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Background: Myhre syndrome, caused by pathogenic variants in SMAD4, is characterized by compact body habitus with short stature, distinctive craniofacial appearance, stiff skin, cardiovascular abnormalities (valve stenosis, coarctation, hypoplasia, or stenosis of aorta), effusions of potential spaces (pericardium, pleura, peritoneum), restricted movement of the joints (including thorax), and hearing loss. Lung and airway disease has been reported, but not always well-defined, to include interstitial lung disease, large airway obstruction, and pulmonary arterial hypertension. Excessive fibroproliferation of tissues especially following trauma or surgical instrumentation has been recognized, although these may also present spontaneously. Method: We report the pathologic features of 1 new patient with progressive choanal stenosis, and 22 literature cases, including the expanded history of 5 patients (3 who died). Results: Examination of patient tissues documents cellular fibroproliferation and deposition of excessive extracellular matrix explaining some of the observed clinical features of Myhre syndrome. Conclusion: Excessive fibrosis is noted in multiple tissues, especially heart, lung, and upper and lower airways. Our research provides the first systematic review to provide a knowledge base of gross and pathologic findings in Myhre syndrome.

We report a case of a 2-year-old girl who was diagnosed with natural killer cell acute lymphoblastic leukemia and treated with an acute lymphoblastic leukemia chemotherapy regimen. Two months posttherapy, the disease relapsed with a myeloid immunophenotype. Complete response was then achieved with acute myeloid leukemia therapy followed by unrelated donor umbilical cord allogenic stem cell transplant. Retrospectively, reanalysis of the diagnostic specimen showed minimal myeloperoxidase expression that was called negative by conventional single parameter linear gating but better appreciated on histogram overlays. This case illustrates that even low levels of myeloperoxidase expression should be considered significant in lineage assignment in acute leukemia.

Purpose The purpose of this study was to evaluate trends in management of urachal anomalies at our institution and the safety of nonoperative care. Methods Based on our experience managing urachal remnants from 2000 to 2010 (reported in 2012), we adopted a more conservative approach, including preoperative antibiotic use, refraining from using voiding cystourethrograms (VCUG), postponing surgery until at least six months of age, and considering nonoperative management. A retrospective analysis of urachal anomaly cases was conducted (2011–2016) to assess trends in practice. Charts indicating anomalies of the urachus were pulled and trends in management (nonoperative versus surgical treatment), VCUG and antibiotic use, and outcomes were reviewed. Results Data from 2000–2010 and 2013–2016 were compared. Our findings indicate care has shifted towards nonoperative management. A smaller proportion of patients from 2013–2016 was treated surgically compared to 2000–2010. Patients receiving nonoperative treatment exhibited lower rates of complication relative to surgically managed cases. VCUGs were eliminated as a diagnostic tool for evaluating urachal anomalies. Prophylactic preoperative antibiotic use was standardized. No patients with a known urachal remnant presented later with an abscess or sepsis. Conclusions We find that a shift towards nonoperative treatment of urachal anomalies did not adversely affect overall outcomes. We recommend observing minimally symptomatic patients, especially those under six months old. Study type Performance improvement. Level of evidence Level IV.

