Report of four cases
Joseph L. Koen, Roger E. McLendon, and Timothy M. George
✓ Intradural spinal teratoma is a rare tumor that can be associated with dysraphic defects. Although the origin of these tumors is traditionally thought to be secondary to primordial germ cells misplaced early in embryogenesis, the pathogenesis of intraspinal teratoma remains unclear. The authors present a series of patients in whom an intradural teratoma arose at the same site as a developmental spinal cord abnormality, including a split cord malformation, myelomeningocele, and lipomyelomeningocele. It is postulated that these lesions were the result of a dysembryogenic mechanism and were not neoplastic.
Ryan T. Mott, Kristi C. Turner, Darell D. Bigner, and Roger E. McLendon
DIFFUSELY infiltrating astrocytomas are the most common primary brain tumors. As a group, they demonstrate an inherent tendency toward malignant progression. Histological grading using the guidelines of the World Health Organization (WHO) remains the gold standard for predicting the biological behavior of these tumors. Although useful, this grading system is often limited due to small sample sizes and the subjectivity in interpretation. Given the important roles for EGFR and PTEN in the malignant progression of astrocytomas, the authors hypothesized that the fraction of tumor cells with aberrations in these genetic loci would correlate with the histological grade.
The authors evaluated 217 consecutive diffusely infiltrating astrocytomas that were graded using the WHO guidelines, including 16 diffuse astrocytomas (WHO Grade II), 72 anaplastic astrocytomas ([AAs] WHO Grade III), and 129 glioblastomas multiforme ([GBMs] WHO Grade IV). Cases were evaluated quantitatively using dual-color fluorescence in situ hybridization with probes for the EGFR and PTEN loci and the centromeres of chromosomes 7 and 10.
The population of tumor cells with polysomy of chromosome 7 and the EGFR locus and monosomy of chromosome 10 and the PTEN locus correlated significantly with histological grade. In particular, high-grade astrocytomas (that is, AAs and GBMs) had elevated fractions of tumor cells with polysomy of chromosome 7 and the EGFR locus and monosomy of chromosome 10 and the PTEN locus. Using these findings, the authors generated a mathematical model capable of subcategorizing high-grade astrocytomas. The successful model incorporated only the percentage of tumor cells with polysomy of EGFR and monosomy of PTEN, as well as patient age. The predictions of this model correlated with survival in a manner similar to histopathological grading.
The findings presented in this study emphasize the utility of combining histological interpretation and molecular testing in the evaluation of infiltrating astrocytomas. These results underscore the utility of building a grading framework that combines histopathological and molecular analysis.
Shahid M. Nimjee, Ciaran J. Powers, Roger E. McLendon, Gerald A. Grant, and Herbert E. Fuchs
Cerebrospinal fluid overproduction resulting in communicating hydrocephalus is observed in patients who have choroid plexus papilloma or choroid plexus carcinoma. Less often, patients with these conditions have diffuse villous hyperplasia. Prior studies report CSF production greater than 3 L per day in these patients. These patients are treated with CSF shunting or by either unilateral choroid plexectomy or staged bilateral choroid plexectomy. The authors present a patient who had a number of congenital anomalies and a karyotype that revealed balanced translocations, 5 to 7 and 9 to 11. She presented with hydrocephalus and had CSF production of 5 L per day, greater output than ever previously reported. She was treated with a single-stage bilateral choroid plexectomy. Histopathological analysis revealed a bilateral choroid plexus papilloma. Postoperatively, the patient responded well clinically and showed radiographic improvement of her hydrocephalus. Bilateral choroid plexus papilloma has been reported in the literature as a cause for neonatal and congenital hydrocephalus. It can result in high CSF output and can be successfully treated with a single-stage bilateral choroid plexectomy. Further studies are ongoing to identify genes involved in embryogenesis of the choroid plexus.
Jong G. Park, Ranjith Babu, Peter G. Kranz, Roger E. McLendon, and Cory Adamson
Intracranial dermoid cysts are rare congenital lesions that typically occur in the cisternal spaces. However, exceptionally rare cases of intraaxial involvement have been reported, with only 8 cases having been described in the literature. The authors report the first case of an intraaxial dermoid cyst located in the medulla and the first occurrence in an elderly patient. They also review the literature of the existing intraparenchymal cases and provide treatment guidelines. A 66-year-old man presented with slowly progressive dysphagia, left lower-extremity numbness, nausea, and hyperhidrosis. Neurological examination revealed decreased pinprick sensation of the left side of his face and body, and decreased vibratory sensation in his left lower extremity. Additionally, he had an unusual extraocular movement in which abduction of the eye resulted in closure of the contralateral eye. Magnetic resonance imaging revealed a nonenhancing cystic lesion centered in the medulla. The patient underwent a suboccipital craniotomy with laminectomy of C1–2 for excision of the cyst, with subtotal resection due to adherence of the cyst wall to the brainstem. At follow-up 7.5 years after surgery, the patient's neurological examination was stable. Magnetic resonance imaging did not reveal any progression or recurrence of the cyst. As the cyst wall is typically adherent to surrounding structures, resection is usually subtotal due to the risk of neurological deficits. As there have been no cases of progression after subtotal resection, gross-total resection is not warranted for the treatment of these lesions.
