Neoplastic cells do not carry bcl2-JH rearrangements detected in a subset of primary cutaneous follicle center B-cell lymphomas.
ABSTRACT Whether primary cutaneous follicular lymphoma (PCFL) may or not represent a cutaneous equivalent to nodal follicular lymphoma (FL) is not determined. We have therefore investigated a series of PCFL to determine if tumoral cells carry or not the t(14;18)(q32;q21) translocation, a cytogenetic hallmark of nodal FL. Thirty cases of PFCL were selected according to the criteria of both the European Organisation for Research and Treatment of Cancer and the World Health Organization with 21 cases classified as grade 1 or 2 and 9 cases as grade 3. First, cutaneous tumors were studied by PCR for the amplification of bcl-2/JH rearrangements and by interphase fluorescence in situ hybridization using a dual color probe spanning t(14;18) breakpoints. Second, we tried to determine the origin of bcl2-JH-positive cells by a parallel bcl2-JH and immunoglobulin heavy chain gene amplification of blood mononuclear cells DNA and of DNA extracted from single microdissected B cells. Bcl2-JH rearrangements were amplified by PCR in skin of 9 of 30 (30%) patients with a similar-sized bcl2-JH rearrangement detected in the blood of 7 of these 9 cases. No t(14;18) breakpoint was detected by interphase fluorescence in situ hybridization analysis of 11 bcl2-JH-negative and 5 bcl2-JH-positive PCFL in contrast with its detection in the secondary cutaneous FL and in the nodal FL cases. Single-cell/multigene analysis showed that no single monoclonal B cells of PCFL carried the bcl2-JH rearrangement. Bystander or nontumoral t(14;18)+ B cells emigrating from blood may account for the detection of bcl2-JH rearrangements within PCFL material. Our study also underlines the diagnostic value of interphase fluorescence in situ hybridization to discriminate between t(14;18)-negative PCFL and extracutaneous FL involving the skin.
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ABSTRACT: Primary cutaneous lymphomas can be difficult to be distinguished from reactive mimics, even when integrating histologic, immunophenotypic, and clinical findings. Molecular studies, especially PCR-based antigen receptor gene rearrangement (ARGR) analysis, are frequently useful ancillary studies in the evaluation of cutaneous lymphoproliferations. The biologic basis of ARGR studies is discussed, as well as a comparison of various current protocols. The pitfalls and limitations of ARGR analysis are also highlighted. Recent advances in the understanding of the molecular pathogenesis of various cutaneous lymphomas are discussed. Some of these nascent discoveries may lead to the development of diagnostically useful molecular assays.Pathology research international. 01/2012; 2012:913523.
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ABSTRACT: Cutaneous lymphoid infiltrates may pose some of the most difficult diagnostic problems in dermatopathology. Immunocytochemistry is often employed in an effort to determine whether an infiltrate is neoplastic or, in the case of clearly malignant infiltrates, to provide a specific diagnosis. The rarity of these disorders and the variant immunocytochemical profiles they may present further thwart understanding and sometimes prevent an accurate diagnosis. In this review the common immunocytochemical profiles of various cutaneous lymphomas are presented and potential pitfalls and problems considered. Immunocytochemistry is not a diagnostic test but, as in other areas of histopathology, is a highly valuable tool that requires critical interpretation within a context: so applied, it is an indispensable part of the pathologist's arsenal in evaluating lymphoid infiltrates and defining different lymphomas.Histopathology 01/2010; 56(1):71-90. · 2.86 Impact Factor
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ABSTRACT: Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.Blood 07/2012; 120(12):2395-404. · 9.78 Impact Factor