This rare neoplasm of infancy is characterize by a voluminous size, intense desmoplasia, and the frequent presence of divergent astrocytic and ganglionic differentiation. A combination of surgery, chemotherapy, and radiotherapy may provide a potential means of effective treatment.
Epidemiology Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis and Treatment Commonly Used Terms
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Very rare AGE RANGE-MEDIAN Infancy, usually <18 months of age
Most common within first 4 months
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ABNORMALITIES
Desmoplastic infantile astrocytoma and ganglioglioma: a search for genomic characteristics.
Kros JM, Delwel EJ, de Jong TH, Tanghe HL, van Run PR, Vissers K, Alers JC.
Department of Pathology, University Hospital Rotterdam-Dijkzigt, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Acta Neuropathol (Berl) 2002 Aug;104(2):144-8 Abstract quote
In the present study the clinical data, histology, proliferation rate, DNA ploidy status and the results of TP53 mutation analysis and comparative genomic hybridization (CGH) of three typical cases of desmoplastic infantile astrocytoma and ganglioglioma are presented.
Postoperative disease-free intervals of 11, 8 and 3 years were recorded and in none of the cases were radiological signs of tumor recurrence.
No TP53 mutations (exons 5-8) were found. CGH analysis revealed loss of 8p22-pter in one case, while in another case gain of 13q21 was detected. In the case with the follow-up of 11 years an aneuploid DNA-flow cytogram along with slightly increased MIB-1 labeling index (LI) was found.
The results demonstrate little genetic instability in these low-grade lesions. DNA-aneuploidy seems not to be indicative of tumor progression.
It is concluded that the genetic aberrations found in desmoplastic infantile ganglioglioma differ from those encountered in common astrocytomas.
Desmoplastic infantile ganglioglioma (DIG): cranial ultrasound findings.
Lababede O, Bardo D, Goske MJ, Prayson RA.
Department of Radiology, Cleveland Clinic Children's Hospital, OH 44195, USA.
Pediatr Radiol 2001 Jun;31(6):403-5 Abstract quote
Desmoplastic infantile ganglioglioma (DIG) is a rare brain tumor encountered in infants.
In spite of its large size at presentation and occasional high mitotic activity on histopathology, the tumor has a good prognosis. A 7-month-old baby girl developed increasing head circumference. On ultrasound, a large multicystic mass was seen.
We report the cranial ultrasound findings for the first time. Correlative imaging of this recently recognized entity is shown.
LABORATORY MARKERS FLOW CYTOMETRY
Ganglioglioma, a malignant tumor? Correlation with flow deoxyribonucleic acid cytometric analysis.
Bowles AP Jr, Pantazis CG, Allen MB Jr, Martinez J, Allsbrook WC Jr.
Department of Surgery, Medical College of Georgia, Augusta.
Neurosurgery 1988 Sep;23(3):376-81 Abstract quote
This study describes the flow cytometric deoxyribonucleic acid (DNA) analysis of a resected ganglioglioma. The initial histopathological analysis revealed a benign tumor characterized by a predominance of mature ganglion cells. The flow cytometric DNA analysis of the necrotic areas, however, demonstrated an aneuploid population of cells. Further examination by histological analysis of the tumor revealed both benign and atypical foci.
The retrospective DNA analysis performed from paraffin sections of tissue with benign-histological findings demonstrated euploid populations of cells consistent with a benign, slow-growing lesion. In contrast, DNA analysis performed from tissue with atypical histological findings revealed aneuploid populations of cells consistent with a malignant phenotype.
Our analysis provides additional data supporting the existence of tumor progression in some gangliogliomas. Results support the concept of tumor cell heterogeneity and the importance of adequate tumor sampling. The finding of aneuploid populations with unfavorable histology further supports the use of flow cytometry as an adjunct method in assessing tumor biology.
Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential ("desmoplastic infantile gangliogliomas"). Report on 11 cases of a distinctive embryonal tumor with favorable prognosis.
VandenBerg SR, May EE, Rubinstein LJ, Herman MM, Perentes E, Vinores SA, Collins VP, Park TS.
J Neurosurg 1987 Jan;66(1):58-71 Abstract quote
Eleven cases of supratentorial neuroepithelial tumor presenting in infancy are reported. The tumors were characterized by their voluminous size, their intense desmoplasia, and the frequent presence of divergent astrocytic and ganglionic differentiation as demonstrated by special neurohistological and immunohisto- and immunocytochemical techniques.
