Utility of post-therapy brain surveillance imaging in the detection of primary central nervous system lymphoma relapse

see also spinal B cell lymphoma.

The B-cell lymphomas are types of lymphoma affecting B cells.

Epidemiology

B-cell lymphomas are the most common type (85%) of non Hodgkin lymphomas

The majority of Primary central nervous system lymphomas (PCNSL) (95%) are considered diffuse large B cell lymphomas (DLBCLs).

B-cell lymphomas include both Hodgkin lymphomas and most non Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.

It is the most common subtype of non Hodgkin lymphoma,

DLBCLs are characterized as high grade and most of them are CD20 positive while the minority of PCNSL consists of types such as Burkitt lymphomas, Burkitt-like lymphomas and lymphoblastic lymphomas.

Clinical features

Clinically heterogeneous.

Outcome

40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease.

Alizadeh et al. proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells (‘germinal centre B-like DLBCL’); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells (‘activated B-like DLBCL’). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer 1).

Case series

2016

Patients were consecutive PCNSL cases treated in Leon Berard Cancer Centre, Lyon, France, from 1985 to 2011. Histology was diffuse large B cell lymphoma in 94%. Patients were treated by methotrexate (92%) and cytarabine (63%) based-chemotherapy followed by radiotherapy for 108 patients (51%). Clinical records were reviewed for details at relapse and relationship to planned imaging. The imaging follow-up strategy was performed according to each treating physicians.

Among 209 PCNSL patients, 127 complete response patients entered in post-treatment observation and 63 (50%) subsequently relapsed. Among the 125 evaluable patients, the majority of relapses (N = 49, 80%) was asymptomatic and identified before the planned brain imaging. Surveillance imaging detected relapses before symptoms in 12 patients who entered in post-therapy observation (10%). The median number of brain imaging during the follow-up was 7 (0-13). A total of 819 MRI/CT-scan were performed leading to the detection of 12 asymptomatic relapses. The one year OS rates were 41% and 58% for symptomatic and non-symptomatic relapses, respectively (P = 0.21).

The majority of PCNSL relapses occurred outside planned follow-up with no difference in patient outcome between symptomatic and asymptomatic relapses. The role of brain imaging for the detection of relapses in the follow-up of PCNSL patients remains to be clarified 2).

Case report

2016

A 49-year-old woman presented with a progressive frontal scalp swelling for one year. Incisional biopsy was performed and histological examination showed diffuse large B-cell lymphoma 3).

2015

A 42-year-old man was admitted for generalized epileptic seizures. CT and MRI examinations revealed a tumor in his right parietal-occipital lobe that was surrounded by edema and was enhancing after gadolinium administration. The patient underwent a navigation-assisted parieto-occipital craniotomy and posterior parietal transcortical approach for tumor biopsy which was not indicative of PCNSL tumor. The surgical team decided to remove the tumor on site. Histological analysis of the resected specimen showed primary diffuse large B-cell lymphoma. Combined chemotherapy and radiation therapy was applied to the patient, and at his last follow-up (16 months), he is tumor free. In this case as in several other studies during the last decade, the outcome after the surgical resection of a PCNSL tumor in combination to radiation and chemotherapy was unexpectedly good. The role of surgery probably should be reconsidered for single lesion PCNSL tumors 4).


1) Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 Feb 3;403(6769):503-11. PubMed PMID: 10676951.
2) Fossard G, Ferlay C, Nicolas-Virelizier E, Rey P, Ducray F, Jouanneau E, Faurie P, Belhabri A, Sunyack MP, Chassagne-Clément C, Thiesse P, Sebban C, Biron P, Blay JY, Ghesquières H. Utility of post-therapy brain surveillance imaging in the detection of primary central nervous system lymphoma relapse. Eur J Cancer. 2016 Dec 21;72:12-19. doi: 10.1016/j.ejca.2016.10.036. [Epub ahead of print] PubMed PMID: 28012348.
3) Chan DY, Chan DT, Poon WS, Wong GK. Primary cranial vault lymphoma. Br J Neurosurg. 2016 Sep 13:1-2. [Epub ahead of print] PubMed PMID: 27619411.
4) Siasios I, Fotiadou A, Fotakopoulos G, Ioannou M, Anagnostopoulos V, Fountas K. Primary Diffuse Large B-Cell Lymphoma of Central Nervous System: Is Still Surgery an Unorthodox Treatment? J Clin Med Res. 2015 Dec;7(12):1007-12. doi: 10.14740/jocmr2376w. Epub 2015 Oct 23. PubMed PMID: 26566417.

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