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Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 943-945

A rare case of primary anaplastic large cell lymphoma of the central nervous system

1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Web Publication15-Feb-2016

Correspondence Address:
Ashok S Komaranchath
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.162115

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 > Abstract 

Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin's lymphoma, confined to the central nervous system (CNS) and is usually seen in immunocompromised patients. The vast majority of cases are of the B-cell type and T-cell PCNSL is rare. Here, we report an 18-year-old male who presented with fever, headache, and history of seizures. On evaluation, he was found to have a left parieto-occipital mass which was completely excised. Histopathology was suggestive of a T-cell neoplasm and immunohistochemistry showed tumor cells positive for leukocyte common antigen, anaplastic lymphoma kinase (ALK), CD30, and CD4 which confirmed the diagnosis of ALK-positive anaplastic large cell PCNSL. There was no evidence of disease outside the CNS. He was started on the DeAngelis protocol for PCNSL. To the best of our knowledge, only 27 cases of anaplastic large cell PCNSL have been previously reported in literature.

Keywords: Anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, lymphoma of the dura mater, non-Hodgkin lymphoma, primary central nervous system lymphoma

How to cite this article:
Kuntegowdenahalli LC, Jacob LA, Komaranchath AS, Amirtham U. A rare case of primary anaplastic large cell lymphoma of the central nervous system. J Can Res Ther 2015;11:943-5

How to cite this URL:
Kuntegowdenahalli LC, Jacob LA, Komaranchath AS, Amirtham U. A rare case of primary anaplastic large cell lymphoma of the central nervous system. J Can Res Ther [serial online] 2015 [cited 2021 Jan 16];11:943-5. Available from: https://www.cancerjournal.net/text.asp?2015/11/4/943/162115

 > Introduction Top

Primary central nervous system lymphoma (PCNSL) is the term applied to non-Hodgkin lymphoma (NHL) arising in and confined to the central nervous system (CNS). It is more commonly seen in the immunocompromised, with the highest incidence in those patients with acquired immunodeficiency syndrome. The incidence is lesser in immunocompetent patients. Histologically, around 98% are B-cell lymphomas. T-cell lymphomas of the CNS are very rare but have similar responses and outcomes as compared to the B-cell neoplasms. Anaplastic large cell lymphoma (ALCL) is an uncommon type of peripheral T-cell lymphoma which is characterized by painless lymphadenopathy and frequent extranodal involvement. However, the involvement of the CNS is very rare and is limited to case reports and small case series. ALCL is broadly sub-classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negative subtypes. ALK-positive tumors tend to have a better response to therapy and better overall survival (OS).

To the best of our knowledge, there have been only twenty-seven cases of primary anaplastic large cell lymphoma of the CNS reported in literature. There are no standard treatment regimens for ALCL of the CNS. Cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone (CHOP)-like regimens are not indicated as the disease is confined to the CNS. With the limited data available, it is a reasonable option to treat such tumors with a high dose methotrexate based regimen along with cranial radiotherapy (RT).

 > Case report Top

An 18-year-old male presented with history of fever and headache of 4 months duration and two episodes of seizures. He was evaluated for the same and magnetic resonance imaging brain showed a left parieto-occipital mass of 4.3 cm × 2.5 cm size, for which he underwent a craniotomy and the lesion was completely excised [Figure 1]. Histopathology was suggestive of ALCL of the dura mater and was referred to our center for further management. Physical examination was unremarkable with no peripheral lymphadenopathy or hepatosplenomegaly. There were no focal neurological deficits. Routine hemogram and biochemical evaluation including serum lactate dehydrogenase (LDH) levels were normal. Contrast-enhanced computed tomography scan of the neck, thorax, abdomen, and pelvis showed no evidence of disease anywhere else in the body. Bone marrow aspiration and biopsy showed no involvement of the marrow. Cerebrospinal fluid examination showed no malignant cells. Histopathology was suggestive of ALCL and immunohistochemistry showed neoplastic cells positive for leukocyte common antigen, ALK, CD30, and CD4 [Figure 2] [Figure 3] [Figure 4], negative for CD3 and CD7. He was started on the DeAngelis protocol with high-dose methotrexate with leucovorin rescue, intrathecal methotrexate, vincristine, procarbazine, and dexamethasone, with whole brain RT and cytarabine planned after 10 weeks of initial chemotherapy. Intrathecal methotrexate was given via lumbar puncture instead of an intraommaya catheter. Oral leucovorin rescue after the intrathecal administration was also not given. He is also on prophylactic antiepileptic medication and has had no further seizures after the initial surgery.
Figure 1: Magnetic resonance imaging brain-T2 axial fluid-attenuated inversion recovery, sagittal, coronal

