MyPACS.net: Radiology Teaching Files > Case 60799757

Never visited LOW GRADE ASTRCYTOMA (ASTROCYTOMA GRADE 2)
Contributed by: antonio aguiar, Radiologist, Real Hospital Português De Pernambuco - Realimagem, Brazil.
History:

Patient 01: 32-year–old man presenting with seizures.

Patient 02: 27-year-old woman with headache. She had a first-time seizure three years prior to this study, when was diagnosed a “low grade” astrocytoma on the left frontal lobe.

Patient 03: 24-year-old woman with “low grade” astrocytoma on left temporal lobe, diagnosed two years prior to this follow-up study.

Patient 04: 32-year-old man presenting with headache.

Images:[small]larger

Fig. 1: a focal hypoattenuated lesion within the right frontal lobe.

Fig. 2: a low attenuation right frontal lesion, without enhancement.

Fig. 3: a well-marginated hypointense mass on the right frontal lobe.

Fig. 4: a well-marginated hypointense nonenhancing mass on the right frontal lobe.

Fig. 5: a hyperintense right frontal lesion, without significant peritumoral edema.

Fig. 6: a right hyperintense frontal mass.

Fig. 7: there is not increased perfusion.

Fig. 8: there is slight elevated choline : creatine ratio, and low amount of N-Acetyl aspartate (NAA).

Fig. 9: a hypointense cortical lesion on the left frontal lobe.

Fig. 10: a hypointense nonenhancing cortical lesion on the left frontal lobe.

Fig. 11: a hyperintense left frontal lesion, without evidence of hemorrhage or necrosis.

Fig. 12: a region of increased T2 signal involving the left frontal lobe.

Fig. 13: there is low amount of N-Acetyl aspartate (NAA).

Fig. 14: a light region of increased T2 signal involving the hippocampal region of the left temporal lobe.

Fig. 15: a region of increased signal involving the hippocampal region of the left temporal lobe.

Fig. 16: a region of increased T2 signal involving the hippocampal region of the left temporal lobe.

Fig. 17: there is no evidence of enhancement on the left temporal lobe.

Fig. 18: an indistinct marginated lesion in deep structures bilaterally.

Fig. 19: a hyperintense lesion in deep structures bilaterally.

Fig. 20: a hyperintense lesion in deep structures bilaterally, with indistinct borders.

Fig. 21: a hyperintense lesion in deep structures bilaterally.

Fig. 22: a diffuse infiltrating lesion, with confluent high signal area involving the deep structures of both cerebral sides.

Fig. 23: The biopsy disclosed diffusely infiltrating grade 2 astrocytoma.
Findings:

Figure 01 (patient 01) axial non enhanced computed tomography (NECT) shows a focal hypoattenuated lesion within the right frontal lobe (red arrows).

Figure 02 (patient 01): axial contrast enhanced computed tomography (CECT) demonstrates a low attenuated right frontal lesion, without enhancement (red arrows).

Figure 03 (patient 01): axial non enhanced T1-weighted MR scan reveals a well-marginated hypointense mass on the right frontal lobe (red arrows).

Figure 04 (patient 01): axial postcontrast T1-weighted MR scan shows a well-marginated hypointense nonenhancing mass on the right frontal lobe. There is no evidence of hemorrhage or necrosis (red arrows).

Figure 05 (patient 01): axial T2-weighted MR scan demonstrates a hyperintense right frontal lesion. “Low-grade” astrocytomas are usually lacking peritumoral edema, which distinguishes them from more malignant astrocytic tumors on magnetic resonance (MR).

Figure 06 (patient 01): axial FLAIR scan reveals a right hyperintense frontal mass, with thickened of the cortical mantle. There is no evidence of important surrounding edema.

Figure 07 (patient 01): perfusion - there is not increased perfusion. Usually “low grade” astrocytomas have iso or slight reduced perfusion. There was not observed signs of restriction on diffusion sequences.

Figure 08 (patient 01): MR spectroscopy – there is slight elevated choline : creatine ratio, and low amount of N-Acetyl aspartate (NAA).

Figure 09 (patient 02): axial non enhanced T1-weighted MR scan shows a hypointense cortical / subcortical lesion on the left frontal lobe (red arrows).

Figure 10 (patient 02): axial postcontrast T1-weighted MR scan demonstrates a hypointense nonenhancing cortical / subcortical lesion on the left frontal lobe (red arrows). There is no evidence of hemorrhage or necrosis.

