Hematopathology Case Studies



CASE 2: Follicular lymphoma


Clinical History:

A 64-year-old man has noted lumps in his neck and axillae for approximately one year. These lumps had disappeared 5 months ago and then had recurred. He is otherwise asymptomatic. On physical examination, he has several non-tender, movable, rubbery 1 to 3 cm lymph nodes palpable in both sides of his neck and in his axillae. On abdominal examination, the spleen tip is palpable. A CBC shows WBC count 7700/microliter, Hgb 11.9 g/dL, Hct 36%, MCV 85 fL, and platelet count 207,000/microliter. An axillary lymph node biopsy is performed.
  1. On low power, how does the architecture differ from that of the normal lymph node?
  2. Under low power, notice that the normal nodal architecture is replaced by tumor cells which form a follicular pattern. In contrast to the benign lymph node in Case 1, there are many more follicles (with a "back- to-back" arrangement) with the normal mantle zone absent.

  3. Under high magnification, how do the lymphocytes in the follicles appear as compared to those in a normal lymph node?
  4. Under higher power, the follicles (nodules) are composed of a uniform population of small cleaved lymphocytes. The nuclei of these neoplastic lymphocytes have twisted or cleaved contours. In contrast to the benign reactive germinal centers of Case 1 in which there is a mixture of cells, the malignant lymphoma seen here has only one cell population present. In this case, the malignant cells are mostly small cleaved lymphocytes.

  5. What is your diagnosis?
  6. The diagnosis is follicular lymphoma in the WHO classification. This is histologically a low grade lymphoma, so it is indolent, but it tends to involve more lymph node groups and, thus, have a higher stage. It is the most common type of non-Hodgkin lymphoma (NHL) seen in adults accounting for almost half of cases. In a third to half of follicular lymphoma cases transformation to a higher grade lymphoma occurs.

  7. What is the molecular biology of this disease and what biotherapy is available to treat it?
  8. Characteristic immunohistochemical findings in the neoplastic cells include CD19, CD20, and CD10 positivity, but not CD5. A karyotype may reveal t(14:18). This translocation brings the BCL2 gene on chromosome 18 next to the B cell specific IgH gene enhancer locus on chromosome 14, and the BCL2 protein, an apoptosis antagonist, is overexpressed.

    In conjunction with chemotherapy, a monoclonal antibody, rituximab, directed against CD20 antigen present on the neoplastic B cells, can produce high response rates.