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Carbone A.,Centro Of Riferimento Oncologico Aviano | Santoro A.,Istituto Clinico Humanitas
Blood | Year: 2011

The "in situ" lymphomas are often incidental findings in an otherwise reactiveappearing 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. © 2011 by The American Society of Hematology. Source

Carbone A.,Centro Of Riferimento Oncologico Aviano | Gloghini A.,Laboratory Medicine
Advances in Anatomic Pathology | Year: 2014

This article reviews the most typical follicular dendritic cell (FDC) patterns displayed by early lymphomas involving follicles. In in situ follicular lymphoma, FDCs form a well-developed round (spherical) dendritic meshwork with a sharp outline. Other patterns that can be seen include contracted/distorted/ disintegrated FDC meshworks. In early mantle cell lymphoma with mantle zone pattern, FDCs compose an ill-outlined and loosely arranged " centrifugal" meshwork. In marginal zone lymphoma, the FDC meshwork forms a relatively well-developed nodular meshwork with irregular outlines. In nodular lymphocyte predominant (LP) Hodgkin lymphoma, LP tumor cells are localized within an environment with prominent FDC meshwork and rare or absent LP cells outside the nodules. In angioimmunoblastic T-cell lymphoma (AITL), scattered regressed germinal centers are usually noted, although hyperplastic germinal centers are seen during the early stages of the disease (EAITL). Identifying the FDC meshwork, mainly in association with blood vessels, constitutes one of the most typical findings of the disease. In conclusion, the morphologic pattern of the FDC meshwork in early lymphomas of follicular origin is heterogenous and differs according to the lymphoma subtypes. These FDC patterns are recognizable in the most typical cases when the lymphoma is in its early stage and still maintains a follicular/nodular pattern of growth. The FDC patterns seen in the CD21 and CD23 stains contribute to the recognition of early stages of lymphomas involving follicles. Conversely, tumor cell immunostains for BCL2, cyclin D1, and other stains form the basis for the definition of lymphoma subtypes. Copyright © 2014 by Lippincott Williams & Wilkins. Source

Carbone A.,Centro Of Riferimento Oncologico Aviano | Santoro A.,Humanitas Cancer Center
Hematological Oncology | Year: 2012

The diagnosis of in situ follicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescence in situ hybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal follicles is notable for its high-level and uniform intensity. In situ FL may be associated with overt FL or with lymphomas other than FL or with other malignancies. The crucial point relies on distinguishing in situ FL arising in asymptomatic patients from cases with presence of lymphoma at the same or other sites. Other open questions remain on the frequency with which in situ FLs occur and the frequency of concomitant systemic disease. © 2011 John Wiley & Sons, Ltd. Source

Aldinucci D.,Italian National Cancer Institute | Gloghini A.,Italian National Cancer Institute | Pinto A.,Italian National Cancer Institute | Colombatti A.,Italian National Cancer Institute | Carbone A.,Centro Of Riferimento Oncologico Aviano
Leukemia and Lymphoma | Year: 2012

Inflammation and cancer are two independent biological events that can play an interdependent role. The model of such interaction is represented by Hodgkin lymphoma (HL), where the microenvironment is dominated by an extensive mixed, potentially cellular inflammatory infiltrate that plays a decisive role in the pathobiology of HL. In this review we summarize updated information on the complex interactions between Hodgkin ReedSternberg (HRS) cells and their tissue microenvironment, highlighting the functional role of CD40/CD40L and interferon regulatory factor 4 (IRF4). © 2012 Informa UK, Ltd. Source

Carbone A.,Centro Of Riferimento Oncologico Aviano | Gloghini A.,Laboratory Medicine | Castagna L.,Humanitas Cancer Center | Santoro A.,Humanitas Cancer Center | And 2 more authors.
Journal of Pathology | Year: 2015

Classical Hodgkin's lymphoma (cHL), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of the cHL microenvironment express molecules involved in cancer cell growth and survival, such as CD30L or CD40L. Moreover, several signal transduction pathways that are critical for the proliferation and survival of neoplastic Hodgkin Reed-Sternberg (HRS) cells, including NF-κB, JAK-STAT, PI3K-AkT and ERK, are deregulated in cHL. Although most patients can be cured with modern treatment strategies, approximately a quarter experience either primary or secondary chemorefractoriness or disease relapse, thus requiring novel treatments. Preclinical and clinical evidence has elucidated a complex crosstalk between malignant HRS cells and the reactive cells of the microenvironment, which suggests that novel therapeutic approaches capable of targeting HRS cells along with reactive cells might overcome chemorefractoriness. In the near future, these novel therapies will also be tested in chemosensitive patients, to reduce the long-term toxicity of chemo-radiotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source

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