Superficial Spreading Research Articles

Standardized Computer-Assisted Analysis of PRAME Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas.

PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen that is frequently expressed in melanoma compared to benign melanocytic proliferations and nevi. However, the interpretation of the intensity and distribution of PRAME immunostaining is not standardized a lot, which makes interpretation difficult. PRAME-stained histological slides of superficial spreading melanomas (SSM) and dysplastic nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. t-tests and ROC AUCs were performed with SPSS. A p-value of <0.05 was used for statistical significance, and a ROC AUC score of >0.8 was considered a good result. A cut-off score was defined in an evaluation cohort and subsequently analyzed in an independent validation cohort. In total, 81 PRAME-stained specimens were included. The evaluation cohort included 32 (50%) SSM and 32 (50%) DN, and the mean of PRAME-positive cells/mm2 for the entire lesion was 455.3 (SD 428.2) in SSM and 60.5 (SD 130.1; p < 0.001) in DN. The ROC AUC of PRAME-positive cells of the entire lesion was 0.866, and in the epidermis it was 0.901. The defined cut-off score to distinguish between DN and SSM was 97.67 cells/mm2. In the validation cohort, 16 out of 17 cases (94.1%) were correctly classified by the cut-off score. The computer-aided assessment of PRAME immunostaining is a useful tool in dermatopathology to distinguish between DN and SSM. Lesions with a moderate expression and indifferent morphologic features will remain a challenge for dermatopathologists.

MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma

Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21-90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient's cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype (p = 0.005) and any melanoma with a high mitotic rate (p = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma.

PD-L1 Tumor Expression as a Predictive Biomarker of Immune Checkpoint Inhibitors' Response and Survival in Advanced Melanoma Patients in Brazil.

Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort of patients. This study assessed clinical and molecular predictors of ICB response and survival in advanced melanoma. A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression was assessed by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues collected prior to ICB therapy. Patients were divided into responders (complete and partial response and stable disease for more than 6 months) and non-responders (stable disease for less than 6 months and progressive disease). Among them, about 82% underwent anti-PD-1 immunotherapy, and 60.5% progressed after the ICB treatment. Patients that received ICB as first-line therapy showed higher response rates than previously treated patients. Higher response rates were further associated with superficial spreading melanomas and positive PD-L1 expression (>1%). Likewise, PD-L1 positive expression and BRAF V600 mutations were associated with a higher overall survival after ICB therapy. Since ICBs are expensive therapies, evaluation of PD-L1 tumor expression in melanoma patients should be routinely assessed to select patients that are most likely to respond.

Incidence of BRAF mutations in cutaneous melanoma: histopathological and molecular analysis of aUkrainian population.

This study aimed to investigate the incidence of BRAF mutation in cutaneous melanoma in the Ukrainian population with respect to clinical and histopathological data. This single-center retrospective cohort study enrolled 299 primary CM with known BRAF status assessed by RT-PCR. The overall BRAF mutation rate was 56.5% in CM and demonstrated a link with the younger age (p<0.001), anatomical site (p<0.001) and histological type of CM (p=0.022). BRAF-positive CM possessed a slightly higher mitotic rate (p=0.015) and Breslow thickness (p=0.028) but did not relate to tumor-infiltrating lymphocytes. The high rate of BRAF mutations in CM patients in the Ukrainian cohort was associated with superficial spreading histology, higher depth of invasion and proliferation.

Melanoma and Nevi Subtype Histopathological Characterization with Optical Coherence Tomography.

Melanoma incidence has continued to rise in the latest decades, and the forecast is not optimistic. Non-invasive diagnostic imaging techniques such as optical coherence tomography (OCT) are largely studied; however, there is still no agreement on its use for the diagnosis of melanoma. For dermatologists, the differentiation of non-invasive (junctional nevus, compound nevus, intradermal nevus, and melanoma in-situ) versus invasive (superficial spreading melanoma and nodular melanoma) lesions is the key issue in their daily routine. This work performs a comparative analysis of OCT images using haematoxylin-eosin (HE) and anatomopathological features identified by a pathologist. Then, optical and textural properties are extracted from OCT images with the aim to identify subtle features that could potentially maximize the usefulness of the imaging technique in the identification of the lesion's potential invasiveness. Preliminary features reveal differences discriminating melanoma in-situ from superficial spreading melanoma and also between melanoma and nevus subtypes that pose a promising baseline for further research. Answering the final goal of diagnosing non-invasive versus invasive lesions with OCT does not seem feasible in the short term, but the obtained results demonstrate a step forward to achieve this.

