ABSTRACT
Background: The recent addition of immunotherapy as a treatment modality to surgery and radiation has vastly improved disease control for patients with keratinocyte-derived carcinomas (KCs) that are incurable with local therapies alone. With the advent of immune checkpoint inhibitors (ICPis) in non-melanoma skin cancers comes diagnostic and therapeutic challenges when considering treatment strategies for patients presenting with clinical perineural invasion (cPNI) of locally advanced KC of the head and neck. Objectives: We report four cases that convey the diagnostic and therapeutic complexity of managing patients with neuropathic symptoms from cutaneous neurotropic carcinomas of the head and neck. We also discuss an updated review regarding immunotherapies and perineural invasion within KC management. Conclusion: Patients presenting with symptoms suspicious for cPNI warrant an expanded diagnostic evaluation to correlate neurological findings with neurotropic spread of disease. While nerve biopsies can be precarious in sensitive areas, a history of skin cancer and clinical presentation suggestive of neurotropism may be enough to pursue timely management in the form of surgery, radiation, and/or systemic therapy given each patient's individual priorities, comorbidities, and prognosis. When adding ICPi as a treatment modality for patients with disease not amenable to local therapies, the potential for immune-related adverse events must be considered. A multi-disciplinary review and approach to the management of patients with KC and cPNI is essential for obtaining optimal patient outcomes.
ABSTRACT
BACKGROUND: Trichilemmal (pilar) cysts are common skin lesions that usually occur on the scalp of elderly women. They differentiate towards the follicular outer root sheath epithelium and show trichilemmal keratinization. Proliferating trichilemmal tumor (PTT) shows features of typical pilar cyst, but additionally shows extensive epithelial proliferation, variable cytologic atypia and mitotic activity. The malignant potential of PTT is controversial, as only a small number of histologically malignant PTTs and a smaller number of clinically malignant PTTs have been reported. METHODS: We retrieved from our archives five PTTs that deviated from ordinary PTTs with regards to either cytology or architecture. We also reviewed all previous reports of histologically malignant PTTs, with the goal of delineating criteria for the diagnosis of malignant PTTs. RESULTS: Five cases of PTT showing atypical cytoarchitectural features were retrieved from our archives and reviewed with respect to size, growth pattern, cellularity, cytologic atypia, and mitotic activity. The patients (four female, one male) ranged from 54 to 83 (mean 65) years. The tumors measured from 1 to 16 cm in diameter (mean 5 cm) and four out of five occurred on the scalp. All tumors showed at least focal areas of typical PTTs. Three cases were circumscribed but had areas of moderate to focally marked cytologic atypia. Two cases showed infiltrative growth, marked cytologic atypia and mitotic activity. Clinical follow-up was available for four of five cases and ranged from 6 to 84 (median 48) months. Follow-up showed two cases with local recurrence and one case with distant metastasis. This last patient died of disease; all other patients are disease-free. CONCLUSIONS: Review of our cases and the published literature suggests that the diagnosis of malignant PTT be given to PTT showing a combination of non-scalp location, recent rapid growth, size greater than 5 cm, infiltrative growth, and significant cytologic atypia with mitotic activity. At the present time the stratification of malignant PTT into low- and high-grade categories is not possible.
