Detection of perineural spread: fat suppression versus no fat suppression.

One could easily argue that, when imaging head and neck malignancy, evaluation of possible perineural spread is more important than identifying the primary tumor or finding metastatic nodes. In almost every case, the clinician has already identified the primary lesion and has made a good estimate of the margins. The location and size of the primary tumor determine the treatment of lymph nodes at least as much as does the imaging assessment. Perineural spread, on the other hand, can be unsuspected and can carry a tumor beyond the region that is to be treated by either surgery or radiation. If the extent of perineural spread is not correctly identified, the patient will likely undergo significant morbidity without hope of cure. Assessment of perineural spread is therefore a key concept in head and neck imaging. The radiologist absolutely must understand the concept and be comfortable with its assessment. The article by Chang et al in this issue of the AJNR presents a series of patients with malignant melanoma exhibiting perineural spread. More specifically, they write that a particular subtype, the desmoplastic melanoma, has a particular propensity for following nerves. Presentation of this material affords an opportunity to examine several points, some controversial, related to perineural spread. By far the most important issue to an imager is how to look for perineural spread and that is the main point of this editorial. At our institution, we avoid fat suppression at the skull base. Before discussing imaging, however, a comment regarding the basic concept and a word about terminology is appropriate as an introduction. Perineural spread refers to extension of tumor along a nerve. The nerve acts as a conduit carrying tumor a significant distance from the original lesion. As indicated in the article by Chang et al, one must distinguish between perineural tumor and perineural spread. Pathology reports frequently refer to perineural tumor or invasion when describing a primary lesion. The pathologist is identifying tumor in and around nerves at the primary site. Perineural tumor or neural invasion has a significant negative effect on prognosis, correlating with recurrence, but this finding does not necessarily imply tumor leaving the original location of the primary lesion. Emphasizing the term “spread” is important in avoiding this ambiguity. The term “perineural” leads to confusion regarding the exact location of tumor traveling along the nerve. Each nerve is organized into compartments by several connective tissues. In a medium to large nerve, the fibers are grouped into fascicles or bundles. The perineurium is a condensed fascia surrounding each bundle of nerve fibers. The endoneurial space is the compartment contained within the perineurium. The endoneurium itself is the wispy, looser connective tissue within that space and surrounding individual fibers. A relatively loose fascia called the epineurium surrounds the multiple bundles making up the final nerve. The most peripheral layer may be more compact or condensed, separating the nerve bundles from the surrounding adipose tissue. This more condensed layer has been referred to as a sheath. There are examples of tumor invading all of the compartments and bordering all of the fascial layers: endoneurium, perineurium, and epineurium. There are examples of the tumor extending along the space between the nerve bundles and the sheath of the nerve in the region of the epineurium. Some tumors do tend to concentrate in the region of the perineurium. Various tumors have a propensity for involving different compartments. Perhaps it is better simply to accept the term and not to dwell on its derivation. It is key, however, to understand that we are referring to tumor selectively traveling along a nerve away from a primary lesion. Exactly why tumor follows the nerve is also unclear. Various theories have been proposed. Perhaps the nerve represents the line of least resistance forming a natural channel through anatomy otherwise difficult to traverse. Intraneural lymphatics have been suggested as a pathway. Because endothelial cells are not seen bordering the traveling tumor, however, this theory is not accepted. There have always been theories that something in the nerve causes the tumor to grow in the vicinity of the nerve. One such theory has focused on various growth factor binding sites. This is particularly pertinent to the current article, because the desmoplastic variant of melanoma described by the authors has shown strong immunologic staining for growth factor receptor p75 (1). During development, Schwann cells migrate to and along a nerve partly because of an interaction between nerve growth factor and a binding site on the Schwann cells called nerve growth factor receptor p75. Adenoid cystic carcinoma has also (in a very small series) shown affinity for the stain for p75 (2). Perhaps the malignant cells use a mechanism similar to the Schwann cells to invade and then travel along the nerve. More work is needed to define exactly why various malignancies follow nerves, but the fact that they do follow nerves has been clearly established. Adenoid cystic carcinoma from the minor and major salivary glands, lymphoma, melanoma, squamous cell carcinoma, and others have all been identified as having the potential to follow nerves. The radiologist’s goal is to be able to identify the Editorials