Question

A 54-year-old man was admitted to the hospital because of visual-field loss and a mass in the brain. He had been well until 3 weeks before admission, when loss of vision in the right eye, associated with diplopia, developed while he was jogging; it resolved spontaneously after several minutes. Four days before admission, the symptoms recurred transiently, and he bumped into a tree while running. On the morning of admission, dizziness and loss of vision in the right lower visual field in both eyes developed, which did not resolve and resulted in difficulty driving. He went to the emergency room at another hospital. On examination, nystagmus was present in both eyes on left and right gaze.

Vital Signs and Laboratory Testing Results:

Blood Count was normal

Blood levels of electrolytes, calcium, and glucose were normal

Patient Referral:

Patient was sent for MRI examination.

MRI Results:

Brain – revealed two adjacent masses in the left occipital and posterior parietal regions. As a result, patient was admitted to the hospital, and dexamethasone

(corticosteroid) was administered. He was then transferred to another hospital for further examination.

Further information from patient:

Patient reported difficulty seeing objects in the right lower visual field and dizziness. He reported no headache, nausea, vomiting, numbness, weakness, bowel or bladder dysfunction, or seizures. He had a history of gastroesophogeal reflux disease and H. pylori infection and had recently had hematuria. A CT scan of the abdomen obtained 3 months before admission showed prostatic enlargement and was otherwise normal. He took esomeprazole (for reflux) and had no known allergies. He was divorced, had children, and was physically active, running daily and competing in multiple marathons. He drank alcohol in moderation, had never smoked, and had no recent exposure to ill persons, tuberculosis, or asbestos.

Family History:

An uncle had had an inoperable primary brain tumor; the patient’s siblings and children were healthy.

Differential Diagnosis:

MRI revealed two masses in the left occipital lobe and edema suspected

Presentation of episodic, reversible neurologic deficits.

A tumor was the leading diagnostic possibility, and a primary brain tumor was more likely than a metastatic tumor.

No systemic symptoms or fever.

Therefore, concluded leading diagnosis was a primary malignant tumor of the brain parenchyma. The appearance on imaging and the patient’s age make glioblastoma the most likely diagnosis.

Treatment regimen:

Resection of a suspected malignant brain tumor

Gluoccorticoids administered to reduce intracerebral edema

Molecular Testing:

MS-PCR evaluation of the methylation status of MGMT performed on FFPE block of tumor revealed methylated alleles

FISH testing revealed normal EGFR signals

Treatment regimen:

Patient administered temozolomide and vatalanib (tyrosine kinase inhibitor) with concurrent radiotherapy

Patient reaction to treatment:

Four weeks after completion of the 6-week course, a routine follow-up cranial MRI was performed, at which time, the patient was asymptomatic, physically active, and managing all his activities of daily living.

MRI 3 months after surgery showed a mass effect on the left lateral ventricle indicating tumor progression.

Three biopsies of the left occipital lobe contained extensive necrotic debris with microcalcifications.

One month later he had a generalized seizure.

MRI revealed new mass in the right temporal lobe.

MS-PCR confirmed the presence of methylation of MGMT in the tumor.

Patient administered radiotherapy and temozolomide.

Patient had progressive neurologic decline while on treatment.

Consultation:

Patient and his family were consulted to stop therapy and the patient was transferred to hospice care. He died 8 months after second diagnosis which was 28 months after the initial diagnosis of glioblastoma.

Based only on all test results, in your opinion, was the second malignant glioma a recurrent tumor or a separate secondary tumor? Explain your answer.

Answer 1

It is Recurrent tumour. As it is malignant glioma it has invasive property so spread.

the predominant site of initial recurrence following radiotherapy alone has been within a few centimeters of the tumor bed and resection site.Despite the addition of temozolomide to radiotherapy for GBM, local failure remains the most common site of initial recurrence., it is essential to remember that malignant gliomas are infiltrative in nature, as the brain offers minimal barriers to spread within its confines, and that distant failures (in the brain) are likely to occur.

Immediately following primary concurrent chemoradiation, many patients with GBM develop pseudoprogression, that is, the false radiographic appearance of progressive disease. This phenomenon has been estimated to occur in approximately 20% of patients with recurrent malignant glioma and typically appears within 6 months of completion of radiotherapy. Conversely, the use of antiangiogenic therapies (vide infra) can produce “pseudoresponses,” in which the disease is disproportionately less apparent radiographically though the change in tumor burden may be minimal. Although a great deal of progress has been made in establishing the radiographic criteria for disease progression in treated malignant glioma,the interpretation of magnetic resonance (MR) imaging studies is complicated by radiotherapeutic effects and concomitant biochemotherapies. Although a variety of other imaging modalities, including single photon emission computed tomography and positron emission tomography with various biomarkers, exist, no method has emerged as providing an unambiguous method of ruling in recurrence or progression and ruling out purely radiation-induced changes.

The gold standard for diagnosis of recurrent disease is, of course, a definitive histologic confirmation. However, before performing a biopsy to establish or deny gross recurrence, it is essential to ask whether the value of making the diagnosis outweighs the risk of the procedure. Inherent in this judgment is the upfront probability that an apparent lesion represents recurrent disease. During the first 6 months following treatment of the primary disease with radiotherapy, there is a substantial probability that radiographic changes represent pseudoprogression and many practitioners may elect to follow up the patient with closely spaced MR imaging examinations in the absence of clinically significant new symptoms. At longer times, the probability that there is recurrent disease, often in admixture with local radiotherapeutic effects, is very high. In addition, biopsy can be complicated by impaired wound healing from previous radiation therapy or ongoing chemotherapy, particularly bevacizumab (BVZ)., the appearance of a new, distinct lesion on MR images may be sufficient to initiate further interventions without histologic confirmation of recurrence, especially when the lesion is outside the high-dose area of initial radiotherapy or appears more than 6–12 months after completion of radiotherapy or both.