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.

In our experience, complete staging allowed detection of systemic lymphoma in two patients initially considered to have PCNSL.

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The increased incidence of second malignancies among cancer survivors is well documented. Thus, differential diagnosis between metastatic spread from a prior malignancy and the occurrence of a new neoplasm should be considered. This is particularly difficult for brain lesions due to their poor prognosis that often discourages diagnostic work-up. In some cases diagnosis of a second primary neoplasm, such as primary central nervous system lymphomas (PCNSL), could change the therapeutic management and the prognosis. About 8% of PCNSL occurs as a second malignancy. Homogeneous and intense tomographic enhancement, deep location of lesions and dramatic response to corticosteroids are suggestive for PCNSL and should be carefully considered before the start of treatment for cerebral lesions. Prognosis and standard management of brain metastases and PCNSL are almost completely different. In addition, while treatment of brain metastases often has a palliative purpose the goal in PCNSL treatment is the cure. Four patients with PCNSL as a second malignancy are reported and literature is reviewed. Diagnosis of PCNSL changes the strategy of treatment which could have a critical therapeutic and prognostic impact.