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LETTER TO EDITOR
Year : 2017  |  Volume : 65  |  Issue : 2  |  Page : 402-405

Primary central nervous system dural-based anaplastic large cell lymphoma: Diagnostic considerations, prognostic factors, and treatment modalities


1 Department of Neurosurgery, NIMHANS, Bengaluru, Karnataka, India
2 Department of Neuropathology, NIMHANS, Bengaluru, Karnataka, India

Date of Web Publication10-Mar-2017

Correspondence Address:
Amey R Savardekar
Department of Neurosurgery, NIMHANS, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/neuroindia.NI_1272_15

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How to cite this article:
Kaku MV, Savardekar AR, Muthane Y, Arivazhagan A, Rao MB. Primary central nervous system dural-based anaplastic large cell lymphoma: Diagnostic considerations, prognostic factors, and treatment modalities. Neurol India 2017;65:402-5

How to cite this URL:
Kaku MV, Savardekar AR, Muthane Y, Arivazhagan A, Rao MB. Primary central nervous system dural-based anaplastic large cell lymphoma: Diagnostic considerations, prognostic factors, and treatment modalities. Neurol India [serial online] 2017 [cited 2017 Mar 26];65:402-5. Available from: http://www.neurologyindia.com/text.asp?2017/65/2/402/201833


Sir,

Primary central nervous system lymphomas (PCNSLs) account for 0.5–1.5% of all intracranial tumors.[1] Most PCNSLs are of B-cell origin and those of T-cell origin are very rare, accounting for only 1.0–3.6% of all PCNSLs.[2],[3] Anaplastic large cell lymphoma (ALCL) is defined as a T-cell lymphoma composed of large pleomorphic lymphoid cells expressing CD30.[4],[5] The majority of ALCLs present as nodal diseases.[4] The involvement of the central nervous system as an extranodal site in ALCLs is rare, and its presentation as a primary dural lesion has been documented in only very few case reports till date.[6]

A 21-year-old immunocompetent male patient presented with progressive left frontal headache of 6-month duration, 2 episodes of right focal seizures with secondary generalization, and intermittent low-grade fever. The patient gave a history of fleeting lymphadenopathy; however on examination, there was no evidence of lymphadenopathy. Magnetic resonance imaging (MRI) of the brain revealed a 5 cm × 2.5 cm × 5.2 cm, well-defined lesion, arising from the left frontoparietal duramater, with significant perilesional edema. The lesion was isointense on T1-weighted imaging [Figure 1]a, hypo- to isointense on T2-weighted imaging [Figure 1]b and [Figure 1]c, and heterogeneously enhancing on contrast [Figure 1]d and [Figure 1]e. A “dural tail” sign was observed. Magnetic resonance spectroscopy (MRS) revealed raised choline-to-creatinine ratio with lipid and lactate peak [Figure 1]g. Radiological differentials included Rosai–Dorfmann disease, meningioma, and tuberculoma. Extensive microbiological serology, including testing for human immunodeficiency virus (HIV), showed no abnormality. Cerebrospinal fluid (CSF) studies were negative for malignancy or infection. After initially being unsuccessfully treated as intracranial Rosai–Dorfmann disease (with steroids), the patient underwent a left frontal craniotomy and gross total resection of the dural-based lesion.
Figure 1: MRI (magnetic resonance imaging) study of the brain showing that the lesion is (a) iso-in-tense on T1-weighted imaging, (b and c) hypo- to iso-intense on T2-weighted imaging and, (d and e) heterogeneously enhancing on contrast; (f) Susceptibility weighted images showing presence of susceptibility in the lesion; (g) On MRS (magnetic resonance spectroscopy), raised choline to creatinine ratio with lipid and lactate peak can be observed

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Histopathology revealed multiple nodules of necrosis rimmed by foamy macrophages, lymphocytes, and plasma cells. The few preserved tumor nodules were composed of anaplastic lymphoid cells with a high nuclear:cytoplasmic (N:C) ratio, and large hyperchromatic nuclei that were pleomorphic with horseshoe morphology at places [Figure 2]a and [Figure 2]b. High mitotic activity and apoptosis were seen. Tumor cells expressed leucocyte common antigen (LCA, CD45), CD 30, anaplastic lymphoma kinase (ALK), and a high Ki-67 (MIB-1) labeling index. Cells were CD3 and CD20 negative. Very occasionally, cells were epithelial membrane antigen (EMA) positive. The histology and immunohistochemistry (IHC) was consistent with ALK-positive anaplastic large cell lymphoma (ALCL) [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d,[Figure 2]e,[Figure 2]f,[Figure 2]g,[Figure 2]h,[Figure 2]i.
Figure 2: (a) Scanner view of dural-based lymphoma showing portions of the cellular nodule on right and the necrotic one on left (H&E stain, ×15); (b) Pleomorphic lymphoma cells with mitosis and few large macrophages with clear cytoplasm containing fragmented cellular debris (tingible bodies). Inset: Characteristic hallmark cell with kidney shaped nucleus and paranuclear eosinophilic region.[H&E stain,×400]; (c-i) Tumor cells are LCA (c), ALK(d) and CD30(e) strongly positive; scant and focally weak EMA positive (g); negative for CD3(h) and CD20(i).[IHC,×200]; (f) Ki-67 proliferative labeling index is very high (×100)

