Breslow Depth Research Articles

Mixed Versus Pure Variants of Desmoplastic Melanoma: The Cleveland Clinic Experience.

Desmoplastic melanoma (DM) is a subvariant of spindle cell melanoma, accounting for less than 4% of all cutaneous melanomas. It occurs later in life and is associated with chronic sun exposure. Desmoplastic melanoma prognosis is considered more favorable than other variants, with lower rates of metastasis and higher survival. Recently, DM has been further subclassified into pure and mixed, calling into question surgical management and patient outcomes as well as viability of current nationwide databases without this distinction. We identified all patients with a histopathologic diagnosis of DM from the Cleveland Clinic electronic melanoma database (n = 58) from 1997 to 2013. Clinical and histopathologic data were collected. Comparison in clinical variables was performed between patients who had pure (n = 15) and mixed (n = 43) variants of DM. There were no differences in age, sex, location of lesion, Breslow depth, ulceration, or regression. Patients with mixed DM were more likely to have lymphovascular invasion (P = 0.03) compared with pure DM. There was no difference in performance of sentinel lymph node biopsy (P = 0.25) or sentinel lymph node positivity (P = 0.31) between the 2 groups. Recurrence was present in 13.3% of pure and 30.2% of mixed patients. Overall, Kaplan-Meier 3-year survival was 75% for pure and 80% for mixed DM (P = 0.53). Pure and mixed DMs seem to have similar clinical characteristics and outcomes. This indicates that analysis of national datasets without this subclassification remains viable.

Similar survival of patients with multiple versus single primary melanomas based on Utah Surveillance, Epidemiology, and End Results data (1973-2011)

Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). We compared MPM versus SPM patient survival using a matching method that avoids potential biases associated with other analytic approaches. Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End Results registry of all melanomas diagnosed or treated in Utah between 1973 and 2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. Survival curves (n=887 for both MPM and SPM groups) without covariates showed a significant survival disadvantage for MPM patients (chi-squared 39.29, P<.001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio 1.07, P=.55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio 0.99, P=.96). Breslow depth, ulceration status, and specific cause of death were not available for all patients. Patients with MPM had similar survival times as patients with SPM.

Duration of Anti-Programmed Death-1 Therapy in Advanced Melanoma: How Much of a Good Thing Is Enough?

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 53-year-old healthy man presented with recurrent in-transit melanoma of the right lower extremity. Eight years prior he had undergone wide local excision and sentinel lymph node biopsy for invasive melanoma of the anteromedial aspect of the distal right thigh. Pathology revealed an ulcerated melanoma, Breslow depth 3.5 mm, and with one involved micrometastatic inguinal lymph node. Staging studies did not demonstrate distant metastases. Superficial inguinal node dissection was performed and did not identify any additional metastatic nodes of 14 retrieved for a final pathologic staging of T3bN1aM0 (stage IIIB) cutaneous melanoma. He received 12 months of adjuvant high-dose interferon alfa-2b. Two years later, he developed a 1.2-cm subcutaneous focus of in-transit recurrence approximately 4 cm proximal to the original melanoma site in the right thigh, which was treated with surgical resection followed by adjuvant radiotherapy. Over the next 4 years, he underwent six additional surgeries for isolated in-transit recurrences affecting the same limb. He was referred for therapeutic options at the time of his latest in-transit recurrence. Examination revealed three palpable subcutaneous nodules in the right thigh in the setting of lymphedema. A core biopsy confirmed recurrent melanoma (Fig 1). Whole-body fluorodeoxyglucose positron emission tomography imaging revealed at least 17 hypermetabolic cutaneous and subcutaneous nodules in the right thigh, four fluorodeoxyglucose-avid nodules below the right knee, but no distant metastases (Fig 2A). Brain magnetic resonance imaging was normal. His serum chemistry profile, including lactate dehydrogenase, was normal. Molecular analysis demonstrated presence of BRAF V600E mutation in the tumor. After multidisciplinary evaluation, an isolated limb infusion procedure of the right lower extremity was not believed to be feasible, secondary to the proximal extent of the recurrence. Therapy was initiated with pembrolizumab at 2 mg/kg intravenously every 3 weeks.