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Figure 2: Histopathology high power field ×40 RMS

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Figure 3: CD4-positive 40 field

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Figure 4: Strong anaplastic lymphoma kinase positivity

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 > Discussion Top

PCNSL is an uncommon variant of extranodal NHL that involves the brain, leptomeninges, eyes, or spinal cord without evidence of systemic disease. The epidemiology and clinical presentation vary depending upon the immunocompetence of the patient. PCNSLs represent approximately 4% of newly diagnosed primary CNS tumors, with an age-adjusted incidence rate of four cases per million persons per year. [1],[2] Histologically, PCNSL may be any type of NHL but more than 98% of PCNSLs are B-cell lymphomas. Around 75% are identical to the diffuse large B-cell subtype. In a series of 33 cases of PCNSLs published from our institute, all were of the diffuse large B-cell variety. [3] T-cell lymphomas are rare but have a comparable response and outcome to treatment as the more common B-cell neoplasms. [4] Age, LDH serum levels, performance status, CSF protein concentrations, and the involvement of deep structures of the brain are independent predictors of survival. [5] Using these risk factors, the 2 years OS rate varies proportionately from 24% to 85%. ALCL, first reported by Stein et al., is a rare type of T-cell lymphoma. [6] It is characterized by large pleomorphic CD30 expressing lymphoid blasts containing horseshoe-shaped nuclei. [7] According to the WHO classification of Tumors of Hematopoietic Lymphoid Tissues-2008, systemic ALCL is divided into ALK-positive and ALK-negative. [8] About 60-85% of all systemic ALCLs are ALK-positive with the typical t(2:5) translocation which results in production of the ALK protein. ALK-positive ALCLs usually present at a younger age group and have a more favorable prognosis as compared to the ALK-negative variant. After treatment with an anthracycline-based chemotherapy regimen such as CHOP regimen, 5 years OS rates for patients with ALK-positive ALCL have ranged from 70% to 93% and 15% to 49% in patients with ALK-negative ALCL. [9],[10],[11],[12],[13]

The most common clinical presentation of ALK-positive ALCL in adults is painless lymphadenopathy. [8] Extranodal involvement is not uncommon and the favored sites are bone (14%), bone marrow (12%), subcutaneous tissue and spleen (10% each), skin and lung (8% each), and liver (3%). [14] It very rarely affects the CNS and ALCL of the CNS is limited to case reports. Nomura et al. published a case series of the twenty-seven cases of ALCL of the CNS in immunocompetent patients that have been so far published in literature along with demographic profile, treatment given and OS. [15] ALCL of the CNS has been found to be more aggressive than either PCNSL (of which the most common histology is DLBCL) or systemic ALCL. [16],[17] However, in the data analyzed by Nomura et al., ALK-positive ALCL of the CNS had a better prognosis than ALK-negative and were comparable to that of systemic ALK-positive ALCL. [15] In our own institutional series of PCNSLs, the median OS was 15 months with the DeAngelis protocol. [3]

As ALCL of the CNS is rare, there is no standard treatment for this entity. Although the number of cases studied was less, the case series of ALCL of the CNS highlighted the importance of chemo RT. Also, since CHOP-like regimens are not indicated in PCNSL, high-dose methotrexate-based regimens were recommended for treating ALCL of the CNS. Also, ALK-negative ALCL of the CNS was found to have a very poor prognosis. Taking this into consideration, this patient was started on the DeAngelis protocol including high-dose methotrexate with leucovorin rescue, vincristine, procarbazine, dexamethasone, and Intrathecal methotrexate, followed by high-dose cytarabine and whole brain RT. [18]

