Case 1 -

Follicular Lymphoma, Grade 1 of 3, with Numerous Signet Ring Cells Judith Ferry Massachusetts General Hospital Boston, MA

Case History: 54-year-old female with isolated left axillary lymphadenopathy. