Therapath Neuropathology

Cancer Related Neuropathy

Neuropathy can result from the underlying cancer, or neurotoxicity of drugs used to treat the tumor.

Peripheral neuropathy is not uncommon in patients with cancer. It can result from the underlying cancer, poor nutritional status, paraneoplastic mechanisms, or neurotoxicity of drugs used to treat the tumor. Pre-existing neuropathy is also a risk factor for development of early or more severe chemotherapy induced neuropathy.1

Commonly used chemotherapeutic agents that can cause neuropathy include taxanes, vinca-alkaloids, platinum compounds, bortezomib, thalidomides, pyrimidine analogs, epothilones, alkylating agents, and topoisomerase inhibitors.2

Detecting the presence of neuropathy prior to initiating cancer treatment is important as it can result in the identification of a potentially treatable underlying cause, help decide on the selection of a less neurotoxic chemotherapeutic agent, and help exclude patients with pre-existing neuropathy from clinical trials of new chemotherapeutic drugs.

Biopsy procedure guide

The typical presentation of sensorimotor neuropathy includes symptoms of numbness, pain, or muscle weakness, with sensory loss on neurological examination, and abnormal EMG and nerve conduction studies. However, the neuropathy can be asymptomatic and only recognized after suffering a cut or burn without feeling pain, or the neurological examination may be normal as is often the case in small fiber neuropathy.3 Electrodiagnostic studies are often not diagnostic in chemotherapy induced neuropathy, as they only measure the large, but not small nerve fibers, and are considered normal if the degree of axonal damage does not exceed the required diagnostic threshold.

Chemotherapy induced neuropathy is typically distal and axonal, with the nerve endings being the earliest affected.4 These can best be assessed by punch skin biopsy, with determination of the Epidermal Nerve Fiber Density (ENFD). Several studies have reported that determination of the ENFD is more sensitive than electrodiagnostic testing in detecting chemotherapy induced peripheral neuropathy.4 Chemotherapeutic agents also cause autonomic neuropathy, in which case the sudomotor fibers in skin can be assessed by determination of the Sweat Gland Nerve Fiber Density (SGNFD).5

Therapath is a specialty neuropathology laboratory that provides testing for Epidermal Nerve Fiber Density (ENFD) and Sweat Gland Nerve Fiber Density (SGNFD) for the diagnosis of small fiber neuropathy. The addition of these tests to the evaluation of oncological patients prior to deciding on treatment or inclusion in trials of new chemotherapeutic agents, or in those suspected of developing neuropathy while on treatment, would provide physicians with valuable tools to help prevent or care for their patients with cancer related neuropathies.


Bruna J, Alé A, Velasco R, Jaramillo J, Navarro X, Udina E. Evaluation of pre-existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model. J Peripher Nerv Syst. 2011;16(3):199-212. [PubMed]
Miltenburg N, Boogerd W. Chemotherapy-induced neuropathy: A comprehensive survey. Cancer Treat Rev. 2014;40(7):872-882. [PubMed]
Lacomis D. Small-fiber neuropathy. Muscle Nerve. 2002;26(2):173-188. [PubMed]
Han Y, Smith M. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol. 2013;4:156. [PubMed]
Giannoccaro M, Donadio V, Gomis P, Borsini W, Di S, Liguori R. Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: an immunofluorescence study. Neurol Sci. 2011;32(2):361-363. [PubMed]