Meningioma

* Primary dural lymphoma is rare, and few of the small number of cases reported to date have been classified using immunohistochemical techniques. To our knowledge, we report the first case ofT-cell-rich B-cell lymphoma (diffuse mixed small cell and large cell) presenting as a solitary intracranial dural mass. Cytologic and frozen sections prepared during intraoperative consultation revealed a polymorphic population of lymphocytes suspicious for an inflammatory process. Permanent sections of the dura showed a diffusely infiltrating mass composed of mature lymphocytes peppered with large atypical lymphocytes. Immunohistochemical stains identified the small lymphocytes as T cells (CD3 and CD43) and the large atypical lymphocytes as B cells (CD20). Evidence of rearranged immunoglobulin heavy-chain genes demonstrated B-cell monoclonality. Differentiating between inflammatory and neoplastic lymphocytic masses of the dura obviously has important therapeutic and prognostic significance and may require immunohistochemical and molecular techniques. (Arch Pathol Lab Med. 2000;124:1700-1703)

The vast majority of intracranial primary lymphomas are of the diffuse large cell, B-cell type arising within the brain parenchyma of immunocompromised or elderly individuals.1,2 Meningeal involvement, when it occurs, is usually a manifestation of disseminated high-grade lymphoma. Primary dura-based lymphoma presenting as a solitary mass is rare. Few cases of intracranial, dura-based lymphoma have been reported,3-11 and only a portion of these cases have been classified using immunohistochemical and molecular techniques. 5,7-9 It has been suggested that primary dura-based lymphomas have a better prognosis than those arising within the brain parenchyma or occurring in other extranodal sites. This report illustrates a case of primary dura-based intracranial lymphoma, which mimicked a meningioma radiographically and an inflammatory process on initial histologic examination.

REPORT OF A CASE

A 49-year-old, right-handed woman with no significant past medical history presented with complaints of intermittent headaches, vomiting, decreased memory, apathy, and right-sided weakness for 3 to 4 months, all of which worsened significantly during the month prior to hospital admission. Initial physical examination revealed a mild right hemiparesis that was more pronounced in the upper than the lower extremity. A right facial droop was noted, indicating a central facial nerve paresis. She was slightly aphasic. Magnetic resonance imaging disclosed a large, left frontal, lentiform, extra-axial mass abutting the brain with underlying edema. The mass was isointense on all sequences and displayed homogeneous enhancement and a dural tail, suggesting a meningioma (Figure 1). An arteriogram revealed a prominent neovascular blush arising from the anterior branch of the left middle meningeal artery, lending credence to the preliminary diagnosis of meningioma. Embolization with 150- to 250vim particles of polyvinyl alcohol was performed, which obliterated the neovascular blush.

A left frontotemporal craniotomy was performed on the day following the embolization. The mass was large, firmly attached to the dura, and superficially adherent to the brain over Broca's area. Samples of the dural mass and underlying brain were sent for immediate histologic examination. The tissue was examined using cytologic and frozen section preparations. The touch imprints showed the tumor to be composed of a polymorphous population of lymphocytes (Figure 2, A). The frozen section revealed the dense collagenous tissue of the dura to be diffusely infiltrated by lymphocytes. No evidence of follicle formation was present. The sample of underlying brain was uninvolved. A differential diagnosis of lymphoma versus an inflammatory process was rendered after examining the cytologic preparations and the frozen section. The bulk of the mass was resected.

The patient's postoperative course was uneventful. Extensive investigation, including lumbar puncture, computerized tomography of the chest and abdomen, and bone marrow biopsy failed to reveal any evidence of extracranial lymphoma. Treatment consisted of intrathecal methotrexate via Omaya reservoir followed by systemic CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy and whole brain irradiation. The patient showed no evidence of local recurrence or systemic lymphoma 14 months after the initial diagnosis.

MATERIALS AND METHODS

The tissue received in the pathology laboratory was preserved in 10% buffered formalin and B5 fixative. Routine morphologic examination was done on 5-(mu)m, paraffin-embedded tissue sections stained with hematoxylin-eosin. Immunoperoxidase studies were performed on paraffin-embedded tissue using the following antibody panel: CD45, CD20, CD43, and CD30 (Dako Corporation, Carpinteria, Calif); CD3 (Novocastra, Newcastle upon Tyne, United Kingdom); CD15 (Becton Dickinson, San Jose, Calif); cyclin Dl (Santa Cruz Biotechnology, Santa Cruz, Calif); CD99 (Signet Laboratories Inc, Dedham, Mass); K and X light chains (Biosource, Camarillo, Calif); and cytokeratin (Zymed Laboratories, South San Francisco, Calif), according to the manufacturers' instructions. Antigen retrieval was performed prior to staining using the microwave method.12 Flow cytometry was attempted but produced unsatisfactory results due to cell lysis. Southern blot hybridization for detection of immunoglobulin heavy-chain rearrangement was done after DNA was extracted from paraffinembedded material using a standard phenol/chloroform technique. Ten micrograms of genomic DNA was digested with each enzyme (BamHI, BamHI/HindI]I, EcoRI, and Bg/II; Gibco-BRL, Gaithersburg, Md) in the following reaction mixture: 10 (mu)g of DNA, sterile double-distilled water to 39 wL total, 5 pL of 10 X buffer, 4 (mu)L of restriction enzyme (50 units/(mu)L stock), and 2 (mu)L of 0.1 mol/L spermidine (Sigma Chemical Co, St Louis, Mo). The samples were incubated at 37 deg.C for a minimum of 3 to 4 hours. The digested samples were electrophoresed through a 0.8% regular agarose gel (Fisher Scientific, Pittsburgh, Pa) containing 1X E buffer (0.04 mol/L Tris-acetate, 0.001 mol/L EDTA, pH 8.3, Fisher Scientific) and run in 1 X E buffer at 45 V for 17 hours. A modification of the Southern method was employed for the transfer of DNA to a nylon membrane. A probe against the immunoglobulin heavy-chain-gene joining region was used at a specific activity of 3 x 10^sup 6^ cpm/mL with Hybrison (Oncor, Gaithersburg, Md). Hybridization was carried out for 16 to 24 hours at 56 deg.C with constant rotation. The membranes were washed with low stringency solution (0.5x SSC, 0.1% sodium dodecyl sulfate [SDS]) at room temperature for 20 minutes, followed by high stringency wash (OAX SSC, 0.5% SDS) at 50 deg. C for 20 minutes with constant shaking. The filters were exposed to x-ray film for the visualization of bands.

