Case Report: Acral MYH10::ALK fusion superficial mesenchymal neoplasm: first proof of metastatic potential

Superficial ALK-rearranged soft tissue tumors are rare mesenchymal neoplasms showing heterogenous morphology and clinical behavior. They usually present as slowly enlarging nodules in young adults and can mimic other spindle cell tumors. While some ALK-altered mesenchymal neoplasms can be classified into defined WHO categories (e.g., inflammatory myofibroblastic tumor, epithelioid fibrous histiocytoma, and a few others), the nosology of many tumors has not yet been delineated, and they are currently reported descriptively. A case of a young man with a three-year follow-up is presented, providing prognostic insights into this entity.

A healthy 23-year-old male presented with a purplish mass on the plantar left foot that had enlarged over one year. MRI showed a well-defined lesion without bone involvement. Histopathology revealed sheets of bland round to oval cells within myxohyaline stroma containing focal pseudorosette-like hyalinized nodules and increased mitotic activity. Immunohistochemistry demonstrated strong cytoplasmic ALK expression with heterogeneous expression for CD34, and S100. Focal EMA and pancytokeratin expression were noted. Next-generation sequencing confirmed a MYH10::ALK fusion. After excision with positive margins, re-excision revealed residual tumor as well. Further surgery was declined, and the patient developed metastatic disease during follow-up.

This case broadens the spectrum of acral ALK-rearranged unclassified mesenchymal tumors and identifies MYH10 as a potential fusion partner in metastatic disease. Although these tumors are typically indolent, features such as increased mitotic activity may indicate more aggressive behavior. Diagnosis requires integrated histologic, immunophenotypic, and molecular assessment. This case highlights the metastatic potential of ALK-rearranged unclassified mesenchymal neoplasms, particularly those exhibiting a tyrosine kinase phenotype (co-expression of S100 and CD34), supporting their classification within the intermediate, rarely metastasizing category according to soft tissue tumor stratification principles. It further emphasizes the need for heightened clinical vigilance and thorough surgical management, which may influence long-term outcomes.