44-year-old man presented in 2008 with acute onset of confusion and dizziness. Brain MRI scan showed a lesion in the left temporal lobe. A biopsy of the lesion was performed in 2009. He presented almost exactly three years later, in 2011, for his regular follow-up Brain MRI scan. The clinical profile of the patient now includes progressive cognitive decline, severe motor dysfunction, muscle weakness and difficulty in speech.
Neurological examination (March 2011) reveals signs of spasticity (muscle weakness, clonus, exaggerated deep tendon reflexes).
His drug screen was negative for meth and heroin. He did have evidence of rhabdomyolysis.
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The first Brain MRI scan (March 2008) demonstrates the presence of an ill-defined , T2 hyperintense, T1 hypointense lesion in the medial part of the left temporal lobe, with no associated edema or mass effect. Post contrast images reveal no enhancement of the lesion. Interestingly, there is enlargement of the areas affected by the lesion.
Brain MRI scan (March 2011) shows an obvious increase in the size of the lesion which extends in the right cerebral hemisphere through the anterior commissure and the corpus callosum. The lesion demonstrates mass effect and is characterized by perilesional angiogenic edema and ring pattern of enhancement. The lesion contains areas of hemorrhage and necrosis.
All the aforementioned features are compatible with the malignant degeneration of a low grade astrocytoma to a high grade brain glioma (Multiforme Glioblastoma).
Differential diagnostic list of a low -grade astrocytoma comprises of infarction , lymphoma and encephalitis.
The main differential diagnosis of a butterfly-type lesion includes GBM, lymphoma, oligodendroglioma and demyelinating disease.
Dx: Secondary Glioblastoma, 3 yrs from primary astrocytoma
Dx Confirmed by: Ιmaging findings and biopsy
He has been receiving chemotherapy schemes and undergoing radiotherapy. Currently, he is in bad clinical condition. He suffers from severe muscle weakness, cognitive decline and visual impairment.
The patient underwent a course of radiation treatment on June 2010. Also, he has been receiving chemotherapy on a regular basis . So, we have to note that part of the tumor necrosis and enhancement as well as some of the white matter T2 hyperintesity changes are due to radiation effects .
Astrocytic tumors are divided into two large catego-
ries. Tumors with diffuse growth, characterised by poor prognosis, belong to the first category. They make up about 75% of all astrocytic neoplasms. Tumors with increasing (different) degree of anaplasia from low-malignant astrocytoma to glio-blastoma, characterised by the absence of clear macro- and
microscopic borders separating tumor with surrounding tissue, belong to this category.
The second category of tumors is delimited tumors, with better prognosis (pilocytic astrocytoma, pleomorphic xanthoastrocytoma and subependymal giant cell astrocytoma). They are characterised by a clear border between tumor and normal tissue.
The WHO classification (2000) divides diffuse astrocytic glioma into three groups according to the
degree of malignancy from low-grade astrocytoma (LGA) to anaplastic astrocytoma (AA) and then to glioblastoma (GBM). The criteria include the presence of nuclear and cellular polymorphisms, proliferation of vessel endothelium, presence of mitosis, and foci of necrosis. It should be noted, however, that despite benign histological structure, all infiltrative low-ma-
lignant astrocytoma have poor prognosis.
Low-degree astrocytoma has better prognosis than does the malignant form. Unfortunately, the prognosis of such diseases is always poor.
Macroscopically LGA has grey colour, various
consistency (from dense to gelatine-like) and it is difficult to separate it from brain tissue .
Microscopically, the fibrillary astrocytoma consists of mature tumor astrocytes, with a rare arrangement of cellular bodies and rather monomorphic nuclei. Mitosis, haemorrhages and proliferation of vessel endothelium are absent.
The CT image of LGA is a hypodense area without clear
borders with surrounding brain tissue . Sometimes,
isodense types of tumor can be observed, leading to their late diagnosis if only CT examinations were conducted. Intravenous contrast administration usually does not lead to density change, or it can result in a separate hyperintense foci on a background of hypodense zone.
On MRI, LGA is iso- or (more often) hypointense on
T1-weighted images . As a rule, the tumor is
hyperintense with relatively homogeneous signal on T2 sequences. FLAIR imaging leads to highly heterogeneous signal from tumor tissue.
However, even MRI poorly detects tumour borders. It should be noted that infiltrative growth leads to the spreading of tumour tissue beyond the area of signal change visible on the T2-weighted image.
