Large‐cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome

Abstract

Large-cell variants are uncommon in mantle cell lymphoma (MCL). Here we describe the pathologic and clinical findings in five patients with large-cell lymphoma related to MCL (L-MCL), and compare them to a group of classic small-cell MCL (s-MCL) cases. Histologically, the MC origin of the large cells was evinced by their association with a small mantle cell component in the same tissue, or their distribution in a classic mantle zone pattern, or their development in a patient with previous s-MCL. The large cells were either pleomorphic mantle cells (case 1) or transformed blast-like cells (case 2-5). The median nuclear diameter, median nuclear area and proliferation index of L-MCLs and s-MCLs, were statistically different. Immunophenotypic characterization of four specimens of L-MCL and 10 of s-MCLs with a large panel of antibodies showed the classic findings of MCL, i.e. the IgM+ D+/-, CD5+, CD10-, CD23- phenotype in all cases except two (one CD5- and one CD23+), and the association with a loose follicular dendritic cell network. Two of four L-MCLs and 5/10 s-MCLs demonstrated rearrangements of the bcl-1 gene by Southern blot or by polymerase chain reaction (PCR); 2/4 L-MCLs and 1/9 s-MCLs had p53 mutations on single-strand conformation polymorphism analysis; none of the 14 specimens showed rearrangement of bcl-2 by PCR or bcl-6 and c-myc by Southern blot. All patients with 'transformed' histology (versus 37% of all others) died of lymphoma; their survival (15-18 months; median 17) was much shorter than that of all the others (28-117+ months; median 43) (P=0.0035). All three patients with p53 anomalies, two of whom had tumours with transformed histology, died of their disease in a short time (15, 18 and 28 months). In contrast, the presence of bcl-1 rearrangements did not have prognostic implications. This study documents the existence of large-cell variants of MCL and the poor prognosis associated with the 'transformed' cytologic type and/or p53 abnormalities.

Mantle cell lymphoma: a retrospective study of 121 cases

“…This is in agreement with other reports suggesting that growth pattern has no impact on outcome. 25,29 However, our number of patients is too low to formerly refute the conclusions from other authors regarding the poor outcome associated with presence of blastoid cells at diagnosis 22,25,28,30,31,34,36 or the indolent course of patients having a mantle zone pattern. 27 In contrast with other authors' finding, 25 histologic transformation during the course of the disease was not associated with a shorter survival, but our number of patients is low and the definition of the transformation is not yet standardized.…”

Blastic Mantle Cell Leukemia: An Unusual Presentation of Blastic Mantle Cell Lymphoma

“…Although the features of blastic or large cell MCL (22)(23)(24) and peripheralizing MCL (13,(25)(26)(27)(28) have each been well described in the literature, cases of blastic MCL presenting with predominant blood and marrow involvement have not been clearly identified to our knowledge. Two previous reports describe primarily leukemic disorders with some similarities to the current patient series presented here.…”

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

“…28 p53 protein overexpression and p53 mutations are also found in the majority of cases. 29,30 Additionally, alterations in cell cycle regulation may participate in the pathogenesis of aggressive cases of MCL and p21 INK4c and p16 NK4c deletions have been reported in BV of MCL. 31,32 An increasing number of genetic abnormalities has recently been outlined in BV of MCL.…”