Figure 11 (patient 02): axial T2-weighted MR scan reveals a hyperintense left frontal lesion, without evidence of hemorrhage or necrosis (red arrows). There is no surrounding edema.

Figure 12 (patient 02): axial FLAIR scan shows a region of increased T2 signal involving the left frontal lobe, without surrounding edema (red arrows).

Figure 13 (patient 02): MR spectroscopy – there is low amount of N-Acetyl aspartate (NAA).

Figure 14 (patient 03): axial T2-weighted SE scan demonstrates a light region of increased T2 signal involving the hippocampal region of the left temporal lobe (red arrows).

Figure 15 (patient 03): axial FLAIR scan reveals a region of increased signal involving the hippocampal region of the left temporal lobe (red arrows).

Figure 16 (patient 03): coronal T2-weighted SE scan shows a region of increased T2 signal and enlargement involving the hippocampal region of the left temporal lobe (red arrows).

Figure 17 (patient 03): axial postcontrast T1-weighted MR scan – there is no evidence of enhancement on the left temporal lobe.

Figure 18 (patient 04): axial non enhanced T1-weighted MR scan demonstrates an indistinct marginated lesion in deep structures, with bihemispheric involvement.

Figure 19 (patient 04): axial T2-weighted MR scan shows a hyperintense lesion in deep structures bilaterally (red arrows). There is no evidence of hemorrhage or necrosis. Extension through compact white matter with enlargement of the affected region can be seen in some cases of gliomatosis cerebri.

Figure 20 (patient 04): axial FLAIR scan demonstrates a hyperintense lesion in deep structures bilaterally (red arrows). The borders are indistinct and not clearly delineated from adjacent normal brain. Despite their benign histology, the margins of many “low-grade” astrocytomas are poorly delineated, as in the present case.

Figure 21 (patient 04): axial FLAIR scan reveals a hyperintense lesion in deep structures with bihemispheric involvement (red arrows). The differential diagnosis of deep structures lesions includes neoplasic, inflammatory and vascular etiologies. Absence of necrosis or haemorrhage argues against a higher grade lesion (i.e unlikely to be a GBM).

Figure 22 (patient 04): coronal T2-weighted SE scan reveals a diffuse infiltrating lesion, with confluent high signal area involving the deep structures of both cerebral sides. The slow-growing lesion has caused compression on the left lateral ventricle. Extension through compact white matter with enlargement of the affected region can be seen in some cases of gliomatosis cerebri.

Figure 23 (patient 04) gradient-echo scan post-biopsy shows magnetic susceptibility artefacts (green arrows) and hemosiderin / ferritin deposition (red arrow) from the prior surgery. The stereotatic biopsy disclosed diffusely infiltrating “low-grade” astrocytoma (WHO II).

Diagnosis: LOW GRADE ASTRCYTOMA (Astrocytoma grade 2)
Discussion:

GENERAL CONSIDERATIONS:

Glial cells are the chief source of central nervous system (CNS) neoplasms. The three major types of gliomas are: astrocytoma, oligodendroglioma and ependymoma. Approximately half of all primary brain tumors are glial cell neoplasms and three quarters of all gliomas are astrocytomas.

Astrocytic tumors can be divided in two major groups: - localized noninfiltrative astrocytomas, World Health Organization (WHO grade I), which correspond to pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma and pilocytic astrocytomas; and - the infiltrative or diffuse astrocytomas (WHO grade II, III and IV).

The most accepted approach to grading of infiltrating astrocytomas derives from the WHO classification of brain tumors into a three-tiered system, consisting of  “low grade” astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III), and glioblastoma multiform (WHO grade IV). The major criteria for this classification are cell density, nuclear and/or cytoplasmic pleomorphism, mitoses, necrosis, and vascular endothelial and/or pericytic proliferation.

Astrocytomas (WHO grade II) have none of these features, except for slight increase cellularity and minimal cellular pleomorphism. The separation between astrocytoma (grade II) and anaplastic astrocytoma (grade III) depends on the degree of cell density, cellular pleomorphism, and mitotic rate, whereas the distinction between anaplastic astrocytoma and glioblastoma multiforme (grade IV) mostly relies on the presence of necrosis and vascular endothelial proliferation.  

It is widely accepted that grading diffuse astrocytomas have limitations, due not only to the intratumoral heterogeneity of these neoplasms and thus the effects of limited biopsy sampling but also to one of the cardinal feature of infiltrative astrocytic tumors: the tendency to dedifferentiate into more malignant lesions over time.

