Retrospective Analysis of 41 Consecutive Patients with Non Gastrointestinal (GI) Extranodal Marginal Zone B-Cell Lymphoma (EMZL): Correlation of Clinical Characteristics and Outcome with Disease Localization.
Authors: Kalpadakis Christina , Siakantaris Marina P. , Kyrtsonis Marie-Christine , Vassilakopoulos Theodoros P. , Tzenou Tatiana , Dimopoulou Maria N. , Dimitriadou Evangelia M. , Kokoris Styliani I. , Angelopoulou Maria K. , Mitropoulos Fotios , Korkolopoulou Penelope , Pangalis Gerassimos A. 
Published: October 2019

Abstract
Extranodal marginal zone B-cell lymphomas of mucosa associated lymphoid tissue (MALT) are indolent lymphomas with specific clinical and pathologic features. MALT lymphomas can arise from any extranodal site. Non-gastrointestinal (non-GI) MALT lymphomas are rarer (<1% of NHL) and have been described in various sites (salivary glands, orbit, lung, skin etc). We retrospectively studied 41 patients with an initial diagnosis of EMZL according to the REAL/WHO classification criteria and presenting with a clinically dominant non-GI site of localization in order to evaluate the clinical characteristics of patients and to correlate disease localization with clinical behaviour, treatment and patient outcome. The studied population included 20 men and 21 women with a median age of 50 years (23–87). The most commonly affected sites were skin (13,32%), salivary glands (11%), followed by lung (7%), orbit (5%), oral cavity non salivary (4%), upper airway (1%) and thyroid (1%). The majority of patients (69%) presented in stage I. Advanced stage disease was due to bone marrow (12%) or/and lymph node involvement (12%), while in 4 patients there was more than one extranodal site involved. Autoimmune disorders were noticed in 7 patients, while monoclonal gamopathy in 5 (12%). Two patients presented B-symptoms (both with BALT ). Patiens with extranodal skin lymphoma (SALT) received treatment with interferon-α (54%), Mabthera iv or intralesionally (31%) or resection alone with a 100% CR rate. With a median follow up of 42 months no disease related death was noticed. Among 11 patients with salivary gland EMZL 5 had stage IV disease at presentation (45%). First line treatment was chlorombucil +/− Mabthera with a 90% CR rate. With a median follow up of 80 months two relapses in another MALT site (stomach) and one disease related death due to disease transformation were noticed. Patients with BALT lymphomas presented some specific clinical characteristics: There was a long time interval between onset of symptoms and diagnosis, B-symptoms were presented in 2 of 7 patients while most of them had symptoms from the respiratory system (cough, dyspnea, expectoration). 3 patients had advanced stage disease. First line treatment was chlorambucil +/− Mabthera +/− surgical excision with response rates of 70%. With a median follow up of 51 months two disease related death were noticed (one due to disease transformation). 4 of 5 patients with orbital MALT lymphoma received chlorambucil while one patient received radiotherapy alone. With a median follow up of 52 months one relapse to another extranodal site was noticed and no disease related death. In conclusion our data confirms the indolent behaviour of MALT lymphomas with a 5- and 10-year overall survival 82±8% and 65±13% respectively. The 5-year overall survival was 90% or more for each non-lung presentation vs 70% for BALT NHL. The optimal management of MALT lymphomas with regard to surgery, chemotherapy, immunotherapy and radiation therapy alone or in combination as well as abstention from therapy is not well defined. Additionally MALT lymphomas of various anatomic sites seem to present a clinical heterogeneity that may reflect heterogeneity at a molecular level.