TEACHING CASE 13

Figure 1: H&E-stained slide of oligodendroglioma showing an infiltrative pattern and containing a monotonous collection of cells with distinctive perinuclear haloes.

Figure 2: Loss of 1p36 (highlighted by arrows). Single 1p36 red signal is accompanied by two 1q25 green reference signals indicating 1p36 loss.

Figure 3: Loss of 19q13 (highlighted by arrows). Single 19q13 red signal is accompanied by two 19p13 green reference signals indicating 19q13 loss.

Clinical Summary:
A 55-year-old male who presents with a frontal lobe mass.

Summary of Histologic and In Situ Hybridization Findings:
The biopsy is remarkable for an infiltrative oligodendroglial proliferation (Figure 1) composed of a monomorphic population of tumor cells with uniform round nuclei and distinctive perinuclear haloes.

By in situ hybridization this glial neoplasm shows convincing loss of 1p36 (Figure 2) and 19q13 (Figure 3).

Final Diagnosis:
Oligodendroglioma showing loss of 1p36 and 19q13 by in situ hybridization studies.

Discussion:
Gliomas are the most common primary neoplasm of the central nervous system and can have strikingly different clinical behaviors and responses to therapy. Distinguishing between different subtypes is often less than perfect with significant inter-observer variability. Although attempts have been made to define clinical and histologic features that correlate with a favorable prognosis, none have been sufficiently reliable at predicting response to adjuvant chemotherapy. However, recent studies have shown that loss of 1p36 and 19q13 are associated with an oligodendroglial phenotype, favorable response to chemotherapy and overall prolonged survival.^1-3 Fluorescence in situ hybridization (FISH) studies provide a direct method for identifying loss of 1p36 and 19q13 in formalin-fixed, paraffin-embedded tissue sections. Loss of 1p36 and 19q13 is performed by assessing the ratio of 1p36 and 19q13 to their corresponding reference genes, 1q25 and 19p13, respectively, and by assessing the number of nuclei showing clear 1p36 and 19q13 deletion, according to guidelines defined by the International Society of Pediatric Oncology.^1-4

References:
1. Burger PC et al. Mod Pathol. 2001 Sep;14(9):842-53
2. Smith JS et al. J Clin Oncol. 2000 Feb;18(3):636-45
3. Gelpi E et al. Mod Pathol. 2003 Jul;16(7):708-15
4. Ambros PF et al. Med Pediatr Oncol. 2001 Dec;37(6):492-504