|Year : 2015 | Volume
| Issue : 3 | Page : 667
Pilomyxoid astrocytoma in an adult woman: Case report
Adam H Kibola1, Shearwood McClelland III2, Joseph Hlavin3, Jonathan A Friedman3
1 Department of Medicine, Rutgers New Jersey Medical School, Newark NJ, USA
2 Department of Neurosurgery, Lahey Clinic, Burlington, MA, USA
3 Departments of Surgery, Neuroscience and Experimental Therapeutics, Texas A and M Health Science Center, College of Medicine, The Texas Brain and Spine Institute, Bryan, TX, USA
|Date of Web Publication||9-Oct-2015|
Shearwood McClelland III
Department of Neurosurgery, Lahey Clinic, 41 Mall Road, Burlington, MA 01805
Source of Support: None, Conflict of Interest: None
Pilomyxoid astrocytoma (PMA) is a recently classified WHO grade II astrocytoma that is histologically similar to pilocytic astrocytoma (PA). Both tumors typically present in childhood, but PMA is more aggressive with higher rates of recurrence and cerebrospinal fluid dissemination. Currently, there is no standardized treatment protocol for PMA although this will change with increased awareness of this disease entity within the neurosurgical community. We present a 22-year-old patient with a left frontal lobe PMA manifesting with atypical radiographic findings. This is the first reported case of PMA in an adult woman.
Keywords: Adult woman, pilocytic astrocytoma, pilomyxoid astrocytoma, supratentorial location
|How to cite this article:|
Kibola AH, McClelland III S, Hlavin J, Friedman JA. Pilomyxoid astrocytoma in an adult woman: Case report. J Can Res Ther 2015;11:667
| > Introduction|| |
Pilomyxoid astrocytoma (PMA) is a recently described clinicohistopathological entity that was previously classified as Pilocytic astrocytoma (PA). Relative to PA, PMA demonstrates unique histological features, more aggressive behavior, and earlier age of onset.  Generally, PA is a slow growing WHO Grade I astrocytoma, the most common intracranial tumor in the pediatric population. It has an excellent prognosis with a 20-year survival rate approaching 70-80% even with subtotal resection. In the past however, there was a subset of PA patients who did not experience a similarly excellent outcome, and it is thought that PMA accounted for this finding. 
In 1999, Tihan and colleagues  described a subtype that was clinically and histologically different from classic PA, a subtype that they later named PMA. Histologically, PA has a biphasic architecture consisting of densely cellular areas alternating with loose, cystic regions. Even more specific to PA is the presence of Rosenthal fibers and eosinophilic granules.  Angiogenesis is present, but the tumor cells do not cluster around these vessels, and mitotic figures are not seen in most cases. , In contrast, PMA demonstrates a monomorphous pattern of angiocentric piloid cells within a myxoid background, absence of Rosenthal fibers, and eosinophilic granules. Focal areas of necrosis, hemorrhage, or vascular proliferation may be seen in addition to a few mitotic figures,  consistent with a more aggressive behavior relative to PA. Based on these distinct histologic findings, in 2007 the WHO classified this subtype of PA as a grade II astrocytoma with a unique clinical behavior.
Although PMA and PA have similar clinical presentations, there are two differences worth noting. First, PMA typically presents at a younger age (mean age of 18 months) relative to PA (mean age of 58 months). Second, PMA is more aggressive than PA demonstrating higher rates of local recurrence despite equal rates of gross total resection.  One study compared the long-term clinical outcomes of 21 patients with hypothalamic PMA with those of 42 patients with PA in the same location.  Patients with PMA experienced shorter progression-free survival (PFS) (mean PFS of 26 and 147 months, respectively; P < 0.001) and significantly shorter survival than those with PA (mean overall survival of 63 and 213 months, respectively; P < 0.001). Furthermore, 33% of patients with PMA died of their disease, compared with 17% of those with PA.  Notably, patients with PMA demonstrated CSF dissemination (14%), whereas none of the tumors in the PA group showed such spread. 
