Perineural spread of tumours is a phenomenon that is often subtle, unobtrusive until very late and below the radar for most physicians, including oncologists. Perineurium is the second of the three nerve covers, and under the perineurium lies a potential space, where tumors can spread freely, unimpeded by immune calls, often spreading centripetally towards the brainstem, and less commonly towards the periphery. One should perhaps start by explaining the difference between perineural spread (PNS) and perineural invasion (PNI).
PNI is of two types- one that is only picked up on miscroscopic examination of the resected tumour specimen, and one that is obvious clinically or radiologicaly (usually on MRI). The former is called microscopic PNI, while the latter is called clinical PNI, named nerve PNI, or PNS.
Therefore PNS can be a clinically manifest phenomenon, presenting with numbness or paralysis, or silent, but radiologically obvious on MRI. PNS, by definition, affects large nerves.
Where does PNS crop up most often? In the head and neck, typically in territories supplies by the cranial nerves V & VII, which tend to be the most commonly affected by PNS.
Cutaneous squamous cell cancer (SCC) is the most common malignancy that leads to PNS. The second most common, in terms of ratio, is adenoid cystic carcinoma of the salivary gland. Other predisposing tumours, albeit less common, include basal cell carcimoma, salivary ductal carcinoma, ex-pleomorphic adenoma, and rarely melanoma. Mucosal (head and neck) SCC is a distinctly uncommon source of PNS.
In most cases, the tumour, usually a SCC, has been removed in the remote past, ranging from a few months to few years ago. There are no signs of metastases anywhere else in a third of cases, just in the perineural space.
One must suspect PNS when a subject with a remote history of treated SCC presents with numbness, or paresthesiae in one or more divisions of the trigeminal nerve. The most commonly affected is the maxillary branch. Symptoms are often attributed to trigeminal neuralgia. Men are affected 5 times more commonly as women. Similarly, the facial nerve may be involved, often partially. Upon exiting the stylomastoid foramen, the VII nerve splits into two divisions which then give rise to 5 branches. Usually one or more such branches are involved, for example giving rise to weakness of muscles of mastication. When the entire VII nerve is involved, an erroneous diagnosis of Bells palsy is often made. However, it is worth remembering that Bells palsy occurs acutely while VII nerve involvement in PNS occurs gradually over months.
The median interval between removal of the primary tumour and manifestation of PNS is 16 months, but can be years. Six out of 7 patients have a previous history of cancer, while around 7.5% have no previous history. In a third of cases there is no evidence of PNI in the excised original tumour. The original tumour may have been unclassifiable, treated early with radiotherapy or cryotherapy or not biopsied at all, and thus a definite history of a preceding primary may be difficult to establish, with the only evidence of the same being sun damaged skin.
MRI with neural imaging is better at diagnosis than CT, and should be used when available. Normal nerves appear isointense to the surrounding tissue on T1- and T2-weighted MRIs, but upon injury the nerves become hyperintense and thus visible on T2-weighted MRI. Survival at 5 years is 50-64%. Most patients are treated with a combination of surgery and radiotherapy.
Read the following article for a more comprehensive review.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846401/
PNI is of two types- one that is only picked up on miscroscopic examination of the resected tumour specimen, and one that is obvious clinically or radiologicaly (usually on MRI). The former is called microscopic PNI, while the latter is called clinical PNI, named nerve PNI, or PNS.
Therefore PNS can be a clinically manifest phenomenon, presenting with numbness or paralysis, or silent, but radiologically obvious on MRI. PNS, by definition, affects large nerves.
Where does PNS crop up most often? In the head and neck, typically in territories supplies by the cranial nerves V & VII, which tend to be the most commonly affected by PNS.
Cutaneous squamous cell cancer (SCC) is the most common malignancy that leads to PNS. The second most common, in terms of ratio, is adenoid cystic carcinoma of the salivary gland. Other predisposing tumours, albeit less common, include basal cell carcimoma, salivary ductal carcinoma, ex-pleomorphic adenoma, and rarely melanoma. Mucosal (head and neck) SCC is a distinctly uncommon source of PNS.
In most cases, the tumour, usually a SCC, has been removed in the remote past, ranging from a few months to few years ago. There are no signs of metastases anywhere else in a third of cases, just in the perineural space.
One must suspect PNS when a subject with a remote history of treated SCC presents with numbness, or paresthesiae in one or more divisions of the trigeminal nerve. The most commonly affected is the maxillary branch. Symptoms are often attributed to trigeminal neuralgia. Men are affected 5 times more commonly as women. Similarly, the facial nerve may be involved, often partially. Upon exiting the stylomastoid foramen, the VII nerve splits into two divisions which then give rise to 5 branches. Usually one or more such branches are involved, for example giving rise to weakness of muscles of mastication. When the entire VII nerve is involved, an erroneous diagnosis of Bells palsy is often made. However, it is worth remembering that Bells palsy occurs acutely while VII nerve involvement in PNS occurs gradually over months.
The median interval between removal of the primary tumour and manifestation of PNS is 16 months, but can be years. Six out of 7 patients have a previous history of cancer, while around 7.5% have no previous history. In a third of cases there is no evidence of PNI in the excised original tumour. The original tumour may have been unclassifiable, treated early with radiotherapy or cryotherapy or not biopsied at all, and thus a definite history of a preceding primary may be difficult to establish, with the only evidence of the same being sun damaged skin.
MRI with neural imaging is better at diagnosis than CT, and should be used when available. Normal nerves appear isointense to the surrounding tissue on T1- and T2-weighted MRIs, but upon injury the nerves become hyperintense and thus visible on T2-weighted MRI. Survival at 5 years is 50-64%. Most patients are treated with a combination of surgery and radiotherapy.
Read the following article for a more comprehensive review.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846401/
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