ArticleJournal of the National Cancer Institute2019
Primary Melanoma Histologic Subtype: Impact on Survival and Response to Therapy.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- A systematic review of microsimulation models for skin cancer.BMC medical informatics and decision making · 2025Pooled it
- Regional Variations in Melanoma Histologic Characteristics: A Multicenter Cohort Study from Two Southeastern European Countries.Journal of clinical medicine · 2026Article
- The impairment of CD3+ T lymphocytes in sentinel lymph node of high-risk cutaneous melanoma patients in stage IIB and IIC.Journal of pathology and translational medicine · 2026Article
- Surgical Management of Stage IV Melanoma: Clinical, Molecular, and Therapeutic Considerations.International journal of molecular sciences · 2026Review
- A Rare Case of Superficial Spreading Melanoma with Prominent Folliculotropism: Dermoscopic and Histological Findings.Dermatology practical & conceptual · 2026Article
- Anatomical site and histological subtype as determinants of Breslow thickness and high-risk features in surgically managed cutaneous melanoma at Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.Frontiers in surgery · 2026Article
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- Article
- P16-CD8-Ki67 Triple Algorithm for Prediction of CDKN2A Mutations in Patients with Multiple Primary and Familial Melanoma.Diagnostics (Basel, Switzerland) · 2024Article
- Primary Cutaneous Melanoma-Management in 2024.Journal of clinical medicine · 2024Article
- High charge of cerebroid nests in nodular melanomas predicts tumor aggressiveness and high mutational tumoral burden: a pilot study.Frontiers in oncology · 2024Article
- The effects of the COVID-19 pandemic on the diagnosis and prognosis of melanoma 2 years after the pandemic in two Romanian counties.Frontiers in medicine · 2024Article
- CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status.Medicina (Kaunas, Lithuania) · 2023Article
- Temporal Recurrence of Cutaneous Melanoma: Analysis of a Case Series.The Journal of clinical and aesthetic dermatology · 2023Article
- Pathology and Molecular Biology of Melanoma.Current issues in molecular biology · 2023Review
- Kissing atypical melanocytic nevus of genital type of the labia majora in a young Bulgarian patient. What's the best approach?Dermatology reports · 2023Article
- Bioinformatic analyses reveal the prognostic significance and potential role of ankyrin 3 (ANK3) in kidney renal clear cell carcinoma.Genomics & informatics · 2023Article
- Incidence ofMelanoma management · 2023Article
- Comprehensive Analysis of Necroptosis Landscape in Skin Cutaneous Melanoma for Appealing its Implications in Prognosis Estimation and Microenvironment Status.Journal of personalized medicine · 2023Article
- Analysis and prediction of 5-year survival in patients with cutaneous melanoma: a model-based period analysis.Frontiers in endocrinology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTwo primary histologic subtypes, superficial spreading melanoma (SSM) and nodular melanoma (NM), comprise the majority of all cutaneous melanomas. NM is associated with worse outcomes, which have been attributed to increased thickness at presentation, and it is widely expected that NM and SSM would exhibit similar behavior once metastasized. Herein, we tested the hypothesis that primary histologic subtype is an independent predictor of survival and may impact response to treatment in the metastatic setting.
methodsWe examined the most recent Surveillance, Epidemiology, and End Results (SEER) cohort (n = 118 508) and the New York University (NYU) cohort (n = 1621) with available protocol-driven follow-up. Outcomes specified by primary histology were studied in both the primary and metastatic settings with respect to BRAF-targeted therapy and immunotherapy. We characterized known driver mutations and examined a 140-gene panel in a subset of NM and SSM cases using next-generation sequencing. All statistical tests were two-sided.
resultsNM was an independent risk factor for death in both the SEER (hazard ratio [HR] = 1.55, 95% confidence interval [CI] = 1.41 to 1.70, P < .001) and NYU (HR = 1.47, 95% CI = 1.05, 2.07, P = .03) cohorts, controlling for thickness, ulceration, stage, and other variables. In the metastatic setting, NM remained an independent risk factor for death upon treatment with BRAF-targeted therapy (HR = 3.33, 95% CI = 1.06 to 10.47, P = .04) but showed no statistically significant difference with immune checkpoint inhibition. NM was associated with a higher rate of NRAS mutation (P < .001), and high-throughput sequencing revealed NM-specific genomic alterations in NOTCH4, ANK3, and ZNF560, which were independently validated.
conclusionsOur data reveal distinct clinical and biological differences between NM and SSM that support revisiting the prognostic and predictive impact of primary histology subtype in the management of cutaneous melanoma.
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