Radiographically, PMA is well circumscribed, having both solid and cystic components with little to no calcifications on computed tomography (CT) [Figure 1].  On MRI, it tends to be hyperintense on T2 and isointense on T1-weighted sequences with homogenous enhancement [Figure 2] and [Figure 3].  It may also exhibit peritumoral edema, mass effect, and some necrosis.  Although PMA may occur throughout the neuraxis, most of these tumors are located in the hypothalamic/chiasmatic region, and rarely the posterior fossa and spinal cord.  It may show infiltration or encasement of adjacent structures.  Finally, although PA differs from PMA in that it enhances heterogeneously and has a predominantly cystic component, no radiographic characteristics have yet been identified that reliably differentiate PMA from PA. 
Currently, there is no standard of care specific for PMA beyond surgical excision.  As a recently discovered tumor with features resembling PA, current treatments are similar. Indications for chemotherapy in PA include tumor recurrence or inoperable tumors. Radiation therapy is generally reserved for children greater than 5 years old who progress after an initial surgical resection and have tumors located in the midline.
|Figure 1: Axial CT scan without contrast showing a left frontal lobe well demarcated 6.2 cm mass with cystic and solid components with absent peritumoral edema at the time of presentation. There is moderate mass effect on the lateral ventricle|
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|Figure 2: (a) Axial MRI with gadolinium enhancement showing a left frontal lobe nonenhancing lesion at the time of presentation. (b) Axial T1 MRI sequence emphasizing the presence of a capsule around the tumor|
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|Figure 3: Coronal T1 MRI sequence showing left frontal tumor with abutting the left lateral ventricle with resultant mass effect|
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| > Clinical presentation|| |
A previously healthy 22-year-old woman presented to the Emergency Room at St Joseph Hospital in Bryan, TX, with a new-onset tonic-clonic seizure that was witnessed by her coworkers several hours earlier. The patient did not recall the event. She denied a history of seizures. In the year prior to her current presentation, the patient had been having paroxysmal attacks consisting of SOB, ear fullness, feeling of impending doom, and a sense that her "hands are frozen" without a loss of consciousness; episodes she called anxiety attacks. These attacks would last for a few seconds, occurring at any time of the day and several times a week without any obvious triggers. Otherwise, she denied constitutional or focal neurologic symptoms.
On admission, head CT showed a 6.2-cm well-circumscribed complex cyst centered in the left frontal lobe abutting the dura and exerting a moderate mass effect on the lateral ventricle. The tumor did not enhance on MRI and lacked peritumoral edema [Figure 1].
The decision to operate was made because of the uncertainty of diagnosis, apparent mass effect on imaging, and patient preference. In the operating room, the tumor was found to have a clear wall in some areas and meaty tissue in others. Incision of the tumor revealed tissue that had the appearance of neoplasm. Although the superficial aspect of the tumor was clearly differentiated from normal brain, the deep and medial aspects infiltrated adjacent brain. Overall, gross total resection was achieved. Tissue was sent for frozen pathology section, which revealed the absence of Rosenthal fibers/eosinophilic granules in the setting of a monomorphous pattern of angiocentric piloid cells within a myxoid background, consistent with the diagnosis of Pilomyxoid variant of PA. This diagnosis was confirmed on final pathologic examination. The patient did well postoperatively and was discharged on POD#3 without any complications. She is being followed by neurooncology and neurosurgery for further management.
| > Discussion|| |
PMA is currently understood to be a pediatric brain tumor with a distinctive monomorphous pilomyxoid histological pattern,  a more aggressive behavior than classical PA and is typically located in the hypothalamic/chiasmatic region. On imaging, PMA is typically well circumscribed without surrounding edema, consisting of solid with some cystic components and enhances homogeneously with contrast.  In this article, we describe an adult female patient who presented with a seizure in the absence of focal neurologic deficits and imaging demonstrating a nonenhancing complex tumor in the left frontal lobe whose histologic features were consistent with PMA. This is the third reported case of PMA in an adult, with the first case presenting in an adult male who also presented with a seizure but the tumor was located in the right amygdala/uncus region;  the second presented in an adult male who presented with tinnitus and hyperacusis and was found to have the mass in the fourth ventricle. 
