A 64-year-old male presented with a 1-month history of progressively worsening headaches. He had no other central neurological symptoms, including ocular symptoms, and examination of the central and peripheral nervous system was normal. Physical examination did not reveal lymphadenopathy or organomegaly and was normal for all systems examined. No constitutional symptoms such as fever, weight loss or night sweats were present. Four years prior to this, he was diagnosed with a lung cancer through cytomorphology, with no immunocytochemistry being available due to the paucity of cells following a computed tomography (CT)-guided procedure. The radiological findings of a spiculated mass in the left upper lobe were typical for lung cancer. The lung multi-disciplinary team (MDT) made a final diagnosis of a stage IIIa non-small cell lung cancer (NSCLC). Due to his underlying medical conditions, the patient was not a surgical candidate. He was treated with six cycles of cisplatin and vinorelbin chemotherapy, followed by radical radiotherapy (36 Gy in 12 fractions), achieving a complete response as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Other medical history included severe peripheral vascular disease requiring abdominal aortic aneurysm repair with an aortobiiliac graft, and mild to moderate chronic renal failure (baseline creatinine clearance of 45 ml/minute).
At presentation he had an elevated lactate dehydrogenase (LDH). An unenhanced CT of the brain revealed a mass lesion within the right parietal lobe with significant associated vasogenic oedema, causing both local and general mass effect with effacement of adjacent sulci and complete effacement of the right lateral ventricle. The subsequent magnetic resonance imaging (MRI) confirmed the presence of a solitary mass lesion with significant mass effect (see Figure 1). A staging CT of the neck, chest, abdomen and pelvis was performed and no evidence of lung cancer recurrence or distant metastatic disease was found. The patient was referred by the lung cancer multi-disciplinary meeting to the neurosurgeons for resection of the intracranial space occupying lesion (ICSOL). Complete resection of the ICSOL was performed and the patient made a full recovery post-surgery. The surgical specimen was reviewed by three independent histopathologists. Immunostaining was negative for CK7 and CK20 and positive for CD3, CD30 (see Figure 2) and aberrant CD20, raising the possibility of anaplastic lymphoma. The morphology was those of anaplastic large cell lymphomas (ALCLs). ALK1 staining was negative. The final diagnosis was primary central nervous system, ALK1- negative, ALCL with aberrant CD-20 expression. The patient underwent further staging investigations for the primary ALCL of the central nervous system (PCNSAL). A bone marrow (BM) trephine and a lumbar puncture showed no evidence of malignant infiltration in the BM and the cerebrospinal fluid (CSF), respectively. A slit lamp examination was negative. The patient received two renal dose-adjusted 21-day cycles of intravenously administered methotrexate (MTX), 3.6 g on day 1 followed by cytarabine, 2,450 mg twice daily on days 2 and 3. Chemotherapy was discontinued because of an infection in the aortobiiliac graft and the patient received whole brain radiotherapy (WBRT), a total of 36 Gy in 20 sessions. A post-treatment MRI (see Figure 3) demonstrated satisfactory post-treatment appearances.
The patient died from bronchopneumonia 3 months after the completion of treatment for the PCNSAL. This was perceived to be unrelated to his PCNSAL treatment. A post mortem was declined by the patient’s relatives.
Primary Central Nervous System Anaplastic Large Cell Lymphoma is an Unusual Brain Tumour
We present a case of a 64-year-old man who was diagnosed with a primary anaplastic large cell lymphoma of the central nervous system (PCNSAL). He had received radical chemotherapy and radiotherapy for a non-small cell lung cancer (NSCLC) in the past. There is no known association between NSCLC and PCNSAL. We describe the diagnostic and therapeutic challenges associated with these rare intracranial lymphomas and highlight the potential role of newer biological agents in patients with anaplastic lymphoma kinase (ALK-1) positive PCNSAL.
An erratum to this article can be found below.
- Behin A, Hoang-Xuan K, Carpentier AF, et al., Primary brain tumours in adults, Lancet, 2003;361:323–31.
- George DH, Scheithauer BW, Aker FV, 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.
- Bataille B, Delwail V, Menet E, et al., Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg, 2000;92:261-6.
- Bhagavathi S, Wilson J, Primary central nervous system lymphoma, Arch Pathol Lab Med, 2008;132:1830–34.
- Kuker W, Nagele T, Korfel A, et al., Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients., J Neurooncol, 2005;72:169–77.
- Ferreri AJ, How I treat primary CNS lymphoma, Blood, 2011;118:510–22.
- Reni M, Ferreri AJ, Garancini MP, et al., Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: Results of a critical review of the literature, Ann Oncol, 1997, 8:227–34.
- Cascoyne RD, Aoun P, Wu D, et al., Prognostic significance of anaplastic kinase (ALK) protein expression in adults with anaplastic large cell lymphoma, Blood, 1999;93:3913-21.
- Lamant L, Meggetto F, al Saati T, et al., High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin’s disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction and p80 immunostaining, Blood, 1996;87:284–91.
- Benharroch D, Meguerian-Bedoyan Z, Lamant L, et al., ALKpositive lymphoma: a single disease with a broad spectrum of morphology, Blood, 1998;91:2076–84.
- Mohile NA, Deangelis LM, Abrey LE, The utility of body FDG PET in staging primary central nervous system lymphoma, Neuro Oncol, 2008;10:223–8.
- Falini B, Pileri S, Zinzani PL, et al., ALK+ lymphoma: clinicopathologic findings and outcome, Blood, 1999;93:2697-706.
- Schorb E, Kasenda B, Atta J, et al., Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation, Haematologica, 2013;98:765–70.
- Gregory G, Arumuwasgamy A, Leung T, et al., Rituximab is associated with improved survival for aggressive B cell CNS lymphoma. Neuro Oncology, 2013;15:1068–73.
- Ferreri AJ, Reni M, Foppoli M, et al., High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial, Lancet, 2009;374:1512–20.
- Gambacorti-Passerini C, Messa C, Pogliani EM.Crizotinib in anaplastic large-cell lymphoma, N Engl J Med, 2011;364:775–6.
- Costa DB, Kobayashi S, Pandya SS, et al., CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib, J Clin Oncol, 2011;29:e443–5.
- Redaelli S, Farina F, Stasia A, et al., High Response Rates To Crizotinib In Advanced, Chemoresistant ALK+ Lymphoma Patients, ASH 2013. Abstract 368.
- Ferreri AJ, Deangelis L, Illerhaus G, et al., Whole-brain radiotherapy in primary CNS lymphoma, Lancet Oncol, 2011;12:118–9.
- Rubenstein JL, Johnson JL, Jung SH, et al., Intensive chemotherapy and immunotherapy, without brain radiation, in newly diagnosed patients with primary CNS lymphoma. Results of CALGB 50202, Blood 2010 (Abstract #763).