The gradual transformation of LGA into AA and then to
GBM is a well-known fact. In such observations, it is possible to simultaneously visualise within the same tumor the density changes (on CT) and MR signal changes (on MRI), typical for separate nosological forms of glioma , a combination of different forms of glioma or transformation of changes on follow-up scans. Moreover, it is known that about 10% of benign lesions can develop into more (sinister) malignant forms.
GBM is the most malignant of all glial tumors, and it occupies a great portion of the astrocytoma spectrum. It is the most frequent primary CNS tumor, whose incidence is about 10â€“20% of all intracranial tumors . GBM makes up approximately half of all gliomas,
and it is the most frequent supratentorial tumor in adults; usually it is observed in patients after age 50 years and is rare before 30 years.
Recently, GBMs have been divided into primary or secondary types. Primary GEMs are more common in adults and arise de novo. Secondary GEMs are found in younger patients and represent the malignant degeneration from originally lower-grade astrocytomas. Tumors undergo a series of mutations before becoming GBMs. Macroscopically, GBM usually is a formation that has a heterogeneous structure with central necrosis and highly vascularised stroma.
According to histological data, GBM is a tumor with a high level of cytological atypia and mitotic activity. The multiple foci of necrosis with the presence of so-called pseudopalisade structures in the form of multinuclear palisade of hyperchromatic nuclei and marked proliferation of the endothelium cells are characteristics of GB .
In the majority of cases, GB affects cerebrum, and it more often is located in deep-seated areas of white matter of temporal, frontal and parietal lobes, and in the corpus callosum, with the spreading into one or two hemispheres in the form of a butterfly; rarely is it found in cortex and posterior cranial fossa, and in basal ganglia .
Tumor density on CT is relatively heterogeneous. The
central area of tumour is a zone of necrosis, with low density, seen in 95% of cases. Calcifications are very rarely found in GBM, whereas haemorrhages of various ages are frequent findings. Usually the tumor is surrounded by intense perifocal oedema spreading into the white matter. After contrast administration is marked, although heterogeneous, contrast
enhancement is observed, more often in a ring shape with uneven internal contour .
Generally, MR signs of GBM reflect pathological changes and demonstrate significant tumour heterogeneity. T1-weighted images reveal badly delimited volumetric formation with mixed (iso-, hypointense) signal and central area of necrosis, which usually has lowered signal in comparison with the rest of a tumor. The tumorâ€™s characters on T2 and FLAIR scans also vary with the areas of hypo-, iso- and hyperintense
signal from tumour stroma, necrotic focus, cysts and foci of haemorrhages . Proton MR spectroscopy shows very high choline, low NAA, and the presence of lipids and lactate, reflecting necrosis .Perfusion studies show elevated rCBV . Perfusion MR studies have been used to differentiate tumor grades, with the highest rCBV found in GBMs. GBM tumor cells can be found outside an area of signal enhancement and perifocal oedema, revealed by MRI. GBM spreads rapidly and widely alongside white matter tracts. The spreading to the opposite site through corpus callosum, anterior and posterior commissures is also typical; however, GBM can also spread along internal and external capsules . In cases of hemispheric lesion, GBM sometimes spreads downward to chiasmâ€“sellar area, cerebral peduncles
and into posterior cranial fossa .
The treatment of glioblastomas remains difficult in that no contemporary treatments are curative. While overall mortality rates remain high, recent work leading to an understanding of the molecular mechanisms and gene mutations combined with clinical trials are leading to more promising and tailored therapeutic approaches. Multiple challenges remain, including tumor heterogeneity, tumor location in a egion where it is beyond the reach of local control, and rapid, aggressive tumor relapse. Therefore, the treatment of patients with malignant gliomas still remains palliative and encompasses surgery, radiotherapy, and chemotherapy. Median time to recurrence after standard therapy is 6.9 months. The addition of radiotherapy to surgery has been shown to increase survival from 3-4 months to 7-12 months. Meta-analyses have suggested that adjuvant chemotherapy results in a 6-10% increase in 1-year survival rate.
ICD-0 code: M9440/3
Associations/Predisposing Factors: The presence of low-grade astrocytic neoplasm and several genetic mutations (Loss of heterozygosity (LOH), p53, Epidermal growth factor receptor (EGFR) gene, MDM2, Platelet-derived growth factorâ€“alpha (PDGF-alpha) gene)
Special Stain:AE1/3 cytokeratin , Assay for GFAP expression
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