Epidemiological and histopathological aspects of primary cutaneous melanoma in residents of Joinville, 2003-2014

BackgroundThe worldwide incidence of cutaneous melanoma (CM) has been continuously increasing over the last decades. Primary and secondary prevention, with attention to risk factors and early diagnosis, remain the cornerstone for reducing the burden of cutaneous melanoma. Detailed information with respect to clinical and pathological data on cutaneous melanoma is scarce in Brazil.ObjectiveThe purpose of our study was to analyze epidemiological and pathological characteristics of primary cutaneous melanoma in Joinville, southern Brazil.MethodsObservational, cross-sectional, retrospective study in which 893 reports of primary cutaneous melanoma from the local population were analyzed in the period 2003-2014. The study was approved by the local Ethics and Research Committee.ResultsWe observed a female predominance of cutaneous melanoma (56.3%). The age standardized incidence rate of primary cutaneous melanoma for the world population in the period 2003-06 was 11.8 per 100,000 population (CI 95%, 10.3-13.4), and 17.5 (CI 95%, 15.7-19.3) in 2011-14, revealing a significant increase of 48.3% (p < 0,05). Six and a half percent of patients had multiple cutaneous melanomas (mean 2.2 years and a maximum of 10.0 years between diagnoses). We observed significant differences between the location head/neck and cutaneous melanoma in situ, lower limb with Breslow depth S III and upper limb with Breslow depth S I. The comparison of the characteristics of cutaneous melanoma in the elderly and non-elderly (< 60 years old) showed significant differences with respect to all the variables studied.Study limitationsUsing secondary data source.ConclusionJoinville has high incidence coefficients for Brazilian standards, showing an increase in the incidence of cutaneous melanoma.

Gender differences in melanoma prognostic factors

Although previous studies identify gender differences in melanoma, limited research on the phenomenon exists. In this retrospective chart review, 1,156 adults diagnosed with melanoma, between 2006-2016, at the University of Colorado were included. Breslow depth, mitotic rate, ulceration status, and location were extracted from charts between March and August 2016. Cochran-Armitage trend tests and cumulative logistic regression were used to examine the association between gender and Breslow depth, univariately and after adjusting for potential confounders. In univariate analysis, males were significantly more likely to present with lesions with higher Breslow depths (p for trend=0.005). In models adjusted for age, melanoma subtype, and location, males were marginally more likely to present with lesions with higher Breslow depths (cumulative OR: 1.261, 95% CI: 0.988-1.611, p=0.060). Males were also marginally more likely to present with lesions with higher mitotic rates, after further adjustments for all other prognostic factors (cumulative OR: 1.244, 95% CI: 0.979-1.580, p=0.074). This was a retrospective single-institution study. Differences in mitotic rates among melanomas in males versus females, even after adjustments for all other prognostic factors, suggests that biological differences may contribute to the female prognosis advantage.

AJCC 8th Edition (2017) versus AJCC 7th Edition (2010) in thin melanoma staging.

In comparison with the 7th Edition, the 8th Edition of the American Joint Committee on Cancer (AJCC) staging system no longer considers the mitotic count in the a or b T1 categorization for melanoma, but it adopts a sub-stratification based on the Breslow's depth. Today, the death burden of thin melanoma is still severe, despite of attempts for early screening. We believe that a bio-histological implementation may explain this evidence. It is generally accepted that melanoma progression includes two subsequent phases: the radial growth phases (RGP) and the vertical growth phase (VGP). If left untreated, RGP is able to move towards VGP. In this second phase, melanoma grows as a malignant, mitotically active, tumor with invasive and metastatic capacities. By our experience, thin melanoma includes three bio-histological subtypes: the non-tumorigenic micro-invasive RGP without significant regression, the micro-invasive RGP with regression of uncertain tumorigenic potential at diagnosis, due to the extensive presence (> 75%) of regression which could contain a VGP clone, and the micro-invasive tumorigenic VGP. Therefore, we are prone to support that the prognosis of thin melanoma is correlated with the type of growth phase inside it.

