SAN FRANCISCO – Patients with high-risk keratinocyte carcinomas sometimes present with neurologic symptoms mimicking Bell’s palsy or trigeminal neuralgia, making the diagnosis of these perineural tumors challenging, Siegrid Yu, MD, said at the annual meeting of the Pacific Dermatologic Association.
Eventually, skin manifestations can land them in a dermatologist’s office. “There is a high incidence of delayed diagnosis and misdiagnosis, which affects the outcome of these patients,” said Dr. Yu of the department of dermatology, University of California, San Francisco.
She presented several cases illustrating the central role that dermatologists can play in the diagnosis and management of high-risk keratinocyte carcinomas. “All of these patients were seen by various doctors, sometimes multiple times, without a diagnosis,” she said.
Perineural invasion occurs in 2.6%-6% of squamous cell carcinoma (SCC) cases and 2% of basal cell carcinoma (BCC) cases. “Perineural invasion presenting with neurologic symptoms is not that common, which is part of why I think it’s easy to misdiagnose these patients,” said Dr. Yu, director of the Mohs Micrographic Surgery and Cutaneous Oncology Fellowship at the UCSF Dermatologic Surgery and Laser Center. In many cases, patients were diagnosed as having Bell’s palsy or trigeminal neuralgia for years before being diagnosed with skin cancer.
Dr. Siegrid Yu
Common features of perineural invasion cases include midface location of the tumor, male gender, tumor size larger than 2 cm, recurrence, and poor histologic differentiation. Symptoms often include formication, pain, numbness, and facial weakness. Diagnosis is often delayed by 6 months to 2 years.
One case she described involved a 57-year-old immunosuppressed man who had previously undergone Mohs micrographic surgery for a primary SCC of the nasal sidewall. He experienced delayed numbness and pain of the upper lip and cheek near the surgical site 1 year later. There was no sign of cutaneous recurrence, and MRIs of the head and neck were normal. Examinations by dermatologists, neurologists, and otorhinolaryngologists yielded no diagnosis.
Two years after his initial surgery, the patient developed thickening of the scar from the Mohs surgery, without any overlying skin change. A punch biopsy showed only scar tissue, but a deeper incisional biopsy revealed a recurrence of the SCC. A second head/neck MRI, using a perineural protocol, showed abnormal enhancement at the V2 branch of the trigeminal nerve leading to the foramen rotundum. The patient underwent intensity-modulated radiation, which relies on computer-modeling to deliver doses to the precise location of the tumor. An MRI 2 months later showed a reduction in tumor size and radiographic resolution of trigeminal nerve involvement.
Another case involved a 75-year-old man with progressive right facial droop, who had experienced neurologic symptoms on the right side of his face, including numbness, tingling, oculomotor dysfunction, and radiating pain. He had been diagnosed with shingles on the right side of his face more than 20 years previously, but there was no history of postherpetic neuralgia. He also had hypertension and hypothyroidism, and had been prescribed levothyroxine, amlodipine, losartan, and gabapentin.
He had been evaluated by primary care, dermatology, and ophthalmology with no diagnosis. He then sequentially sought the opinion of four neurologists, and underwent lumbar puncture, serologic evaluation, head CT, and MRI with no findings that correlated with his symptoms. The patient’s neurological symptoms improved transiently with prednisone, and his pain improved slightly with gabapentin.
Finally, a skin biopsy of an ill-defined firmness in the right temple revealed infiltrative SCC. A repeat MRI, this time with perineural protocol, showed perineural spread along the trigeminal nerve, with involvement of the V2 and V3 branches, and possibly the V1 branch.
In another case, complete hemifacial palsy due to perineural spread of SCC was overlooked as having been related to the patient’s history of stroke. However, upon further questioning, the facial palsy involved all branches of the facial nerve, while the patient’s residual stroke symptoms of expressive aphasia and dysphagia were improving. “If you think about head and neck anatomy, an upper motor neuron lesion would not lead to complete facial nerve palsy. It could lead to palsy of the lower two-thirds of the face, sparing the temporal nerve due to cross innervation of the forehead. Only a lower motor neuron can result in progressive palsy of all branches of the facial nerve,” Dr. Yu said. In this case, the facial palsy was due to a large SCC of the external auditory canal.
Dr. Yu highlighted several considerations to keep in mind when examining these patients, including vigilance around prior skin cancer surgeries in cases with neurologic symptoms, the potential need for repeated imaging along with communication with the radiologist regarding suspicion of perineural spread, consideration of anatomy during the clinical exam, and correlation of clinical exam, histopathology, and radiographic findings.
When it comes to imaging, MRI is the most sensitive technique, she noted. It can show increase in nerve diameter, destruction of the nerve-blood barrier, obliteration of the fat below a foramen, nerve enhancement, and denervation atrophy.
Dr. Yu reported having no financial disclosures.