Update: Fourth ventricle lymphoma

J.Sales-Llopis
Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain
A primary central nervous system lymphoma should be listed in the differential diagnosis of fourth ventricle tumors with well-circumscribed margins and homogenous contrast enhancement. ¹⁾.
A primary central nervous system lymphoma (PCNSL) frequency map showed that these tumors tended to occur around the lateral, third and fourth ventricles. Moreover, subtypes were classified as germinal center B (GCB) (27 cases) and non-GCB (63 cases) PCNSL frequency maps showed GCB lymphomas located at the upper tegmentum and cerebellum around the fourth ventricle, while non-GCB lymphomas tended to occupy the anterior fornix. These differences were significant and confirmed by the existence of voxels with P values <.05 (random permutation analysis with voxel-wise Fisher’ exact test). This is the very first report to address phenotypical and spatial distributional differences between GCB and non-GCB PCNSL using an MR group analytical method ²⁾.

Craniotomy and tumor resection, if feasible, should be the initial line of management in similar cases to relieve hydrocephalus and achieve the diagnosis ³⁾.

A 61-year-old male presenting with 3 months of headache and dizziness followed with unsteady gait for days. The MR imaging of brain revealed a homogeneously enhancing lesion occupying almost the whole 4th ventricle.The tumor was removed subtotally via suboccipital craniotomy. Histopathology revealed the lesion be a diffuse large B-cell lymphoma.
Primary central nervous lymphoma (PCNSL) is an important consideration in the differential diagnosis of intracranial mass lesion. The unusual location in surgically accessible fourth ventricle in posterior fossa, the isolation of the tumor may present a compelling indication for surgical resection.
Hsu et al. suggest that primary lymphoma should be considered with homogenous lesions of the 4th ventricle. Also aggressive surgical resection in this surgically accessible location, instead of biopsy only, is rational. ⁴⁾.

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A 66-year-old man with 2-month history of dizziness and 1-month history of diplopia. Cranial magnetic resonance imaging (MRI) disclosed two solid masses, one in the right lateral ventricle and another in the fourth ventricle. A surgical biopsy was performed on the basis of safety. The diagnosis of large B-cell lymphoma was made postoperatively. The patient recovered without additional deficits and was then commenced on chemotherapy and remained well 6 months after the diagnosis. It is an extremely rare case of primary central nervous system lymphoma with multifocal ventricular involvement. ⁵⁾

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A 65-year-old man presented with a two-week history of weight loss, headaches, blurred vision, asthenia and quickly worsening walking impairment. He denied photophobia, neck stiffness, fever, nausea or vomiting.Neurological examination showed global motor slowing, tendency to fall asleep during the clinical examination, generalized weakness against resistance to head and limbs, and osteotendon reflexes present in the upper limbs, but not evoked in the lower limbs. No sensitive deficit or focal neurologic sign was recognizable.Non-contrast multislice computed tomography (MSCT) of the head was performed in the emergency department, showing diffuse periventricular white matter and thalamic mild hyperdensity.Lumbar puncture, blood tests, including serology for HIV and other infections, were negative.On the third day the patient, showing decreased consciousness, underwent magnetic resonance imaging (MRI) with contrast medium injection. MRI revealed the presence of multiple pseudonodular avidly enhancing lesions, supra and infratentorial, crossing the midline, involving the ventricular system, including the fourth ventricle, with extension into the surrounding white matter, the corpus callosum, the thalamus and the hypothamalus.A stereotactic biopsy led to a diagnosis of diffuse large B-cell lymphoma, primarily located in the central nervous system (PCNSL).After the completion of the first phase of treatment (immunotherapy with intravenous Rituximab and corticosteroid), the MRI showed a marked regression of tumor masses ⁶⁾.

An 18 year-old immunocompetent male presented with multiple cranial nerves palsies and was found to have a mass predominantly in the 4th ventricle of the brain. Tumor was surgically removed and showed morphological and immunohistochemical features consistent with Burkitt lymphoma. The patient responded very well to anthracycline based chemotherapy with high dose methotrexate (HD MTX) and intrathecal (IT) chemotherapy delivered by Ommaya reservoir ⁷⁾.

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Grossman et al. report a case of primary CNS lymphoma located in the floor of the fourth ventricle that showed intense fluorescence after preoperative administration of 5 aminolevulinic acid. The authors believe that this is the first demonstration of a 5 aminolevulinic acid fluorescence guided resection in primary CNS lymphoma ⁸⁾.

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A 77-year-old man had a 1 week history of intermittent vertigo, nausea, vomiting, and progressively unsteady gait. CT scans of the brain showed a fourth ventricle tumor. MRI revealed a 2.5 cm dumbbell-shaped avidly-enhancing tumor in the fourth ventricle. Metastasis or high-grade glioma was suspected. The neuropathological findings were compatible with a diffuse large B-cell lymphoma. A slit lamp examination, bone marrow biopsy, and imaging studies for extracranial lesions were unremarkable ⁹⁾.
Primary fourth ventricular B-cell lymphoma in an immunocompetent patient ¹⁰⁾

Case report ¹¹⁾.

