Biomedical subjects

Christine E Fuller

Publications and source records attributed to Christine E Fuller.

At least 19 recordsLinked to original sources

PubMed2006

Ewing sarcoma-family tumors that arise after treatment of primary childhood cancer.

BACKGROUND: Unlike osteosarcoma, the Ewing sarcoma family of tumors (ESFT) has rarely been reported as secondary malignant neoplasms after treatment of childhood cancer. ESFT arising as a second cancer was reviewed and characterized at our childhood cancer center. METHODS: A retrospective review was undertaken of 11,183 patients age <21 years who were treated for a primary cancer between March 1962 and December 2003 at St. Jude Children's Research Hospital. All cases of ESFT were confirmed to have a rearranged EWS gene. RESULTS: Six cases of ESFT (1.3% of 479 second cancers) were identified in patients previously treated for lymphoma (n = 3), leukemia (n = 1), retinoblastoma (n = 1), or Wilms tumor (n = 1). None of these patients had a family history suggestive of a familial cancer syndrome. The median time between diagnosis of primary cancer and diagnosis of ESFT was 5.9 years (range, 3.1-18.3 years). ESFT occurred in typical anatomic locations: rib (n = 2), chest wall soft tissues (n = 2), pelvis (n = 1), and extremity (n = 1). One tumor arose at the margin of a previous radiotherapy field and 1 arose distant from previous radiotherapy fields; all other patients had not received radiotherapy. Three patients are alive at the time of this report, including 2 whose ESFT was diagnosed more than 8 years ago. CONCLUSIONS: ESFT occurs rarely after treatment of a primary cancer during childhood, and most cases do not appear to be related to radiation therapy. Long-term survival can be achieved in some patients, and therefore secondary ESFT should be treated with curative intent.

Adolescent↗

PubMed2006

Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma.

Both epidermal growth factor receptor (EGFR) and ErbB-2 play an important role in cancer biology and constitute promising molecular targets of therapy. EGFR and ErbB-2 expression has been observed in rhabdomyosarcoma cell lines but not analyzed systematically in rhabdomyosarcoma tumors. Tissue microarray sections representing 66 rhabdomyosarcoma tumors (34 embryonal rhabdomyosarcoma, 32 alveolar rhabdomyosarcoma) were surveyed by immunohistochemistry using antibodies specific for EGFR and ErbB-2. Immunostains were assessed for intensity (0: no immunostaining; 1: weak; 2: moderate; 3: strong) and percentage of at least 500 neoplastic cells exhibiting membranous or membranous and cytoplasmic immunostaining. EGFR and ErbB-2 expression was considered positive if the product of intensity and percentage was greater than 10. Patients had a median age of 5.7 years (range 8 months-19.1 years), and of 65/66 patients, 38 were males and 27 were females. Expression of ErbB-2 was identified in 22/66 (33%) cases and tended to be more frequent in the alveolar subtype (13/32, 41%, vs 9/34, 26%, P=0.30). Expression of EGFR was identified in 31/66 (47%) cases and correlated with the embryonal subtype (26/34, 76%, vs 5/32, 16%, P<0.0001) independent of stage, age, and gender. Coexpression of EGFR and ErbB-2 was identified in eight tumors, of which six were embryonal rhabdomyosarcoma. None of the cases exhibited EGFR or ErbB-2 gene amplification, as assessed using fluorescence in situ hybridization. Furthermore, analysis of 11 additional rhabdomyosarcoma tumors (six alveolar; five embryonal) revealed no evidence of mutations in EGFR exons 18, 19, 20, and 21. In summary, expression of EGFR and/or ErbB-2 is detected in a sizeable subset of rhabdomyosarcoma tumors without evidence of EGFR or ErbB-2 amplification or mutations in the EGFR tyrosine kinase domain. Notably, expression of EGFR correlates with the embryonal subtype, which is also more likely to coexpress EGFR and ErbB-2.

Adolescent↗

PubMed2006

Pediatric surface osteosarcoma: clinical, pathologic, and radiologic features.

