SANTA ANA PUEBLO, N.M. Perineural invasion can occur in 2.5%15% of patients with squamous cell carcinoma, and 60%70% of patients are asymptomatic on presentation, Dr. Tri. H. Nguyen said at a meeting of the American Society for Mohs Surgery.
Patients who present with symptomatic perineural involvement most commonly have paresthesia, followed by sharp or achy pain, motor deficits, and formication (sensation of bugs crawling on the skin), said Dr. Nguyen, director of Mohs micrographic and dermatologic surgery at the University of Texas M.D. Anderson Cancer Center, Houston.
Clinical risk factors for perineural invasion include male gender, large tumor size (2 cm or greater), central face location, and recurrent tumor. Histologic risk factors for perineural invasion include moderate to poorly differentiated histology, intravascular or lymphatic invasion, deep invasion, and extensive subcutaneous infiltration.
Imaging studies are valuable in staging and prognosis. For bony invasion, a CT scan is best. To evaluate lymph nodes, a CT scan followed by MRI is preferred. "However, if you have access to an expert radiologist and ultrasound, then [ultrasound] is also an excellent technique to evaluate lymph nodes in the head and neck," Dr. Nguyen said.
Ultrasonography of the head and neck permits fine-needle aspiration of suspicious nodes in real time. If large nerve involvement is suspected, consider an MRI, he said.
"There is greater tissue destruction with perineural squamous cell cancers, which results in a larger defect size, higher rates of recurrences and metastasisup to 50% in some studiesand definitely a worse prognosis," said Dr. Nguyen, who also directs the procedural dermatology fellowship program at M.D. Anderson.
This is why adjuvant radiation therapy is recommended for these higher-risk squamous cell cancers.
Perineural disease alone, however, is not an absolute indication for radiation. "Only when there are other risk factors should radiation be considered in the adjuvant setting," he said. (See box.)
Radiation therapy "is not a benign process," he said. "There is significant cost ranging from $1,000 to $3,000 per treatment dose. There are logistics to work out, with treatments ranging from three to five times per week."
Radiation dermatitis, delayed wound healing, and functional impairment may occur with radiation.
Despite such risks, most adjuvant radiotherapy for cutaneous skin cancer is relatively well tolerated. "When you're talking about radiating oral, pharyngeal, or laryngeal cancer, that's a whole different ball game," he said.
In one early study, when radiation was added to wide local excision in patients with squamous cell carcinoma of the head and neck and perineural invasion, the 5-year local control rate was 38%, compared with 20% with radiation alone (Head Neck 1989;11:3018). "I look at radiation as only one tool to treat these higher-risk squamous cell cancers," Dr. Nguyen said.
He divides perineural involvement of squamous cell carcinoma into two groups: incidental disease and clinical disease. Patients with incidental disease are asymptomatic, have isolated perineural involvement of small peripheral nerves in the high dermis, and are imaging negative. "In this group, the local control rate without radiation is 78%87%," he said.
Patients with clinical disease have perineural tumor of larger nerve trunks, have more extensive perineural involvement, are asymptomatic, and are imaging positive. "These patients have a positive MRI or CT and a worse prognosis," he said. "The local control rate without radiation therapy is 50%55%."
Tumors that are recurrent worsen the prognosis, especially in the setting of perineural disease. "For example, the local control rate is 50%75% in a primary squamous cell cancer with perineural disease," he said. "Contrast this to the local control rates of 11%50% in a recurrent squamous cell cancer with perineural disease."
Despite the risks, most adjuvant radiotherapy for cutaneous skin cancer is relatively well tolerated. DR. NGUYEN
Perineural involvement in a stage IV squamous cell carcinoma can be seen in the above pathology image. Courtesy Dr. Tri. H. Nguyen
Indications for Adjuvant Radiation Therapy After Surgery
Dr. Nguyen refers patients for postoperative adjuvant radiotherapy if:
▸ Recurrence morbidity would be catastrophic.
▸ Perineural involvement of large or extensive nerve trunks is confirmed.
▸ There is extensive microscopic disease or subcutaneous extension.
▸ The size of the tumor is greater than 2 cm and is located on the central face.
▸ The tumor is recurrent.
▸ The tumor is poorly differentiated or has deep invasion.
▸ Disease involves the lymph nodes.
▸ The patient is immunosuppressed.