Background: In pediatrics, acquired aplastic anemia (AA) is most commonly due to infection, particularly viruses, when a cause can be identified. Coronavirus disease 2019 (COVID-19) has affected more than 197 million people worldwide, and children typically experience a less severe disease course. COVID-19 is known to cause transient hematologic abnormalities, including leukopenia, lymphopenia, anemia and thrombocytosis or thrombocytopenia in severe cases. Objectives: Describe three cases of COVID-19 associated acquired aplastic anemia in immunocompetent pediatric patients. Design/Methods: Case series established by retrospective review of the electronic medical record. Results: Case 1: An 8-year-old Hispanic male presented with a three-week history of increased bruising and a one-week history of progressive exercise intolerance, shortness of breath, pallor and fatigue. Labs showed pancytopenia. Bone marrow aspirate and biopsy was markedly hypocellular at 5-10% consistent with aplastic anemia (Figure 1). Work-up for the etiology of his aplastic anemia was only significant for positive SARS-COV-2 antibodies and a SEC23B variant of unknown significance on a comprehensive bone marrow failure (BMF)/myelodysplastic syndrome (MDS)/leukemia panel from the Children's Hospital of Philadelphia (CHOP). He was treated with eltrombopag olamine and then proceeded to immunotherapy with cyclosporine (CsA) and horse antithymocyte globulin (ATG) when a sibling match was not identified for hematopoietic stem cell transplant (HSCT). Three months later, his peripheral blood counts have improved, and he is no longer transfusion-dependent. Repeat bone marrow aspirate and biopsy continues to show markedly hypocellularity at Case 2: A 5-year-old non-Hispanic white female presented with a two-week history of easy bruising, petechial rash, fatigue and bone pain. Labs showed pancytopenia, and bone marrow aspirate and biopsy showed marked hypocellularity at 5-10% consistent with aplastic anemia (Figure 2). Her aplastic anemia work-up was significant for positive SARS-COV-2 antibodies and subclinical RBC and WBC paroxysmal nocturnal hemoglobinuria (PNH) clones. She was started on eltrombopag olamine and then proceeded to immunotherapy with CsA and ATG when a matched sibling donor was not identified. Three months later, she continues to be severely neutropenic, anemic and thrombocytopenic requiring multiple transfusions. Repeat bone marrow aspirate and biopsy showed variable cellularity with some areas 10-20% and others 70% with an overall cellularity of 50%. Case 3: An 8-year-old non-Hispanic white female presented with a 10-day history of fatigue, bilateral leg pain and pallor. Labs showed pancytopenia, elevated inflammatory markers and elevated hemoglobin F. Bone marrow aspirate and biopsy demonstrated mild-moderate hypocellularity at 40-50%, left-shifted myelopoiesis and dyspoiesis in the erythroid and megakaryocytic cell lines (Figure 3). MDS and acute lymphoblastic leukemia (ALL) fluorescence in situ hybridization (FISH) panels were negative. Additional work-up revealed positive SARS-COV-2 antibodies. Her pancytopenia resolved within two weeks of her initial hospitalization. Four months later, she presented with increased bruising and fatigue. Labs showed leukocytosis, thrombocytopenia, anemia and circulating peripheral blasts. Bone marrow aspirate and biopsy was consistent with B-cell ALL. She is receiving chemotherapy on study COG AALL1732. Conclusion: Severe aplastic anemia (SAA) has high morbidity and mortality, and timely diagnosis is needed for appropriate treatment. Multiple different viral infections have been known to cause acquired aplastic anemia. Data on all the sequelae of COVID-19 infection is still emerging, but it is plausible that COVID-19 infection may cause SAA. All three patients were found to have positive COVID-19 antibodies but did not have any evidence of previous COVID-19 infection. Further research and follow-up is needed to determine if previous COVID-19 infection is indeed a risk factor for development of SAA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR‐1253, a brain‐enriched microRNA that regulates bone morphogenic proteins during cerebellar development. We hypothesized miR‐1253 confers novel tumor‐suppressive properties in medulloblastoma. Using two different cohorts of medulloblastoma samples, we first studied the expression and methylation profiles of miR‐1253. We then explored the anti‐tumorigenic properties of miR‐1253, in parallel with a biochemical analysis of apoptosis and proliferation, and isolated oncogenic targets using high‐throughput screening. Deregulation of miR‐1253 expression was noted, both in medulloblastoma clinical samples and cell lines, by epigenetic silencing via hypermethylation; specific de‐methylation of miR‐1253 not only resulted in rapid recovery of expression but also a sharp decline in tumor cell proliferation and target gene expression. Expression restoration also led to a reduction in tumor cell virulence, concomitant with activation of apoptotic pathways, cell cycle arrest and reduction of markers of proliferation. We identified two oncogenic targets of miR‐1253, CDK6 and CD276, whose silencing replicated the negative trophic effects of miR‐1253. These data reveal novel tumor‐suppressive properties for miR‐1253, i.e., (i) loss of expression via epigenetic silencing; (ii) negative trophic effects on tumor aggressiveness; and (iii) downregulation of oncogenic targets.

