer-related factors on QoL.

Adjuvant treatment of melanoma.

Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50–80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon-α2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas.

Lichtblicke beim schwarzen Hautkrebs aus der Sicht von Pathologen

Malignant melanoma is the most common cause of death from skin cancer. Wide surgical excision of localized melanoma in its primary stages remains the main curative therapy. Identifying patients at an early tumour stage is therefore one of the most significant steps for treatment. In the last decades, molecular pathology rapidly established itself in melanoma research. We present new molecular methods, their significance and their application, especially focusing on BRAF( V600) mutation and BRAF-inhibiting tumor targeting therapy. Resistance to tumor targeting therapies and cell line experiments, which have evidenced a sub population with stem cell properties, illustrate melanoma heterogeneity. Efforts to develop drugs that target more than a single target gene are currently underway.

Patients' perspectives of long-term follow-up for localised cutaneous melanoma

BackgroundLittle is known about the value of long-term follow-up for localised cutaneous melanoma from the patients' perspective. This study aimed to explore the benefits and potential downsides of follow-up; feelings about changes to frequency of follow-up, and patient-centred recommendations for improving follow-up care. MethodsQualitative analysis of 29 in-depth interviews conducted with Australian patients undergoing long-term follow-up after surgical treatment of stage I/II melanoma. ResultsPatient-perceived benefits of follow-up included reassurance, early detection of new melanomas and non-melanoma skin cancers, education about skin self-examination, the opportunity to ask questions, and reinforcement of ‘sunsafe’ behaviours. Downsides included anxiety leading up to and during follow-up visits; inconvenience of travel to attend visits; and lost work time. Patients varied in their engagement with skin self-examination, and their views on multiple skin excisions, but highly valued access to specialists for unscheduled visits. Most patients felt their follow-up intervals could be extended to 12 months if recommended by their clinician. ConclusionThe benefits and potential downsides of follow-up should be discussed with patients when deciding on a melanoma follow-up plan to achieve a balance between inducing additional patient anxiety and providing reassurance. Follow-up intervals of 12 months appear to be acceptable to patients.

The Role of Surgical Methods in the Treatment of Anorectal Malignant Melanoma (AMM)

Purpose : Anorectal malignant melanoma (AMM) is a rare tumor with a poor prognosis. The aim of this study was to investigate the clinicopathological characteristics and treatment outcomes in patients with AMM. Methods : The study included 21 patients diagnosed with AMM between 2000 and 2010 that were evaluated with regard to age, sex, disease stage, treatment modality, and survival. Stage I, II, and III were defined as localized primary malignant melanoma, regional lymph node metastasis, and distant metastasis, respectively.Results : In all, 12 (57%) patients were female and 9 (43%) were male; median age was 61 years (range: 30–84 years). Among the 21 patients, 7 (47%) underwent abdominoperineal resection and 8 (53%) were treated using wide local excision. Four (19%) patients were classified as stage I, 10 (48%) as stage II, and 7 (33%) patients as stage III. In total, 10 patients received adjuvant therapy. Median overall and progression-free survival was 12 and 9 months, respectively. The 1-year and 5-year overall survival estimates were 59% and 42%, and progression free survival were 49% and 7%, respectively. Patients aged > 60 years (P = 0.145), female patients (P = 0.076), patients with localized disease (P = 0.045), patients that underwent wide local excision (P = 0.619), and patients that received adjuvant therapy (P = 0.962) had longer survival.Conclusions : The prognosis of AMM remains very poor and disease stage is the only predictor of survival. Abdomino-perineal resection does not confer an advantage, in terms of survival, in patients with AMM.

Prediction of Sentinel Node Status and Clinical Outcome in a Melanoma Centre

Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph node (SLN) as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%). Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management.

