Histological and molecular analysis of a progressive diffuse intrinsic pontine glioma and synchronous metastatic lesions: a case report

Abstract

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary tumor as well as concomitant metastatic deposits obtained at autopsy are discussed. While some mRNA differences were demonstrated, all analyzed sites of disease shared similar mutational arrangements, suggesting that targeting the mutations of the primary tumor may be effective for all sites of disease.

Rapid and fulminant leptomeningeal spread following radiotherapy in diffuse intrinsic pontine glioma

“…However, given limited tissue resources, coupled with the relative rarity with which distant metastatic disease is observed in DIPG, this will likely be a difficult question to answer. Of note, molecular analysis of a matched primary progressive DIPG tumor and concomitant metastatic deposits from a single patient failed to reveal significant differences in mutational spectra, suggesting, at least in this limited sample, that primary tumor‐directed therapy may be relevant for sites of metastasis …”

“…Of note, molecular analysis of a matched primary progressive DIPG tumor and concomitant metastatic deposits from a single patient failed to reveal significant differences in mutational spectra, suggesting, at least in this limited sample, that primary tumor-directed therapy may be relevant for sites of metastasis. 4 Hypofractionated radiotherapy, or the delivery of larger doses over smaller number of treatments, has recently emerged as a potential treatment approach in DIPG. Several retrospective reports from Europe have suggested this regimen may provide similar survival out-comes with a side-effect profile in line with that seen with conventionally fractionated RT.…”

Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience

“…Radiation therapy (RT) is currently the only established lifeprolonging therapy [6,[8][9][10][11], with chemotherapy and targeted therapeutics showing no added efficacy [7]. DIPG typically progresses locally, although loco-regional and distal metastasis can occur [2,3,[12][13][14]. Pharmacologic therapies in the recurrent setting are generally ineffective and characterized by rapid neurological decline with median overall survival (OS) of 1 to 4 months following recurrence [7,15].…”

Diffuse Intrinsic Pontine Glioma: Molecular Landscape, Evolving Treatment Strategies and Emerging Clinical Trials

“…Hh pathways play a major role in the regulation of processes such as cell proliferation and stem cell maintenance [ 6 , 63 ]. Abnormal signaling in the Hh pathway has shown ventral pontine hyperplasia within pre-clinical murine models [ 7 , 63 ].…”

“…DIPG was previously thought to resemble adult high-grade gliomas (HGG), but recent advancements have shown this not to be true. In 2021, the World Health Organization (WHO) updated the original brain tumor classifications, taking markers into consideration and classifying pediatric gliomas with a K27M mutation in histone H3 (3.1 or 3.3) as diffuse midline gliomas (DMG), H3 K27 -altered [ 6 , 7 ]. Due to the poor prognosis of tumors with this mutation, they were assigned a grade 4 designation regardless of conventional histologic features [ 8 ].…”