Purpose To present the case of a 12-year-old female with an epibulbar osseous choristoma. Observations The patient presented with right-sided conjunctival mass, which caused her discomfort. Slit lamp examination revealed a 5×5-mm, firm nodule in the superotemporal quadrant of the bulbar conjunctiva. The nodule had feeder vessels, adhered firmly to the sclera, and lacked signs of malignancy. The patient underwent excisional biopsy under general anesthesia. During this procedure, great care was taken to avoid perforation of the globe. The pathologic sections were significant for well-circumscribed osseous tissue without atypia. Conclusions and importance We describe diagnosis and successful surgical management of osseous choristoma the rarest subtype of ocular choristoma. With only 65 cases reported since mid-19th century, the condition remains poorly described. This report provides additional information on diagnosis and treatment of this rare condition.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is a leading cause of childhood related morbidity and mortality. Large-scale transcriptional profiling and mutational analyses have facilitated the stratification of medulloblastoma into four primary subgroups, i.e. SHH (sonic hedgehog), WNT (wingless), and non-SHH/WNT groups 3 and 4. The most frequent cytogenetic abnormality in medulloblastoma, i.e. i17q, distinguishes the non-SHH/WNT subgroup. Haploinsufficiency of 17p13.3 is reported in up to 50% of human MB cases. Included within this locus is miR-1253, which is exclusively expressed in the brain and an important regulator of bone morphogenic proteins that play a critical role in cerebellar development. Recently, two oncogenic targets of miR-1253, i.e. TGIF2 and ALX4, were identified in SHH medulloblastoma. Based upon these observations, we hypothesized that miR-1253 may be a putative tumor suppressor gene that undergoes epigenetic silencing in pediatric medulloblastoma. We first discovered reduced expression of miR-1253 in 24 pediatric medulloblastoma specimens and in 7 medulloblastoma cell lines. We then learned that miR-1253 silencing is accomplished via hypermethylation; expectedly, de-methylation of miR-1253, resulted in the recovery of expression with a subsequent decline in MB cell proliferation. MiR-1253 restoration was further concomitant with activation of apoptotic pathways and cell cycle arrest at G(0)/G(1) phase. Moreover, miR-1253 overexpression led to a reduction in cell proliferation, colony formation, migration and invasive potential of MB tumor cell lines. Using high throughput RNA sequencing analysis and luciferase reporter assay, we further identified several oncogenic targets of miR-1253, including CDK-6 and CD276. Taken together, these data strongly support a tumor suppressive role for miR-1253. This would be the first time such an effect has been attributed to miR-1253 in the context of medulloblastoma.

Medulloblastoma (MB) is the most common malignant pediatric tumor of the central nervous system (CNS) and a leading cause of childhood morbidity and mortality. Haploinsufficiency of 17p13.3 is reported in up to 50% of human MB cases. Included within this locus is miR-1253, which is exclusively expressed in the brain and an important regulator of bone morphogenic proteins that play a critical role in cerebellar development. Recently, two oncogenic targets of miR-1253, i.e. TGIF2 and ALX4, were identified in SHH medulloblastoma. Based upon these observations, we hypothesized that miR-1253 may be a putative tumor suppressor gene that undergoes epigenetic silencing in pediatric medulloblastoma. We first discovered reduced expression of miR-1253 in 24 clinical specimens and in 7 medulloblastoma cell lines. We then learned that miR-1253 silencing is accomplished via hypermethylation; expectedly, de-methylation of miR-1253 using 5-AzaC, resulted in recovery of expression with a subsequent decline in MB cell proliferation. MiR-1253 restoration was further concomitant with activation of apoptotic pathways and cell cycle arrest at G(0)/G(1) phase. Moreover, miR-1253 overexpression led to a reduction in cell proliferation, colony formation, migration and invasive potential of MB tumor cell lines. Taken together, these data suggest that miR-1253 may possess tumor suppressor qualities, i.e. 1) loss of expression via epigenetic silencing and 2) negative trophic effects on tumor cell growth and migration. This would be the first time such an effect has been attributed to miR-1253 in the context of medulloblastoma.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is divided into four primary subgroups, i.e. SHH, WNT, and non-SHH/WNT groups 3 and 4. The most frequent cytogenetic abnormality in MB, i.e. i17q, distinguishes the non-SHH/WNT subgroups. Haploinsufficiency of 17p13.3 is reported in up to 50% of non-SHH/WNT MB cases and has been correlated with poor prognosis. At the terminal end of this locus is miR-1253, which is exclusively expressed in the brain and an important regulator of bone morphogenic proteins that play a critical role in cerebellar development. Recently, miR-1253 was identified as a tumor suppressor gene in non-small cell lung cancer (NSCLC) and osteosarcoma. Two oncogenic targets of miR-1253, i.e. TGIF2 and ALX4, have recently been identified in SHH medulloblastoma. Based upon these observations, we hypothesized that miR-1253 may be a tumor suppressor gene in pediatric medulloblastoma. Starting with an expression analysis of miR-1253, we found deregulation in 28 pediatric clinical samples (5 SHH, 10 Grp 3, 13 Grp 4) and 7 medulloblastoma cell lines. Moreover, the locus is hypermethylated in Grp 3 and Grp 4 MB. Expectedly, de-methylation using 5-AzaC resulted in rapid recovery of expression with a concurrent decline in cell proliferation, a property abrogated using an miR-1253 inhibitor. Overexpression of miR-1253 in tumor cell lines led to a reduction in cell proliferation, colony formation, migration and invasiveness, concomitant with activation of apoptotic pathways and reduced stemness. In subcutaneously transplanted HDMB03 cells overexpressing miR-1253, tumor size was noted to be significantly lower. Using high throughput RNA sequencing analysis and luciferase reporter assay, we further identified 2 putative oncogenic targets of miR-1253, i.e. CDK6 and CD276. Taken together, these data purport that in pediatric medulloblastoma, miR-1253 is epigenetically silenced by hypermethylation and possesses tumor suppressor qualities by downregulating its oncogenic targets CDK6 and CD276.