The rise in thick melanomas: can early detection reduce the burden?

We sought to describe trends in the incidence of invasive melanoma by histological subtype and thickness in two populations with different approaches to the early detection of melanoma (the US White population and Queensland, Australia). The incidence of thick melanoma (&amp;gt; 4.00 mm) increased over the period 1999–2018 at a faster rate than thinner melanomas in both populations, and the increase was driven primarily by increases in melanoma of the nodular subtype. Thin melanomas (&amp;lt; 1.00 mm) were overwhelmingly of the superficial spreading subtype, whereas thick melanomas (&amp;gt; 4.00 mm) were dominated by nodular melanomas.

Prognostic Factors and Outcomes of Cutaneous Malignant Melanoma: A 174-Patient Cohort Study in a Tertiary Hospital in Thailand.

Malignant melanoma is a common skin cancer among Asians. However, some features, such as tumor type and initial stages, are not comparable with those found in Western countries. We audited a large cohort of patients at a single tertiary referral hospital in Thailand to identify factors affecting the prognosis. A retrospective study was conducted of patients diagnosed with cutaneous malignant melanoma between 2005 and 2019. Details of demographic data, clinical characteristics, pathological reports, treatments, and outcomes were collected. Statistical analyses of overall survival and factors affecting survival were investigated. The study enrolled 174 patients (79 men and 95 women) with pathologically confirmed cutaneous malignant melanoma. Their mean age was 63 years. The most common clinical presentation was a pigmented lesion (40.8%), with the plantar area being the most common site (25.9%). The mean duration of onset and hospitalization was 17.5 months. The 3 most common types of melanoma were acral lentiginous (50.7%), nodular (28.9%), and superficial spreading (9.9%). Eighty-eight cases (50.6%) had concomitant ulceration. Pathological stage III was the most common (42.1%). The 5-year overall survival was 43%, and the median survival time was 3.91 years. Multivariate analysis showed that clinically palpable lymph nodes, distant metastasis, a Breslow thickness ≥ 2 mm, and evidence of lymphovascular invasion were poor prognostic factors for overall survival. In our study, most patients with cutaneous melanoma presented with a higher pathological stage. Independent factors affecting survival are palpable lymph nodes, distant metastases, Breslow thickness, and the presence of lymphovascular invasion. The overall 5-year survival rate was 43%.

Melanoma diagnosis at a specialist dermatology practice without the use of photographic surveillance.

Photographic aides are increasingly used in melanoma surveillance. We report melanoma characteristics detected using traditional surveillance without photographic technologies. Retrospective study of melanomas diagnosed by three dermatologists at a private dermatology practice over 7 years. Patients underwent full skin examinations with dermoscopy and suspect lesions were excised or biopsied. Total body photography (TBP) and serial digital dermoscopic imaging (SDDI) were not used. Patient demographics, melanoma subtype and thickness, location, biopsy technique and keratinocyte cancers diagnosed at the same visit were recorded. Ratio of in situ to invasive melanomas was calculated. Melanoma risk factors were recorded for 69 randomly-selected patients. 492 patients were diagnosed with 615 melanomas during 579 visits. 505 (82%) were in situ (in situ to invasive ratio of 4.6:1). Of the invasive melanomas, 85.5% had a Breslow thickness <0.8 mm, 10 (9.1%) 0.8-1 mm and 6 (5.5%) >1 mm. 43.3% of in situ melanomas were lentiginous or lentigo maligna and 41.6% were superficial spreading melanomas (SSM). Of invasive melanomas, 24.3% were lentigo maligna melanoma and 59.5% were SSM. 48.4% of melanomas were diagnosed by shave procedures. Where risk factors were known, 25% were very-high-risk and 43% had a history of melanoma. Keratinocyte carcinoma was diagnosed by biopsy at 26.1% of visits. Studies using TBP and/or SDDI report in situ to invasive ratios of 0.59:1 to 2.17:1. Tradiational melanoma surveillance with immediate biopsy of suspect lesions results in high in situ to invasive ratios. Studies using photographic surveillance show lower ratios of in situ to invasive disease.