Osseointegrated Prosthetic Ear Reconstruction in Cases of Skin Malignancy: Technique, Outcomes, and Patient Satisfaction.

Ear reconstruction with osseointegrated prosthetic implants is a well-established method of reconstruction after resection of skin malignancies on the external ear. There is limited literature reporting technique, outcomes, and patient satisfaction. We evaluated our outcomes over a 5-year period looking at osseointegrated prosthetic reconstruction after auriculectomy for external ear skin malignancies. We report demographics, disease characteristics, technique, and complications. The patients were surveyed looking at 6 domains: satisfaction, stability, comfort, ease of use, level of self-consciousness, and preoperative education. Of the 21 patients included in the study, 14 (67%) were treated for invasive melanoma (Breslow depth, >0.8mm), 4 (19%) for squamous cell carcinoma, 2 (10%) for basal cell carcinoma, and 1 (5%) for an atypical fibroxanthoma. Complications rates were low. There were no cases of infection, hematoma, or bleeding. In 2 patients (9.5%), 1 of the 3 implants failed to osseointegrate and was removed, but the prosthesis was able to be secured with the remaining 2 posts. There were 3 cases (14%) of delayed healing and 1 with excessive granulation tissue growth. Survey results showed high satisfaction in all measured domains. In cases of skin malignancy requiring total or subtotal auriculectomy, prosthetic ear reconstruction with osseointegrated implants is a good alternative to reconstruction with autologous tissue. Our experience demonstrates good outcomes and with low complication rates and high patient satisfaction.

Genetic polymorphisms may influence the vertical growth rate of melanoma.

Background: Identification of new predictive markers in melanoma is of great clinical importance. This study was aimed to analyze association between selected common variants in the cancer susceptibility genes and melanoma progression at the time of diagnosis.Material and Method: The study included 243 consecutive patients with melanoma. Genotyping was performed using real-time PCR.Results: Our data revealed modest association between xeroderma pigmentosum complementation group D (XPD) codon 312 polymorphism and tumor thickness (as defined by Breslow score; XPD D312N CC: 3.00 ± 3.78mm, CT: 1.71 ± 2.48mm, TT: 2,53 ± 3,24mm, P=0.023). The CT genotype in XPD D312N polymorphism was more frequently represented in non-invasive melanomas compared to deeply penetrating tumors. None of the common SNPs in cyclin dependent kinase inhibitor 2A (CDKN2A), vitamin D receptor (VDR), melanocortin 1 receptor (MC1R) were associated with Breslow depth.Conclusion: These findings suggest that genetic alteration in XPD contributes to melanoma progression and may be a potential diagnostic and molecular prognostic marker.

Differences in the diagnosis of primary cutaneous melanoma in the public and private healthcare systems in Joinville, Santa Catarina State, Brazil