Clinical data simplified
John H. Sampson, James E. Herndon II, Roger E. McLendon, Vic Hasselblad, Anthony L. Asher, Matthew J. McGirt, and Eric D. Peterson
Ranjith Babu, Jeffrey Hatef, Roger E. McLendon, Thomas J. Cummings, John H. Sampson, Allan H. Friedman, and Cory Adamson
Rhabdoid glioblastoma (GB) is an exceedingly rare tumor in which some of the tumor cells possess rhabdoid features such as eccentric nuclei, abundant eosinophilic cytoplasm, and pseudopapillary formations. These tumors are exceptionally aggressive, and leptomeningeal dissemination is common. In the 9 previously reported cases, the longest survival was only 9 months, with a median survival of 17.8 weeks. The authors report the clinicopathological characteristics of 4 cases of rhabdoid GB and demonstrate the utility of intensive temozolomide and adjuvant therapy in these tumors. The authors also review the literature to provide the most comprehensive understanding of these rare tumors to date.
A retrospective review was performed of patients treated for GB at the Duke University Medical Center between 2004 and 2012. One of two experienced neuropathologists identified 4 cases as being rhabdoid GBs. Immunohistochemistry and fluorescence in situ hybridization analyses were performed in all cases. Kaplan-Meier analysis was used to assess overall survival, with the log-rank test being used to evaluate differences between survival curves. An extensive review of the literature was also performed.
The median age of patients with rhabdoid GB was 30 years. Clinical presentation varied with location, with headache being a presenting symptom in 90% of patients. All lesions were supratentorial, and 45.5% of the cases involved the temporal lobe. Leptomeningeal dissemination occurred in 63.6% of patients, with 1 patient having extracranial metastasis to the scalp and lungs. Fluorescence in situ hybridization revealed epidermal growth factor receptor gain or amplification in all study cases. The median survival in the authors' cohort was significantly higher than that of all previously reported cases (27.5 vs 4.5 months, p = 0.003). Postoperative treatment in the authors' cohort included radiotherapy with concurrent temozolomide, bevacizumab, interleukin 13, CCNU, and/or etoposide.
Enhanced survival in the authors' 4 patients suggests that the current standard of care for the treatment of GB may be beneficial in rhabdoid GB cases, with postoperative radiotherapy and concomitant temozolomide treatment followed by adjuvant therapy. Due to the rapid tumor dissemination associated with these lesions, aggressive and timely therapy is warranted, with frequent surveillance and/or continued therapy despite stable disease. Additionally, patients should undergo full craniospinal imaging to monitor the development of distant metastatic disease.
Albert Moghrabi, Henry S. Friedman, David M. Ashley, Krystal S. Bottom, Tracy Kerby, Elizabeth Stewart, Carol Bruggers, James M. Provenzale, Martin Champagne, Linda Hershon, Melody Watral, Janis Ryan, Karima Rasheed, Shelley Lovell, David Korones, Herbert Fuchs, Timothy George, Roger E. McLendon, Allan H. Friedman, Edward Buckley, and Darryl C. Longee
In this study, the authors sought to investigate the response rate and toxicity of carboplatin in patients with progressive low-grade glioma (LGG). Thirty-two patients with progressive LGG were treated with carboplatin at a dosage of 560 mg/m2. Treatment was given at 4-week intervals and continued until the disease progressed, unacceptable toxicity supervened, or for 12 additional courses after achieving maximal response. Patients with stable disease were treated with a total of 12 cycles. All patients were treated as outpatients. Patients were evaluated for response to treatment and toxicity.
All patients received a minimum of two cycles of carboplatin, and were examined for response. A partial response was achieved in nine patients (28%) and a minimal response in two (6%), for an overall response rate of 34% (11 of 32 patients). Eighteen patients (56%) had stable disease. A partial response was achieved in the nine patients after a median of six cycles (range 4-11 cycles), a minimal response was achieved in the two patients after five cycles. Glioma progression was noted in three patients after three, five, and five cycles, respectively. The 11 patients in whom some response was achieved had either an optic pathway tumor or a juvenile pilocytic astrocytoma. Twenty-six of the 32 patients had those characteristics, making the response rate in that group 42% (11 of 26 patients). Thirty-two patients received a total of 387 cycles of chemotherapy. Hematological toxicity was moderate. Twenty-one patients developed thrombocytopenia (platelet count < 50,000/μl); three patients required one platelet transfusion each. Nine patients developed neutropenia (absolute neutrophil count < 500/μl); one developed fever and required administration of antibiotic agents. One dose adjustment in each of the patients prevented further thrombocytopenia and neutropenia. Two patients with stable disease died of respiratory complications. One patient developed Grade III ototoxicity after receiving five cycles, one patient developed hypersensitivity to carboplatin, and none developed nephrotoxicity.
Carboplatin given at a dosage of 560 mg/m2 every 4 weeks has activity in patients with progressive LGG. This drug regimen is relatively simple and well tolerated. Further investigation and longer follow-up study are warranted.