Primary Dural Lymphomas: A Review

Fabio M. Iwamoto, MD; Lauren E. Abrey, MD

Disclosures

Neurosurg Focus. 2006;21(5) 

In This Article

Epidemiology

The incidence of PDL is unknown, but it is a rare form of primary intracranial lymphoma. This lesion accounted for 2.4% of 335 patients with PCNSL in our institution.[18] Most published cases of PDL are single-patient reports, and of the two largest series of PDL, one had only 15[38] and one had eight[18] patients. This lesion occurs more often in middle-aged women, in contrast to brain parenchyma PCNSL, which has a slight male predilection. In the two series of PDL mentioned earlier, the female/male ratio was 4:1 in one and 3:1 in the other. In contrast with parenchymal PCNSL, there has been no clear association be tween acquired and congenital immunosuppression and the development of PDL.

Pathogenesis

The pathogenesis of PDL is not well understood be cause the dura is devoid of any lymphoid tissue. One hypothesis is that a benign inflammatory condition of the dura could attract polyclonal lymphocytes from which a monoclonal lymphoma could arise. Chronic infections and autoimmune diseases have been associated with MZL. The most common type of MZL occurs in the stomach and is associated with chronic infection with Helicobacter pylori.17Campylobacter jejuni[26] and Chlamydia psittaci[13] probably play a similar role in the pathogenesis of small bowel and ocular adnexal MZL, respectively. Chronic hepatitis C has been associated with nodal and splenic MZL.[7] Primary MZL of the dura has not been definitively associated with any infectious or autoimmune disease, but patients with hepatitis C,[12] scleroderma,[29] Graves disease,[33] and Sjögren disease[22] have been reported.

Clinical Presentation

Symptoms are usually dependent on the location of the tumor. The most common clinical presentations are head aches, seizures, focal sensory or motor deficits, and visual disturbances.[18] Other described symptoms include nausea, vomiting, and ataxia.[38] More rarely reported presentations include progressive cranial nerve dysfunction causing bilateral visual and hearing loss due to progressive dural involvement by MZL.[12] Another unusual presentation was reported in a patient who had headaches and acute hemiparesis mimicking an acute subdural hematoma.[15] In patients with PDL arising in the spinal cord dura, radicular pain and paraparesis are the most common presenting symptoms.[30]

Neuroimaging

Magnetic resonance imaging reveals single or multiple extraaxial masses that enhanced diffusely after administration of gadolinium contrast (Fig. 1). Up to 50% of patients in one series had more than one mass.[18] The cerebral convexities are the most common site, but the falx, tentorium, and sellar/parasellar regions can also be involved.[38] More rarely, intraventricular[18,23] and spine[30] masses can occur. Other MR imaging findings include en plaque thickening of the meninges, dural tail sign, underlying parenchymal vasogenic edema, early invasion of the underlying brain, calvarial hyperostosis, and bone erosion.

Figure 1.

Brain MR images demonstrating a left frontal hypointense extraaxial mass on a T1-weighted sagittal view (A); the tumor enhances diffusely after gadolinium injection (B). On a coronal T1-weighted MR image obtained after injection of gadolinium (C), a dural tail tumor is evident.

Differential Diagnosis

Unquestionably, the most important differential diagnosis is meningioma. In a series of 15 patients with PDL, a clinical and radiographic diagnosis of meningioma was made in 14 prior to the pathological diagnosis.[38] The PDLs and meningiomas share many features, including higher incidence in women, similar age of onset ( Table 1 ), and frequent occurrence of more than one extraaxial lesion. Neuroimaging findings are also similar; both tumors present with extraaxial lesions that appear iso- or hypointense on T1-weighted MR images and diffusely enhance with administration of gadolinium. Moreover, a dural tail is a frequent finding in both meningiomas and PDL.[38] On the other hand, underlying vasogenic edema appears to be more common in PDL.

Other differential diagnoses include dural metastasis, solitary fibrous tumors, gliosarcomas, leiomyosarcomas, hemangiopericytomas, melanocytomas, plasmacytomas, inflammatory pseudotumors, neurosarcoidosis, plasma cell granulomas, Rosai–Dorfman disease, Castleman disease, xanthomas, rheumatoid nodules, and tuberculomas.[21]

Pathological Findings

In patients with PDL, the most frequent histopathological diagnosis is MZL ( Table 1 ). Very rarely, cases of high-grade non-Hodgkin lymphoma,[2,30] low-grade follicular lymphoma,[10] and Hodgkin disease[20] have been reported.