BACKGROUND: Osteosarcoma (OS) arising from the surface of bone is far less common than its intramedullary counterpart. Although surface OSs share some radiographic and clinical features, they can be divided into three distinct histologic subtypes. PROCEDURE: We reviewed the clinical, radiographic, and pathologic features of 14 cases of pediatric surface OS treated at St. Jude Children's Research Hospital between 1970 and 2003. RESULTS: Seven patients had parosteal, five had periosteal, and two had high-grade surface OS. The median age at diagnosis was 16.2 years (range, 13.6-18.5 years). Nine patients were male; 11 were Caucasian. None had metastatic disease at diagnosis. Primary tumor sites included distal femur (n = 6), mid to proximal femur (n = 4), and mid to proximal tibia (n = 4). All 14 patients were treated with surgery, and 7 (1 with parosteal, 4 with periosteal, 2 with high-grade tumors) received chemotherapy. One patient experienced pulmonary metastasis of periosteal OS 16 months and 43 months after diagnosis; long-term disease-free survival followed resection of the metastatic tumors. Twelve patients remained alive and disease-free a median of 10 years (range, 1.5-25.4 years) after diagnosis. One patient died of high-grade surface OS 1.8 years after diagnosis, and one patient with periosteal OS died of gastric cancer 18.2 years after diagnosis of OS. CONCLUSIONS: The histologic grade predicts the clinical behavior of pediatric surface OS. Complete resection is the treatment of choice regardless of tumor subtype. Whereas chemotherapy is not indicated for parosteal OS, its role in periosteal OS remains controversial.

Adolescent↗

PubMed2006

Immunohistochemical detection of multidrug-resistant protein expression in retinoblastoma treated by primary enucleation.

PURPOSE: To compare the expression of multidrug-resistant proteins in retinoblastoma tumors among eyes treated with primary enucleation. METHODS: A group of 18 patients with unilateral retinoblastoma with advanced intraocular disease was selected for the study. All patients had undergone primary enucleation. A histologic specimen from each patient was retrieved from the pathology archives and a tissue gene microarray was constructed (0.6 x 3-4 mm). Standard immunohistochemical techniques were used to study the tissue microarrays for the expression of the ATP-binding cassette (ABC) transporters: breast cancer resistance protein (BCRP; ABCG2), multidrug-resistant protein 1/P-glycoprotein (MDR1/Pgp; ABCB1), multidrug-resistant-associated protein 1 (MRP1; ABCC1), MRP2 (ABCC2), and MRP4 (ABCC4). RESULTS: Of the 18 specimens retrieved, 16 had adequate tissue for study. MRP1 was expressed in 8 (50%) of 16 tumors, and MRP2 was expressed in 5 (31%) of 16 tumors. MDR1/Pgp was found in 2 (12%) of 16 retinoblastomas. MRP4 and BCRP were not detected in any of the tumors studied. CONCLUSIONS: The results show that multiple ABC transporters were present in a cohort of sporadic patients with unilateral retinoblastoma who underwent primary enucleation. Studies are planned of the expression of ABC transporters in eyes treated by chemotherapy and/or radiation as a comparison with this group.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Percutaneous biopsy of pediatric solid tumors.

BACKGROUND: The objective of the current study was to determine the diagnostic accuracy of percutaneous biopsy of pediatric solid tumors, a procedure that is less invasive than open biopsy. METHODS: The authors conducted a retrospective analysis of clinical data related to 202 percutaneous core-needle biopsies of solid tumors at St. Jude Children's Research Hospital over 5.5 years (from 1997 to 2003). In 103 patients, the procedure was performed to establish an initial diagnosis of a suspected malignancy; and, in 99 patients, disease recurrence was suspected. Biopsies were guided by ultrasound, computed tomography, or fluoroscopic imaging. From each tumor, 1-17 core biopsy samples (median, 6 samples) were obtained; the median needle size was 15 gauge (range, 13-20 gauge). The specimens were submitted for histopathologic analysis and other ancillary procedures (molecular pathology and/or cytogenetic analyses). The accuracy of the diagnoses from the biopsies was determined by subsequent surgery with or without pathologic assessment or by outcome. RESULTS: When the biopsy samples were assessed for the presence of malignancy, there were 121 true-positive results (90% sensitivity), 67 true-negative results (100% specificity), and 14 false-negative results (93% accuracy). In 103 tumors, when the procedure was performed for initial diagnosis, percutaneous needle biopsy showed a sensitivity of 97%, a specificity of 100%, and an accuracy of 98%. The 99 procedures for suspected recurrence were less reliable (sensitivity, 83%; specificity, 100%; accuracy, 88%). CONCLUSIONS: Image-guided percutaneous biopsy was highly accurate and safe in the diagnosis of pediatric malignant solid tumors. This technique may be able to supplant diagnostic open biopsy.