BRAFV600E Expression Is Homogenous and Associated with Nonrecurrent Disease and Better Survival in Primary Melanoma

Background: Superficial spreading melanomas (SSMs) are the most common type of melanoma and cause the majority of skin cancer deaths. More than 50% of cases harbor a mutation in the BRAF gene that activates the mitogen-activated protein kinase (MAPK) cancer signaling pathway. BRAF^V600E is the most common BRAF mutation, and it represents an important biomarker that guides treatment selection. However, the relationship between the BRAF^V600E gene expression and intratumoral protein distribution, on one side, and clinicopathological factors and patient outcomes, on the other, is not fully described. Additionally, whether MAPK cancer signaling activation in melanoma is due to increased biochemical activity of BRAF^V600E, increased mRNA levels, or both requires further investigation. Here, we addressed these questions by examining expression patterns of BRAF^V600E in primary treatment-naive melanomas and correlating them to clinicopathological factors and patient outcomes. Methods: In 166 SSM cases, we performed immunohistochemical staining to investigate the protein expression of BRAF^V600E, and we measured BRAF mRNA levels using NanoString nCounter system. Results: Ninety-seven (49%) melanomas stained positive for BRAF^V600E, with nearly 100% intratumoral homogeneity observed. Positive BRAF^V600E expression was significantly associated with nonrecurrent disease and was found to be an independent predictor of better prognosis in univariate and multivariable analyses. Furthermore, presence of tumor-infiltrating lymphocytes, sentinel lymph node biopsy negativity, and low Breslow thickness were all independent predictors of better prognosis. We observed no difference in the BRAF mRNA levels in BRAF^V600E-negative and BRAF^V600E-positive melanomas, respectively. Validation in a larger publicly available cohort confirmed that there is only a weak correlation (Spearman 0.4) between BRAF^V600E mRNA and protein levels and no differences in mRNA between BRAF^V600E mutated and non-mutated patients. Conclusion: Our findings indicated that BRAF^V600E is homogeneously present throughout the whole tumor and is associated with nonrecurrent disease and better survival in primary melanoma. We also showed that BRAF^V600E mutation does not result in higher transcriptional levels, suggesting that activation of the MAPK signaling pathway in BRAF^V600E mutated patients can be attributed to the increased biochemical activity caused by the mutation.

Histopathological Overview of Experimental Ulcer Models.

Histopathology is the process of examining tissue that includes all the changes, when a diseased tissue shows compared to a healthy group with a result of a histological observation. Histopathology has become an essential process in medical experimental research and medical experimental models. Scientists have developed medical experimental animal models for these reasons and have pioneered new drug research for many years. One of these experimental researches is experimental ulcer models. This model, which was initially a single method, has led to the emergence of new models with the discovery of physiological processes on ulcers by scientists. Nowadays, researchers have performed many new peptic ulcer models on experimental animals over the years. The main point in the creation of the ulcer model is the increase in the stomach acid level and the removal or corruption of the gastric mucus. When the experimental models were examined histopathologically, it was seen that the most severe models were those induced by pyloric ligation, acetic acid application, and indomethacin. In these models, ulcer foci that progressed to the submucosa were common, while the superficial damage spreading to the entire surface was striking in the ethanol model. While epithelial losses are shown on the surface of the mucosa, foci of necrotic apoptotic cell clusters extending to the submucosa are shown according to the weight of the model. In addition, evidence of inflammation has been shared in almost all studies. All these results show that ulcer models can be created by many different mechanisms. However, similar findings were observed in almost all experiments. Whether the experimental model caused severe or mild ulceration changed the histological findings.