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A 50-year-old male who developed signs and symptoms of increased intracranial pressure. Imaging revealed the presence of a fourth ventricle mass with obstructive hydrocephalus. First, the patient underwent emergency endoscopic third ventriculostomy followed, few days later, by complete tumor resection via a posterior fossa craniotomy. Postoperative histopathology revealed the lesion to be a PCNSL. He received adjuvant chemotherapy and radiation and remained with no recurrence on regular imaging studies for 18-month followup ¹²⁾.

Multifocal lateral and fourth ventricular B-cell primary CNS lymphoma ¹³⁾
A case report ¹⁴⁾.

A 69-year-old man presenting with 6 weeks of intractable vomiting. Magnetic Resonance Imaging showed a homogenously enhancing mass in the caudal fourth ventricle. Surgical exploration and biopsy was performed and pathological examination demonstrated a high-grade B-cell lymphoma. The lesion was a primary tumour in an immuno-competent patient. . We suggest that primary B-cell lymphoma should be considered with homogenous lesions of the fourth ventricle. ¹⁵⁾

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A 51-year-old woman presented with a 2-month history of double vision and numbness around her left ear. She subsequently became unsteady on her feet and developed further cranial nerve abnormalities, before complaining of headache, nausea and vomiting. Imaging revealed features suggestive of two intracranial lesions; one non-contrast-enhancing high-signal area in the cerebellum with associated calcification, and a second contrast-enhancing low-signal area in association with the fourth ventricle, and at surgery there were two apparent components to the tumor. The histopathological features were those of a low-grade, focally calcified tumor comprising atypical ganglion and glial cells with interspersed Rosenthal fibres. Mitotic figures were not seen, and there was no necrosis. An infiltrate of small reactive lymphocytes was interspersed among the neoplastic cells. Immunohistochemistry revealed expression of synaptophysin by many of the dysplastic ganglion cells, with some co-expressing neurofilament protein and occasionally glial fibrillary acidic protein (GFAP). Several of the dysplastic ganglion cells also expressed CD34. The glial cell population was highlighted by GFAP. Ki-67 (MIB-1) activity was not noted among the neoplastic populations–the few positive nuclei in these areas were those of interspersed reactive CD3-positive T lymphocytes. In addition, at the edge of one of the biopsies was a dense infiltrate of mitotically-active large atypical CD 20-positive B lymphocytes, among which the Ki-67 (MIB-1) labeling index reached 80%. The final diagnosis was diffuse large B cell lymphoma arising within a ganglioglioma of the cerebellum, and this is believed to be the first reported case ¹⁶⁾.

A 33-year-old woman presenting with a 4-week history of vertigo and headaches. Physical examination revealed an isolated static cerebellar syndrome. Magnetic resonance imaging showed a homogeneously enhancing tumor located in the fourth ventricle. Complete surgical removal was performed and microscopic examination revealed a high-grade B-cell lymphoma. Postoperative investigations confirmed it to be primary ¹⁷⁾.

A 31-year-old man had Hodgkin’s disease (stage IIA, nodular sclerosis) in apparent remission after radiotherapy. Nine months after the diagnosis of Hodgkin’s disease, he developed neoplastic meningitis with eosinophilic pleocytosis and neurologic findings suggestive of peri-fourth ventricle infiltration. Morphologic and surface marker analysis of cerebrospinal fluid cells showed large numbers of T-lymphocytes and Reed-Sternberg variant cells positive for CD15, the Lex hapten expressed on myeloid cells and on a variety of malignant cells. Therapy with intrathecal methotrexate, oral dexamethasone, and cranial irradiation resulted in prompt resolution of his cerebrospinal fluid abnormalities and neurologic deficits. Ten months after the diagnosis of eosinophilic meningitis, systemic relapse of Hodgkin’s disease occurred in right iliac and inguinal lymph nodes ¹⁸⁾.

A case of primary malignant lymphoma of the central nervous system is described in which lesions seen on computed tomography scans disappeared, and clinical remissions occurred with the administration of corticosteroids. The tumor affected the region of the fourth ventricle and parietal and frontal lobes. In our patient, three remissions occurred over a span of 24 months, each in conjunction with corticosteroid administration. This supports other observations that steroids alter the natural history of primary malignant lymphoma of the central nervous system, leading to both radiologic and clinical remissions ¹⁹⁾.

A 43-year-old man underwent a surgical total removal of a tumor followed by radiotherapy (a total of 6,000 rad of 60Co) and chemotherapy. In the preoperative CT scan, a well-defined, nodular-shaped tumor was found in the left parietal region. This tumor disappeared when the combination treatment had been completed. Subsequently, CT scan demonstrated multifocal tumors with involvement of the roof of the fourth ventricle, frontal cortex and lateral ventricle. The patient expired 20 months after the onset of symptoms. The tumors in the frontal lobes, left thalamus and subdural space of the upper cervical cord showed dense sheets of polymorphous, large to medium-sized lymphocytes. The microscopic findings were interpreted as showing malignant lymphoma, lymphocytic, poorly differentiated, diffuse. Immunologically, E rosettes were formed by sheep red blood cells around the tumor cells. Immunofluorescence technique failed to demonstrate IgG, IgM and/or IgA in the cytoplasm of the tumor cells. By scanning electron microscopy, the tumor cells were devoid of microvilli ²⁰⁾.