Melanoma of unknown primary: a comprehensive review of immune-mediated pathogenesis and therapies

Dec 13, 2025The oncologist

Immune-related causes and treatments of melanoma when the original tumor site is unknown

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Abstract

(MUP) is a rare subtype of melanoma with unique genomic alterations.

  • MUP may result from spontaneous regression of the primary tumor, influenced by immune responses from T cells and natural killer cells.
  • Whole-exome/genome analyses show that MUP shares a UV damage-driven mutational landscape with cutaneous melanoma but has distinct genomic changes.
  • Recurrent mutations have been identified in key genes associated with MUP, including those in the telomerase reverse transcriptase promoter and isocitrate dehydrogenase 1.
  • Current treatments for MUP are similar to those for advanced melanoma, involving surgery and immune checkpoint inhibitors.
  • While immune checkpoint inhibitors have improved survival rates, the effectiveness of targeted therapies for MUP is not yet fully established.

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Key numbers

47% to 56%
5-year survival rate
Survival rates for patients after surgical resection combined with lymph node dissection.
92%
3-year overall survival rate
Survival rates for vs. melanoma with known primary treated with ICIs.
45%-53%
BRAF mutation prevalence
Percentage of cases with BRAF mutations.

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