There are several differences between the adult PMAs that highlight the complexity of this disease. In the previously reported cases, the tumor presented as a mildly enhancing lesion in the right temporal lobe, and as a fourth ventricular lesion, both in male patients. However, in our case, the tumor presented as a nonenhancing lesion in the left frontal lobe in a female patient. These current differences underscore the fact that PMA demonstrates some heterogeneity in adult patients.
In adults, PA most commonly occurs in the cerebrum with a predilection for the temporal and parietal lobes. At the time of diagnosis, these patients are usually young adults, with a reported mean age of 20-25 years presenting with headaches or seizures in 40-60% of patients.  Based on the two adult PMA cases reported thus far, the presentation and epidemiology coincide with that of adult PA, illustrating the fact that PMA and PA in adults are clinically related.
Even though PMA is histologically aggressive, the clinical and radiographic presentations in the two adult patients reflect a more benign natural history similar to classic PA. The fact that the tumor in our patient was large (6.2 cm in diameter) at presentation is evidence of slow growth. In addition to this growth rate, the absence of focal neurologic deficits and moderate rather than severe mass effect in these two adult low-grade tumors confer a more favorable prognosis.  This contrasts to the more clinically aggressive nature of PMA in the pediatric patient.  Despite this apparent benign clinical picture, more experience with PMA is required to determine the disease-free survival as well as survival and recurrence rates of PMA in the adult relative to the pediatric patient.
In summary, this is the first case of PMA presenting in an adult woman and the third reported case in an adult patient. Although PMA is a WHO grade II low-grade astrocytoma, it appears to follow a more benign clinical course in the two adult patients reported thus far. This natural history is more consistent with classic PA in adults, suggesting that PMA may be clinically more benign in the adult relative to the pediatric patient. However, due to the paucity of experience with this tumor, future long-term follow-up will be necessary to definitively determine the rates of PFS and overall prognosis of PMA in adult patients.
| > References|| |
Komotar RJ, Mocco J, Zacharia BE, Wilson DA, Kim PY, Canoll PD, et al
. Astrocytoma with Pilomyxoid features presenting in an adult. Neuropathology 2006;26:89-93.
Komotar RJ, Mocco J, Carson BS, Sughrue ME, Zacharia BE, Sisti AC, et al
. Pilomyxoid astrocytoma: A review. Med Gen Med 2004;6:42.
Tihan T, Fisher PG, Kepner JL, Godfraind C, McComb RD, Goldthwaite PT, et al
. Pediatric Astrocytomas with monomorphous pilomyxoid features and a less favorable outcome. J Neuropathol Exp Neurol 1999;58:1061-8.
Komotar RJ, Mocco J, Jones JE, Zacharia BE, Tihan T, Feldstein NA, et al
. Pilomyxoid astrocytoma: Diagnosis, prognosis, and management. Neurosurg Focus 2005;18:E7.
Fuller C, Narendra S. Pilocytic astrocytoma and pilomyxoid astrocytoma. In: Adesina AM, Tihan T, Fuller CE, Poussaint TY, editors. Atlas of Pediatric Brain Tumors. New York: Springer; p. 5-8.
Omura T, Nawashiro H, Osada H, Shima K, Tsuda H, Shinsuke A. Pilomyxoid astrocytoma of the fourth ventricle in an adult. Acta Neurochir (Wien) 2008;150:1203-6.
Newton HB, Dropcho EJ. Pilocytic astrocytoma in adults. In: Gilman S, editor-in-chief. MedLink Neurology. San Diego: MedLink Corporation. Available from www.medlink.com
. [Last updated on 2013 Sep 20].
Bauman G. Lote K, Larson D, Stalpers L, Leighton C, Fisher B, et al
. Pretreatment factors predict overall survival for patients with low-grade glioma: A recursive partitioning analysis. Int J Radiat Oncol Biol Phys 1999;45:923-9.
[Figure 1], [Figure 2], [Figure 3]