Background:Cutaneous melanoma accounts for up to 80% of deaths caused by skin cancer. Diagnostic suspicion and access to medical care and early intervention in suspected cases is vital to the patient’s prognosis. Objectives:To compare demographic and histopathological characteristics of primary cutaneous melanoma diagnosed in the public healthcare system (Sistema Único de Saúde SUS) and the private system in Joinville, Santa Catarina State, Brazil. Methods:This cross-sectional retrospective study analyzed primary cutaneous melanoma cases recorded from 2003 to 2014 in the resident population of Joinville. Ethical approval was obtained from the local Research Ethics Committee. Results:893 cases of primary cutaneous melanoma were identified. Patients in the private system were mostly younger, while there were more elderly patients in the public healthcare system (p <0.001). There was no statistically significant association between type of care (public/private) and gender or presence of multiple primary cutaneous melanomas. Histological diagnosis of superficial spreading melanoma was more common in patients treated in private healthcare, while nodular melanoma was more frequent in patients in the public healthcare system (p <0.001). Mean Breslow depth in patients treated in private healthcare was 1.35mm, compared to 2.72mm in the public system (p <0.001). Study limitations:This was a retrospective study using secondary databases. Conclusions:thin cutaneous melanoma (in situ cutaneous melanoma and Breslow T1) showed the strongest association with the private healthcare system, while thick cutaneous melanoma was more frequent in the public system (Breslow category T3 and T4) (p <0.001).

Neurotropism as a prognostic factor in cutaneous melanoma patients

Neurotropism is a feature that is encountered rarely in melanoma and is considered to be associated with increased risk of local recurrence. However, its prognostic significance still remains controversial. The objective of this study was to deter- mine the clinical significance of neurotropism in cutaneous melanoma patients. A total of 519 cutaneous melanoma patients were enrolled into this study and their data were analyzed in a retrospective fashion. The melanomas without neurotro- pism (n=496; 95.6%) were larger in number than those with neurotropism (n=23; 4.4%). Compared to non-neurotropic melanomas, neurotropic melanomas were more likely localized in the extremities (p=0.007) and they were more frequently associated with non-superficial spreading histologic subtype (p=0.029), advanced Clark invasion level (IV-V) (p=0.007), thick Breslow depth (p=0.001), high mitotic rate (p=0.041), ulcerated lesions (p<0.001), lymphovascular invasion (p<0.001), and lymph node metastasis (p=0.013). The neurotropic melanomas were significantly associated with both unfavorable relapse-free survival (RFS) (p=0.045) and overall survival (OS) (p<0.001). However, neurotropism lost its prognostic signifi- cance in both RFS (p=0.767) and OS (p=0.644) in multivariable analyses. In conclusion, the presence of neurotropism predicts a greater risk for nodal involvement and is associated with worse survival in patients with cutaneous malignant melanoma, on the other hand it is not an independent risk factor when other powerful prognostic variables are considered.

CKS1 expression in melanocytic nevi and melanoma.

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway.

Anemia in Cutaneous Malignant Melanoma: Low Blood Hemoglobin Level is Associated with Nodal Involvement, Metastatic Disease, and Worse Survival

ABSTRACTAnemia is common in cancer patients and also affects survival. However, its clinical role and prognostic significance remains unknown in cutaneous melanoma patients (CMPs). The aim of this study was to determine the clinical significance of blood hemoglobin levels in CMPs. Of 446 CMPs were enrolled into this study and were investigated retrospectively. The median value of hemoglobin levels was 13.4 g/dL (7.9–17.4 g/dL). The female patients (P < 0.001) and those with nodular histology (P = 0.040), elevated erythrocyte sedimentation rate (P < 0.001), higher serum lactate dehydrogenase (P < 0.001), lymph node involvement (P = 0.018), and metastatic disease (P < 0.001) had more likely low hemoglobin concentrations compared with other CMPs. However, serum hemoglobin levels were not significantly associated with age, anatomic localization, and various pathological features including Breslow depth, mitotic rate, and ulceration. We found that hemoglobin levels were significantly associated with outcome; the patients with low hemoglobin concentrations had worse survival than other CMPs (P < 0.001). On multivariate analyses, however, hemoglobin level lost its significance, thus, it was not found independently associated with the outcome. In conclusion, low blood hemoglobin concentration is associated with nodal involvement and metastatic disease. Although anemia in diagnosis was not an independent prognostic factor for survival in CMPs, it was associated with poor prognostic factors.

