[Paraneoplastic lymphadenopathy]

To study a spectrum of histologic patterns in patients with paraneoplastic lymphadenopathies, to analyse repeating changes and the causes of diagnostic mistakes.

In a retrospective analysis of 457 patients observed in Hematology Research Center of the RF in 1994-2004, and diagnosed as having non-malignant lymphadenopathies, we identified 40 patients in whom the second or third biopsy showed lymphoma. Nineteen patients (47.5%) had Hodgkin's lymphomas, 11 (27.5%)--B-cell lymphomas and 10 (25%) T-cell lymphomas.

In patients subsequently diagnosed with Hodgkin's lymphoma there were 4 repeating histologic patterns in paraneoplastic lymph nodes: sinus histiocytosis (7 patients, 37%), paracortical reaction with numerous plasma cells and macrophages (7 patients, 37%), marked fibrotic changes (4 patients, 21%) and necrotizing lesions (3 patients, 16%). In 15 patients the second biopsy was performed within 4 weeks, while in 4 patients intervals between biopsies were 2, 4, 10 and 24 months. Eight patients (42%) had paraneoplastic changes in lymph nodes located not in the adjacent zones (in 7 patients above the diaphragm, and in 1 patient in both sides of the diaphragm). Amongst patients with B-cell lymphomas 7 had follicular lymphomas, 3--diffuse large B-cell lymphomas and 1--mantle cell lymphoma. In paraneoplastic lymph nodes there were 3 cases of sinus histiocytosis, 1--necrosis. In 5 patients with follicular lymphoma initially diagnosed as having follicular hyperplasia, retrospective analysis and immunohistochemistry showed partial involvement of lymph nodes with lymphoma. In two of them the presence of malignancy was clinically evident at the moment of the first biopsy, while three had a long history of lymphadenopathy (time to diagnostic biopsies were 5, 13 and 34 months). Amongst patients with T-cell lymphomas 5 had undetermined peripheral T-cell lymphomas, 2--anaplastic large cell lymphomas, 1--angioimmunoblastic lymphoma, 1--hepatolienal lymphoma and 1--Lennert's lymphoma. Median of time to the second biopsy was 4 months, range 1-48 months. Five patients (50%) had in the first lymph node sinus histiocytosis, 3 (30%)--paracortical hyperplasia, and 2--granulomatous lesions. Clonal rearrangements of gamma-chain T-cell receptor genes were found in 2 patients from 3 tested.

Histologic patterns in lymph nodes not involved by lymphomas in patients with lymphomas are not random. While sinus histiocytosis and necrosis are universal findings, some patterns are disease specific. Paracortical hyperplasia is typical for T-cell lymphomas, prominent fibrosis--for Hodgkin's lymphoma. We believe that paraneoplastic changes in lymph nodes are caused by partial tumor involvement, cytokine reaction, or antitumor immune response. From practical point of view, finding of necrosis, prominent sinus histiocytosis, or prominent fibrosis of a lymph node in the absence of a history of chronic lymphadenitis or inflammation in the draining area should be considered as possible indication to second biopsy. Interpretation of such paraneoplastic phenomena as paracortical hyperplasia and formation of epithelioid-cell granulemas is not easy and must consider context of a clinical picture.