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Objective <p>Melanotic schwannoma (MS) is a rare peripheral nerve sheath tumor accompanied by melanin deposition and severe refractory pain. However, its molecular pathogenesis remains unclear. This study aimed to explore the histomorphological, transcriptomic, and proteomic characteristics of MS, and to identify key molecules related to melanin production, pain generation, and targeted therapy.</p> Methods <p>Histomorphological characteristics of MS were observed by Luxol Fast Blue (LFB) staining and hematoxylin and eosin (HE) staining in tumor tissues from 3 MS patients. Combined transcriptomic and proteomic analyses were performed to screen differentially expressed genes and proteins. The expression levels of tyrosinase-related protein 1 (TYRP1), transient receptor potential ankyrin 1 (TRPA1), and Bruton’s tyrosine kinase (BTK) were validated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence staining.</p> Results <p>Histomorphological examination revealed typical melanin deposition and prominent compression of adjacent nerve fibers in MS. Transcriptomic and proteomic analyses showed activation of the melanin synthesis pathway and transient receptor potential (TRP) channel-related neuroinflammatory pathway. The expression of TYRP1 and TRPA1 was significantly upregulated, suggesting that these related pathways are associated with melanin production and neuropathic pain in MS. In addition, the expression of BTK, a known molecular target of targeted drugs, was significantly increased, suggesting that BTK inhibitors have potential therapeutic effects on MS.</p> Conclusion <p>This study delineates the histomorphological features, transcriptomic and proteomic profiles of MS. TYRP1, TRPA1, and BTK are identified as key molecules involved in melanogenesis, pain generation, and targeted therapy, respectively. These findings provide novel insights into the pathogenesis and potential therapeutic strategies for MS.</p>

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Decoding the Histomorphological and Multi-Omic Characteristics of Melanotic Schwannoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Yi Jiang,
  • Rui Zhao,
  • Hang Xian,
  • Lin Shi,
  • Jin-kang Zhang,
  • Song-lin Li,
  • Ye Peng,
  • Jun-jie Du,
  • Rui Cong,
  • Han Wang

摘要

Objective

Melanotic schwannoma (MS) is a rare peripheral nerve sheath tumor accompanied by melanin deposition and severe refractory pain. However, its molecular pathogenesis remains unclear. This study aimed to explore the histomorphological, transcriptomic, and proteomic characteristics of MS, and to identify key molecules related to melanin production, pain generation, and targeted therapy.

Methods

Histomorphological characteristics of MS were observed by Luxol Fast Blue (LFB) staining and hematoxylin and eosin (HE) staining in tumor tissues from 3 MS patients. Combined transcriptomic and proteomic analyses were performed to screen differentially expressed genes and proteins. The expression levels of tyrosinase-related protein 1 (TYRP1), transient receptor potential ankyrin 1 (TRPA1), and Bruton’s tyrosine kinase (BTK) were validated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence staining.

Results

Histomorphological examination revealed typical melanin deposition and prominent compression of adjacent nerve fibers in MS. Transcriptomic and proteomic analyses showed activation of the melanin synthesis pathway and transient receptor potential (TRP) channel-related neuroinflammatory pathway. The expression of TYRP1 and TRPA1 was significantly upregulated, suggesting that these related pathways are associated with melanin production and neuropathic pain in MS. In addition, the expression of BTK, a known molecular target of targeted drugs, was significantly increased, suggesting that BTK inhibitors have potential therapeutic effects on MS.

Conclusion

This study delineates the histomorphological features, transcriptomic and proteomic profiles of MS. TYRP1, TRPA1, and BTK are identified as key molecules involved in melanogenesis, pain generation, and targeted therapy, respectively. These findings provide novel insights into the pathogenesis and potential therapeutic strategies for MS.