30 Year‐Old Male with Headaches

Clinical History and Radiology

A 30‐year‐old Chinese male presented with an 8 week history of headaches, visual changes, lightheadedness and balance problems. These symptoms were attributed to increased intracranial pressure secondary to obstructive hydrocephalus. Computed tomography (CT) scans demonstrated an iso‐or slightly hyperdense mass within both lateral ventricles. The septum pellucidum was not seen well on imaging studies and the tumor was centered on the midline. Contrast enhancement was mild to moderate. An MRI scan revealed a large midline mass obliterating large portions of the lateral ventricles and giving rise to obstructive hydrocephalus and transependymal edema. The mass was isointense on T1 weighted imaging and contained calcification On T2 weighted images it was relatively isointense with cortex (Fig 1a). There was moderate enhancement after the administration of gadolinium. Postoperative MRI scan showed gross total resection and some blood. After radiotherapy, the nerval symptoms had lapse to. But repeated MRI scans in the following 12 months showed recrudescence in the MRI findings and patient had more nerval symptomatic. Finally, the patient died of hydrocephalus and brain edema 20 months after the surgery.

Figure 1.

 

Gross Pathology

The operative specimen was a broken tissue which had a lobulated, well‐circumscribed, gray‐colored mass, 5 cm × 4cm × 3 cm, soft in character, attend by intratumoral hemorrhage and putrescence.

Microscopic Pathology

Microscopic examination showed sheets of monotonously small‐ to medium‐sized neoplastic cells with uniform round‐to‐oval nuclei and inconspicuous nucleoli. The nuclei were surrounded by perinuclear halos. Cellular borders were indistinct and cells appeared to contain a moderate amount of amphophilic cytoplasm. The tumor cells were dense in some areas and alternate with anuclear, less dense tumor parts. And the anuclear areas had a fine fibrillary matrix. Delicate vasculature formed a branching network in a pattern similar to oligodendroglioma. Focal calcification can be seen. The remarkable characteristic was that there were mitoses, nuclear atypia, necrosis and microvascular proliferation (Fig 1b, 2a,b).

Figure 2.

 

Tumor cells had strong cytoplasmic reactivity for NSE (Fig 2c), NeuN (Fig 2d), Synaptophysin, and CD99. A few entrapped astrocytes reacted appropriately with GFAP, but the tumor cells were negative. The MIB‐1 (Ki67) labeling index was estimated at 10% in all areas (Fig 2e). What is your diagnosis?

Diagnosis

Anaplastic central neurocytoma of both lateral ventricles.

Discussion

CN is a well‐established pathological entity and is generally regarded as a low‐grade well‐differentiated neuronal tumor, with limited growth potential. Some doctors theorize CN may derive from bipotential precursor cells of the periventricular germinal matrix, which are capable of both neuronal and glial differentiation, but maintain a low proliferative potential after birth. However, there are multiple reports of local recurrence, abundant mitosis, necrosis, extraventricular extension of tumor, and even craniospinal dissemination.

Eng et al 3, was the first to report clinical evidence of CN's aggressive nature; he reported two cases of craniospinal dissemination after craniotomy and subtotal resection of neurocytoma. Yasargil et al 10, reported that two patients had evidence of anaplasia and were treated with radiotherapy after total excision. Those tumors did not relapse at the time of the report after a follow‐up of 5–12 months. Three patients in the same study had recurrences 38–92 months after total excision and none had evidence of anaplasia. So, it is not clear if tumors with anaplasia have a higher relapse rate or if they need additional treatment. With GFAP positivity increases and vascular proliferation in CN, might suggest a more malignant course, 2. There have a report, the MIB‐1 index tended to be higher in central neurocytoma with mitosis and necrosis, 7. The MIB‐1 labeling index showed that a LI of 2% might be critical in determining recurrence. which MIB‐1 labeling index cut‐off of 2% demonstrated tumor recurrence of 63%, 8. In a larger of 15 central neurocytomas, an elevated MIB‐ labeling index was felt to be indicative of biological activity comparing histological atypia, proliferation, and clinical outcome, 4. Two other patients who had histological anaplasia and MIB‐labeling index <2 did not recur. So, it appears that there is a clinically more aggressive subgroup of central neurocytomas with elevated proliferative potential as determined by labeling index studies. This is testified in another case report of a patient with a recurrent central neurocytoma who had a four‐fold increase in MIB labeling index after a 9‐year disease free interval, 1. The MIB‐1 labeling index at the initial resection was 0.7% compared to 3.9% at the time of relapse. McKenzie showed in a small series of 15 cases of CN that the typical criteria for grading brain tumors such as cellular pleomorphism, necrosis, mitotic activity and endothelial vascular proliferation do not correlate with MIB‐1 labeling index. Moreover, he found that the proliferation index was a useful predictor of poor outcome; 4 of 15 patients had tumor recurrence and a MIB‐1 labeling index >2%, 4. These results were reiterated in a 129 patient meta analysis which showed 48% recurrence rate for MIB‐1 labeling index >3% versus12% for <3%, 5. In 2003, Takao et al reported a patient who had hyperacusis, oscillating vision, and headaches, 9, who was found to have a large left intraventricular mass. She underwent a craniotomy and excisional biopsy of the tumor. Although there was no pleomorphism or mitotic figures, the MIB labeling index was as high as 4.6%. The patient had a recurrence after only 11 months.

The most important therapeutic modality is surgery. Tumor total resection and radiotherapy remain the main treatment options for central neurocytomas. The effect of chemotherapy on central neurocytomas has uncertain curative effect. Long‐term responses to chemotherapy have not yet been reported. Total resection was suggested to be the best treatment for patients with atypical central neurocytomas, and that postoperative radiotherapy appeared to improve both local control and survival in patients who could not safely undergo total tumor resection 6.

The concept that central neurocytomas are benign is not entirely correct and is questioned. Of hundreds of CN reported to date, the incidence of recurrence is low, which makes aggressive forms of this tumor difficult to study. In our case in particular, there was mitoses, nuclear atypia, necrosis and microvascular proliferation appears to be primary, likely correlates with a high MIB‐1 labeling index of 10%, display atypical behavior, and finally made the patient die for the tumor recurrence. Our case is an example of a more aggressive CN, we designate anaplastic neurocytoma, WHO grade III is appropriate.