Adolescent↗

PubMed2005

Definitive surgery and multiagent systemic therapy for patients with localized Ewing sarcoma family of tumors: local outcome and prognostic factors.

BACKGROUND: The local management of Ewing sarcoma family of tumors (ESFT) often centers on the surgical resectability of the primary lesion and physician biases regarding differences in the morbidity between primary surgical and radiotherapeutic management. METHODS: The authors retrospectively reviewed the records of 33 patients with localized ESFT who underwent surgery and received systemic chemotherapy at St. Jude Children's Research Hospital (Memphis, TN). Two multiagent systemic chemotherapy regimens were used: 14 patients received vincristine, doxorubicin, cyclophosphamide, and actinomycin D (VACA), and 19 received VACA in combination with ifosphamide and etoposide. The primary tumor was surgically resected via a wide, local excision (n = 32) or a marginal excision (n = 1)performed either at diagnosis or after 3-5 months of systemic chemotherapy. Clinical outcome and prognostic factors for disease control were reported in the current study. RESULTS: The median follow-up for patients was 9.9 years. The 5-year and 10-year survival rates were 84.5% and 75.8%, respectively. At 5 years, the cumulative incidence of local disease recurrence was 12.5%, and the event-free survival (EFS) rate was 71.7%. The same values were found at 10 years. The site of tumor origin was a significant predictor of EFS. The survival rate of patients whose tumors arose in bone was 78.6%, and the survival rate of patients whose tumors originated in soft tissue was 25.0% (P = 0.028). No other factors investigated were predictive of outcome. CONCLUSIONS: Local disease control and overall outcome for patients with ESFT managed by multiagent systemic therapy and surgery was excellent. Local disease control rates remained near 90% at 10-year follow-up. Patients with extraosseous primary sites of disease may fare less well with this approach to therapy.

Adolescent↗

PubMed2005

Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy.

PURPOSE: To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH). PATIENTS AND METHODS: Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed. RESULTS: Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy. CONCLUSION: Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.

Central Nervous System Neoplasms↗

PubMed2005

INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas.

Rhabdoid cells are encountered in specific entities, such as malignant rhabdoid tumor and atypical teratoid/rhabdoid tumor, as well as in composite rhabdoid tumors derived secondarily from other tumor types. Although rhabdoid tumors are uniformly aggressive, distinction of the entity from the phenotype remains important for its therapeutic implications. The majority of malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors affect infants and young children, harbor chromosome 22q deletions, and inactivate the INI1/hSNF5/BAF47 tumor suppressor gene on 22q11.2. In contrast, most composite rhabdoid tumors are diagnosed in adults, with FISH detectable 22q losses the exception rather than the rule. However, this assay remains limited since 22q dosages are maintained in 20-30% of malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors. Furthermore, chromosome 22 losses are common in some parent tumor types, particularly meningiomas. The recently developed INI1 antibody shows loss of nuclear expression in malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors, though its status in composite rhabdoid tumors is largely unknown. Therefore, we utilized immunohistochemistry and FISH to study INI1 expression and 22q dosages, respectively, in 40 composite rhabdoid tumors, including 16 meningiomas, 15 carcinomas, three melanomas, two sarcomas, two glioblastomas, and 1 neuroblastoma. Approximately 70% of rhabdoid meningiomas had a 22q deletion, but this was rare in other tumor types. Except for one retroperitoneal leiomyosarcoma, nuclear INI1 expression was retained in all composite rhabdoid tumors, including meningiomas with 22q deletion. Therefore, we conclude that INI1 immunohistochemistry is a relatively simple, sensitive, and specific technique for distinguishing malignant rhabdoid tumor and atypical teratoid/rhabdoid tumor from composite rhabdoid tumor.

