Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System

Did you ever wonder why primary CNS lymphoma stays restricted to the CNS? Over the years, I have been asked that by several students and trainees, but I could never give a good answer. An article published online in the Journal of Neuropathology and Experimental Neurology on May 3rd points toward an answer. The phenomenon may be related to the unique lymphatic drainage system of the CNS. The brief report, entitled Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System, is authored by Martina Deckert and colleagues from the Department of Neuropathology at the University Hospital of Cologne (Germany) and the Institute of Human Genetics at Christian-Albrechts-University Kiel (Germany).

Deckert and colleagues investigated PCNSL for the presence of lymphatic vessels using immunohistochemistry for Lyve-1, podoplanin, and Prox-1 expression in a series of 20 intraparenchymal PCNSL biopsies in comparison with 8 dural/meningeal-based foci of systemic diffuse large B-cell lymphoma (DLBCL) as well as 20 glioblastomas lacking any contact with the meninges.

Absence of lymphatic vessels in PCNSL demonstrated by
negative Prox-1 staining
(inset: human tonsils serve as positive control) 

All PCNSLs and glioblastomas investigated lacked lymphatic vessels as evidenced by absence of immunohistochmemical lymphatic vessel markers. However, dural/meningeal DLBCL foci harbored lymphatic vessels that expressed Lyve-1 (3/8 tumors), podoplanin (5/8 tumors), and Prox-1 (5/8
tumors) in areas where the tumors had invaded the fibrous tissue of the dura. Taken together, the immunohistochemical panel demonstrated lymphatic vessels in 7 out of 8 (87.5%) of the DLBCLs investigated.

The authors note that although cerebrospinal fluid drains to lymph nodes through a variety of routes, these passages are presumably too small to allow passage of large neoplastic lymphocytes.

This report leaves one glaring question unanswered: If one investigated glioblastomas that did have contact with the dura/meninges, would those show evidence of lymphatic vessels? If so, why do those glioblastomas not metastatize to areas outside the CNS?