Targeted Therapy; From Advanced Melanoma to the Adjuvant Setting

Targeted Therapy; From Advanced Melanoma to the Adjuvant Setting

Melanoma of the female urethra

Primary melanoma of the female urethra is a very rare malignant tumor with high mortality. Due to its rarity, there are no guidelines and recommendations on the diagnosis and treatment of such patients, so we aimed to review the reported cases and case series, their treatment, and outcome. We searched through PubMed for all articles reporting on female urethral melanoma. We found 73 articles (case reports and case series) reporting on 112 patients. There are no clinical trials on the topic due to the rarity of the condition. Median patient age at presentation is 68 years. Due to the late presentation, the prognosis of the disease is poor, and median survival is 16 months, with 5-year survival in around 10 % (12 reported patients). Regarding treatment, most authors use either less radical approach (partial or total urethrectomy) or radical approach (anterior pelvic exenteration). We found no evidence that either of the treatment modalities results with higher survival. In local excision, there are indications that margins less than 2-2.5 cm result in high percentage of local recurrence suggesting that resection width should be at least 2.5 cm. For localized urethral melanoma, local resection with margins of 2.5 cm can be recommended and there is no foundation to support radical surgery in such patients. Chemotherapy and immunotherapy can also recommend. For locally advanced disease, the prognosis is poor, and radical surgery will not improve survival significantly.

An update on pegylated IFN-α2b for the adjuvant treatment of melanoma

For patients with localized melanoma, excision of the primary tumor, including lymphadenectomy for nodal metastases, is standard treatment. However, patients with large primary tumors (stage IIB and IIC) or stage III melanoma have a relatively poor prognosis owing to the high risk of recurrence. High-dose IFN-α2b and pegylated IFN-α2b (PEG-IFN-α2b) are the only approved options for adjuvant therapy of stage III melanoma, but the lack of comparative data has led to considerable confusion in choosing between these options. In this article, current evidence regarding the pharmacokinetics, efficacy, safety and tolerability of adjuvant PEG-IFN-α2b in patients with melanoma is reviewed, with frequent reference to and comparisons with data using IFN-α2b. Particular focus is given to the pharmacokinetic differences between IFN-α2b and PEG-IFN-α2b and their implications for the treatment of high-risk patients. In addition, emerging evidence suggests that PEG-IFN-α2b therapy may provide clinically significant overall survival benefit for selected high-risk patients.

Role of Tip60 in Human Melanoma Cell Migration, Metastasis, and Patient Survival

The tumor suppressor Tip60 regulates gene transcription, DNA damage response, apoptosis, and cancer development, but its role in melanoma is unknown. In this study, we investigated the expression pattern of Tip60 in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 448 cases of melanomas (201 for the training set and 247 for the validation set) and 105 cases of nevi, we found that Tip60 expression was significantly reduced in metastatic melanoma compared to common nevi (P=0.045), dysplastic nevi (P=0.047), and primary melanoma (P=0.001). Kaplan-Meier survival curve and univariate Cox regression analyses showed that reduced Tip60 expression was associated with a poorer 5-year disease-specific survival in primary melanoma (P=0.016) and metastatic melanoma patients (P=0.027). Multivariate Cox regression analyses indicated that Tip60 expression was an independent prognostic marker for primary (P=0.024) and metastatic melanomas (P=0.035). In vitro wound healing assay showed that enforced Tip60 expression inhibited but Tip60 knockdown enhanced melanoma cell migration, suggesting that Tip60 might regulate melanoma metastasis. Finally, we showed that overexpression of Tip60 in melanoma cells resulted in significantly increased chemosensitivity. Our data indicate that Tip60 may serve as a potential biomarker for melanoma patient outcome as well as a potential therapeutic target.

Safety of Pars Plana Vitrectomy in Eyes With Plaque-Irradiated Posterior Uveal Melanoma