Stratifying SLN incidence in intermediate thickness melanoma patients

BackgroundGuidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for positive SLNB. MethodsA retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01–4.00 mm) who had SLNB, and assessed predictors for positive SLNB. Results3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm2 (p = .01), and microsatellitosis (p < .001). Multivariate analysis revealed age, location, and Breslow depth as significant predictors. Patients ≥75 with lesions 1.01–1.49 mm on the head/neck/upper extremity and 1.5–1.99 mm without high-risk features had <5% risk of SLN positivity. ConclusionsIntermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.

Mitotic rate is associated with positive lymph nodes in patients with thin melanomas

The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018. Using a large nationally representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas. A total of 149,273 thin melanomas in the National Cancer Database were examined for their association of high-risk features of mitotic rate, ulceration, and Breslow depth with lymph node status. Among 17,204 patients with thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R2=0.96, P<.0001, β=3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (odds ratio, 1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean mitotic rate of 1.54 plus or minus 2.07 mitoses/mm2 compared with 3.30 plus or minus 3.54 mitoses/mm2 for those with positive nodes (P<.0001). The data collected do not allow for survival analyses. Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports.

Transected thin melanoma: Implications for sentinel lymph node staging.

Indications for sentinel lymph node (SLN) biopsy in patients with thin melanoma (≤1 mm thick) are controversial. We asked whether deep margin (DM) positivity at initial biopsy of thin melanoma is associated with SLN positivity. Cases were identified using prospectively maintained databases at two melanoma centers. Patients who had undergone SLN biopsy for melanoma ≤1 mm were included. DM status was assessed for association with SLN metastasis in univariate and multivariate analyses. 1413 cases were identified, but only 1129 with known DM status were included. 39% of patients had a positive DM on original biopsy. DM-positive and DM-negative patients did not differ significantly in primary thickness, ulceration, or mitotic activity. DM-positive and DM-negative patients had similar incidence of SLN metastasis (5.7% vs 3.5%; P = 0.07). Positive DM was not associated with SLN metastasis on univariate analysis (OR 1.69, 95% CI: 0.95-3.00, P = 0.07) or on multivariate analysis adjusted for Breslow depth, Clark level, mitotic rate, and ulceration (OR = 1.59, 95% CI: 0.89-2.85; P = 0.12). For patients with thin melanoma, a positive DM on initial biopsy is not associated with risk of SLN metastasis, so DM positivity should not be considered an indication for SLN staging in an otherwise low-risk patient.

The diagnostic value and histologic correlate of distinct patterns of shiny white streaks for the diagnosis of melanoma: A retrospective, case-control study

Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P<.001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P=.009), and SWSs correlated with greater Breslow depth among melanomas (P=.007). This study was retrospective. Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma.

Elevated erythrocyte sedimentation rate is associated with metastatic disease and worse survival in patients with cutaneous malignant melanoma.

Elevated erythrocyte sedimentation rate (ESR) is common in cancer patients and it may affect survival. However, its clinical role and prognostic significance remain unknown in melanoma patients. The objective of the present study was to determine the clinical significance of the ESR levels in cutaneous melanoma patients. A total of 139 cutaneous melanoma patients were enrolled in this study and were retrospectively investigated. The median age of the patients was 52 years (range, 16-88 years). The median ESR was 22 mm/h (range, 2-122 mm/h). Significant differences in ESR were found to be associated with sex, histology, blood hemoglobin level, lactate dehydrogenase (LDH) and metastatic disease. Female patients (P=0.006) and those with nodular histology (P=0.005), low hemoglobin concentration (P<0.001), higher LDH levels (P=0.003) and metastatic disease (P<0.001) were more likely to have elevated ESR levels. However, ESR was not found to be significantly associated with age, site of lesion, or pathological indicators, including Clark's level of invasion, Breslow's depth, mitotic rate, ulceration, vertical growth phase, tumor-infiltrating lymphocytes, regression, neurotropism, lymphovascular invasion and BRAF (V600E) mutation (P>0.05). ESR was also not associated with lymph node involvement (P=0.188) or responsiveness to chemotherapy (P=0.390). However, ESR was found to be significantly associated with outcome; patients with increased ESR had worse survival compared with those with normal values (hazard ratio=2.033; 95% confidence interval: 1.156-3.577; P=0.012). In conclusion, elevated ESR was found to be associated with metastatic disease and was also found to be a prognostic factor adversely affecting survival in patients with cutaneous melanoma.

