Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study

Velasco, Roser; Mercadal, Santiago; Vidal, Noemí; Alañá, Mónica; Barceló, María Inés; Ibáñez-Juliá, María-José; Bobillo, Sabela; Agud, Rocío Caldú; Molina, E.; Martı́nez, Pilar; Cacabelos, Purificación; Muntañola, A.; García-Catalán, G; Sancho, Juan‐Manuel; Camro, I; Lado, Tamara; Erro, María Elena; Gómez-Vicente, Lidia; Salar, Antonio; Caballero, A; Solé‐Rodríguez, M.; Pérez-Larraya, Jaime Gállego; Huertas, N.; Estela, Jordi; Barón, Manuel González; Barbero-Bordallo, N; Encuentra, Maite; Dlouhy, Iván; Bruna, Jordi; Graus, Francesc; Geltamo,

doi:10.1007/s11060-020-03547-z

Cited by 38 publications

(44 citation statements)

References 38 publications

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“…Timely diagnosis represents a major goal in patients with primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL). 1 At presentation, this tumour is suspected on neuroimaging findings, site of disease and response to corticosteroids, used to control related symptoms. 2 However, prolonged corticosteroid therapy causes blurring of diagnostic criteria on neuroimaging and consequent biopsy delay, metabolic disorders and immunodepression.…”

Section: Introductionmentioning

confidence: 99%

MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study

et al. 2021

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Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.

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Section: Introductionmentioning

confidence: 99%

MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study

et al. 2021

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“…This could lead to a significant delay of diagnosis and definitive treatment with uncertain implications on the prognosis. On the other hand, recent reports showed that the impact of preoperative CST on the diagnostic yield of biopsy may not be as high as formerly described [ 11 – 16 ].…”

Section: Introductionmentioning

confidence: 79%

“…There was no detectable statistically significant difference on rate of inconclusive surgeries with 9.4% (17 out 180) in patients with ongoing CST and 7.2% in patients with paused CST (6 out of 83). Median pause, if documented, was either 8.5 days ( n = 28, range 1–58, current study; NB: exact duration of preoperative pause could not be determined in 4 patients) or 15 days ( n = 51, IQR 4–42, Velasco et al) [ 16 ].…”

Section: Resultsmentioning

confidence: 99%

Influence of preoperative corticosteroid treatment on rate of diagnostic surgeries in primary central nervous system lymphoma: a multicenter retrospective study

et al. 2021

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Background Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. Methods A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. Results A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7–6.4). Conclusions Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.

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“…MRI scanning has already been a routine research method in Finland during the study period of 2007-2017 for patients suffering from neurological symptoms as well as for elderly patients. Moreover, in PCNSL, the symptoms progress rapidly, leading to patient deterioration, hospitalization, and diagnosis [26].…”

Section: Incidencementioning

confidence: 99%

Primary Central Nervous System Lymphoma Increasing Incidence and Poor Survival: A Finnish Population-based Analysis

Puhakka¹,

Kuittinen²,

Jäkälä³

et al. 2021

Preprint

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PurposeWe report here the first population-based incidence rates and prognosis of primary central nervous system lymphoma (PCNSL) in Finland. MethodsFinnish Cancer Registry data by histological diagnosis and tumor location (2007-2017) for cases with diffuse large B-cell lymphoma.ResultsDuring 2007–2017, 416 new cases of PCNSL were reported (202 males, 214 females). The average age-adjusted incidence in males vs. females for 2007-2009, 2010-2012, 2013-2015 and 2016-2017 was 0.57/100,000 vs. 0.48/100,000 person-years, 0.66/100,000 vs. 0.55/100,000, 0.53/100,000 vs. 0.63/100,000, and 0.76/100,000 vs. 0.66/100,000 respectively. The incidence was highest, 3.27/100,000, among people aged 75–79 years. From 2007–2012 to 2013–2017, the 2-year age-adjusted survival rate increased from 36% to 41%, and the 4-year survival rates from 31% to 37%. Among patients aged 70+ years, the corresponding 2-year survival rates were 25% and 29%, and the 4-year survival rates 25% and 22%.ConclusionAge-adjusted incidence of PCNSL increased from 0.57/100,000 (2007–2012) to 0.63/100,000 (2013–2017). The annual increase was 3.8% being among the highest reported in the world. The prognosis was poor, although a minor improvement in 4-year survival was found.

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Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study

Cited by 38 publications

References 38 publications

MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study

MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study

Influence of preoperative corticosteroid treatment on rate of diagnostic surgeries in primary central nervous system lymphoma: a multicenter retrospective study

Primary Central Nervous System Lymphoma Increasing Incidence and Poor Survival: A Finnish Population-based Analysis

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