Myhre syndrome, a connective tissue disorder characterized by deafness, restricted joint movement, compact body habitus, and distinctive craniofacial and skeletal features, is caused by heterozygous mutations in SMAD4. Cardiac manifestations reported to date have included patent ductus arteriosus, septal defects, aortic coarctation and pericarditis. We present five previously unreported patients with Myhre syndrome. Despite varied clinical phenotypes all had significant cardiac and/or pulmonary pathology and abnormal wound healing. Included herein is the first report of cardiac transplantation in patients with Myhre syndrome. A progressive and markedly abnormal fibroproliferative response to surgical intervention is a newly delineated complication that occurred in all patients and contributes to our understanding of the natural history of this disorder. We recommend routine cardiopulmonary surveillance for patients with Myhre syndrome. Surgical intervention should be approached with extreme caution and with as little invasion as possible as the propensity to develop fibrosis/scar tissue is dramatic and can cause significant morbidity and mortality.

Purpose We have noted an increasing frequency of diagnosed urachal anomalies. The purpose of this study is to evaluate this increase, as well as the outcomes of management at our institution over 10 years. Methods A retrospective analysis of urachal anomalies at our institution was performed. Inclusion criteria were Anomalies of Urachus (ICD 753.7) or Urinary Anomaly NOS (ICD 753.9) between January 2000 and December 2010. Exclusion criteria were having an asymptomatic urachal remnant incidentally excised. Results Eighty-five patients (49 male, 36 female) presented between 0 and 17 years of age (mean 1.5 years). Diagnoses increased from 0 in 2000 to 21 in 2010. Zero was surgically managed in 2000 while 21 were managed in 2010 (p = 0.0145). Fifteen patients (17.6%) were observed with 13 (13/15, or 15.3%) resolving without complication while 2 were operated on. Average time to resolution (clinical or radiologic) was 4.9 months (Range: 0.4–12.6). A total of seventy-two patients (84.7%) underwent excision. Thirty-nine (54%) surgical cases were outpatient while 33 (46%) were admitted. Thirteen (18%) had post-operative complications. Ten (77%) of the complications were wound infections. Patients under 6 months of age accounted for 60% (6 of 10) of all wound infections and 52% (17 of 33) of hospitalizations. Conclusions Our experience and review of the literature suggest a high complication rate with surgical management in young patients, mostly from infections and support non-operative management of all non-infected urachal remnants in children.