RESULTS

Microscopic examination of the tissue sections demonstrated a heavy, diffuse lymphocytic infiltrate in the dural collagen. The lesion was composed predominately of small mature lymphocytes with round nuclei and scant cytoplasm (Figure 2, B). In addition, scattered, large, atypical lymphocytes with vesicular nuclei and discernable clear cytoplasm were identified. No other inflammatory cells were present in this infiltrate, and lymphoid follicle formation was not present. The dual population showed uniform immunoreactivity with leukocyte common antigen (CD45). The large neoplastic lymphocytes were identified as B cells (CD20), and the small mature lymphocytes were identified as T cells (CD3, CD43) (Figure 2, C and D). Southern blot analysis demonstrated the presence of a monoclonal B-cell population. Evidence of rearranged immunoglobulin heavy-chain genes was detected in the HindIII, BamHI/HindIII, and Bg/II digests. The bands were weak due to the small number of neoplastic B cells in the overall population of lymphocytes (Figure 3). The tumor was classified as diffuse mixed small cell and large cell (T-cell-rich B-cell) lymphoma using the Working Formulation13 and diffuse large B-cell lymphoma in the Revised European-American Lymphoma Classification (REAL).14

COMMENT

This case illustrates that a dural mass composed of a polymorphic population of lymphocytes lacking the usual histologic features of meningioma evokes a differential diagnosis of an inflammatory versus a neoplastic process. Inflammatory masses of the dura have been described previously as having 1 of 3 possible phenotypes. They may represent (a) meningiomas with a marked inflammatory infiltrate, (b) a dura-based mass with a minor meningothelial component and marked inflammation, or (c) a mass composed solely of inflammatory cells attached to the dura.15 In all cases of inflammatory masses of the dura, the possibility of infection, hematologic malignancy, and systemic disease must be considered.'S Despite extensive studies, the etiology of such so-called inflammatory pseudotumors remains undetermined in some cases.

Various subclasses of lymphoma have been described as primary intracranial dura-based tumors. Most of the reported cases are of the B-cell type,5.7-9 and to our knowledge, T-cell-rich B-cell lymphoma has not been reported previously. T-cell-rich B-cell lymphoma has been described as an intermediate-grade lymphoma that most frequently involves the lymph nodes, although there have been some reported cases of extranodal involvement.16 Morphologic features of T-cell-rich B-cell lymphoma include a polymorphous population of lymphocytes that are greater than 50% reactive T cells and a variable mixture of other reactive cells, such as eosinophils, plasma cells, and macrophages. Thus, extranodal T-cell-rich B-cell lymphoma may closely mimic a nonneoplastic inflammatory mass, primary T-cell lymphoma, and Hodgkin disease. Recognizing T-cell-rich B-cell lymphoma has therapeutic and prognostic implications in that it may not respond to the chemotherapeutic agents given for Hodgkin disease and it may have a better prognosis than primary T-cell lymphoma.16

The lesion can be classified as diffuse mixed small and large cell lymphoma by the Working Formulation. Since all the neoplastic cells appear large, and tumors are usually classified on the basis of the neoplastic cells, the more appropriate designation may be diffuse large B-cell lymphoma, as in the World Health Organization's recently released classification and the Revised European-American Lymphoma Classification.17

Following treatment of primary dura-based lymphoma, the disease-free interval can range widely. One study reported disease-free intervals of 7 to 63 months.6 Reasons for the perceived favorable prognosis of dura-based lymphomas are not known. The clinical outcome of primary dura-based lymphoma may depend on the phenotype of the lymphoma rather than the solitary, focal nature of the lymphoma. The rarity of these tumors, however, makes long-term, randomized, prospective studies difficult, if not impossible. Recognition of these tumors and utilization of improved molecular and immunohistochemical techniques to classify these tumors adequately may have important clinical and therapeutic implications.

References

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30 cases, supporting its histologic heterogeneity and lack of clinical distinctiveness. Am J Surg Pathol. 1994;18:455-465.

17. Harris NL, Jaffee ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November 1997. Histopathology. 2000;36:69-87.

Accepted for publication March 17, 2000.

From the Department of Pathology (Drs Amaker, Ghatak, FerreiraGonzalez, and Kornstein) and Department of Surgery, Division of Neurosurgery (Dr jebraili), Medical College of Virginia, Virginia Commonwealth University, Richmond, Va.

Reprints: Barbara H. Amaker, MD, Department of Pathology, Division of Neuropathology, Medical College of Virginia/Virginia Commonwealth University, PO Box 980017, Richmond, VA 23298-0017.

Copyright College of American Pathologists Nov 2000
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