Adult↗

PubMed2005

Molecular diagnostics in central nervous system tumors.

Central nervous system (CNS) neoplasms can be diagnostically challenging, due to remarkably wide ranges in histologic appearance, biologic behavior, and therapeutic approach. Nevertheless, accurate diagnosis is the critical first step in providing optimal patient care. As with other oncology-based specialties, there is a rapidly expanding interest and enthusiasm for identifying and utilizing new biomarkers to enhance the day-to-day practice of surgical neuropathology. In this regard, the field is primed by recent advances in basic research, elucidating the molecular mechanisms of tumorigenesis and progression in the most common adult and pediatric brain tumors. Thus far, few have made the transition into routine clinical practice, the most notable example being 1p and 19q testing in oligodendroglial tumors. However, the field is rapidly evolving and many other biomarkers are likely to emerge as useful ancillary diagnostic, prognostic, or therapeutic aids. The goal of this article is to highlight the most common genetic alterations currently implicated in CNS tumors, focusing most on those that are either already in common use in ancillary molecular diagnostics testing or are likely to become so in the near future.

Animals↗

PubMed2004

Second neoplasms in pediatric patients with primary central nervous system tumors: the St. Jude Children's Research Hospital experience.

BACKGROUND: Details on second neoplasms (SNs) following pediatric central nervous system (CNS) tumors are scant, because of the rarity of such SNs. The goal of the current study was to investigate and characterize these rare SNs. METHODS: The authors reviewed clinical and treatment data on all institutional patients age < 22 years at diagnosis of a primary CNS tumor who developed any type of SN. Patients with neurofibromatosis type 1 were excluded. Cumulative incidence rates were estimated, and putative risk factors were analyzed. RESULTS: The SNs investigated in the current study included 10 gliomas (42%), 5 meningiomas (21%), 2 desmoid tumors, 2 myelodysplastic syndromes, 2 basal cell carcinomas, 1 leukemia, 1 malignant fibrous histiocytoma, and 1 thyroid carcinoma. Twenty-one patients had previously received radiotherapy, and 12 patients had received chemotherapy. The SN was related to a genetic cause in 7 patients (29%). Eleven patients died of their SNs, including 8 patients with glioma and 2 patients with myelodysplastic syndromes. The estimated 15-year cumulative incidence rate for malignant SNs was 4%. Children with choroid plexus tumors had an estimated 10-year cumulative incidence rate of 20.2%; 2 of those patients had germline TP53 mutations. Age </= 2 years was a significant risk factor (P = 0.016) for development of an SN only when patients with genetic conditions were included in the analysis. No significant difference in the estimated cumulative incidence of SNs was found among patients who had received different types of therapy. CONCLUSIONS: The risk of lethal SNs after pediatric CNS tumors is small. Young patients and patients with choroid plexus tumors appear to have an increased risk of SNs that is associated with genetic factors.

Adolescent↗

PubMed2004

The TP53-ARF tumor suppressor pathway is frequently disrupted in large/cell anaplastic medulloblastoma.

We analyzed the TP53 and INK4A/ARF loci in 29 pediatric medulloblastomas. Mutually exclusive mutation in TP53, methylation of P14(ARF) or deletion of INK4A/ARF were identified in 21% (6/29) of tumors. Five of these alterations were detected in large cell/anaplastic medulloblastomas or tumors with significant anaplasia. Our data provide the first evidence that alterations within the TP53-ARF tumor suppressor pathway contribute to development of aggressive forms of medulloblastoma.

Anaplasia↗

PubMed2004

Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors.