Coincidence of primary adrenocortical carcinoma and melanoma: three CASE reports

BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous prognosis, while adrenal metastasis from other primary cancers, including melanoma, may occur more frequently. ACC may rarely occur as part of familial cancer syndromes, but even in sporadic cases, a significant proportion of patients had other malignancies before or after diagnosis of ACC. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma.Case descriptionPatient 1 - A 37-yr-old man with a superficial spreading BRAF-positive melanoma was found to harbour a progressively growing left adrenal mass. Initially, he was suspected of having adrenal metastasis, but the histology after adrenalectomy confirmed ACC. Patient 2 - A 68-year-old man with a history of recurrent BRAF-positive melanoma was diagnosed with disseminated metastatic melanoma recurrence, including a rapidly enlarging left adrenal mass. Consequently, he underwent left adrenalectomy, and histology again confirmed ACC. Patient 3 – A 50-yr-old man was referred with histological diagnosis of metastatic ACC. He had a background history of pT1 melanoma.We undertook targeted sequencing of ACC tissue samples in all cases. Somatic variants were observed in the known driver genes CTNNB1 (Patient 1), APC and KMT2D (Patient 2), and APC and TP53 (Patient 3). Germline TP53 variants (Li-Fraumeni syndrome) were excluded in all cases.Retrospective review of our patient cohort in the last 21 years revealed a frequency of 0.5% of histologically diagnosed melanoma metastasis among patients referred for adrenal masses. On the other hand, 1.6% of patients with histologically confirmed ACC had a previous history of melanoma.ConclusionSporadic ACC can occur in the background of melanoma, even if adrenal metastasis might appear to be the most likely diagnosis. Coexistent primary adrenal malignancy should be considered and investigated for in all patients with a history of melanoma with suspicious adrenal lesions.

Abstract C075: Increasing incidence of cutaneous malignant melanoma in the Hispanic population of the United States from 2006-2017

Abstract Melanoma is the fifth most commonly diagnosed cancer in the United States (US), and its incidence has been rapidly increasing within the past several decades. Previous studies have shown that individuals with darker skin tones are less likely to survive melanoma than those with lighter skin tones. Despite this increased morbidity in skin of color populations, limited studies have investigated how melanoma affects different races and ethnicities. Herein, we conducted a population-based registry study to assess the incidence and survival pattern of cutaneous malignant melanoma (CMM) subtypes in the US from 2006 to 2017. In addition, we examined the four major histological CMM subtypes (superficial spreading, lentigo maligna, nodular, and acral lentiginous melanoma) and its distribution by race, gender, and tumor grade. Data from 17 population-based cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed, and 58,666 histologically confirmed cases of CMM were evaluated. Acral lentiginous melanoma was diagnosed predominantly in non-Hispanic whites (56%) and Hispanic whites (45%). Melanomas that were not of the four major histological CMM subtypes were predominant in the Asian (54%) and Black (77%) populations. Superficial spreading and lentigo maligna melanomas presented more commonly in males (69% and 63%, respectively). Nodular and lentigo maligna melanomas had the poorest survival rates (median of 26 and 21 months, respectively). The incidence rate of CMM has been steadily increasing in the Hispanic population, with Hispanic whites having the highest incidence of acral lentiginous melanoma when compared to other skin of color populations. Thus, it is important we continue to assess and trend the epidemiological characteristics of CMM subtypes. In addition, future studies should investigate the possible genetic and environmental factors that may be contributing to the increased incidence of CMM in skin of color populations and its associated morbidity. Citation Format: Yae L. Kye, Cicilyn Xie, Hannah Riva, Michelle Samaniego, Fabiola Ramirez, Lorena Fernandez, Luis Alvarado, Alok Dwivedi, Jessica Chacon. Increasing incidence of cutaneous malignant melanoma in the Hispanic population of the United States from 2006-2017 [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C075.

Clinicopathologic Evaluation of CD80, CD86, and PD-L1 Expressions with Immunohistochemical Methods in Malignant Melanoma Patients.

Diagnostic and prognostic biomarkers for malignant melanoma are crucial for treatment and for developing targeted therapies. Malignant melanoma is a highly immunogenic tumor, and its regression, treatment, and prognostic evaluation are directly related to escape from immune destruction. Therefore, we aimed to determine the expression levels of CD80, CD86, and PD -L1 in malignant melanoma tissue samples by immunohistochemistry and to investigate the possible relationship between these proteins and the clinicopathological features in this study. Hematoxylin and eosin staining and immunohistochemical staining for CD80, CD86, and PD-L1 were evaluated for clinical data, survival, prognosis, tumor location, malignant melanoma subtypes, tumor size, and prognostic findings. Higher survival rates were observed in patients with lower PD-L1 staining scores in the tumor. The 5-year survival was higher in patients with CD80-positive and CD86-positive biopsies. Mortality was lower in superficial spreading melanoma and Lentigo maligna melanoma types, whereas staining positivity of CD80 and CD86 was higher. Furthermore, a relationship between clinical stage and Breslow thickness ( < 2mm/≥2mm), tumor ulceration, lymph node metastasis, and CD80 and CD86 expression was also identified. Our findings suggest that PD-L1, CD80, and CD86 expression are essential in malignant melanoma and could be used as prognostic markers.

