Smoldering mantle cell lymphoma

Haige Ye, Aakash Desai, Dongfeng Zeng, Krystle Nomie, Jorge Romaguera, Makhdum Ahmed, Michael L. Wang

Mantle cell lymphoma (MCL) is an aggressive disease, with poor prognosis and a limited survival. However, some patients with indolent MCL can survive beyond 7~10 years. These patients remain largely asymptomatic and can be in observation for a long time without any treatment. The process of "wait and watch" leaves these patients with the potential risk of evolution to classic, aggressive MCL. On the other hand, early treatment for these patients may not impact overall survival but rather affects the quality of life. Therefore, it is essential to clearly identify this type of indolent MCL at the time of diagnosis. Reported findings of indolent presentation of MCL include: lack of B symptoms, normal serum lactic dehydrogenase (LDH) and β2-microglobulin levels (β2M), low MCL-International Prognostic Index (MIPI) score, maximum tumor diameter less than 3 cm, spleen size < 20 cm, positron emission tomography/computerized tomography with the Standard Uptake Value max <6, Ki-67 less than 30%, with some particular immunophenotype, such as CD5 and CD38 negative, markedly increased CD23 positive lymphocytes proportions, high expression of CD200, kappa light chain restriction, without C-myc, TP53 and NOTCH1/2 mutations, non-blastoid/pleomorphic histology, and no tumor growth on reevaluation every 2~3 months (followed for at least 6 months). Imaging evaluation may only be performed in the presence of disease-related symptoms or organ involvement. Meanwhile, if novel nodal or extranodal lesion is found, biopsy is mandatory to exclude lymphoma. Common clinopathological forms of indolent presentations include monoclonal B lymphocytosis with t (11; 14); "indolent leukemic" presentation of MCL with involvement of peripheral blood, bone marrow involvement, splenomegaly, and minimal lymphadenopathies and in situ lymphoma (often found in lymph nodes removed for other reasons, and in gastrointestinal biopsies). Considering these distinct indolent clinical presentations with particular features in cytology and gene mutational status, we propose to include these MCL clinical presentations under the umbrella of "Smoldering Mantle Cell Lymphoma".