Segment of nerve involved by adult T cell leukemia/lymphoma (ATLL).
The acute onset of progressive cranial neuropathies, abnormal CSF studies, and MRI showing enlargement of the involved nerves with abnormal enhancement suggested either a neoplastic disease or, less likely, an inflammatory process. Although infectious diseases (including HIV, Lyme disease, herpes simplex type I, and varicella-zoster) were considered in the differential diagnosis, the negative test results for a battery of infectious agents suggested otherwise. Gallium scan did not reveal a primary neoplasm to suggest a metastatic disease. Work-up for hematologic malignancy, including flow cytometry of CSF and peripheral blood, had also been inconclusive. Inflammatory disease, particularly sarcoidosis, was therefore considered and a trial of high-dose steroid was given that did not improve the patient's symptoms. In order to make a definitive diagnosis, a biopsy of the enlarged infraorbital nerve was performed and the histological examination demonstrated an ATLL involving the cranial nerves.
Nerve infiltration by neoplastic lymphocytes, also called neurolymphomatosis, can be seen in B-cell and T-cell non-Hodgkin lymphomas when the neoplastic cells spread to the peripheral nervous system with or without involvement of the leptomeninges and central neuraxis (1-3). Very rarely, neurolymphomatosis can present as the primary manifestation of lymphoma (1-3). Cranial neuropathy is seen in about 13-51%. Of nearly 200 cases of neurolymphomatosis reported in the literature (1-3) cranial nerves III, V, VI, and VII are most often affected (1-3). Although the peripheral nerves may be the initial site of involvement, most cases eventually spread to systemic sites or to the central nervous system. Only very rarely is neurolymphomatosis the primary manifestation of lymphoma (1-3).
T-cell neoplasms involving peripheral nerves are exceedingly rare. In fact, B-cell lymphomas account for 66-82% of all neurolymphomatosis cases, most of which are diffuse large B-cell lymphomas (2, 3). ATLL, a T-cell malignancy caused by HTLV-1 infection, has been reported in the literature as the cause of neurolymphomatosis in only three cases (4, 5, 7). Interestingly, two of these three cases initially presented with neuropathy (one case with peripheral polyneuropathy; another with cranial neuropathy involving cranial nerves VII and VIII). A significant fraction of our patient population is of Caribbean origin, whose HTLV-1 prevalence is 3.8% and annual incidence of ATLL is approximately 20 cases/100,000 population (8). The immunoprofile of the lymphoma cells (CD4+/CD8-/CD25+/FOXP3 focally +/CD30-/TIA-1-) together with the positive HTLV-1 serologic test and detection of HTLV-1 antigen Tax in the CD4+ cells established the diagnosis (8). If a biopsy is not available, the diagnosis of neurolymphomatosis may be difficult and relies on integration of clinical information, imaging studies, and CSF evaluation. However, in only 40% of the neurolymphomatosis cases diagnostic malignant cells can be detected in the CSF specimen (2, 3). It is therefore not surprising that often the diagnosis of neurolymphomatosis can only be made at autopsy.
A CSF flow cytometry immediately following the biopsy showed an identical immunoprofile as the nerve biopsy including loss of a pan-T-cell antigen CD7, a characteristic phenomenon in ATLL that suggests a more aggressive course (6). The patient received chemotherapy and his CSF evaluations have been negative on follow-up for more than 6 months.
Contributed by Jiancong Liang, MD, PhD, Jenny Libien, MD, PhD, Yuetsu Tanaka, PhD, Constantine A. Axiotis, MD, Charles Shao, MD, PhD, Jinli Liu, MD