A 4‐Year‐Old Girl With a Supratentorial Mass

Clinical History

A 4‐year‐old girl presented with right hemiparesis and ataxia. Her symptoms progressed rapidly and she could no longer ambulate without assistance. Her exam was remarkable for severe right‐sided weakness of both upper and lower extremities. The MRI showed a left thalamic, hemorrhagic mass measuring up to 42 × 33 × 38 mm (Figure 1A,B). Mass effect on the third ventricle was noted with resultant acute obstructive hydrocephalus. Interval placement of an EVD at the time of presentation helped mildly improve ventricle size. Gross total resection was performed by a parietal craniotomy and inner hemispheric, transcallosal approach.

Figure 1.

 

Microscopic Pathology

Histology revealed a hypercellular tumor with small blue cells, scant cytoplasm, nuclear pleomorphism, and increased mitotic activity (Figure 1C). Tumor cells stained diffusely for synaptophysin (Figure 1E) and were negative for GFAP (Figure 1D). Due to its midline location and atypical morphology, immunostaining for the mutant histone H3 p.K27M protein and H3 K27Me3 were also performed. Tumor cells stained negative for H3K27Me3 (Figure 1G) and positive for H3K27M (Figure 1F). What is your diagnosis?

Diagnosis

Diffuse glioma, H3K27M‐mutant.

Discussion

Historically, the diagnosis of pediatric tumors of the central nervous system (CNS) has relied on histology and immunohistochemistry, with glial tumors staining with glial fibrillary acidic protein (GFAP) and embryonal tumors with neuronal markers like synaptophysin. The 2016 WHO classification of tumors of the CNS, for the first time, incorporated pathognomonic molecular features in the diagnosis of tumors and defined new tumor entities like diffuse glioma, H3 K27M‐mutant 1, 2, 4. The immunohistochemistry with antibodies specific to the H3K27M mutation has a 100% sensitivity and 100% specificity, and is a highly reliable diagnostic tool for this disease entity 3.

We report the second case, in the literature, of a tumor staining diffusely positive for synaptophysin and being negative for GFAP, but harboring the mutant histone H3 p.K27M protein. This pathognomonic molecular finding established the diagnosis of a high‐grade glioma, for a tumor that based on immunohistochemistry, resembled an embryonal tumor. High‐grade glioma with H3 K27M‐mutant is an aggressive tumor with median survival of 6 months. The incorporation of molecular features can augment histopathological evaluation in the diagnostic process, and in some instances even alter the diagnosis, with a significant impact on prognosis and treatment.