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Computed tomography (CT) scans of the chest, neck, and abdomen were done, which were normal, thus confirming the presence of primary dural lymphoma. The patient received the Memorial Sloan Kettering Cancer Center (MSKCC) “DeAngelis” protocol for CNS lymphoma, which included five cycles of methotrexate (2.5 gm/m 2), vincristine, and oral procarbazine (MVP) with intrathecal methotrexate preceding whole brain radiotherapy (WBRT) [45 Gy] and post-WBRT high-dose cytarabine.[7] The patient had a good clinical outcome at a 2-year follow-up.

Primary dural lymphomas are usually low-grade mucosa-associated lymphoid tissue (MALT) type B-cell lymphomas.[8] ALCL, a T-cell lymphoma commonly involving lymph nodes, occurring as a PCNSL is extremely uncommon, and presenting primarily as a dural-based lesion is very rare.[4],[6] The most frequent genetic abnormality observed in ALCL is the translocation between the anaplastic lymphoma kinase (ALK) gene on 2p23 and the nucleophosmin (NPM) gene on 5p35, resulting in a hybrid gene encoding an 80-kDa chimeric protein termed NPM-ALK.[5] The upregulation of ALK is known to induce mitogenic activity and this is likely to be involved in the neoplastic transformation process of ALCL.[5]

Diagnostic considerations

Based on the clinical history (past history of fleeting lymphadenopathy) and MRI findings, the differentials included Rosai–Dorfman disease, meningioma, and tuberculoma. Imaging studies in Rosai–Dorfman disease typically show an enhancing, solitary, meningeal-based mass, with a variable degree of edema surrounding the lesion.[9] The perilesional edema surrounding a small dural-based lesion was in favor of Rosai–Dorfman disease. The hypointensity on T2-weighted images and significant perilesional edema were factors against the radiological diagnosis of meningioma. Considering the endemicity of tuberculosis in India, dural-based tuberculoma was an important differential diagnosis. As lymphomas presenting as solitary dural-based lesions is a rarity, we did not consider PCNSL preoperatively. Moreover, primary dural lymphomas usually present as plaque-like thickening of the dura, which was not the finding in our case.[6]

Prognostic factors

The most important prognostic factor in ALCL is the presence of ALK-positivity on IHC.[4],[6],[10] ALK-positive ALCL predominantly affects young males, and if treated with chemotherapy, has a favorable prognosis; whereas, ALK-negative ALCL occurs in elderly patients, affecting both genders equally and with an unfavorable prognosis.[4] ALK positivity, age <40 years, unifocal lesion, and treatment with chemotherapy have been associated with long-term survival for primary ALCL of the CNS.[6],[10]

Treatment modalities

Due to its relative rarity, standard treatment of primary CNS ALCL has not been established. The role of surgery is limited to obtaining tissue for histopathological and IHC analysis.[11] For PCNSL, a multicenter trial has demonstrated improved survival with the combination of chemotherapy plus WBRT compared with previous reports of WBRT alone; however, neurotoxicity is a delayed risk of this approach.[12],[13] For primary leptomeningeal CNS lymphoma, multimodality treatment consisting of systemic chemotherapy, fractioned radiotherapy, and intraCSF chemotherapy has shown good outcomes as per the International Primary CNS Lymphoma Collaborative Group report.[14]

ALCL, a T-cell lymphoma, occurring as a primary dural lymphoma is extremely rare; however, histopathological diagnosis and IHC characterization is vital in dispensing the appropriate modality of treatment. Young male patients, ALK-positive tumors, solitary lesions, and treatment with chemotherapy are good prognostic factors, which were reflected in our patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K, et al. CD30(+) anaplastic large cell lymphoma: A review of its histopathologic, genetic, and clinical features. Blood 2000;96:3681-95.  Back to cited text no. 4
    
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Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th Edition. Lyon: IARC Press; 2008; p. 312-6.  Back to cited text no. 5
    
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Kim MK, Cho CH, Sung WJ, Ryoo HM, Lee HJ, Youn SW, et al. Primary anaplastic large cell lymphoma in the dura of the brain: Case report and prediction of favorable prognosis. Int J Clin Exp Pathol 2013;6:1643-51.  Back to cited text no. 6
    
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Nomura M, Narita Y, Miyakita Y, Ohno M, Fukushima S, Maruyama T, et al. Clinical presentation of anaplastic large-cell lymphoma in the central nervous system. Mol Clin Oncol 2013;1:655-60.  Back to cited text no. 10
    
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Manoj N, Arivazhagan A, Mahadevan A, Bhat DI, Arvinda HR, Devi BI, et al. Central nervous system lymphoma: Patterns of incidence in Indian population and effect of steroids on stereotactic biopsy yield. Neurol India 2014;62:19-25.  Back to cited text no. 11
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