Answer: Follicular lymphoma grade 1

Histology: The mass is primarily a lymphoid proliferation within predominantly adipose tissue with very little breast tissue identified. The lymphoid tissue demonstrates a distinctly nodular pattern of proliferation. The nodules are composed of small irregular lymphocytes with very little cytoplasm and only scattered mitoses. Within these germinal center-like structures there is no evidence of polarization of the cells and there are no tingible body macrophages. These nodules lack the features commonly seen in florid reactive germinal centers. In addition, within the germinal center-like structures and in the interfollicular area there is no evidence of monocytoid-appearing B-cells or plasmocytic differentiation, typical of MALT Lymphoma. The cells are clearly lymphoid in nature and the case does not raise any question regarding the diagnosis of an epithelial neoplasm. The primary distinction in this case is whether this is a neoplastic or reactive lymphoid proliferation, and if neoplastic, whether it is a follicular lymphoma or a so-called MALT-type B-cell lymphoma which can on occasion be seen within the breast.

Discussion: The primary differential diagnosis in this case rests between a follicular lymphoma, a follicular hyperplasia within an intramammary lymph node and a MALT lymphoma. The distinctly nodular infiltrate would be unusual for a MALT lymphoma. Moreover, the nodules lack the typical features of reactive germinal centers in that they lack polarization or tingible body macrophages and appear more monotonous than a typical reactive germinal center. These features, in addition to the back-to-back growth pattern of the nodules suggests that this may indeed be a mammary presentation of a follicular lymphoma.

The distinction between follicular hyperplasia and follicular lymphoma can be made often based solely on morphology. The monotony of the nodules, the lack of tingible body macrophages, and polarization of the nodules suggest that this is a follicular lymphoma based solely on morphology. The immunohistochemical studies as well as flow cytometry can be helpful in verifying this diagnosis. In this case, the immunohistochemical studies demonstrated that the neoplastic cells were B-cells that were positive for CD-20. The most helpful immunohistochemical studies to distinguish follicular lymphoma from follicular hyperplasia was the fact that the neoplastic cells within the germinal center stain positive for BCL-2. This correlates with the 14/18 translocation associated with the BCL-2 oncogene most commonly seen in follicular lymphomas. When doing stains for BCL-2, it is important to do additional stains such as CD-3 to verify that the cells that are staining for BCL-2 are actually the tumor cells and not the T-cells which may also be positive for BCL-2. In this case, the majority of the cells within the neoplastic nodules are strongly positive for BCL-2, indicating that this is a follicular lymphoma. Flow cytometry was not performed, but if done it should show a monoclonal B cell proliferation with light chain restriction. Follicular lymphomas are now graded into three histologic grades, grades 1, 2, and 3 based on the relative proportion of large transformed B-cells to smaller cleaved B-cells. In this case, the neoplastic nodules are composed primarily of small cleaved lymphocytes and this case would be characterized as a follicular lymphoma grade 1 which was previously called follicular lymphoma, small cleaved-cell type.