“Low grade” astrocytomas is also often referred to as diffuse astrocytoma, grade 2 Astrocytoma (WHO II) or simply astrocytoma - These grade II astrocytomas tend to invade surrounding tissue and grow at a relatively slow pace.

Astrocytomas (WHO II) have a more favorable prognosis compared to anaplastic astrocytomas and gliobastomas multiformes. Astrocytomas can appear in various parts of the brain and nervous system, including the cerebellum, the cerebrum, the central areas of the brain, the brainstem, and the spinal cord.

These tumors arise in any part of the cerebral hemisphere, with relative sparing of the occipital lobes. In pediatric population infiltrative astrocytomas are mainly situated in the brainstem. When the lesions are located in deep structures, there may be bihemispheric involvement. They may involve the thalamus bilaterally. This morphology is most commonly encountered in children but occasionally occurs in adults.

EPIDEMIOLOGY:

The annual incidence of glioma in the United States is 5.4 cases per 100,000 population.

Astrocytomas  grade II, III and IV comprise approximately 75% of astrocytic tumors of CNS, whereas localized tumors (WHO grade I) make up the remainder.

“low-grade” astrocytoma (WHO grade II) accounts for 25% to 30% of hemispheric gliomas in adults and up to 30% of cerebellar gliomas found in childhood. The peak incidence of supratentorial  grade 2 astrocytomas lies between the ages of 20 and 50 years.

10% percent of “low-grade” astrocytomas occur in people younger than 20 years; 30% of “low-grade” astrocytomas occur in people older than 45 years; 60% of “low-grade” astrocytomas occur in people aged 20-45 years.

There is a slight male predominance, with a male-to-female ratio of 1.18:1 for development of “low-grade” astrocytomas.

Etiology:

The precise etiology of astrocytomas has not yet been established. There is an association of diffuse astrocytomas and therapeutic irradiation and, perhaps, nitroso compounds.  The identification of others specific causal environmental exposures or agents as a potential risk factor for development of gliomas has been unsuccessful.

 

Evidence exists for genetic susceptibility to glioma development. For example, familial clustering of astrocytomas is well described in inherited neoplastic syndromes, such as Turcot syndrome, neurofibromatosis type 1 (NF1) syndrome, and p53 germ line mutations (eg, Li-Fraumeni syndrome).

CLINICAL PRESENTATION:

Clinical symptoms and signs are directly related to the specific location, the size and the extent of tumor growth in CNS. Seizures, often generalized, are the initial presenting symptom in about 30% - 50% of patients with “low-grade” astrocytoma. The onset of seizures in an adult is a worrisome event. Cerebral masses are detected in approximately 20% of such cases. 

Other symptoms may include personality changes, focal neurologic deficit, motor impairment, sensory anomalies, or visual disturbances.  attention should be paid to Signs of increased intracranial pressure (ICP), such as headache, nausea and vomiting, decreased alertness, cognitive impairment, papilledema, or ataxia to determine the likelihood of mass effect, hydrocephalus, and herniation risk.

DIGNOSIS:

Laboratory findings:

No specific laboratory tests are used to screen for “low-grade” astrocytoma.

Pathology:

Four histological variants of “low-grade” astrocytomas are recognized: protoplasmic, gemistocytic, fibrillary, and mixed. Protoplasmic astrocytomas constitute approximately 28% of infiltrating astrocytomas. Gemistocytic astrocytomas constitute 5-10% of hemispheric gliomas. Fibrillary astrocytomas are the most frequent histological variant.

Astrocytomas are unencapsulated tumors that may appear grossly circumscribed but usually infiltrate diffusely. Most “low-grade” astrocytomas are solid, which vary from soft to almost gelatinous in consistency. Cystic degeneration may occur, but necrosis is absent. The microcysts found in astrocytomas are typically filled with clear fluid. Calcification may be present.

Microscopically, there is usually a clear region of hypercellularity , with only mild nuclear pleomorphism. Mitoses are few and cell density is low to moderate. Vascular proliferation is absent and hemorrhage is rare. The tumor can show marked infiltration of structures without significant distortion of gross morphology. Even on microscopy, the tumor is not distinctly demarcated; consequently, it is virtually impossible to completely surgically resect these lesions.