The pathological features of MZL arising in the dura are similar to MZL in other extranodal sites.[39,40] This tumor has a predominance of small B-cell lymphocytes, but plasma cells, monocytoid-appearing lymphocytes, and scattered large lymphocytes can also be present.[17] The B cells of this type of lymphoma share the cytological features and immunophenotype of marginal zone B cells, and MZL is also characterized by negative markers for CD10, CD5, and CD23.[17]

Staging Evaluation

Neurological staging is of primary importance. This includes an MR image of the brain and/or spine (depending on the symptoms and signs) with gadolinium or, if MR imaging is contraindicated, a computed tomography scan with contrast material. Involvement of the leptomeningeal space due to direct tumor contiguity is common and occurred in 63% of patients with PDL in one series.[18] Consequently, all patients should undergo a lumbar puncture for cytological evaluation of the cerebrospinal fluid unless it is contraindicated. Other cerebrospinal fluid studies that may be helpful include protein, cell count, β2-microglobulin, immunoglobulin H gene rearrangement, and flow cytometry.[3]

Patients with presumed PDL need to undergo an evaluation to exclude systemic involvement. Although it is typically considered a localized tumor, more than 25% of patients with nongastric MZL presented with Stage IV disease.[40] A computed tomography scan of the chest, abdomen, and pelvis, and a bone marrow biopsy sampling with aspirate are the recommended staging procedures.

Prognosis

A PDL is more indolent and has a better prognosis than parenchymal PCNSL or systemic lymphoma with CNS metastasis. However, further studies with longer clinical follow up are necessary to assess the final outcome in these patients. In general, patients with MZL have a favorable outcome, with a 5-year overall survival rate greater than 86%, without significant differences between gastrointestinal and nongastrointestinal and between localized and disseminated disease.[35,36,40]

Treatment

Because of the paucity of cases described in the literature, no standard treatment is available for PDL. Clinical Stage IE MZL (extranodal disease limited to a single site) responds favorably to local treatments such as surgery or focal radiation.[35,37,40] Complete resection of MZL in the dura can be difficult due to multiple tumors, infiltrative behavior, or en plaque presentation. If complete resection is achieved, clinical and radiological follow up with no additional treatment is appropriate. However, for most cases, adjuvant treatment with either radio- or chemotherapy is necessary. Radiotherapy is preferable be cause MZL is very radiosensitive and requires relatively low doses of radiation; doses as low as 20 Gy have excellent results and minimize the risk of late neurotoxicity.[18] The radiotherapy port is determined by the extent of the dural lesions and the presence of leptomeningeal involvement.

High-dose methotrexate is the most effective drug for parenchymal PCNSL, but it is unclear if it has a role in PDL, because most patients respond to radiotherapy alone. Furthermore, high-dose methotrexate in conjunction with cranial irradiation can be neurotoxic, leading to progressive leukoencephalopathy, especially in older patients. For patients with disease that was localized to the dura and responded to radiotherapy, chemotherapy is unnecessary. Standard chemotherapy regimens for non-Hodgkin lymphoma and anti-CD20 monoclonal antibodies[28] are effective therapies for systemic MZL, but these regimens have not been studied in dural MZL. Moreover, limited data from a retrospective study of patients with nongastric MZL showed no clear advantage of systemic chemotherapy over radiotherapy or surgery.[40] If the leptomeninges are involved, intrathecal chemotherapy or whole-brain radiotherapy is required.

Conclusions

Complete response is achieved in most patients, even in those with leptomeningeal spread of the disease,[18,38] although nongastrointestinal MZL has a lower cure and higher relapse rate than gastrointestinal MZL.[35] In one study, relapses were found in three of eight patients with PDL; all of the tumors were outside the CNS.[18] Systemic recurrences can occur several years after the initial diagnosis of PDL.[8] The dura is outside the blood–brain barrier, which may explain the increased risk of systemic relapse compared with other types of PCNSL. Therefore, continued follow up and clinical surveillance are recommended for all patients.

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