History of Imaging and Recognition of DIPG

Historically, tumors in the brainstem were both regarded and treated as a single entity, namely “brainstem glioma.” In the early 1990s, as MRI became more widely available and utilized, several attempts were made to characterize brainstem tumors based on MRI criteria. An early classification system based on MRI was established by Dr. A. James Barkovich of the University of California, San Francisco, and several of his North American colleagues. Specifically, tumor characterization was based upon:

• the site of primary involvement in the brainstem;
• the longitudinal and axial extent of the tumor within the brainstem;
• the tumor growth pattern (diffuse or focal);
• the enlargement of the brainstem;
• and the presence or absence of exophytic growth (i.e. growth extending outside the brainstem) enhancement, cysts, hydrocephalus, hemorrhage or necrosis.

Later correlation of such MRI criteria against survival statistics found several imaging characteristics to be significant. The particular segment or region of origin within the brainstem was found to be important. Tumors arising from the midbrain have the best prognosis. Tumors arising from the medulla have an intermediate prognosis. Tumors arising from the pons have the worst prognosis. A diffusely infiltrative appearance of the tumor was also found to have a significantly worse prognosis. A diffusely infiltrative appearance referred to tumors that had ill defined margins and involved more than one half of the brainstem segment of origin, or infiltrated the segments of the brainstem both superior and inferior to the segment of origin (i.e. infiltration of both the midbrain and the medulla if the segment of origin was the pons).

Finally, enlargement of the brainstem by the tumor was found to be negatively related to survival, with a tumor that enlarges the brainstem having a poorer survival.

As a result of these findings, attempts were made to develop new classification systems that better reflected prognosis. Dr. N.J. Fischbein and colleagues of Germany proposed a classification system in which tumors were divided into 6 groups, each having its own prognostic implications. The six groups included: 1) focal midbrain tumors, 2) diffuse midbrain tumors, 3) tectal tumors, 4) focal pontine tumors, 5) diffuse pontine tumors, and 6) cervicomedullary tumors.

It soon became clear that brainstem tumors were a diverse group of tumors with variable prognoses. Accordingly, management of the tumor needed to be tailored to the suspected tumor type. Studies in which biopsies were obtained for larger numbers of patients confirmed this observation. Of note, Dr. Paul Fischer and colleagues working at Stanford School of Medicine found that most brainstem tumors could be divided into two classes: pilocytic astrocytomas (World Health Organization grade I tumor) or fibrillary astrocytomas. Pilocytic astrocytoma had a favorable prognosis (5 year survival of 95%) and were associated with a location outside of the ventral (anterior) pons and a dorsal (posterior) exophytic growth. Fibrillary astrocytomas had a poorer prognosis (5 year survival of 15%) and were associated with a location in the ventral pons that engulfed the basilar artery.

In addition to these two main tumor types, other tumor types which are less frequently found within the brainstem include: ganglioglioma, primitive neuroectodermal tumor (PNET), atypical teratoid rhabdoid tumor (AT/RT), oligodendroglioma, and lymphoma.