Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network

Abstract

Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87AE5%), small cell (3AE6%), pleomorphic (5AE9%) and blastic (2AE6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1AE6%) or transitions (classical/pleomorphic type; 1AE6%), which, however, did not differ significantly in overall survival time. Exactly 80AE5% of cases displayed a diffuse growth pattern, whereas 19AE5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0AE0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.

Sequence analysis proves clonal identity in five patients with typical and blastoid mantle cell lymphoma

“…In the literature, 10-30% of patients with typical MCL subsequently develop blastoid variant MCL. [3][4][5][6] It seems reasonable to assume that blastoid MCL represents histologic transformation of typical MCL. However, as this is not the case in patients with Richter's Histologic transformation of mantle cell lymphoma CC Yin et al syndrome, in which the CLL/SLL and diffuse large B-cell components are clonally related in only 50% of patients, 7,8 there is precedent for hypothesis that typical and blastoid MCL are not clonally related.…”

“…Two types of blastoid MCL are described, consisting of either lymphoblast-like (classic type) or large (pleomorphic type) cells with a high proliferative fraction. [3][4][5][6] In patients who have both typical and blastoid variant MCL, either simultaneously or sequentially, the relationship between these neoplasms is not well studied. One might assume that both the typical and blastoid variant MCL are clonally related, analogous to low-grade follicular lymphoma and diffuse large B-cell lymphoma.…”

Nodal and leukemic small B-cell neoplasms

“…59,[61][62][63] 63,64 MCL is typically positive for the B-cell markers CD19 and CD20 with surface immunoglobulin light chain restriction, positive for CD5, FMC7, and Cyclin D1, and negative for CD23. Absence of CD5 expression has been reported in a minority of cases, perhaps 5-10% of MCL overall.…”

Allelic genotyping reveals a hierarchy of genomic alterations in mantle cell lymphoma associated to cell proliferation

“…The classical MCL is composed of small to medium-sized lymphoid cells with small, irregular nuclei and a relatively low proliferative index [2,48]. The blastoid variant is characterized by either pleomorphic or larger blast-like nuclei with a fine and dispersed chromatin and occasional small nucleoli.…”

“…The blastoid variant is characterized by either pleomorphic or larger blast-like nuclei with a fine and dispersed chromatin and occasional small nucleoli. This variant displays a higher cell proliferation and a more aggressive clinical course than typical MCL [35]; [48]. Secondary transformations towards the blastoid variant forms have been observed in 26-70% of MCL patients.…”