Patient age and cutaneous malignant melanoma: Elderly patients are likely to have more aggressive histological features and poorer survival.

Patient age has been reported as a highly significant and strong predictor of the outcome in patients with cutaneous melanoma. The aim of the present study was to determine the clinical significance of patient age in Turkish patients with cutaneous melanoma. A total of 1,169 patients with pathologically proven cutaneous melanoma were enrolled. Age of patients was classified as young (<40 years), middle-aged (40-59 years) and old (≥60 years). The median age of the patients was 51 years (range, 16-104 years). Non-superficial spreading histology was significantly more observed in old patients than in the other age groups (P<0.001). A lower Clark invasion level was significantly more observed in young patients compared with the other age groups (P=0.013) and higher levels were significantly more observed in older patients compared with the other age groups (P=0.002). Furthermore, the rate of thin Breslow depth was significantly higher in young patients compared with others (P=0.038). Although a lower mitotic rate was observed predominantly in young patients compared with others (P=0.007), ulceration was significantly more present in older patients (P<0.001) and absent in the young patients (P=0.003). Patient age was not significantly associated with relapse-free survival (P=0.327), whereas a significant correlation was demonstrated for overall survival (OS) (P=0.007). The old patients had poorer survival compared with the other ages (P=0.009 for young patients and P=0.012 for middle-aged patients). However, patient age did not remain significant for OS in multivariate analysis (P=0.768). In conclusion, although patient age does not have a significant predictive role on nodal involvement, recurrence and metastasis, an age of ≥60 years may be associated with more aggressive histological features and poorer outcome in patients with cutaneous melanoma.

Metastatic melanoma patients' sensitivity to ipilimumab cannot be predicted by tumor characteristics.

Background:Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers.Methods:We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Patients in this study were not treated on clinical trials. To investigate the relationship between patient characteristics at the time of diagnosis and survival following melanoma diagnosis we utilized Cox proportional hazards models, accounting for delayed entry into the study cohort. Cox models estimate the age and institution adjusted hazard ratios for risk of death.Results:Of patients (n=385) treated with ipilimumab for stage IV melanoma, 302 met inclusion criteria. The complete response to ipilimumab was 5%, partial response was 13%, 18% had stable disease, 62% had progressive disease, and 5 unknown. The median overall survival rate was 2.03 years [95% confidence interval (CI): 0.13, 3.05]. Primary tumor Breslow depth, lymphovascular invasion, BRAF status, and ulceration did not predict sensitivity to ipilimumab. In this study patient cohort, BRAF mutation (adjusted hazard ratio: 1.43, 95% CI: 0.98, 2.07) and presence of ulceration (adjusted hazard ratio: 1.47, 95% CI: 0.95, 2.26) contributed to an increased risk of death.Conclusions:The presence of ulceration did not correlate with sensitivity to ipilimumab. Ulceration of the primary tumor and a BRAF mutation were moderately associated with worse survival in patients with metastatic melanoma treated with ipilimumab.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. A total of 123 patients with BM were matched by initial presenting stage to 237 patients without BM. The characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020), and Breslow depth more than 4 mm (P=0.048), whereas location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, P=0.007) than nonscalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in the clinical outcomes between patients whose BM were detected upon routine screening versus those detected upon symptomatic presentation. In summary, factors predictive of development of BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type, and ulceration, but not detection setting, were associated with worse clinical outcomes.