Primary central nervous system (CNS) lymphomas form 0.85–2.0% of all primary brain tumors.1 The most common location of primary CNS lymphomas is the periventricular area.2 The hypothalamus is one of the rare locations of lymphoma in adults. Other lesions that can involve the hypothalamus are chordoid glioma, pituitary mass, metastasis, and meningioma.3

Case report

A 50-year-old male reported with complaints of memory disturbances and irritability of three weeks duration. His family had noticed that his short-term memory was grossly impaired. There was no associated history of headache, vomiting, fever, seizures, urine incontinence, or gait disturbance. His medical history was insignificant. On examination, he was irritable and confused. Assessment of his higher mental functions could not be done. There was no cranial nerve involvement or motor deficit.

Complete blood, cerebrospinal fluid (CSF), and radiological evaluation were performed. Serum electrolytes revealed hypernatremia (sodium 155 mEq/dL), which was corrected. His remaining electrolytes, blood sugar, kidney, and liver function tests were normal. His hemoglobin level was 9.6 g/dL, and leucocyte count was 7600/mm3. Lumbar CSF had 56 mg/dL proteins, 49 mg/dL sugar, and 8% lymphocytes. Serology test for tuberculosis with the polymerase chain reaction method and adenosine deaminase (ADA) activity were negative. Computed tomography (CT) scan of the chest, abdomen, and pelvis did not reveal any abnormality. His screening for anterior and posterior pituitary hormones was normal. Before subjecting the patient to a surgical procedure, a routine HIV-screening test was done, which was negative. Brain imaging revealed an enhancing suprasellar mass with areas of restricted diffusion within the mass [Figure 1 and 2].

A stereotactic tissue biopsy from the lesion showed features of large B-cell lymphoma. Histopathological examination showed a uniform population of large lymphoid cells. The cells had scanty cytoplasm and were arranged in a typical angiocentric pattern. Immunohistochemistry showed the tumor cells positive for leukocyte common antigen (LCA), and B-cell markers CD20 and CD19 [Figure 3]. Based on these histological and immunohistochemical features, a diagnosis of a diffuse primary large B-cell lymphoma was made. He was referred to a medical oncologist for further management. The patient was given six cycles of an intravenous high-dose methotrexate-based regimen (methotrexate 3.5 gm/m2, vincristine 2 mg/m2, procarbazine 100 mg/m2, and cytarabine 100 mg/m2 (post-radiation)) followed by consolidation therapy of one cycle of whole-brain radiotherapy (40 Gy to the whole brain, 2 Gy/day × 20 days). The patient was put on methylprednisolone 60 mg/day to reduce cerebral edema. After commencement of treatment and as edema subsided there was a significant improvement in his cognition and headache. At three-month follow-up, he was doing well and repeat scans showed noticeable regression of the lesion.

Discussion

Primary CNS lymphoma is a rare malignant primary CNS neoplasm comprising 0.85–2.0% of all primary brain tumors and 0.2–2.0% of malignant lymphomas.1 The incidence of primary CNS lymphomas is increasing relative to gliomas and meningiomas probably due to increasing number of transplant and patients with acquired immunodeficiency syndrome.4 Primary CNS lymphomas usually present with signs of focal mass lesion in 61% of patients, neuropsychiatric signs in 43%, features of raised intracranial pressure in 33%, and seizures in 14% of patients.4,5 Seizures are less common than with other types of brain tumors probably because primary CNS lymphoma involves predominantly subcortical white matter rather than epileptogenic gray matter. The lesion is commonly located in the periventricular region, especially around the lateral ventricles. Other sites involved are the thalamus, basal ganglia, corpus callosum, cerebellum, and spine. CNS lymphoma presenting as a unique, solitary mass located in the hypothalamic, and/or third ventricular region is very unusual. Only a few cases have been reported [Table 1].6–23

Table 1: Case reporting of central nervous system lymphoma located in the hypothalamic and/or third ventricular region.

Our patient presented with memory disturbances and irritability because of the hypothalamic involvement. There were no raised intracranial pressure symptoms. Other lesions that involve the hypothalamus and third ventricular region include pituitary macroadenomas, craniopharyngiomas, meningiomas, metastases, optic and hypothalamic pilocytic astrocytomas, Rathke cleft cysts, hamartomas of the tuber cinereum, chordoid glioma, and granulomatous diseases such as sarcoid, tuberculosis, and eosinophilic granuloma.13

Pomper et al,3 reported that chordoid gliomas located in the region of the hypothalamus and anterior third ventricle are ovoid in shape and well circumscribed. They also reported that vasogenic edema seen in these gliomas might help to distinguish them from meningiomas.3 As tuberculosis is a very common entity in Asia, it was considered among the differential diagnosis in our patient. However, our patient’s CSF was negative for markers of tuberculosis. Metastasis from a primary tumor can also sometimes involve the hypothalamic region, however, in our patient, preliminary screening for primary tumor by CT scan of the chest, abdomen, and pelvis was negative. The possibility of neurosarcoidosis, which often involves the meninges, cranial nerves, hypothalamus, and infundibular stalk should also be considered in such type of settings as it occasionally presents as a focal extra-axial or parenchymal mass.24,25

CT scan shows lymphomas to be iso- to hyperdense lesions. This feature is because of their hypercellularity. Also, lymphomas are homogenously enhancing lesions. Diffusion-weighted magnetic resonance imaging (MRI) shows restricted diffusion because of the hypercellularity of the lesion.

The most common histopathological subtypes seen in the CNS are large B-cell lymphoma. The cells are LCA positive (a leukocyte marker) and CD20 positive. Treatment options for primary CNS lymphoma (PCNSL) include corticosteroids, chemotherapy, and radiation. Resection of PCNSL is not a viable treatment option except in those with brain herniation due to mass effect.25,26 Although PCNSL is a potentially curable brain tumor in an immunocompetent patient; the best treatment strategy has yet to be defined. Current treatment options include biopsy with corticosteroids, radiation therapy, and chemotherapy. Many PCNSLs respond to corticosteroid sensitively but will relapse rapidly when used alone. Whole-brain radiation therapy alone does not produce remissions but is usually combined with chemotherapy as consolidation therapy, but we should be aware of treatment-related neurotoxicity, especially in elderly patients. Our patient was finally diagnosed subsequent to biopsy. He responded well to the initial chemotherapy and subsequent whole-brain radiation therapy. Today, he is in complete resolution in terms of clinical appearance and MRI imaging.

Conclusion

Lymphoma should be included in the differential diagnosis of lesions involving the hypothalamic/third ventricular area. Imaging and stereotactic tissue biopsy are of immense help when establishing the diagnosis. Chemoradiotherapy is the treatment of choice.

Disclosure

The authors declared no conflicts of interest.

references

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