Prognostic model for predicting overall and cancer-specific survival among patients with superficial spreading melanoma: A SEER based study

Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology and results database of the National Cancer Institute and randomly divided into a training cohort (8353 cases) and a validation cohort (5569 cases). Univariate and multivariate Cox regression analysis were used to determine prognostic factors, and these factors were used to construct OS and CSS nomograms for patients with SSM. Finally, the discrimination and consistency of the nomogram model were evaluated by the consistency index (C-index), area under the curve (AUC) and calibration curve. Multivariate Cox regression analysis suggested that age, sex, tumor site, the American joint committee on cancer T stage and the first primary melanoma were independent predictors of OS and CSS in patients with SSM and that the American joint committee on cancer N stage was also an independent predictor of CSS in patients with SSM. Based on the above prognostic factors, this study constructed a predictive model. The C-index of the model OS and CSS for this training cohort was 0.805 [95% CI: 0.793-0.817] and 0.896 [95% CI: 0.878-0.913], respectively. The AUC values for 1-, 3-, and 5-year OS were 0.822, 0.820, and 0.821, respectively, and the AUC values for CSS were 0.914, 0.922, and 0.893, respectively. The data indicated that both nomograms showed better predictive accuracy. The calibration curves of the training cohort and the validation cohort were in good agreement. The nomogram has superior predictive performance in predicting 1-, 3-, and 5-year OS and CSS prognosis in patients with SSM and can provide a reference for individualized treatment and clinical counseling of SSM.

Trends in three major histological subtypes of cutaneous melanoma in the Netherlands between 1989 and 2016.

Time trend analysis of cutaneous melanoma (CM) mortality in fair skin populations shows both a gradual decrease and/or an increase. To explain these differences, we analyzed long-term time trends in the incidence of the most common histological subtypes of CM: superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM), and nodular melanoma (NM). Using data from the Netherlands Cancer Registry and Statistics Netherlands, the number and rates of cases diagnosed with SSM, LLM, and NM from 1989 to 2016 were analyzed by age, calendar period, and birth cohort of people born in successive periods from 1925 to 1973. Primary CM was diagnosed in 52,000 men and 66,588 women in the study period. The annual age-standardized incidence rate increased three-fold from 14 to 42 per 100,000 person-years. The most common subtype was SSM (50%), followed by LMM (23%) and NM (14%). Age-specific subtype rates showed an upward trend over time for both men and women. Younger birth cohorts had higher rates of SSM and LMM diagnosis than older birth cohorts. This birth cohort pattern was not observed for NM. We observed a strong increase in the melanoma epidemic curves in the light-skinned Dutch population over the last three decades. This increase is explained by younger generations having higher rates of SSM and LMM than older generations.

Deep Margins Melanoma: How Deep Is Deep Enough?

Wide excision (WE) to muscular fascia for invasive melanoma is common practice but excision to subcutaneous tissue may be adequate. We evaluated practice patterns regarding depth of biopsy and excision as well as risks for recurrence. Retrospective review of patients with pT1-4 melanoma (cN0) treated with WE at a single institution was performed. Patient factors were evaluated. Biopsy and excision techniques were compared to pathology and reviewed for recurrence. 385 patients from 2006 to 2020 were included. Lesions were on the extremity (n = 189), head/neck (n = 48), trunk (n = 148). Biopsy techniques included shave (n = 330), excisional (n = 36), punch (n = 10), incisional (n = 9). Deep biopsy margins were positive for IM/melanoma in situ in 139 patients. WE specimens were taken to muscular fascia (n = 218) or mid/deep fat (n = 144). 51 patients had recurrent disease or a new primary lesion: locoregional (n = 31), distant (3), or new lesions (n = 17). Patient characteristics associated with recurrence include older age and female gender. Tumor characteristics associated with recurrence include lesions located on the trunk, superficial spreading melanoma, ulceration, perineural invasion, and clinical T and P stage. Patients that recurred were more likely to have WE taken to or including muscular fascia. Biopsy type, deep margin on biopsy, and depth of dissection was not associated with recurrence.

