Kanyalakshmi Ayyanar

Successful Treatment With Dabrafenib (GSK2118436) in a Patient With Ganglioglioma

Case Report A 21-year-old man presented to our clinic in June 2012 after being diagnosed with a recurrent ganglioglioma (GG) in the left temporal lobe and posterior brainstem. His original diagnosis was made at Kosair Children’s Hospital (Louisville, KY) in 1996 when he presented with headaches and neck pain. At that time, a magnetic resonance imaging (MRI) scan revealed a 2.5-cm enhancing mass at the edge of the tentorium and adjacent to the brainstem. The patient underwent craniotomy and gross total resection of his tumor. Pathology revealed a biphasic population of neoplastic neuronal and glial cells. Neuronal differentiation was confirmed in the larger neoplastic cells through immunohistochemistry (IHC) that documented expression of synaptophysin and neurofilament protein. Glial differentiation was confirmed in the smaller spindled cells through IHC that documented expression of glial fibrillary acidic protein. The tumor had no significant mitotic activity, with a Ki-67 proliferation index of less than 1%. The patient underwent chemotherapy with vincristine and carboplatin in 1997. In August 2008, he suffered a relapse with a new 1.4 1.0 cm contrast-enhancing mass in the brainstem. MRI of his cervical, thoracic, and lumbar spine was unremarkable, but a positron emission tomography (PET) scan demonstrated a hypermetabolic abnormality in his left pons that confirmed recurrence and suggested malignant transformation. He received radiotherapy (60 Gy in 30 fractions) with temozolomide but experienced disease progression approximately 6 months later. He subsequently received irinotecan and bevacizumab without clinical benefit. His tumor progressed and his clinical status deteriorated with worsening visual disturbances, mobility, and gait. In June 2012, an MRI revealed a 2.4 3.4 4.1 cm diffusely enhancing mass in the central and left vermis as well as surrounding the fourth ventricle on T1-weighted imaging with gadolinium (Fig 1A, arrows). Abnormal hyperintensity in the pons and

Cancer Predisposition Syndromes

Several decades ago, genetic predisposition was first identified as a risk factor for the development of secondary malignant neoplasms (SMN) with the observation of second tumors, namely sarcomas, in survivors of hereditary retinoblastoma. The two-hit hypothesis, originally proposed in 1971 by Knudson, may explain why some individuals may be more prone to the development of primary tumors, or of subsequent tumors after tumorigenic therapies, as a result of inheriting a cancer-associated gene mutation. Such a germline mutation is the first of the two ‘‘hits’’ required for tumorigenesis. This model has since been applied to other cancer susceptibility syndromes, such as LiFraumeni, associated with early-onset cancers. Some recent publications suggest that the two-hit model may be overly simplistic and that other chromosomal and epigenetic phenomena drive cancer tumorigenesis. Though only a small proportion of primary brain tumors appear to be due to a genetic predisposition syndrome in adults, genetic predisposition syndromes may account for a larger portion of primary brain cancers in children. In some series of cancer survivors who have developed SMN, nearly one-third had confirmed genetic abnormalities or suspected cancer predisposition syndromes. Prospective search for a genetic predisposition can involve complex and conflicting ethical, legal, social, and medical issues for patients and may have wide-ranging repercussions for patients and family members. Although these syndromes are uncommon, genetic testing for cancer susceptibility syndromes in particular individuals may assist patient management, influence family screening, and guide clinicians about surveillance protocols in affected individuals and ‘at risk’ family members; this information may strongly impact outcomes in some cases.

Metachronous mediastinal seminoma occurring after intracranial germinoma in an adolescent.

We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-year-old boy with headaches and visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2 years later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.

Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma

Background Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment. Results Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%). Conclusions Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.

Pilomatrixoma in an infant: diagnostic challenges of fine-needle aspiration.

Fine-needle aspiration biopsy (FNAB) is a well-recognized minimally invasive tool in the diagnosis of neoplasia of various organ systems. Several reports in the literature suggest that FNAB can be an accurate method for the preoperative diagnosis and treatment planning. We describe a case to caution the interpretation from a FNAB that contains suboptimal contents (basaloid cells only) and highlight a clinical–pathologic-based algorithm that can provide the appropriate management for the patient when the cytopathologic diagnosis does not fit the clinical impression.