We aimed to study ferritin as an acute phase marker in pediatric infections, and investigate its' clinical significance in the emergency department management of the febrile child. Multiple inflammatory markers, including C-reactive protein, procalcitonin, and serum ferritin, and other iron studies were measured in 37 children, from 3 months through 8 years of age, presenting to the emergency department with temperature of ≥ 39 degrees Celsius, and 38 patients in the same age group with non-febrile illness. Mean serum ferritin was significantly higher in the febrile group 71.4 ng/mL compared to the non-febrile group 45.1 ng/mL (p

Castleman disease is a rare disorder characterized by lymphoid hyperplasia which rarely manifests in children. We present 2 cases which highlight both histologic variants of this disease, and provide suggestions regarding workup and treatment with the goal of making practitioners aware of Castleman disease in the differential diagnosis of a child presenting with vague symptoms.

Background Cardiac fibroma (CF) is a rare benign tumor that is poorly characterized genetically. CF is more commonly encountered in patients with Gorlin syndrome (3%) than the general population. Mutations of the tumor suppressor gene PTCH1 are the underlying cause of Gorlin syndrome. Methods Conventional cytogenetic analysis was performed on a peripheral blood and a CF sample from a 2-week-old male. In addition, fluorescence in situ hybridization (FISH) studies were performed to assess the copy number of the PTCH1 gene locus (9q22.3) on metaphase and interphase cells from these same specimens using yeast artificial protein (YAC) probe 891G1 and on representative paraffin-embedded tissue sections of two additional CFs (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome. Results Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF and in the CF arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining CF from the 2-month-old female. A mutational mechanism other than deletion may be responsible for PTCH1 inactivation on the other locus in this latter patient. Conventional cytogenetic and FISH studies of the peripheral blood sample from the 2-week-old male were normal. Conclusion These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic CFs.

This article describes a teaching strategy used in an undergraduate gerontological nursing clinical course to familiarize students with evidence-based practice. Students are required to read and summarize an assigned evidence-based practice guideline published by The University of Iowa Gerontological Nursing Interventions Research Center. They then develop a “tip sheet,” based on the assigned guideline, to disseminate to health care staff at their practicum sites, which is either a long-term care facility or a hospital-based skilled nursing facility. Nursing students’ reactions to the assignment and nursing staff’s responses to the tip sheets are discussed.

A lack of quality, cost-effective alternatives to nursing home care for community-dwelling older adults exists. The evidence suggests that case management provides quality care in a cost-efficient manner to help older adults remain at home safely and as independently as possible. This article describes HomeSafe, a nurse-managed membership plan that assists older individuals to enhance their health and quality of life, and to age in place in their homes and communities. HomeSafe serves as an innovative model of care and a teaching site for undergraduate and graduate nursing students and nursing faculty at The University of Iowa.

This study tested a 3-month ankle-strengthening and walking program designed to improve or maintain the fall-related outcomes of balance, ankle strength, walking speed, risk of falling, fear of falling, and confidence to perform daily activities without falling (falls efficacy) in elderly nursing home residents. Nursing home residents (N = 81) between the ages of 64 and 100 years participated in the study. Two of the fall-related outcomes, balance and fear of falling, were maintained or improved for the exercise group in comparison to the control group.

The practice of pediatric laboratory medicine involves unique challenges related to development, nutrition, growth, and diseases during different periods of infancy, childhood, and adolescence. This article discusses key aspects of pediatric laboratory medicine faced by clinical pathologists, clinical laboratory scientists, and clinicians, including point-of-care testing, preanalytic variables, analytic factors, age-specific reference intervals, esoteric laboratory tests, clinical impact, and future opportunities. Although challenging, pediatric laboratory testing offers many opportunities for improved patient care, clinical- and laboratory-based research, and education.

In this article, we overview 1 year's activities of an after-school project convening immigrant, low-income Latino parents and elementary schoolchildren for the purpose of learning and publishing together. The intent of the project is to help parents acquire a working familiarity with computers and computer-related technologies as tools for learning and communication in collaboration with their children. We describe the evolution and design of the project into a community-based learning community involving the family, teachers, university staff, and community members. We also present a description of computer learning and publishing activities. We then summarize data showing parents' growth in computer skills. In addition, qualitative research findings on parents' and children's interaction are provided with connections to sociocultural theory. In the concluding section we give attention to a cultural-historical theoretical account of the learning community and implications for thinking about the ways in ...

