(Radiology. 2000;214:223-226.)
© RSNA, 2000
Spontaneous Involution of Pilocytic Astrocytoma in a Patient without Neurofibromatosis Type 1: Case Report1
Massimo Gallucci, MD,
Alessia Catalucci, MD,
Bernd W. Scheithauer, MD and
Glenn S. Forbes, MD
1 From the Department of Radiology, University of L'Aquila, Nuovo S. Salvatore Hospital, Coppito, 67100 L'Aquila, Italy (M.G., A.C.), and the Departments of Laboratory Medicine and Pathology (B.W.S.) and Radiology (G.S.F.), Mayo Clinic, Rochester, Minn. Received April 21, 1998; revision requested July 2; final revision received March 10, 1999; accepted June 15. Address reprint requests to M.G. (e-mail: nradaq@tin.it).
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Abstract
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Serial magnetic resonance imaging findings are described in a patient with a sporadically occurring pilocytic astrocytoma that underwent spontaneous regression over 6 years. To the authors' knowledge, this is the first report in which spontaneous involution of a pilocytic astrocytoma not associated with neurofibromatosis type 1 has been described. A literature review regarding sporadic and syndrome-associated pilocytic astrocytoma was undertaken, with particular reference to treatment and natural history.
Index terms: Astrocytoma, 15.313 • Brain, MR, 15.121411, 15.12143 • Neurofibromatosis, 15.313
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Introduction
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Pilocytic astrocytoma, a slow-growing, relatively benign tumor, is considered to be a "favorable prognostic variant" of astrocytic tumor (1,2). Astrocytic tumors include pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell astrocytoma (3). The authors of previous studies (3,4) of pilocytic astrocytoma emphasized the slow growth of such tumors, particularly of supratentorial tumors and those that occur in patients older than 20 years of age.
Spontaneous regression of pilocytic astrocytoma in association with neurofibromatosis type 1 (also called von Recklinghausen disease) has rarely been reported in cases where the tumor involves the optic pathway (5,6). To our knowledge, spontaneous regression has never been described in cases of sporadic tumor.
We report a case of histologically proved pilocytic astrocytoma not associated with neurofibromatosis type 1, arising in the subthalamic-mesencephalic region; the patient was not treated with surgery, chemotherapy, or radiation therapy, but the tumor underwent spontaneous involution over 6 years. A literature review of sporadic and neurofibromatosis type 1–associated pilocytic astrocytoma was undertaken, especially with regard to the natural history and management of the tumor.
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Case Report
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The patient, a 19-year-old man, presented with complaints of "writer's cramp." In clinical terms, the patient's complaints consisted of focal dystonia characterized by involuntary muscle contractions that were mainly position related and selectively involved fingers of the right hand. Within a few weeks, the patient developed dyskinetic unintentional ticlike movements of the right shoulder, as well as subjective weakness on the right side. The patient underwent computed tomography and, immediately thereafter, magnetic resonance (MR) imaging at 0.2 T (Esatom PM 4000; Esaote Biomedica, Genoa, Italy) without and with contrast material enhancement. T1-weighted (650/30 [repetition time msec/echo time msec] and 300/30), intermediate-weighted (2,500/30), and T2-weighted (2,500/120) spin-echo sequences were performed before and after administration of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) at a conventional dose of 0.1 mmol/kg. On the basis of the finding of a solid, homogeneously enhanced mass in the subthalamic-mesencephalic region, a radiologic diagnosis of pilocytic astrocytoma was established (Fig 1).
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Figure 1a. MR images obtained at the time of clinical onset. (a-c) Transverse images reveal a rounded, well-circumscribed lesion (arrow) approximately 2 cm in diameter in the subthalamic-mesencephalic region. (a, b) On T2-weighted spin-echo images (2,500/120), the tumor has markedly high signal intensity. (c) On a T1-weighted spin-echo image (650/30), the tumor has moderately low signal intensity, with mild perilesional edema. (d) Coronal contrast-enhanced T1-weighted spin-echo image (300/30) shows intense, homogeneous contrast enhancement of the lesion (arrow).
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Figure 1b. MR images obtained at the time of clinical onset. (a-c) Transverse images reveal a rounded, well-circumscribed lesion (arrow) approximately 2 cm in diameter in the subthalamic-mesencephalic region. (a, b) On T2-weighted spin-echo images (2,500/120), the tumor has markedly high signal intensity. (c) On a T1-weighted spin-echo image (650/30), the tumor has moderately low signal intensity, with mild perilesional edema. (d) Coronal contrast-enhanced T1-weighted spin-echo image (300/30) shows intense, homogeneous contrast enhancement of the lesion (arrow).
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Figure 1c. MR images obtained at the time of clinical onset. (a-c) Transverse images reveal a rounded, well-circumscribed lesion (arrow) approximately 2 cm in diameter in the subthalamic-mesencephalic region. (a, b) On T2-weighted spin-echo images (2,500/120), the tumor has markedly high signal intensity. (c) On a T1-weighted spin-echo image (650/30), the tumor has moderately low signal intensity, with mild perilesional edema. (d) Coronal contrast-enhanced T1-weighted spin-echo image (300/30) shows intense, homogeneous contrast enhancement of the lesion (arrow).
