[1726] Histology and Immunohistochemical Profile of Diffuse Intrinsic Pontine Glioma (DIPG)

Leomar Y Ballester, Zengfeng Wang, Shaefali Shandilya, Markku Miettinen, Peter C Burger, Charles Eberhart, Fasto J Rodriguez, Eric Raabe, Katherine E Warren, Martha M Quezado. NIH/NCI, Bethesda, MD; Johns Hopkins University, Baltimore, MD

Background: Pediatric tumors of the CNS are the 2nd most common malignancy in children. In particular, DIPGs are aggressive tumors with poor prognosis and account for 10-25% of pediatric brain tumors. The majority are of astrocytic origin with an infiltrative pattern and localized to the Pons. The diagnosis of DIPG is based on the presentation on MRI, although distinction from primitive neuroectodermal tumors (PNETs) on imaging studies alone is difficult. Surgical treatment is often not possible due to the sensitive location. Treatment strategies have traditionally been limited to radiotherapy and chemotherapy, with very poor effectiveness. Most studies have shown median survival times of less than a year with 90% of children dying within 2 years.
Design: We built 2 multi-tissue arrays with 24 DIPG samples obtained from autopsy material, most patients had received prior radiation treatment. The mean age of patients at the time of death was 7.9 years with 38% female and 46% male. We analyzed morphology and expression of several proteins by immunohistochemistry, with the goal of identifying potential treatment targets and improving our understanding of the biology of these tumors.
Results: We analyzed the morphologic characteristics of 24 brainstem gliomas. The majority of the cases were high grade (22) with 17 cases having features of glioblastoma with pseudopalisading necrosis (14) and/or vascular proliferation (12), WHO grade IV and 5 cases with high grade features consistent with anaplastic astrocytoma, WHO grade III. One case was low grade (WHO grade II) and one case showed intermediate features between a grade II and grade III glioma. Microcalcifications were seen in 3 cases, 2 cases showed the presence of giant cells and gemistocytes were present in 2 other cases. The results for the different immunohistochemical markers were scored by 2 pathologists. The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), Olig2 (22/24), p16 (20/24), p53 (20/24), Sox2 (19/24), EGFR (16/24) and BMI1 (9/24).
Conclusions: Our results suggest that dysregulation of EGFR and p53 may play an important role in the development of a majority of DIPGs. A majority of the tumors express stem cell markers such as Sox2 and Olig2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors. In conclusion, we have an excellent resource in which to study the morphologic diversity and protein expression of 24 DIPGs. These could aid in the identification of potential novel therapeutic and prognostic makers.
Category: Neuropathology

Wednesday, March 6, 2013 1:00 PM

Poster Session VI # 245, Wednesday Afternoon


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