Cerebellar Large B-cell Lymphoma: A Case Report

Malik Ghannam; Shaden Mansour; Fareed Jumah; Brent Berry; Albertine Beard

Disclosures

J Med Case Reports. 2018;12(341) 

In This Article

Discussion

PCNSL is a malignant NHL. It was first described by Bailey in 1929 as perivascular sarcoma.[5] The vast majority (90%) of cases are diffuse large B-cell lymphomas. Less common variants include Burkitt, T-cell, immunoblastic, or low-grade malignant B-cell lymphomas.[1,5,6] PCNSL can arise in the brain, spinal cord, eyes, cranial nerves, or meninges.[7] The aggressive parenchymal involvement of PCNSL almost always invades only locally, rarely metastasizing outside the nervous system. PCNSL itself is rare, comprising only 2–6% of all primary brain tumors and 1–2% of all NHLs.[2] However, its incidence is rising the fastest among all intracranial tumors.[8] The median age at diagnosis is 53–57 years in immunocompetent patients, as in our case, the patient was immunocompetent when he was diagnosed with a 1.2:1 male-to-female sex distribution, whereas in immunocompromised patients, the median age at diagnosis is 31–35 years with a clear male predominance (male-to-female ratio of 7.38:1).[9] Immunocompromise in these patients is typically secondary to HIV, organ transplant, or a primary immunodeficiency syndrome[10] such as ataxia telangiectasia; severe combined and common variable immunodeficiency; Wiskott-Aldrich syndrome; or autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, and sarcoidosis.[9]

The location of the PCNSL determines the clinical picture. The most common presentation, seen in 70% of patients, is focal neurological symptoms. Forty percent present with neuropsychiatric symptoms, followed in frequency by signs of increased intracranial pressure such as headache, nausea, and vomiting in 33%, seizure in 14%, and ocular symptoms in 4% of cases.[11] Determining a diagnosis of PCNSL can be challenging, owing to the absence of stereotypical clinical symptoms, the heterogeneity of the pathological morphology, the lack of specific diagnostic laboratory testing, and the variable appearance on imaging.[12] Initial evaluation should include head CT and MRI to visually characterize the lesion; scanning of the chest, abdomen, and pelvis and testicular ultrasound, bone marrow biopsy, and slit-lamp examination to evaluate for other sites of lymphoma involvement; and HIV testing.[13] Imaging-guided stereotactic biopsy, including histopathology and immunohistochemical staining, remains the preferred method of diagnosing PCNSL.[10] Macroscopically, PCNSL appears as a well-circumscribed, firm, gray to tan-yellowish mass with areas of hemorrhage.[9] PCNSL has a characteristic appearance on both CT and MRI scans,[14] commonly appearing isodense or hyperdense on CT scans and enhancing with contrast.[15] Microscopically, it shows a characteristic angiocentric growth pattern with splitting of blood vessels.[13] PCNSLs are typically derived from late germinal center exit B cells.[16] Thus, tumor cells often express pan B-cell markers (cluster of differentiation 19 [CD19], CD29, CD79a) and in 90% of cases express BCL-6 and MUM1, whereas plasma cell-associated proteins such as CD38 and CD138 are usually absent.[17]

PCNSL usually presents as a single homogeneous mass with surrounding edema; therefore, a wide differential diagnosis must be considered because many malignant and benign lesions present with a similar radiographic pattern. Malignant lesions that can appear similar include glioblastoma multiforme (GBM) and brain metastasis from primary cancers such as prostate and lung adenocarcinomas. Although histologically high-grade gliomas such as GBM have a greater degree of cellular and nuclear pleomorphism, infiltrative borders, and central necrosis with pseudopalisading, radiologically they can be difficult to distinguish from PCNSL because both can cross the corpus callosum ("butterfly pattern")[18] and can present with subependymal lesions.[19] However, PCNSL exhibits more restricted diffusion and lower apparent diffusion coefficient values on diffusion-weighted imaging (DWI) than GBM.[2] PCNSLs are hypointense on T2-weighted MRI signals owing to low intratumoral water content, unlike gliomas, metastasis, and tumefactive demyelinating lesions, which are T2-hyperintense.[18,20] However, brain metastases are more likely than PCNSL to have blood products, and they present as multiple enhancing lesions at the gray-white matter junction (from hematogenous spread),[19] though our patient's case highlights that these distinctions are not always diagnostically useful.