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Figure 1d. MR images obtained at the time of clinical onset. (a-c) Transverse images reveal a rounded, well-circumscribed lesion (arrow) approximately 2 cm in diameter in the subthalamic-mesencephalic region. (a, b) On T2-weighted spin-echo images (2,500/120), the tumor has markedly high signal intensity. (c) On a T1-weighted spin-echo image (650/30), the tumor has moderately low signal intensity, with mild perilesional edema. (d) Coronal contrast-enhanced T1-weighted spin-echo image (300/30) shows intense, homogeneous contrast enhancement of the lesion (arrow).
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Given the opinion in the literature (7) that imaging characteristics are unreliable for prediction of tumor behavior (aggressive vs nonaggressive), stereotactic biopsy was performed. Three small specimens were obtained, and a diagnosis of World Health Organization grade 1 pilocytic astrocytoma was established on the basis of the tumor growth pattern and cytologic results, as well as the presence of Rosenthal fibers and the formation of microcysts (Fig 2).
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Figure 2a. (a) Photomicrograph shows elongated bipolar cells associated with granular bodies (arrowhead) and Rosenthal fibers (arrow). (Hematoxylin-eosin stain; original magnification, x40.) (b) Photomicrograph shows loose-knit multipolar astrocytes forming mucin-containing microcysts (arrow). (Masson trichrome stain; original magnification, x40.)
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Figure 2b. (a) Photomicrograph shows elongated bipolar cells associated with granular bodies (arrowhead) and Rosenthal fibers (arrow). (Hematoxylin-eosin stain; original magnification, x40.) (b) Photomicrograph shows loose-knit multipolar astrocytes forming mucin-containing microcysts (arrow). (Masson trichrome stain; original magnification, x40.)
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After consideration of the risks associated with surgery and radiation therapy, which were primarily related to lesion location and the relative paucity of symptoms, the decision was made to withhold therapy pending neuroradiologic assessment of the growth potential of the tumor. The patient was discharged the 2nd day after biopsy. Medications included a tapering dosage of dexamethasone (initial dose of 4.5 mg gradually reduced over 5 days).
Thereafter, the patient was examined by using the same MR imaging equipment and techniques as for the initial MR examination. MR studies were obtained every 3 months during the 1st year, every 6 months during the 2nd year, and annually thereafter. One year after the onset of the patient's symptoms, dystonia and other signs had completely abated. The patient was again able to use his right hand, and the ability to write was restored. Follow-up MR studies showed the tumor to be stable during the first 3 years. During the 4th year, a gradual but distinct reduction in tumor size became evident (Fig 3). A decision was made to repeat the studies at 6-month intervals. MR images obtained at four subsequent examinations showed progressive volume reduction that terminated in subtotal tumor regression (Fig 4).
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Figure 3a. Follow-up MR images obtained during the 4th year. (a) Transverse T2-weighted (2,500/120) and (c) T1-weighted (650/30) spin-echo images show no evidence of the lesion. The area of moderately high signal intensity in the left putamen (arrowhead) is related to the reparative processes consequent to biopsy. (b) Transverse T2-weighted spin-echo image (2,500/120) shows the lesion (arrow). (d) Coronal T1-weighted contrast-enhanced image (300/30) shows a distinct reduction in the size of the tumor (arrow).
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Figure 3b. Follow-up MR images obtained during the 4th year. (a) Transverse T2-weighted (2,500/120) and (c) T1-weighted (650/30) spin-echo images show no evidence of the lesion. The area of moderately high signal intensity in the left putamen (arrowhead) is related to the reparative processes consequent to biopsy. (b) Transverse T2-weighted spin-echo image (2,500/120) shows the lesion (arrow). (d) Coronal T1-weighted contrast-enhanced image (300/30) shows a distinct reduction in the size of the tumor (arrow).
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Figure 3c. Follow-up MR images obtained during the 4th year. (a) Transverse T2-weighted (2,500/120) and (c) T1-weighted (650/30) spin-echo images show no evidence of the lesion. The area of moderately high signal intensity in the left putamen (arrowhead) is related to the reparative processes consequent to biopsy. (b) Transverse T2-weighted spin-echo image (2,500/120) shows the lesion (arrow). (d) Coronal T1-weighted contrast-enhanced image (300/30) shows a distinct reduction in the size of the tumor (arrow).
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Figure 3d. Follow-up MR images obtained during the 4th year. (a) Transverse T2-weighted (2,500/120) and (c) T1-weighted (650/30) spin-echo images show no evidence of the lesion. The area of moderately high signal intensity in the left putamen (arrowhead) is related to the reparative processes consequent to biopsy. (b) Transverse T2-weighted spin-echo image (2,500/120) shows the lesion (arrow). (d) Coronal T1-weighted contrast-enhanced image (300/30) shows a distinct reduction in the size of the tumor (arrow).
