Abstract
Objective: Proliferating trichilemmal tumors (PTT) are rare skin neoplasms arising from the hair root sheath. Although benign, PTT can be recurrent and locally destructive, rarely undergoing malignant transformation into malignant PTT (MPTT), with potential for distant metastases. Current treatments for MPTT are largely anecdotal and poorly validated.
Method: We report a patient who presented with multiple recurrences and distal metastases of MPTT. SNaPShot analysis utilizing multiple PCR was performed on both mediastinal nodes and MPTT neck mass in order to detect cancer-related mutations. Cell culture and biochemical assays were performed to correlate with clinical response to targeted therapy.
Results: A PIK3CA activating mutation (H1047R) was found in a distant metastasis and local MPTT tissue. Specific activating PIK3CA mutations have been found in many human epithelial tumors, including head and neck squamous cell carcinoma and lung cancer. The reported patient enrolled in a Phase IA trial using BYL719, a selective PI3Kα tyrosine kinase inhibitor. Primary cells derived from the patient tumor were very sensitive to multiple agents targeting the PI3K pathway (eg, PI3K, PI3K/mTOR, and AKT). Five additional patients with PTT from our institution had SNaPShot performed on formalin-fixed, paraffin-embedded tissue.
Conclusion: There are no suggested treatment guidelines for patients with rare tumors like MPTT. They receive a variety of chemotherapeutic agents based on limited clinical data. We suggest that rare tumors be screened for common oncogenic mutations. This will allow clinicians to personalize medical treatment based on identified dysregulated molecular pathways.
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