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Only 11 embryonal rhabdomyosarcomas (E-RMS) have previously been subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 12 E-RMS specimens from 10 patients entered into Intergroup Rhabdomyosarcoma Study (IRS) I-IV and two local patients were analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (50%), 7 (42%), 8 (67%), 11 (42%), 12 (58%), 13q21 (33%), and 20 (33%) and losses of 1p35–36.3 (42%), 6 (33%), 9q22 (33%), 14q21–32 (25%), and 17 (25%) were most prominent. Chromosomal regions 1p35–36.3 and 9q22 represent novel regions of loss. Importantly, loss of 9q22 corresponds to the locus of a putative tumor suppressor gene (PTCH), which has been shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome. Loss of 1p36 corresponds to the locus for PAX7, a paired box containing gene characteristically altered in alveolar rhabdomyosarcoma. Moreover, loss of 1p36 is prominent in another common pediatric soft tissue tumor, neuroblastoma. Gains of 2, 7, 8, 12, and 13 and loss of 14 were seen in the sole prior E-RMS CGH series; thus, these data provide important confirmatory results. In contrast to this previous study, however loss, not gain, of chromosome 17 was observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss of 17p (TP53) in E-RMS. In summary, CGH and FISH analyses of 12 E-RMS specimens revealed novel genomic imbalances that may be useful in directing further molecular studies for the determination of E-RMS critically involved genes. Genes Chromosomes Cancer 27:337–344, 2000. © 2000 Wiley-Liss, Inc.

Informal caregiving and outcomes for caregiving are an important part of health care and of particular importance in nursing. The purpose of this research is to report the results of a survey mailed to nursing experts for validation of the outcome labels Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care and their accompanying indicators. Experts were asked to rate how important the identified indicators were for assessing those two outcomes. In addition, the respondents were asked to what extent nursing interventions influence the achievement of each identified indicator for Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care. In general, the validity of the concept analysis work by the caregiver focus group was supported. Ten indicators for Caregiver Performance: Direct Care were retained, 1 was dropped that was considered most appropriate for indirect care, and 3 new indicators were added to reflect the nurse experts surveyed. For Caregiver Performance: Indirect Care, all of the indicators were retained.

TOPIC.Concept analysis of the nursing diagnosis risk for trauma. PURPOSE.To examine the nursing diagnosis risk for trauma and to specify the risk factors for falling. SOURCES.Research and informational articles on falling, and NANDA Nursing Diagnoses: Definitions and Classification, 1999–2000. CONCLUSIONS.Replace the current nursing diagnosis risk for trauma with the more specific nursing diagnosis unintentional injury risk: falls. The other risks included in risk for trauma (e.g., burns) also will need to be developed.

Background.—From both epidemiologic and pathologic viewpoints, gangliogliomas exhibiting components of giant cell glioblastomas are extraordinary neoplasms. We report herein the case of a 6-year-old girl who presented initially with a World Health Organization grade IV anaplastic ganglioglioma (a mixed ganglion cell tumor–giant cell glioblastoma). Despite aggressive management, the patient died of disease in a relatively short period. Methods.—Formalin-fixed, paraffin-embedded tissue blocks were sectioned at 5 μm for histochemical and immunohistochemical analyses. Hematoxylin-eosin–stained sections and immunohistochemically stained sections from the primary and secondary resections were reviewed. Reactivity for glial fibrillary acidic protein, neurofilament protein, synaptophysin, and Ki67 nuclear antigen was evaluated. Results.—Histologically, 2 distinct cell populations were noted on both the primary and secondary resections. The primary resection revealed a neoplasm having a predominant glial component consistent with a glioblastoma. Interspersed were dysmorphic ganglion cells supporting a diagnosis of ganglioglioma. The second resection (following therapy) demonstrated a much more prominent dysmorphic ganglion cell component and a subdued glial component. Conclusion.—Although immunohistochemical analysis clearly distinguished the 2 tumor cell populations, the identification of Nissl substance in neurons proved to be equally helpful. Although other cases of grade III gangliogliomas and rare cases of grade IV gangliogliomas have been reported, the present case is exceptional in that, to our knowledge, it is the only report of a patient who presented initially with a composite grade IV ganglioglioma and who was clinically followed up to the time of death. This case allows direct comparison between the histologic findings in a giant cell glioblastoma and a ganglioglioma and documents the aggressive biologic behavior of this complex neoplasm.