Abstract
Primary central nervous system anaplastic large cell lymphoma (PCNS ALCL) is rare, with only three adult patients reported. We describe a patient with PCNS ALCL with the longest follow-up period so far reported. The patient was successfully treated with chemotherapy and radiotherapy. The patient is well, independent and in full-time employment and has no residual neurological deficit. He has normal mental status, has a full head of hair and has fathered a healthy child.
Background
Anaplastic large cell lymphoma (ALCL) is a T cell lymphoma accounting for approximately 3% of adult non-Hodgkin's lymphomas. The tumour cells are usually large and show marked cytological atypia. Most cases express, in addition to T cell markers, the activation antigen CD30 and are associated with a translocation involving the anaplastic lymphoma kinase (ALK) gene. There is frequently nodal and extranodal disease at presentation; skin, bone, soft tissue, lung and liver involvement are commonly seen. Central nervous system (CNS) involvement is very rare, with only 12 patients reported. Primary CNS (PCNS) involvement is rarer still. Only three of the adult patients reported full-staging investigations confirming a diagnosis of PCNS ALCL.1–3
We describe a fourth patient with CNS ALCL in an adult with full-staging investigations who underwent successful treatment with sequential chemotherapy and radiotherapy. He remains well after a follow-up period of 8 years.
Case presentation
A 20-year-old left-handed male with no significant medical or family history presented following two seizures 1 week apart. His neurological and fundus examinations were unremarkable. There were no palpable lymph nodes, and Waldeyer's ring was clear.
Investigations
The full blood count, calcium, urea, electrolytes and liver function tests were all within the normal range. The lactate dehydrogenase was 302 U/l, and erythrocyte sedimentation rate was 18 mm/h. An MRI spine and a CT neck, chest, abdomen and pelvis were normal. Bone marrow aspirate and cerebrospinal fluid examinations were unremarkable, and there was no evidence of immunodeficiency.
MRI of his brain showed a peripherally based enhancing lesion in the region of the right sylvian fissure. This lesion was resected with 99% clearance, and the histology revealed a 2.5 cm mass of reactive brain tissue with a small focus of highly atypical cells, which was found to be stage 1 EA meningeal non-Hodgkin's lymphoma of anaplastic T cell type, positive for CD30 and ALK. Representative histology slides are shown in figures 1–4.
Figure 1.
400× H+E shows a tumour composed of sheets of large cytologically atypical lymphoid blast cells interspersed with frequent neutrophil polymorphs.
Figure 4.
The anaplastic large cell lymphoma associated antigen CD30 is also strongly expressed.
Figure 2.
600× H+E highlights the abnormal morphology of the lymphoid population, which possess vesicular nuclei and prominent nucleoli, together with relatively abundant amphophilic cytoplasm.
Figure 3.
The T cell antigen CD3 is strongly expressed by the atypical cells.
Treatment
Postoperatively, the patient was treated with one cycle of CHOD (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 2 mg intravenously, dexamethasone 4 mg four times a day for 7 days, allopurinol 300 mg once daily) followed by BCNU (carmustine 100 mg/m2 on day 8) and by three cycles of VAM (vincristine 2 mg intravenously, methotrexate 1.5 g/m2 intravenously over 4 h with folinic acid rescue and cytarabine 3 g/m2 on day 2).4 Three weeks following the completion of three cycles of VAM, the patient underwent CT-planned radiotherapy of 40 Gy in 25 fractions over 5 weeks to the right parietal region only, rather than the whole brain. It was thought that this approach offered the best compromise in terms of not being too aggressive but sufficient to eradicate any spread of lymphoma in the brain. He attended sperm banking before commencing treatment.
Outcome and follow-up
The patient was commenced on sodium valproate and had no further seizures. Sodium valproate was stopped after treatment, and he has now regained his driving licence. He remains in remission 8 years from initial presentation and has an excellent quality of life. He is in full-time employment, has no neurological deficit, has normal mental function, a full head of hair and has fathered a healthy child without using banked sperm.
Discussion
PCNS ALCL is very rare. Our case is only the fourth to be described in an adult with clearly reported full-staging investigations. Owing to the small number of cases being reported, there are currently no guidelines for therapy or survival data available.
Our patient has the longest follow-up period ever reported following successful treatment with chemotherapy and radiotherapy. Following treatment, the patient has an excellent quality of life. Prior to this report, the longest follow-up period reported in a fully staged adult with PCNS ALCL was 19 months, but no information was given on quality of life.2 The patient was treated with four cycles of combination chemotherapy of methotrexate 3.5 g/m2 on day 1, idarubicin 15 mg/m2 on day 1, cytarabine 2 g/m2 twice daily on day 2, thiotepa 25 mg/m2 on day 3, followed by whole brain radiotherapy of 36 Gy and by tumour bed boost of 9 Gy. Paulus et al1 described a patient with a fatal outcome at 11 weeks from onset of symptoms where the patient was treated with postoperative radiotherapy alone. The patient reported by Carmichael was treated with whole brain radiotherapy (28 Gy), followed by high dose methotrexate/folinic acid, vincristine, procarbazine, dexamethasone, intrathecal methotrexate and by cytarabine. The patient had some residual neurological deficit at 6 months of follow-up.3
Although there are no specific guidelines for PCNS ALCL, there are guidelines for PCNS in general.5 Methotrexate, in combination with other drugs (particularly cytarabine), is recommended followed by whole brain radiotherapy (except in the older patients with significant mental impairment).6 7 Patients treated with CHOD-BVAM or BVAM who are aged below 50 years at diagnosis have a median survival of 67 months and a 10-year survival of 43%.4
This case highlights the importance of early diagnosis and treatment of PCNS ALCL as it can be successfully treated with the patient having an excellent quality of life.
Learning points.
-
▶
PCNS ALCL is rare, however, should be considered in all patients presenting with a rapid clinical course and single or multiple lesions on CT brain.
-
▶
Biopsy of the lesion is essential, and full-staging investigations are necessary to confirm that the disease is localised to the CNS.
-
▶
PCNS ALCL can be successfully treated with postoperative chemotherapy and radiotherapy.
Footnotes
Competing interests None.
Patient consent Obtained.
References
- 1.Paulus W, Ott MM, Strik H, et al. Large cell anaplastic (KI-1) brain lymphoma of T-cell genotype. Hum Pathol 1994;25:1253–6 [DOI] [PubMed] [Google Scholar]
- 2.Ponzoni M, Terreni MR, Ciceri F, et al. Primary brain CD30+ ALK1+ anaplastic large cell lymphoma (ALKoma): the first case with a combination of ‘not common’ variants. Ann Oncol 2002;13:1827–32 [DOI] [PubMed] [Google Scholar]
- 3.Carmichael MG. Central nervous system anaplastic large cell lymphoma in an adult: successful treatment with a combination of radiation and chemotherapy. Mil Med 2007;172:673–5 [DOI] [PubMed] [Google Scholar]
- 4.Bessell EM, Graus F, Lopez-Guillermo A, et al. Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors. Int J Radiat Oncol Biol Phys 2004;59:501–8 [DOI] [PubMed] [Google Scholar]
- 5.Abrey LE, Batchelor TT, Ferreri AJ, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 2005;23:5034–43 [DOI] [PubMed] [Google Scholar]
- 6.Bessell EM, Hoang-Xuan K, Ferreri AJ, et al. Primary central nervous system lymphoma: biological aspects and controversies in management. Eur J Cancer 2007;43:1141–52 [DOI] [PubMed] [Google Scholar]
- 7.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 [DOI] [PubMed] [Google Scholar]