The borderline between “low-grade” and anaplastic astrocytoma is indistinct. 50% of surgically treated “low-grade” astrocytomas evolve into anaplastic astrocytomas or glioblastoma. Degeneration into a higher-grade neoplasm is the most common cause of death in patients with grade 2 astrocytomas. 

Diagnostic imaging:

MR is the modality of choice for characterising these lesions. They may be subtle and difficult to see on CT, especially as they tend not to enhance.

CT

“Low-grade” infiltrating astrocytomas usually appear as isodense or hypodense lesion, or as poorly defined areas of low attenuation. Mass effect is variable and contrast enhancement is rarely impressive. Enhancement of the lesion would suggest high grade (e.g. WHO III or IV tumours). 

The deep temporal lobe is a common location for these lesions in young adults. Many low-grade gliomas are found in the perisylvian region, where they may mimic recent infarction at CT in the distribution of the middle cerebral artery.

Some “low-grade” gliomas occur more superficially and may demonstrate good definition. The slow growth of such tumors may cause erosion of the adjacent inner table, which is best demonstrate at bone window. This feature combines with the absence of contrast enhancement to suggest a long-standing, low-grade lesion. The localized erosion of the adjacent inner table is an evidence of chronic mass effect, and may accompany superficial lesions of any kind.

The low attenuation of a superficial astrocytoma can mimic cerebral infarction, especially when tumor margins are sharply defined. Clues to the correct diagnosis include rounded rather than linear borders of the lesion, relative sparing of the cortical ribbon (best assessed at wide CT windows), and the absence of an acute clinical event

The well-differentiate astrocytoma has a variable appearance after contrast administration, but classically astrocytoma shows no significant contrast enhancement. However, it has been reported that even up to 40% of “low-grade” astrocytomas demonstrate enhancement on CT. In general, contrast enhancement is not recognized as a reliable indicator of the grade of infiltrative astrocytomas. As many as 30% of anaplastic astrocytoma may not enhance with contrast.

CT is estimated to identify calcification in approximately 10% - 20% of astrocytomas, a finding that is not usually evident on MR imaging due to its lack of sensitivity and specificity for calcification when using spin echo techniques.

MR

MR imaging demonstrates adult astrocytomas as relatively homogeneous mass lesions of the cerebral hemispheres, although heterogeneity can be seen in a proportion of cases. Cystic change is also often encountered. These lesions are usually lacking significant peritumoral edema, which distinguishes these lesions from more malignant astrocytic tumors on MR. 

The signal intensity of “low-grade” astrocytomas on T1-weighted images is usually homogeneous and comparable to or lower than that of gray matter. The signal intensity of these lesions on T2 spin echo images may range from isointensity to very high values. High intensity is more common, reflecting high water content in the tumor region.

MR imaging may displays these lesions with distinct and smooth margins as compared to their poor definitions on CT studies. This sharp demarcation belies the biological potential of the tumors: most are infiltrating neoplasms that tend to increase in grade over time. It has been documented that tumor tissue may extend beyond the confines of the regions of abnormal signal. Surrounding edema is typically minimal or absent.

Enhancement of “low-grade” astrocytoma usually is more impressive on MR images than on CT scans. “Low-grade” lesions should not have prominent enhancement. When present, enhancement of grade II astrocytomas is often partial or patchy. The presence of prominent contrast enhancement does not necessarily imply high grade malignancy of a glial tumor, as well as the absence of contrast enhancement does not exclude malignant hytology. 

Intratumoral regions suggestive of flow in vessels on MR imaging are not typical for astrocytoma. They should not have increased perfusion. Sometimes they may have reduced perfusion. They should not show increased metabolism.

MR spectroscopy may show elevated choline : creatine ratio, and low amount of N-Acetyl aspartate (NAA).

NAA is an amino acid found within nerve cells; its abundance correlates with the presence of healthy neurons and/or axon, with reduction of NAA suggesting damage to and/or replacement of the normal neuron population. Creatine is a component of cellular energy metabolism. Choline is incorporated in the metabolism of cell membranes; elevation of this peak is believed to reflect increased turnorver of membranes or myelin and can be seen in neoplastic, demyelinatin, or reparative states.

Usually, astrocytomas (WHO II) demonstrate little mass effect, suggesting a long-standing, slow-growing lesion. The absence of reactive cerebral edema also supports a chronic, low grade process. As already seen on CT, subtle erosion of the overlying calvarium may be present on MR images, favoring a long history of gradual evolution.