All the tumors presented in subjects below the age of 18 months, usually within the first 4 months of life. They most often involved the frontal and parietal regions and were composed predominantly of a dense desmoplastic tissue superficially resembling a moderately cellular fibroma. The fibroblastic elements were admixed with variable numbers of pleomorphic neuroepithelial cells. Divergent astrocytic and neuronal differentiation was demonstrable in nine of the 11 tumors. All showed astrocytic differentiation.
The study of one example by electron microscopy, immunocytochemistry, and tissue culture disclosed that the astrocytic tumor cells were partly invested by a pericytoplasmic basal lamina. Successful total or near-total surgical resection has been followed by a favorable postoperative course extending in some cases over many years of tumor-free survival.
The name "desmoplastic infantile ganglioglioma" is proposed for this apparently distinct clinicopathological entity, whose massive size is indicative of a pre- or perinatal origin. Its identification can be achieved by careful histological analysis and is of obvious prognostic significance.
Clinical, radiological and histological findings in desmoplastic infantile ganglioglioma.
Sperner J, Gottschalk J, Neumann K, Schorner W, Lanksch WR, Scheffner D.
Universitats-Kinderklinik (KAVH), Universitatsklinikum Rudolf Virchow, Freie Universitat Berlin, Germany.
Childs Nerv Syst 1994 Sep;10(7):458-62 Abstract quote
The clinical course and radiological and histological findings in a 30-month-old boy suffering from desmoplastic infantile ganglioglioma are reported. The child's development was normal until a series of complex partial seizures occurred at the age of 7 months.
Cranial computed tomography and magnetic resonance imaging revealed a cystic mass with intensive ring-shaped contrast enhancement in the right temporal fossa without shift of intracranial structures. Histologically, the firm, grayish tumor showed an enormous amount of connective tissue, cystic areas, and some mitoses. Glial and neuronal cell lines were identified by immunocytochemical methods. Eighteen months after surgery the boy had developed well without any neurological dysfunction; no radiation or chemotherapy was given. For the first time a synopsis of radiological findings in this rare brain tumor is correlated with the results of multiple histological and immunocytochemical studies.
Despite some malignant characteristics, the prognosis of this dysontogenetic brain tumor is good.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL VARIANTS ANAPLASTIC
Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis.
Jay V, Squire J, Becker LE, Humphreys R.
Department of Pathology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Cancer 1994 Jun 1;73(11):2862-8 Abstract quote
BACKGROUND. Malignant transformation of a ganglioglioma is rare and is generally restricted to the glial component. The authors described a unique case in which neuronal and glial elements exhibited anaplasia in a ganglioglioma. A subtotal resection of a large left temporal tumor extending into the diencephalon and brain stem in a 10-year-old boy revealed a ganglioglioma with no atypical features. The histologic findings were unchanged at further resections 4 and 12 months later. Radiotherapy was instituted with 5500 cGy in 30 fractions 21 months after initial resection. The patient returned 3 years later with a massive midline tumor recurrence.
METHODS. The tumor was studied by conventional histologic methods, immunohistochemistry, flow cytometric methods, transmission electron microscopy, immune electron microscopy, and cytogenetic analysis.
RESULTS. Although the first three resections revealed a typical ganglioglioma, the fourth resection revealed a cellular pleomorphic tumor with many multinucleated cells and mitoses. The tumor cells expressed glial fibrillary acid protein (GFAP) and synaptophysin on double labeling. By electron microscopy, intermediate filaments, microtubules and abundant rough endoplasmic reticulum, and neurosecretory granules were seen. Immune electron microscopy showed GFAP and synaptophysin within tumor cells. Flow cytometric studies revealed G0G1, 78%; S-phase, 9%; and G2M, 13%. Tumor cytogenetics on short term cultures revealed a complex abnormal karyotype with three sublines containing several structural chromosomal abnormalities.
CONCLUSIONS. A unique anaplastic transformation of a ganglioglioma is reported with the anaplastic cells exhibiting neuronal and astrocytic features.
Recurrent anaplastic ganglioglioma: pathological characterization of tumor cells. Case report.
Sasaki A, Hirato J, Nakazato Y, Tamura M, Kadowaki H.
