Pleomorphic Hyalinizing Angiectatic Tumor: Exploring Potential Targeted Therapies and the Limitations of Biopsy

Summary: Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, non-metastasizing mesenchymal neoplasm characterized by ectatic, fibrin-filled vessels surrounded by pleomorphic cells with low mitotic activity. It typically presents as a long-standing, painless subcutaneous mass. We report a 52-year-old woman who presented with a painful and enlarging left calf mass associated with significant weight loss. Initially observed in 2019, the lesion showed progressive growth from 8.6 to 11.3 cm, increased edema, necrosis, and a PET/CT scan suggestive of malignancy. Biopsy revealed spindle cells with pleomorphic nuclei, hemosiderin deposits, and hyalinized vessels. Immunohistochemistry demonstrated vimentin positivity, weak CD99, focal desmin, and negativity for CD34 and S100. The patient was diagnosed with a low-grade undifferentiated soft-tissue sarcoma and underwent neoadjuvant chemo/radiotherapy followed by radical resection. Next-generation sequencing identified mutations of uncertain significance in genes including MAP2K1, NRG1, ALK, XPC, RAD50, ZFHX3, MKI67, ATP7B and BCR, with stable tumor mutational burden. This case emphasizes the importance of chemo/radiotherapy in managing PHAT, demonstrating their effectiveness as both neoadjuvant and post-resection therapies. A comprehensive understanding of PHAT's histopathology, immunohistochemistry, and genetic profile enables dermato/soft-tissue pathologists to achieve accurate diagnoses, minimize unnecessary procedures, and improve patient outcomes.