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Eliminate Perineural Invasion By Taking Wider Margins


 

SAN DIEGO — Tumors travel within the nerve structure, so if a Mohs surgeon has a habit of taking superficial margins, he or she will miss perineural tumors, Dr. Alexander Miller said at a meeting sponsored by the American Society for Mohs Surgery.

The nerve structure includes the endoneurium (nerve fibers), perineurium (mostly collagen), and epineurium (connective tissue). All these components vary with the nerve size, and tumors can travel through all of them.

"A perineural tumor doesn't care which nerve it gets into, and it will go anywhere and in any direction," Dr. Miller said. "It could attack several nerves simultaneously," said Dr. Miller of the University of California, Irvine.

About 60%–70% of perineural tumors are asymptomatic and unknown to the patient. With symptomatic tumors, patients report burning, aching, numbness, or even a complete lack of sensation. The nerves are rarely palpable, although they may be more palpable at points where they cross over bones.

Although most perineural invasion is localized, there are cases in which it travels far beyond the general body of the tumor. "Your challenge is to discriminate between localized and not localized," he said. The majority of perineural tumors are localized to areas within 1 cm or less of the general body of the tumor. That said, some invasions extend several centimeters beyond the general body of the tumor, Dr. Miller said.

"Perineural tumors are hard to see under the microscope, and some people forget to look," he said.

Tumors that are most likely to become perineurally invasive are basal cell carcinoma and squamous cell carcinoma, but microcystic adnexal carcinoma, neurotropic malignant melanoma, and other adnexal tumors, particularly salivary or sweat gland tumors, also are candidates for perineural invasion.

An estimated 1% of basal cell carcinomas have perineural invasion. Those most likely to become perineural are morphealike, micronodular, metatypical, and basal cells invading as long arms of tumor surrounded by concentric fibrous sleeves of collagen.

About 3%–4% of squamous cell carcinomas are perineural, usually those that are moderately to poorly differentiated, and show tumor spreading like a narrow cord.

Squamous cell carcinomas more than 2 cm in diameter or greater than 4-mm thickness are more likely to be perineural than smaller ones; if they are 8 mm in thickness the risk is substantial.

Most microcystic adnexal carcinomas, approximately 80%, invade perineurally and subclinically, and it is crucial for the Mohs surgeon to be aware of this, Dr. Miller said. "Take a wider margin than you would with other tumors, be careful about tracking out the edges, and get good-quality slides."

Regardless of the type of tumor, tumors that are perineurally invasive share a uniform histology and display similar behaviors.

"They all pretty much look the same once they get into the perineural space," Dr. Miller said. The tumor cells can be tightly packed, clustered, or in a line. "In order to tell the tumor of origin, you have to go back to the original histology and look elsewhere on the slide" he said.

The pattern of growth can be spotty or concentric, and perineural tumors tend to be multifocal. "It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve," he said.

"Be aware of multifocality in the subcutaneous layer," Dr. Miller advised. "If you have poor-quality slides that are consistently destroying fat, you may miss crucial structures." Obvious inflammation around a nerve is a helpful indicator of perineural invasion, he added.

Tumor depth has been shown to correlate with perineural invasion, as has tumor recurrence and fibrous sleeve growth. Also, pay attention to nerve orientation on the microscope slides. A tumor may invade concentrically around the nerve, or just crawl along a portion of the nerve circumference. When a tumor invades along only one edge of a nerve, it can easily be missed.

"Multiple Mohs sections and slides must be examined for perineural tumor, or you will miss it," Dr. Miller emphasized.

"When perineural tumors recur, they are unpleasant; they are deep, and they can grow subclinically for a long time," Dr. Miller said. "Meticulous, compulsive evaluation is needed to successfully treat these patients and prevent recurrence."

'It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve.' DR. MILLER

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