 > Conclusion Top

PCNSL's are rare NHL's, which are confined to the CNS. Although PCNSLs of T-cell histology are very rare, the treatment options remain the same, and the outcome is comparable to that of B-cell neoplasms.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Hoffman S, Propp JM, McCarthy BJ. Temporal trends in incidence of primary brain tumors in the United States, 1985-1999. Neuro Oncol 2006;8:27-37.  Back to cited text no. 1
Villano JL, Koshy M, Shaikh H, Dolecek TA, McCarthy BJ. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer 2011;105:1414-8.  Back to cited text no. 2
Lakshmaiah KC, Sathyanarayanan V, Babu KG, Lokanatha D, Lokesh KN, Babu MC, et al. Primary central nervous system lymphoma: An Indian perspective. Clin Cancer Investig J 2014;3:514-20.  Back to cited text no. 3
  Medknow Journal  
Shenkier TN, Blay JY, O'Neill BP, Poortmans P, Thiel E, Jahnke K, et al. Primary CNS lymphoma of T-cell origin: A descriptive analysis from the international primary CNS lymphoma collaborative group. J Clin Oncol 2005;23:2233-9.  Back to cited text no. 4
Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, et al. Prognostic scoring system for primary CNS lymphomas: The International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003;21:266-72.  Back to cited text no. 5
Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: Evidence that reed-sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985;66:848-58.  Back to cited text no. 6
Jaffe ES, Harris NL, Stein H, Vardiman JW. Anaplastic large cell lymphoma. In: Pathology and Genetics: Tumors of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001. p. 230-5.  Back to cited text no. 7
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, et al. Anaplastic large cell lymphoma. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4 th ed. Lyon: IARC Press; 2008. p. 312-6.  Back to cited text no. 8
Shiota M, Nakamura S, Ichinohasama R, Abe M, Akagi T, Takeshita M, et al. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: A distinct clinicopathologic entity. Blood 1995;86:1954-60.  Back to cited text no. 9
Nakamura S, Shiota M, Nakagawa A, Yatabe Y, Kojima M, Motoori T, et al. Anaplastic large cell lymphoma: A distinct molecular pathologic entity: A reappraisal with special reference to p80 (NPM/ALK) expression. Am J Surg Pathol 1997;21:1420-32.  Back to cited text no. 10
Falini B, Pileri S, Zinzani PL, Carbone A, Zagonel V, Wolf-Peeters C, et al. ALK+lymphoma: Clinico-pathological findings and outcome. Blood 1999;93:2697-706.  Back to cited text no. 11
Gascoyne RD, Aoun P, Wu D, Chhanabhai M, Skinnider BF, Greiner TC, et al. Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood 1999;93:3913-21.  Back to cited text no. 12
Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ALCL and peripheral T-cell lymphoma, not otherwise specified: Report from the international peripheral T-cell lymphoma project. Blood 2008;111:5496-504.  Back to cited text no. 13
Vose J, Armitage J, Weisenburger D, International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: Pathology findings and clinical outcomes. J Clin Oncol 2008;26:4124-30.  Back to cited text no. 14
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;1:655-660.  Back to cited text no. 15
George DH, Scheithauer BW, Aker FV, Kurtin PJ, Burger PC, Cameselle-Teijeiro J, et al. Primary anaplastic large cell lymphoma of the central nervous system: Prognostic effect of ALK-1 expression. Am J Surg Pathol 2003;27:487-93.  Back to cited text no. 16
Kodama K, Hokama M, Kawaguchi K, Tanaka Y, Hongo K. Primary ALK-1-negative anaplastic large cell lymphoma of the brain: Case report and review of the literature. Neuropathology 2009;29:166-71.  Back to cited text no. 17
DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation therapy oncology group study 93-10. J Clin Oncol 2002;20:4643-8.  Back to cited text no. 18


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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