Perineural spread
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In
pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...
, perineural invasion, abbreviated PNI, refers to the
invasion An invasion is a Offensive (military), military offensive of combatants of one geopolitics, geopolitical Legal entity, entity, usually in large numbers, entering territory (country subdivision), territory controlled by another similar entity, ...
of
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
to the space surrounding a
nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the Electrochemistry, electrochemical nerv ...
. It is common in head and neck cancer, prostate cancer and colorectal cancer. Unlike perineural spread (PNS), which is defined as gross tumor spread along a larger, typically named nerve that is at least partially distinct from the main tumor mass and can be seen on imaging studies, PNI is defined as tumor cells infiltrating small, unnamed nerves that can only be seen microscopically but not radiologically and are often confined to the main tumor mass. The transition from PNI to PNS is not precisely defined, but PNS is detectable on MRI and may have clinical manifestations that correlate with the affected nerve. Text was copied from this source, which is available under
Creative Commons Attribution 4.0 International License


Significance

Cancers with PNI usually have a poorer prognosis, as PNI is thought to be indicative of perineural spread, which can make resection of malignant lesions more difficult. Cancer cells use nerves as routes of
metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
, which could explain why PNI is associated with poorer outcomes.


Prostate cancer

In prostate cancer, PNI in needle biopsies is poor prognosticator; however, in
prostatectomy Prostatectomy (from the Ancient Greek language, Greek , "prostate" and , "excision") is the surgical removal of all or part of the prostate gland. This operation is done for benignity, benign conditions that cause urinary retention, as well as ...
specimens it is unclear whether it carries a worse prognosis. In one study, PNI was found in approximately 90% of radical prostatectomy specimens, and PNI outside of the prostate, especially, was associated with a poorer prognosis. However, there exists controversies about whether PNI has prognostic significance toward cancer malignancy. In perineural invasion, cancer cells proliferate around peripheral nerves and eventually invade them. Cancer cells migrate in response to different mediators released by autonomic and sensory fibers. Tumor cells secrete CCL2 and CSF-1 to accumulate endoneurial macrophages and, at the same time, release factors that stimulate perineural invasion. Schwann cells release TGFβ, increasing the aggressiveness of cancer cells through TGFβ-RI. Schwann cells drive perineural invasion, cancer cells interact directly with Schwann cells via NCAM1 to invade and migrate along nerves.


Head and neck cancer

PNI and PNS are considered an unfavorable prognostic factors in
head and neck cancer Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...
of virtually all sites, associated with poor local and regional disease control, probability of locoregional and distant metastases, disease recurrence, and lower survival rate. Although adenoid cystic carcinoma accounts for only 1-3% of head and neck tumors, it has the highest relative incidence of PNI. PNI is also commonly found in patients with salivary duct carcinomas, polymorphous low-grade adenocarcinomas, cutaneous malignancies, desmoplastic melanomas, myelomas, lymphomas, and leukemias. If PNS is not detected, there is a high risk of cancer progression. PNS recurrence is rarely resectable, and repeated irradiation has greater toxic side effects and fewer benefits compared with initial early treatment. The trigeminal nerve and facial nerve are the most commonly affected nerves primarily because of their extensive innervation area, although virtually any cranial nerve and its branches can provide a route for the PNS.


Additional images

Image:Perineural invasion prostate high mag.jpg,
Micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...
demonstrating perineural invasion. HPS stain.


See also

* Lymphovascular invasion *
Malignancy Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...


References

{{reflist, 2 Pathology