To determine the long-term safety of pars plana vitrectomy (PPV) in eyes with plaque-irradiated posterior uveal melanoma. In this retrospective case series, patients with plaque-irradiated posterior uveal melanoma subsequently underwent PPV for vitreous hemorrhage. The main outcome measures are the rates of intraocular melanoma dissemination, extrascleral extension of melanoma, local melanoma recurrence, and systemic melanoma metastasis after PPV. Forty-seven eyes of 47 patients underwent PPV for vitreous hemorrhage after iodine 125-labeled plaque radiotherapy for choroidal melanoma. The mean interval between the onset of vitreous hemorrhage and PPV was 13 (median, 10; range, 0-52) months. The mean time from PPV to last follow-up was 5 (range, 0.5-16) years. There were no cases of intraocular melanoma dissemination or extrascleral extension of melanoma. One patient (2%) developed local choroidal melanoma recurrence (2 years after PPV and 5 years after initial plaque radiotherapy) and was successfully managed with transpupillary thermotherapy. Systemic melanoma metastasis occurred in 4 patients (9%) during a mean interval of 5 years after plaque radiotherapy. During follow-up, 43 patients (91%) were alive without systemic metastasis and 4 patients (9%) were alive with metastasis. Management of vitreous hemorrhage by PPV in eyes with previously irradiated uveal melanoma appears to be safe and without increased risk for intraocular, local, orbital, or systemic dissemination of the tumor.

Illness-Related Distress in Women with Clinically Localized Cutaneous Melanoma

Women may experience distress or changes in their quality of life following treatment for early-stage melanoma. In order to plan future interventions and identify areas of primary concern, we conducted a cross-sectional survey to describe the experiences of women treated for clinically localized melanoma. We examined quality of life, levels of distress, appearance perceptions, body image, fear of recurrence, and reproductive concerns in 100 patients (age 21-90 years, M = 54.34 years). Most (61 %) had melanoma of the extremity, with a median depth of 1.1 mm (range, 0-10.5 mm). Significant depressive symptomatology occurred in 10 % of patients, and 12 % reported a clinically established high level of intrusive thoughts related to melanoma. Quality-of-life scores indicated more disruption on psychological, compared with social and physical functioning. Also, 64 % of women rated their appearance as worse post-treatment; 23 % were unsatisfied with the appearance of the surgical site. Recurrence concerns indicated significant worry about health and death. Most patients (>85 %) were not concerned about fertility, but 52 % worried that future children would have an increased risk of cancer. Some women treated for clinically localized melanoma reported high levels of distress associated with their altered body image and fear of recurrence. Improvements in patient education prior to surgical intervention may reduce the distress associated with the diagnosis and treatment of melanoma.

Tumor-Infiltrating Lymphocyte Grade Is an Independent Predictor of Sentinel Lymph Node Status and Survival in Patients With Cutaneous Melanoma

To determine whether density and distribution of tumor-infiltrating lymphocytes (TILs; TIL grade) is an independent predictor of sentinel lymph node (SLN) status and survival in patients with clinically localized primary cutaneous melanoma. From the Melanoma Institute Australia database, 1,865 patients with a single primary melanoma ≥ 0.75 mm in thickness were identified. The associations of clinical and pathologic factors with SLN status, recurrence-free survival (RFS), and melanoma-specific survival (MSS) were analyzed. The majority of patients had either no (TIL grade 0; 35.4%) or few (TIL grade 1; 45.1%) TILs, with a minority showing moderate (TIL grade 2; 16.3%) or marked (TIL grade 3; 3.2%) TILs. Tumor thickness, mitotic rate, and Clark level were inversely correlated with TIL grade (each P < .001). SLN biopsy was performed in 1,138 patients (61.0%) and was positive in 252 (22.1%). There was a significant inverse association between SLN status and TIL grade (SLN positivity rates for each TIL grade: 0, 27.8%; 1, 20.1%; 2, 18.3%; 3, 5.6%; P < .001). Predictors of SLN positivity were decreasing age (P < .001), decreasing TIL grade (P < .001), ulceration (P = .003), increasing tumor thickness (P = .01), satellitosis (P = .03), and increasing mitoses (P = .03). The 5-year MSS and RFS rates were 83% and 76%, respectively (median follow-up, 43 months). Tumor thickness (P < .001), ulceration (P < .001), satellitosis (P < .001), mitotic rate (P = .003), TIL grade (P < .001), and sex (P = .01) were independent predictors of MSS. Patients with TIL grade 3 tumors had 100% survival. TIL grade is an independent predictor of survival and SLN status in patients with melanoma. Patients with a pronounced TIL infiltrate have an excellent prognosis.