NL is characterized by lymphomatous infiltration of PNS. From the first report of the large series of NL by Diaz-Arrastia et al., the most common clinical presentation was progressive sensorimotor neuropathy, although less common syndromes including Guillain-Barre, focal peroneal or sciatic neuropathy, a relapsing neuropathy, cauda equina syndrome and multiple cranial neuropathy were described. Therefore, clinicians should consider several differential diagnoses, such as leptomeningeal lymphomatosis, nerve damage from herpes zoster, chemoradiotherapy, nerve root compression, lymphoma-associated vasculitis, or paraneoplastic syndromes . The patterns of clinical presentations in NL are categorized into four: 1) painful involvement of nerves or roots, 2) cranial neuropathy with or without pain, 3) painless involvement of peripheral nerves and 4) painful or painless involvement of a single peripheral nerve.5 The present case showed complicated and mixed type of these four characteristics. In contrast, IVL is also known to show the diversity of non-specific clinical symptoms, including fever elevation, respiratory distress, and neurologic abnormalities, e.g., sensory and motor deficits or altered consciousness . In the current case, it is very difficult to make it clear to distinguish IVL-induced neurological signs from NL-induced ones, since detailed gross and microscopic examinations have never been performed within limited specimens obtained. Additionally, most of previous studies have not addressed PNS involvement in patients with IVL, however, Matsue et al., based on the collection of 4 IVL patients complicated with NL, have described that it is very likely that IVL has a predilection not only for the vascular vessels but for the PNS . Despite the extreme rarity of IVL, DLBL complicated with IVL and NL may be more common than generally considered.
Odabasi et al. reported a review of 52 NL cases that approximately one-half of them had also widespread systemic lymphoma found at the time of autopsy . The diagnosis in many cases had been difficult, since a multidisciplinary approach for obtaining an adequate biopsy specimen of the suspected nerve was required for clinicians. Moreover, it is well known that the prognosis is very poor due to the progressive characteristics, as shown in the present case. When NL occurs in the context of established malignant lymphoma, the main cause of death is disseminated disease with associated multiple organ failure, but respiratory failure secondary to severe neuropathy might also occur . Thus, early and accurate diagnosis and aggressive treatment (e.g., high-dose chemotherapy and/or radiation therapy) can increase their survival rates [4, 5, 9, 11, 14]. MRI would be essential and helpful to diagnose, because it can detect the number of the NL lesions and the extent of NL involvement. From the previous report by Amar Swarnkar et al., MRI showed mild persistent enlargement, hyperintensity on T2-weighted images and enhancement after gadolinium administration in the involved nerves. However, these radiographic findings are nonspecific and nondiagnostic, very similar to our case. More recently, PET scanning is considered to be a useful diagnostic tool to evaluate the distribution of involvement for patients with suspected NL, but is even unlikely to be 100% positive and at least one report of a false-negative case has been published . After all, nerve biopsies are required to obtain an accurate and correct diagnosis of NL. Approximately 83% of nerve biopsies are reported to show lymphomatous infiltration especially in the endoneurium, less commonly in the subperineurium [4–6]. Therefore, suspicion of NL needs a multidisciplinary approach because a biopsy would be performed on the most likely both clinically and radiologically suspected nerve. Consultation with surgeons, who experienced in peripheral nerve procedures including fascicular nerve biopsy, should be recommended .