Department of Pathology, Gunma University School of Medicine, Japan.
J Neurosurg 1996 Jun;84(6):1055-9 Abstract quote
A total resection of a left frontal lobe tumor in a 26-year-old man revealed differentiated ganglioglioma with small foci of atypical glial cells exhibiting mild atypia. Six and one-half years later, a large, well-demarcated tumor recurred; at that time, histological analysis revealed both typical ganglioglioma and highly cellular anaplastic areas, the latter predominating. Although the patient subsequently underwent total and subtotal resections, radiation therapy, and chemotherapy, tumors continued to recur at progressively shorter intervals and he died at the age of 35 years.
Biopsies of tissue obtained at the last three resections and the autopsy revealed only anaplastic tumor cells. Routine histological examinations indicated that these tumors were uniformly composed of undifferentiated cells. However, pathological studies using immunohistochemical analysis, electron microscopy, and immunoblot analysis demonstrated that a small number of recurrent anaplastic cells had astrocytic features. Results of Ki-67/MIB-1 labeling and silver nucleolar organizer region counts for those cells were high for glial tumors. A retrospective study of the initial tumor showed slightly high MIB-1 labeling for atypical glial cells. This case is characterized by pathological findings of recurrent tumors that correspond to an unusual form of malignant glioma exhibiting slight astrocytic differentiation.
The present case suggests that a longer follow-up period ( > 5 years) is necessary in cases of ganglioglioma with mild atypia and that careful examinations, including proliferating potential analysis of initial tumor cells, could be important for the diagnosis and treatment of ganglioglioma.
Anaplastic ganglioglioma with dissemination to the spinal cord: a case report.
Nakajima M, Kidooka M, Nakasu S.
Department of Neurosurgery, Shiga University of Medical Science, Seta, Ohtsu, Japan.
Surg Neurol 1998 Apr;49(4):445-8 Abstract quote
BACKGROUND: Gangliogliomas are rare tumors that generally arise in the temporal lobe. Although most are benign, malignant gangliogliomas have been reported. The clinical course of anaplastic gangliogliomas has not been well understood.
CASE REPORT: An anaplastic ganglioglioma of the right parieto-occipital lobe is reported in a 7-year-old girl who presented with left homonymous hemianopsia and papilledema. Neurologic examination revealed a choked disc and a left homonymous hemianopsia. A computed tomographic scan and magnetic resonance imaging showed a large enhancing mass with calcification. Radiation therapy was administered after subtotal resection of the tumor. Histologic and immunohistochemical studies showed a typical appearance of anaplastic ganglioglioma. Spinal dissemination developed 3 months after the operation. In spite of spinal axis radiation and chemotherapy, she expired 15 months after the diagnosis.
CONCLUSION: Although the clinical course of anaplastic gangliogliomas is not always aggressive, our case indicates the importance of strict follow-up assessments of the whole craniospinal axis.
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE
Desmoplastic infantile ganglioglioma - clinicopathological and immunohistochemical study of four cases.
Rout P, Santosh V, Mahadevan A, Kolluri VR, Yasha TC, Shankar SK.
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore-560029, India.
Childs Nerv Syst 2002 Oct;18(9-10):463-7 Abstract quote
CASE REPORTS. Four cases of desmoplastic infantile ganglioglioma (DIG) seen in India are described. These patients presented with large, supratentorial, superficially situated cystic tumours that showed glial and ganglionic differentiation; accompanied by a severe desmoplastic reaction. MIB-1 labelling was rare, despite foci of apparently primitive neuroepithelial cells. There was lacking p53 protein expression by tumour cells in all cases. The prognosis was good following either partial or complete tumour resection. DIGs are a distinct form of developmental neuroepithelial tumour, probably arising from neural progenitor cells in subcortical zone along with mature subpial astrocytes.
CONCLUSIONS. In view of its favourable prognosis, this tumour has to be diagnosed accurately by immunohistochemical techniques using glial and neuronal markers. The absence of p53 protein expression suggests that DIG probably has different molecular genetic pathways from other supratentorial astrocytomas.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES ASTROBLASTOMA
Astroblastomas: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients.
Bonnin JM, Rubinstein LJ.
Department of Pathology, University of Virginia School of Medicine, Charlottesville.