“low-grade” astrocytomas may involve the thalamus and others deep structures bilaterally, crossing through and expanding the massa intermedia. This morphology is most commonly encountered in children but occasionally occur in adults.  

Sometimes MR identify cortical involvement by these tumors, which is seen as thickened of the cortical mantle, a finding that may be similar with that seen in acute cortical infarction. Distinction can often be made if one discerns that the lesion does not obey a vascular territory, thereby indicating tumor rather than infarct. Occasionally, the radiologist must recommend follow-up scan in 4 to 6 weeks to assess for the expected evolution of infarction.

“Low-grade” astrocytomas eventually undergo malignant degeneration.

PROGNOSIS:

The histologic grade of astrocytomas is of primary importance when determining prognosis. WHO Grade II astrocytoma - most simply called just "astrocytoma" represents the benign end of the spectrum of infiltrative astrocytomas and shows a more indolent course than anaplastic astrocytoma and glioblastoma.

The overall prognosis of such “low-grade astrocytomas is still grim, with median survival rates reported as approximately 7 to 8 years. Furthermore, it is recognized that about 10% of these low-grade lesions “dedifferentiate into more malignant forms over time. When astrocytomas recur, progression to anaplastic astrocytoma is seen in 50% to 75% of cases.

TREATMENT:

There is no accepted standard of treatment for “low-grade” astrocytoma. Treatment depends on clinical presentation, size of the tumour and location. In general, therapeutic options include observation, radiation, and resection with and without radiation. There are no data to support early intervention being better than watchful waiting for “low-grade astrocytoma. the patient should be engaged in a full discussion about the risks and benefits of intervention versus watchful waiting.

Decisions on operative intervention and the use of radiation therapy and chemotherapy are generally best made by a team approach, including input from the involved neurosurgeon, radiation oncologist, medical oncologist or neurologist, and radiologist. The role of maximal surgical resection, timing of radiotherapy, and the role, timing, and appropriate agents of chemotherapy are not clear.

The controversy due to a lack of strong data is compounded by the relatively young age of the patients, the relatively indolent natural history of “low-grade” astrocytomas, and the morbidity associated with these interventions.

If after a full discussion with the patient, one chooses watchful waiting, consideration of more frequent imaging over the first 1–2 years should be discussed. An imaging frequency of every 3–4 months during the first year would allow the rate of change of the lesion to be determined without allowing for unmonitored, significant tumor growth. If the rate of change were determined to be small, one might feel more comfortable with an imaging frequency of every 6 months to every year.

Removal of all tumor visible by MR imaging or to the surgeon may result in longer survival than partial resection or biopsy alone. not uncommonly, total resection of astrocytoma is often impossible because the tumors often invade into eloquent regions of the brain and exhibit tumor infiltration that is only detectable on a microscopic scale. Therefore, surgical resection only provides for improved survival advantage and histological diagnosis of the tumor rather than offering a cure.

References:

REFERENCES:

1. Yock, Douglas H. Imaging of CNS disease: a CT and MR teaching file. 2nd ed. Mosby Year Book, Inc. St. Louis, MO. 1991.

2. Osborne, Anne G. Diagnostic neuroradiology. 1st ed. Mosby-Year Book, Inc. St. Louis, MO. 1994.

3. Atlas Scott W. Magnetic resonance imaging of the brain and spine. 3rd ed. Lippincott Williams & Wilkins.  Philadelphia, PA. 2002.  

4. Yock, Douglas H. Magnetic resonance imaging of CNS disease: a teaching file. 2nd ed. Mosby, Inc. St. Louis, MO. 2002.

5. Leite, Claudia da Costa; Amaro junior, Edson; Lucato, Leandro Tavares. Neuroradiologia: diagnóstico por imagem das alterações encefálicas. 1ª ed. Editora Guanabara Koogan S.A. Rio de Janeiro, RJ. 2008.

6. Benjamin Kennedy; Jules E Harris. Astrocytoma. Medscape. Emedicine. http://emedicine.medscape.com/article/283453-overview   Jan 17, 2012.

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Additional Details:

Case Number: 60799757Last Updated: 2012-06-03
Anatomy: Cranium and Contents   Pathology: Neoplasm
Modality: CT, MRAccess Level: Readable by all users
Keywords: Tumors of the central nervous system; Glial tumors; Glial neoplasms; Astrocytomas; Low grade astrocytomas; Grade 2 astrocytomas; astrocytomas WHO IIACR: 13.3632

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