Smoldering mantle cell lymphoma

Abstract

BackgroundMantle 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.ResultsReported 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).ConclusionsConsidering 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”.

GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea

“…[59] In addition, since EGCG decreased constitutive activity of GPRC6A, it might also be considered an inverse agonist at high concentrations. Since GPRC6A regulates T production and PCa progression, [44,60] the inhibitory effects on GPRC6A are consistent with known effects of EGCG to suppress T, [60] and would also provide a mechanism to account for EGCG reduction in PCa risks. Future studies in preclinical models will be needed prove that the beneficial effects of green tea on PCa progression is mediated by EGCG inhibition of GPRC6A.…”

“…[36,43] Ablation of GPRC6A attenuates, whereas Ocn administration exacerbates, PCa progression in xenograft models. [44] In this study, we used a combination of functional studies and computational molecular dynamics-based docking using structural models of both VFT and 7-TM domains to investigate the effects of GA and EGCG on GPRC6A activation.…”

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

“…The clinical course of MCL (Table ) can be smoldering nodal/extra‐nodal or asymptomatic non‐blastoid leukemic non‐nodal, and these clinical variants (about 10%‐20% of MCL cases) generally do not need immediate systemic treatment, meaning the watch‐and‐wait strategy is safely pursued. On the other hand, most MCL patients (70%‐80% of MCL cases) present with symptomatic lymphadenopathy or symptomatic extra‐nodal disease requiring systemic therapy.…”

Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma

“…The expression of CD23 is closely associated with CD200 expression. Ye H et al 5 reported similar findings and referred to such cases as smoldering mantle cell lymphoma. CD200 is an important marker of CLL/SLL in the differential diagnosis from other CD5-positive indolent lymphomas.…”