Clinical, histopathological and molecular characterization of mantle cell lymphoma with MALToma‐like presentation

AIMS: Recently a subset of mantle cell lymphoma (MCL) with predominant extranodal disease and frequent involvement of mucosa-associated lymphoid tissues (MALT-MCL) has been described, showing a more indolent course and favourable prognosis than classical nodal MCL (CN-MCL). Herein we detail the clinicopathological features of a single centre series of 12 MCL patients with primary MALT presentation, including immunogenetic profile and mutational landscape. METHODS AND RESULTS: The most frequently affected extranodal sites were nasopharynx and Waldeyer's ring (five patients, 41.7%), gastrointestinal tract (three patients), ocular adnexa and salivary glands (two patients each), and a single case with maxillary sinus involvement. All patients were treated, achieving a complete (seven patients) or partial response (five patients). Isolated extranodal relapse occurred in three patients; three patients died of disease. At median 12-years follow-up, OS was 11.3 years; 10-years OS and PFS were 65.5% and 54.7%, respectively. Waldeyer's ring involvement was associated with increased deaths for disease and shorter 10-years OS (33.3% vs 85.7% in patients lacking Waldeyer's ring involvement). All cases carried t(11;14)(q13;q32)-CCND1-IGH translocation whereas IGH clonal rearrangements were detected in eight patients; six cases, including all patients with Waldeyer's ring involvement, carried unmutated or minimally mutated rearrangements, whereas two cases involving stomach and ocular adnexa showed highly mutated rearrangements. Targeted NGS mutational analysis identified ATM mutations in two cases but did not reveal recurrent alterations involving TP53, CDKN2A or CCND1. CONCLUSIONS: Our data seem to confirm that MALT-MCL shares histological, phenotypic and IGHV rearrangements with CN-MCL, but pursues a more indolent clinical course than CN-MCL, thus suggesting a putative different genetic pathway.