The initial flare or enlargement of measurable areas of the tumor or the appearance of new lesions after the start of immunotherapy is known as pseudoprogression [12]. tumor and blood tissues revealed an homozygous c.1883G A mutation consistent with CMMRD. Given her CMMRD status, she was treated with nivolumab (3 mg/kg doses every 2 weeks for 36 weeks) and showed a 60% reduction in tumor size, improved clinical symptoms, and an ongoing durable response lasting 10 months to date. Our study highlights a durable response to the ICPI nivolumab in a pediatric patient with recurrent/refractory CMMRD\associated GBM. We show that incorporating genomic and/or molecular testing for CMMRD into TCS JNK 5a routine pediatric oncology clinical care can identify a subset of patients likely to benefit from ICPI. Key Points. Constitutional mismatch repair\deficiency (CMMRD) syndrome, alternatively known as biallelic mismatch repair deficiency syndrome, occurs in subset of pediatric cancer patients, including those with primary brain tumors. Patients from Arab and other developing countries are predicted to have higher incidence of CMMRD due to high prevalence of consanguinity. Integration of molecular and/or genomic testing into routine clinical care for pediatric cancer patients is important to identify patients with CMMRD syndrome. Patient with CMMRD\associated cancers may show increased responsiveness to immune checkpoint inhibitors. To the authors’ knowledge, this is the first report in the Arab world of a durable response to immune checkpoint inhibitors in a pediatric glioblastoma patient. Patient Story A 5\12 months\old girl from the northern region of Saudi Arabia with no prior medical history presented to King Fahad Medical City (KFMC) emergency room in November 2016 with a history TCS JNK 5a of TCS JNK 5a headache, vomiting, left vision strabismus, and lethargy. She had no history of abnormal movement or seizure activity. Her examination was amazing for mild facial dysmorphism and multiple small caf\au\lait spots on her trunk. She was small for her age, with both height and weight below the fifth percentile. A computed tomography brain scan at presentation showed a large intra\axial infiltrating mass in the left frontal and parietal lobes, with cystic and hemorrhagic components causing right midline shift and compression of the left lateral ventricle. Diffuse cerebral edema was seen with raised optic discs (papilledema) reflecting the presence of increased intracranial pressure. Magnetic resonance imaging (MRI) of her brain showed a large intra\axial left frontal predominately cystic complex mass with solid hemorrhagic components causing severe mass effect, right midline shift, and obstructive hydrocephalus (Fig. ?(Fig.1A,1A, ?A,1B).1B). The patient underwent a gross total resection and had an excellent recovery without complications or significant deficit. Open TCS JNK 5a in a separate window Physique 1. Histological, radiological images of the patients with the family pedigree. MRI with (A) or without (B) contrast showing large intra\axial left frontal predominately cystic complex mass with solid hemorrhagic components causing a severe mass effect is usually observed together with a right midline shift and obstructive hydrocephalus. (C): H&E staining demonstrating a densely cellular high\grade glioma. (D): PD\L1 immunohistochemistry with Dako 22C3 antibody is usually unfavorable for immunoreactivity. (E): Four\generation family pedigree of index patient. Mouse monoclonal to GABPA Abbreviations: H&E, hematoxylin and eosin; MRI, magnetic resonance imaging; PD\L1, programmed death\ligand 1. Neuropathological analysis of resected tissues revealed a densely cellular and diffusely infiltrating high\grade glioma (World Health Organization grade 4) with abundant mitoses, microvascular proliferation, and necrosis (Fig. ?(Fig.1C).1C). Although a majority of the tumor cells were characterized by ovoid\to\elongated nuclei with moderate nuclear pleomorphism and tapered cell morphology, focal areas were consistent with a primitive neuroectodermal component. Cytological examination of cerebrospinal fluid showed no evidence of malignant cells. Immunohistochemistry for programmed death\ligand 1 (PD\L1) protein using the Dako 22C3 antibody.