PURPOSE: The purpose is to estimate the maximum-tolerated dose (MTD) of temozolomide and irinotecan given on a protracted schedule in 28-day courses to pediatric patients with refractory solid tumors. EXPERIMENTAL DESIGN: Twelve heavily pretreated patients received 56 courses of oral temozolomide at 100 mg/m(2)/day for 5 days combined with i.v. irinotecan given daily for 5 days for 2 consecutive weeks at either 10 mg/m(2)/day (n = 6) or 15 mg/m(2)/day (n = 6). We assessed toxicity, the pharmacokinetics of temozolomide and irinotecan, and the DNA repair phenotype in tumor samples. RESULTS: Two patients experienced dose-limiting toxicity (DLT) at the higher dose level; one had grade 4 diarrhea, whereas the other had bacteremia with grade 2 neutropenia. In contrast, no patient receiving temozolomide and 10 mg/m(2)/day irinotecan experienced DLT. Myelosuppression was minimal and noncumulative. No pharmacokinetic interaction was observed. Drug metabolite exposures at the MTD were similar to exposures previously associated with single-agent antitumor activity. One complete response, two partial responses, and one minor response were observed in Ewing's sarcoma and neuroblastoma patients previously treated with stem cell transplant. Responding patients had low or absent O(6)-methylguanine-DNA methyltransferase expression in tumor tissue. CONCLUSIONS: The MTD using this schedule was temozolomide (100 mg/m(2)/day) and irinotecan (10 mg/m(2)/day), with DLT being diarrhea and infection. Drug clearance was similar to single-agent values, and clinically relevant SN-38 lactone and MTIC exposures were achieved at the MTD. As predicted by xenograft models, this combination and schedule appears to be tolerable and active in pediatric solid tumors. Evaluation of a 21-day schedule is planned.

Adolescent↗

PubMed2004

Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors.

BACKGROUND: Local tumor control for patients with Ewings sarcoma family of tumors (ESFT) is favorable when the primary tumor is resectable or small. Local failure rates for patients who received combined surgery and RT were reviewed to determine outcome and prognostic factors. PROCEDURES: We performed a retrospective review of all patients with localized ESFT treated with combined definitive surgery and RT between 1978 and 2001, at St. Jude Children's Research Hospital. Rates of local failure, survival, and prognostic factors for recurrence were determined in 39 patients who received combined local therapy. Systemic treatment included vincristine, actinomycin D, cyclophosphamide, and doxorubicin (6 patients), with the addition of ifosfamide and etoposide (33 patients). RESULTS: With a median follow-up of 8.7 years the 5- and 8-year survival estimates were 89.2 +/- 5.4% and 82.8 +/- 7.3%. The 8-year incidence of local failure was 10.8 +/- 5.2%. The 8-year local failure rate for patients with positive surgical margins was 17% and for negative surgical margins 5% (P = 0.25). Overall survival was improved for patients with negative surgical margins (94 vs. 71%, P = 0.052). Tumor size, site, histologic response, and radiation dose did not significantly alter the rate of local failure. CONCLUSIONS: Patients with ESFT managed with definitive surgery and irradiation have favorable local control rates. Even among patients with unfavorable prognostic factors local tumor control remained excellent.

Adolescent↗

PubMed2004

Primary pelvic telangiectatic osteosarcoma metastatic to both orbits.

We report a case of a 23-year-old man with primary pelvic telangiectatic osteosarcoma metastatic to both orbits. The patient had proptosis with optic neuropathies and intermittent third nerve palsies. His disease was unresponsive to chemotherapy or radiotherapy, and extensive craniofacial involvement precluded surgical resection. The patient died of his disease. Telangiectatic osteosarcoma, a rare variant of osteosarcoma that is distinguished by blood-filled cystic spaces, may metastasize to the orbit and skull base. Because telangiectatic osteosarcoma may radiographically resemble other benign and malignant lesions, biopsy is essential for accurate diagnosis that will ultimately dictate clinical therapy. However, patients with this disease have a poor prognosis.

Adult↗

PubMed2003

Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics.

