Clinical Features and Prognostic Assessment of Nodal Marginal Zone B-Cell Lymphoma, a Rare Disease with Follicular-Like Behaviour.
Authors: Arcaini Luca , Paulli Marco , Burcheri Sara , Boveri Emanuela , Rossi Andrea , Spina Michele , Passamonti Francesco , Montanari Mauro , Gallamini Andrea , Uziel Lilj , Crugnola Monica , Montanari Francesca , Pascutto Cristiana , Morra Enrica , Lazzarino Mario 
Published: October 2019

Abstract
Background. Primary nodal marginal zone B-cell lymphoma (MZL) is a rare entity recognized by the WHO classification. Diagnosis requires a lymph node localization in the absence of prior or concurrent involvement of extranodal sites. Most studies reported so far focus mainly on histopathology, while the clinical features and outcome of this uncommon lymphoma remains less defined.
Aim. To define the clinical features and to assess prognosis of primary nodal marginal zone B-cell lymphoma. Methods. We studied a series of 47 newly diagnosed patients with primary nodal marginal zone B-cell lymphoma. Diagnosis was made on histologic examination of lesional tissues integrated with immunohistochemical data. No patient showed MALT or splenic localisation of lymphoma at diagnosis.
Results. Patients: 17 males and 30 females, median age 63 years (25–79) with 64% aged more than 60 years. 13% of patients had stage I disease, 10% stage II, 32% stage III, 45% stage IV (bone marrow involvement). 11% had peripheral blood involvement, 11% had bulky disease, 15% B symptoms, 6% ECOG score ≥ 2. 23% had hemoglobin <12 g/dl. LDH was above normal in 15% and β2-microglobulin in 45%. 11% had an autoimmune background. HCV serology was positive in 24% (9/38). With the IPI score 37% ranked in the low risk, 22% in the low-intermediate, 35% in the intermediate-high, and 7% in the high risk category. Using the FLIPI score, 33% were classified as low risk, 34% as intermediate risk, and 33% as high risk. After treatment, 57% achieved a complete response and 24% a partial response, for an overall response rate of 81%. At a median follow-up of 2.6 years, no patient developed splenic or MALT involvement. 5-years and 10-years OS is 69% (95% CI 52–86%). Death occurred in 10 pts (related to NHL in 9, to another neoplasm in one). In univariate analysis the following factors were associated with shorter event-free survival (EFS): B symptoms (p=0.001), high vs intermediate vs low risk FLIPI score (p=0.009). The following factors were associated with worse overall survival: high vs intermediate vs low risk FLIPI score (p=0.02), age > 60 years (p=0.05), LDH above normal (p=0.05). HCV positivity was of borderline significance (p=0.06). In multivariate analysis hemoglobin < 12 g/dl (p=0.02, HR 14.3) was predictive of shorter EFS. Concerning overall survival, only the FLIPI retained statistical significance in predicting a worse outcome (p=0.02, HR 3.5). Positive HCV serology was of borderline significance (p=0.06, HR 4.4).
Conclusions: among marginal zone neoplasms, primary nodal marginal zone lymphoma appears a distinct disorder with an indolent behaviour. The association with HCV infection (25%) is particularly high in comparison with non-marginal zone lymphomas. Considering the prognostic assessment of this rare disease, the FLIPI score is effective in detecting patients at worse prognosis with the same power as in follicular lymphoma. Thus, the application of the FLIPI may be of clinical value for treatment decision also in primary nodal marginal zone lymphoma.