Melanomas in children and adolescents: Clinicopathologic features and survival outcomes

Melanoma in the first two decades of life is uncommon and poorly understood. To assess clinicopathologic features and survival of children (≤11 years) and adolescents (12-19years) diagnosed with melanoma. A pooled cohort of 514 patients was analyzed (397 Dutch, 117 Australian; 62 children, 452 adolescents). Pathology reports were re-evaluated to determine melanoma subtypes. Multivariable Cox models were generated for recurrence-free survival (RFS) and overall survival (OS). Melanoma subtypes were conventional melanoma (superficial spreading, nodular, desmoplastic, acral lentiginous), spitzoid melanoma, and melanoma associated with a congenital nevus in 428, 78, and 8 patients, respectively. Ten-year RFS was 91.5% (95%CI 82.4-100%) in children and 86.4% (95%CI 82.7-90.3%) in adolescents (p=0.32). Ten-year OS was 100% in children and 92.7% (95%CI 89.8-95.8%) in adolescents (p=0.09). On multivariable analysis possible only for the adolescent cohort due to the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status and melanoma subtype were not. Breslow thickness >4mm was associated with worse RFS. Retrospective study. Survival rates for children and adolescents with melanomas were high. Ulceration, head or neck location and Breslow thickness >4mm predicted worse survival in adolescents.

Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry.

Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7-4.2) compared with SSM patients at 3.1 years (CI 95% 1.3-6.2) (p &lt; 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85-1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81-1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis.

Melanoma of the Upper Limb and Shoulder: A Surveillance, Epidemiology, and End Results Analysis of Epidemiology and Survival 2000-2019.

(1) Background: Melanoma is the most common life-threatening cancer among skin cancers. Almost all locations of the skin can be affected by melanoma, and the upper limbs are one of the most frequent locations. We aimed to study the epidemiology and survival outcomes of patients with melanoma localized in the upper extremities compared with other sites. (2) Methods: The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database is considered the most representative of the U.S. population; we extracted melanoma cases diagnosed between 2000 and 2019. Several characteristics, including demographical, pathological, and therapeutic, were recorded, and upper extremity melanomas and melanomas from other areas were compared. Overall survival was assessed, and the groups were compared. (3) Results: 69,436 patients had melanoma in the upper limbs and shoulders and 204,794 in other body parts. Overall, 35,267 patients with upper extremity melanoma were males, 34,169 were females, and the mean age was 60. For the rest of the body, there were 118,654 males and 86,140 females, with a mean age of 59. Surgery alone was the most commonly used treatment, while radiation therapy was the least used for all sites. Women appear to have better survival than men. Superficial spreading melanoma is the least lethal subtype, while nodular melanoma is the most dangerous. (4) Conclusion: Women under 50 are more at risk than men of the same age. The trend reverses after age 50 where men are at greater risk. In addition to gender and age, disease stage and major histologic subtypes influence survival.

Prognostic significance of age on superficial spreading melanoma after resection: lessons from SEER database involving 12 536 patients.

This study sought to analyse the impact of elderly age on long-term prognosis of superficial spreading melanoma (SSM) after surgery. A population-based cohort of patients undergoing resection for SSM from 2004 to 2015 was collected, using data from National Cancer Institute' Surveillance, Epidemiology, and End Results (SEER)* Stat software. Patients were divided into the non-elderly group (≤70 years) and elderly group (>70 years). Baseline characteristics and long-term survivals were compared between the two groups. A 1:1 propensity score matching (PSM) was used to reduce the risk of bias. The impact of the elderly age on overall survival (OS) and cause-specific mortality (CSM) was estimated by Cox-regression and competing-risk regression models. Among 12 536 patients with SSM after resection included into the cohort, 8664 patients were ≤70 years, and 3872 were >70 years. Patients in the elderly group had higher incidences of multiple tumours, worse tumour stage and infiltration degree, lymphatic metastasis, and larger size of primary lesions. Using PSM, 3581 pairs of patients were created. On matched analysis, the elderly group was associated with worse OS and CSM. On multivariable Cox-regression and competing-risk regression analyses, elderly age was identified as an independent risk factor of OS and CSM after adjusting for other prognostic variables. The elderly age of patients was independently associated with worse OS and CSM after resection of SSM when baseline and tumour characteristics were balanced. Adjuvant therapy and individualized strategy on follow-up should be made for elderly patients after resection of SSM.