Neurotropic Cutaneous Malignancies: Case Report on Keratinocyte Derived Malignancies of the Head and Neck With Perineural Invasion

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.

Keywords: basal cell carcinoma; cutaneous oncology; cutaneous squamous cell carcinoma; immune checkpoint inhibitors; immunotherapy; neurotropic cutaneous malignancies; non-melanoma skin cancer; perineural invasion.

Figure 1

Case 1: a 74-year-old man with squamous cell carcinoma. (A) Coronal fat-suppressed contrast-enhanced T1-weighted image shows a thickening, abnormally enhancing right C4 nerve (arrow). (B) Axial fat-suppressed contrast-enhanced T1-weighted image shows thickening and abnormal enhancement of the right C3 nerve, from the dorsal root ganglion through its course through the posterior cervical space (arrows).

Figure 2

Case 2: a 50-year-old woman with basosquamous carcinoma. (A) Coronal fat-suppressed contrast-enhanced T1-weighted image shows asymmetric enhancement along the superior orbit (arrow), adjacent to the superior rectus muscle. (B) Pre-operative forehead recurrence. (C) Intra-operative dissection of the distal sensitive branches of the forehead sensory nerves. (D) Defect of the forehead after resection of the recurrence with 2 cm margins. (E) Pathological sample. Red arrows showing the tagged distal sensory branches. 1 = right supraorbital nerve; 2 = right supratrochlear nerve; 3 = left supraorbital nerve dissected until its entrance in the superior orbital fissure. The left supratrochlear nerve is missing and was dissected separately as interrupted by a pre-operative biopsy. (F) Pre - and 14-month post-operative clinical photos. Post-operative proton radiotherapy spared the reconstructed forehead and focused on the retro-orbital and skull course of the supratrochlear nerve including the Gasser nerve.

Figure 3

Case 3: an 81-year-old man with squamous cell carcinoma and perineural spread along V1 to the cavernous sinus. (A) MRI with coronal fat-suppressed T2-weighted image shows intermediate signal intensity tumor involving V1 (straight arrow) adjacent to normal superior rectus muscle (curved arrow). (B) Axial fat-suppressed contrast-enhanced T1-weighted image shows abnormal enhancement in the superior orbit (arrow). (C) Coronal contrast-enhanced T1-weighted image, obtained just posterior to the superior orbital fissure, shows asymmetric enhancement and fullness along the lateral margin of the cavernous sinus (arrow).

Figure 4

Case 4: a 74-year-old-man with squamous cell carcinoma. (A) Axial fat-suppressed contrast-enhanced T1-weighted image shows a thickened, abnormally enhancing left V2 nerve extending from the premaxillary fat to the inferior cavernous sinus and along the left Vidian nerve (arrows). (B) Axial fat-suppressed contrast-enhanced T1-weighted image performed 6 months after permanently discontinuing pembrolizumab shows mild asymmetric enhancement of the left V2 nerve that is improved compared to pre-treatment (arrows).