How I treat: diagnosing and managing "in situ" lymphoma.

The "in situ" lymphomas are often incidental findings in an otherwise reactive-appearing lymph node. Notably, the risk of progression to clinically appreciable lymphoma is not yet fully known. The diagnosis of "in situ" lymphoma is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. "In situ" follicular lymphoma is characterized by the presence within the affected germinal centers of B cells that strongly express BCL2 protein, a finding that supports their neoplastic nature, in the absence of interfollicular infiltration. In "in situ" mantle cell lymphoma, the lymphoma involvement is typically limited to the inner mantle zone, where lymphoma cells are cyclin D1(+) and weakly BCL2(+), CD5(+). A staging workup to exclude other site of involvement is highly recommended for the possible coexistence of an overt lymphoma. Biopsy of all sites of suspicious involvement should be mandatory. No evidence for starting therapy also in the presence of multifocal "in situ" lymphoma exists, and a "wait-and-see policy" is strongly suggested. A follow-up strategy reserving imaging evaluation only in the presence of disease-related symptoms or organ involvement appears to be a reasonable option. For patients with concomitant overt lymphoma, staging and treatment procedures must be done according to malignant counterpart.