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Figure 4a. Follow-up MR images obtained 5 years 7 months after the first examination. (a) On a transverse T2-weighted spin-echo image (2,500/120), the tumor (arrowhead) can barely be identified. (b) Coronal T1-weighted contrast-enhanced image (300/30) shows residual moderate contrast enhancement (arrow) in the subthalamic region.
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Figure 4b. Follow-up MR images obtained 5 years 7 months after the first examination. (a) On a transverse T2-weighted spin-echo image (2,500/120), the tumor (arrowhead) can barely be identified. (b) Coronal T1-weighted contrast-enhanced image (300/30) shows residual moderate contrast enhancement (arrow) in the subthalamic region.
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Discussion
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The histologically distinct pilocytic variant of astrocytoma generally is considered to be benign. Usually limited in its infiltrative capacity, pilocytic astrocytoma seldom undergoes malignant transformation. Malignant transformation has been associated with prior radiation therapy (8,9). Local recurrence after total resection is an uncommon event, and craniospinal metastasis is rare (7,10,11). It must be noted, however, that other authors (7) have reported aggressive tumor behavior in approximately 30% of cases, independent of patient age, with tumor progression or recurrence within a median of 7.5 months.
In a cellular kinetics study in which bromodeoxyuridine was used to help characterize the proliferative potential and biologic behavior of pilocytic astrocytoma, Ito et al (2) confirmed that most pilocytic astrocytomas grow slowly. Furthermore, they found that the growth potential of pilocytic astrocytoma decreases progressively with patient age, although they had no explanation for this phenomenon. Although the time of growth deceleration varies from tumor to tumor, it appears to be maximal at about the age of 20 years. The results in the present patient conform to this notion: Lesion size has been stable for 3 years since the patient reached the age of 20 years.
The unexpected and remarkable aspect of the present case was regression of the tumor. Even if we consider this involution not to be spontaneous in the purest sense, because a biopsy had previously been performed, we do not believe that the process of biopsy resulted in marked tissue destruction, such as that which occurs when there is an interruption in blood supply. The fact that the tumor remained neuroradiologically stable for 3 years before showing signs of involution provides a strong argument against the influence of a precipitous vascular mechanism.
Because, to our knowledge, no previous examples of spontaneous involution of pilocytic astrocytoma have been reported in a patient without neurofibromatosis type 1, definitive conclusions about the basis of tumor regression cannot be made. In general, the mechanisms involved in tumor regression are spontaneous or pharmacologically induced apoptosis (12,13) and a humoral or cellular immune response (14). Because repeat biopsy was not performed, we cannot address the issue of whether immunity due to humoral or cellular immunity or apoptosis played a role.
Similar examples of spontaneous tumor regression have been described, particularly in the setting of neurofibromatosis type 1. A review of the literature revealed several reports of pilocytic optic pathway tumor in association with neurofibromatosis type 1 that did not progress during long-term observation. In these instances, neuroradiologic changes in signal intensity and contrast enhancement occurred over time in the absence of therapy (2,5,6). Such cases are similar in many ways to our case.
The lesion described in the present report did not fulfill the diagnostic criteria for neurofibromatosis type 1 established by the National Institutes of Health Consensus Development Conference (15). There were no major or minor signs, and the patient had no first-degree relative with neurofibromatosis type 1. Moreover, the tumor was located at a site other than the optic pathway or mesencephalic tectum, which are typical locations for tumors associated with neurofibromatosis type 1.
It is clear that our understanding of the natural history of pilocytic astrocytoma is incomplete. Factors underlying changes in tumor growth rate, the mechanism responsible for the rare occurrence of regression, and the reason why such behavior is most often associated with neurofibromatosis type 1 remain to be explained.
Neurofibromatosis type 1 is an autosomal dominant disorder mapped to the long arm of chromosome 17 (11). Allelic losses on the long arm of this chromosome have been demonstrated in both sporadic and neurofibromatosis type 1–associated pilocytic astrocytomas (16), which suggests the presence of a tumor suppressor gene on the long arm of chromosome 17. This gene may well be the neurofibromatosis type 1 tumor suppressor gene.
The question remains whether a subgroup of patients exist who are affected by a form of neurofibromatosis type 1 that manifests exclusively as a solitary pilocytic astrocytoma located in an atypical site and subject to the infrequent occurrence of spontaneous resolution. The patient described in the present report, in whom no other syndrome-associated manifestations were present, may well belong to such a clinical subgroup.
In conclusion, neither the patient's age nor the radiologic features of the lesion were accurate predictors of the future course of the tumor. The findings in this patient suggest that surgery may be delayed, and close observation may be warranted in cases of a high surgical risk.
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Footnotes
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Author contributions: Guarantor of integrity of entire study, M.G.; study concepts and design, M.G.; definition of intellectual content, M.G., A.C.; literature research, A.C.; clinical studies, all authors; data acquisition, M.G., G.S.F., B.W.S.; data analysis, A.C.; manuscript preparation, M.G., A.C., B.W.S.; manuscript editing, all authors; manuscript review, B.W.S., M.G., A.C.
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Abstract
Introduction