Deletions of chromosomes 1p and 19q are associated with chemosensitivity and enhanced survival in oligodendrogliomas. Therefore, we have utilized FISH analysis as an ancillary tool for diffuse gliomas with suspected oligodendroglial features. To date, 246 gliomas have been analyzed in 131 male and 93 female patients, including 109 oligodendrogliomas (O), 109 mixed oligoastrocytomas/equivocal gliomas (MOA), and 28 astrocytomas (A). To address specificity, we also analyzed 41 oligodendroglioma mimics, including 12 central and 12 extraventricular neurocytomas (EVN), 12 dysembryoplastic neuroepithelial tumors, and 5 clear cell ependymomas. Aside from 2 EVNs, no mimics demonstrated codeletion. Three patterns were associated with glioma cell type (O vs. MOA/A): -1p/19q, -19q alone, and polysomies. Long-term survivals of >5-years (N=47) and >10-years (N=16) were associated with 1p/19q codeletion in 60% and 75% respectively, whereas solitary 19q deletion accounted for 11% and 6% respectively. Survivals<2-years (N=10) were associated with lack of deletions in 70%. A few older patients with high-grade, "genetically favorable" tumors did poorly, whereas prolonged survival was observed in several low-grade glioma patients despite a lack of the "genetically favorable" pattern. Our data suggests that: 1) FISH-detectable 1p/19q codeletion is relatively specific for oligodendrogliomas with long survival, 2) solitary 19q deletion may also portend a favorable prognosis in a smaller subset, and 3) combined clinicopathologic and genetic assessment likely provides a more accurate means of patient stratification than either one alone.

Adolescent↗

PubMed2003

Status of the NF1 tumor suppressor locus in uveal melanoma.

BACKGROUND: A clinical association has been observed between uveal melanoma and neurofibromatosis type 1 (NF1). This study aims to determine whether the NF1 tumor suppressor gene is mutated in uveal melanoma. METHODS: Thirty-eight uveal melanomas, as well as normal uveal melanocytes, were examined for NF1 deletions by dual-color fluorescence in situ hybridization, and for expression of the NF1 protein (neurofibromin) by immunohistochemistry and Western blot analysis. RESULTS: Normal uveal melanocytes strongly express neurofibromin. Eighteen (47%) of uveal melanomas demonstrated weak expression of neurofibromin. One large tumor contained a deletion of the NF1 locus and lacked neurofibromin expression. Two other tumors contained additional copies of the NF1 chromosomal region. CONCLUSION: Mutations of the NF1 gene may occasionally play a role in the pathogenesis of uveal melanoma. Clinical Relevance A search for biallelic NF1 mutations in uveal melanomas from patients with neurofibromatosis will be of interest to determine whether germline NF1 mutations may predispose to uveal melanoma.

Adult↗

PubMed2003

Clinical utility of fluorescence in situ hybridization (FISH) in morphologically ambiguous gliomas with hybrid oligodendroglial/astrocytic features.

Gliomas with hybrid oligodendroglial/astrocytic features are diagnostically problematic, and our ability to predict tumor behavior is limited. Some likely represent intermingled mixed oligoastrocytomas (MOAs), though precise diagnostic criteria and specific markers for this lesion are lacking. From the files at Washington University (1987-2000), 155 "ambiguous" glioma/intermingled MOA candidates were independently classified and graded by 5 neuropathologists, with consensus-derived pure oligodendrogliomas and astrocytomas excluded from further study. The 90 remaining cases (grades II = 29, III = 44, IV = 17) were analyzed by FISH on formalin-fixed, paraffin-embedded sections. Detectable deletions included combined 1p/19q (9%), solitary 19q (22%), PTEN/DMBT1 (26%), and p16 (32%). EGFR amplification was found in 11%. Patients were followed until death (47%) or a median of 3.3 years. Similar to prior glioma series, patient age (p < 0.0001) and tumor grade (p < 0.0001) were strongly associated with survival times. EGFR amplification (p = 0.0007) and deletions of PTEN/ DMBT1 (p = 0.016) or p16 (p = 0.014), either individually or as a group (p = 0.04), portended a shorter median survival compared with tumors lacking these alterations. We conclude that 1) distinct genetic subsets are identifiable by FISH in morphologically ambiguous gliomas, and 2) both histological grading and molecular analysis yield prognostically useful information.

Adolescent↗

PubMed2003

Clinical and pathological features of intracranial chordoma with orbital involvement in a child.

We examined a 44-month-old girl with proptosis of the left eye. Magnetic resonance imaging showed a dumbbell-shaped mass involving the cavernous sinus with orbital extension. Biopsy and immunohistochemistry showed the tumor to be a primitive chordoma. Intracranial chordoma should be considered in the differential diagnosis of children with orbital lesions. Immunohistochemistry is helpful in differentiating chordomas from other primitive round-cell or spindle-cell tumors.

Brain Neoplasms↗