Benign lesions with radiographic appearance similar to PCNSL include subacute infarction, demyelinating diseases, infectious lesions, and neurosarcoidosis. Rich macrophage infiltrates seen on biopsy may point toward infarction or demyelination. Demyelinating disorders are characterized by axonal sparing, whereas infarcts show axonal loss. One particularly important infectious etiology to consider is toxoplasmosis, which is the most common brain lesion in patients with HIV. Distinguishing features include greater diffusion on DWI and clinical improvement with pyrimethamine-sulfadiazine can help establish a diagnosis of toxoplasmosis.[21] Neurosarcoidosis rarely presents as a tumor-like lesion within the brain, but on MRI it displays T2-hypointensity with perivascular dissemination and variable contrast enhancement without necrosis.

The clinical picture of PCSNL can also mimic posterior circulation stroke presentation, as did our patient. Therefore, this condition must be excluded, keeping in mind that it represents nearly 20% of all ischemic strokes. A posterior circulation stroke is defined as infarction of the vertebrobasilar arterial system.[22] The underlying pathophysiology involves occlusion or embolism (from large vertebrobasilar atherosclerosis or from the heart), dissection, vasculitis, and dolichoectasia (elongation and tortuosity of the vertebral and basilar arteries), among other less common causes. The posterior circulation mainly supplies the cerebellum, brainstem, and occipital cortex, and symptoms of stroke usually range from dizziness (47%) to unilateral limb weakness and dysarthria (41% and 31%, respectively). Posterior circulation stroke should be suspected in patients presenting with acute neurological symptoms, and this is diagnosed on the basis of history and clinical examination mainly, assisted by imaging studies. Diffusion-weighted MRI is the imaging modality of choice. Acute-phase CT provides suboptimal visualization of the posterior fossa structures; however, it allows identification of large-vessel occlusions or dissection if MRI is contraindicated or unavailable.[23] Subtle hypodensities, sulcal effacement, and loss of gray-white matter differentiation have been used to assess for signs of early ischemia on noncontrast head CT. Current international guidelines recommend conservative management, including the use of antiplatelet agents or anticoagulants. However, these interventions can be complicated with intracerebral hemorrhage or the need of ventriculoperitoneal shunting for hydrocephalus. Microsurgical intervention for cranial nerve compression may be lifesaving, and superficial temporal artery and superior cerebellar artery bypass have been reported.[22]

Many conditions can mimic posterior circulation ischemic stroke. Acute peripheral vestibular dysfunction is much more common and typically causes vertigo only with no other neurological symptoms. A head impulse test or Dix-Hallpike maneuver may aid in diagnosis. Acute intracranial hemorrhage, subarachnoid hemorrhage, and tumors may also mimic posterior stroke, which can be distinguished using proper imaging. Moreover, basilar migraine with aura should always be excluded, as well as other metabolic disturbances, such as hypoglycemia or central pontine myelinolysis, which can initially present with stroke-like features. Sarcoidosis or Whipple and Behçet disease can present acutely but with preceding systemic clinical features. Antibody-associated disorders such as Miller Fisher syndrome (ophthalmoplegia, ataxia, and areflexia) should be excluded as well.[23]

Unfortunately, PCNSL is an aggressive tumor with high rates of recurrence after treatment. It has a poor prognosis without treatment, with an expected survival of only 3–6 months. Chemotherapy alone or combined with radiation can boost the estimated survival time up to 25–60 months.[24] Relapses occur in the first and second years in 30–60% of patients, with survival after relapse averaging 2–4 months.[25]

The combination of chemotherapy and radiation is the standard treatment and can markedly improve the poor survival rates. High-dose methotrexate combined with whole-brain radiation has been widely used.[26] The preferred radiation therapy includes whole-brain radiation of 40–50 Gy followed by local radiation on regions of edema of 60 Gy. Other combination chemotherapies may be used, including methotrexate, temozolomide, and rituximab.[27] Rarely is surgical excision of these tumors possible, owing to their typically deep location, carrying significant risk of postoperative neurological complications. Moreover, resection carries no benefit in survival rates. Surgical resection should routinely be used only in cases of solitary lesions and in cases where intracranial pressure is increased.[28]

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