Neurosurgery 1989 Jul;25(1):6-13 Abstract quote
Astroblastomas are rare, usually circumscribed, supratentorial tumors of young subjects and are characterized by a perivascular arrangement of the tumor cells. Their clinical behavior is unpredictable and their prognosis has been regarded as intermediate between that of astrocytomas and glioblastomas.
A personal series of 23 astroblastomas was reviewed, adequate postoperative follow-up being available in 13 patients. Two distinct histological types were encountered: low-grade and high-grade. The low-grade type comprised tumors with better differentiated and more benign-appearing microscopical features.
Five of the 8 patients with tumors of this type who were available for follow-up have survived from 3 to 20 years after treatment; in 1 patient the tumor converted into a fatal glioblastoma after 4 1/2 years. The high-grade type consisted of tumors with more anaplastic features. Three of the 4 patients with tumors of this type available for follow-up died after 1 1/2 to 2 1/2 years, the astroblastomas in 2 of them having converted into a glioblastoma and a gliosarcoma, respectively. One patient, however, has had an unexpected length of postoperative survival of 11 1/2 years.
The best clinical results were obtained after total or subtotal resection of the tumor, followed by radiotherapy. The role of chemotherapy is still uncertain. This form of glioma illustrates the discrepancies that may sometimes be apparent between histopathological features and length of postoperative survival. The prognosis is also further complicated by the potential of the astroblastoma to convert into a more malignant type of glioma.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS TREATMENT
Desmoplastic infantile gangliogliomas: an approach to therapy.
Duffner PK, Burger PC, Cohen ME, Sanford RA, Krischer JP, Elterman R, Aronin PA, Pullen J, Horowitz ME, Parent A, et al.
State University of New York, Buffalo School of Medicine.
Neurosurgery 1994 Apr;34(4):583-9 Abstract quote
Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm.
Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures.
All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy.
All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course.
If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.
Gangliogliomas: experience with 34 patients and review of the literature.
Selch MT, Goy BW, Lee SP, El-Sadin S, Kincaid P, Park SH, Withers HR.
Department of Radiation Oncology, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-6951, USA.
Am J Clin Oncol 1998 Dec;21(6):557-64 Abstract quote
Ganglioglioma is an uncommon central nervous system tumor. The role of adjuvant postoperative radiation therapy is undefined.
The authors retrospectively reviewed the clinicopathologic features and results of therapy for 34 patients with ganglioglioma treated at the University of California at Los Angeles. There were 18 women and 16 men. Median age was 18 years. Twenty-five tumors were low grade. Twenty-one patients underwent gross total resection. Three patients received adjuvant radiotherapy. The 4-year actuarial progression free and overall survival rates were 67% and 75%, respectively. The median time to progression was 14 months and all relapses were local.
Factors significantly influencing progression-free or overall survival according to univariate analysis included degree of resection and tumor grade. Survival and relapse were not significantly influenced by any factor according to multivariate analysis. The progression-free survivals after gross total resection of low- and high-grade tumors were 78% and 75%, respectively. Respective rates after subtotal resection were 63% and 25%.
Review of the literature demonstrates no role for radiotherapy after total resection of ganglioglioma or after partial removal of low-grade tumor. Radiation therapy appears to reduce the relapse rate after partial removal of high-grade lesions. A dose in excess of 5,000 cGy is necessary for ganglioglioma.
Desmoplastic infantile ganglioglioma: a potentially malignant tumor?
De Munnynck K, Van Gool S, Van Calenbergh F, Demaerel P, Uyttebroeck A, Buyse G, Sciot R.
Am J Surg Pathol 2002 Nov;26(11):1515-22 Abstract quote
Desmoplastic infantile ganglioglioma is a rare intracranial tumor of early childhood with a usually excellent prognosis despite malignant features both radiologically and histologically.
We present the case of a desmoplastic infantile ganglioglioma with histologically highly anaplastic features and both intracerebral and pial metastases. After partial resection the tumor was rapidly progressive and new metastases appeared. A combination of vincristine and carboplatinum was used according to the Low Grade Glioma Protocol of the International Society of Pediatric Oncology, with a temporary good response.
When histologically characterized by highly anaplastic features, it seems the biologic behavior of this tumor remains uncertain. The aggressive behavior and the responsiveness to chemotherapy in this case may challenge the belief in the benign nature of these rare tumors.
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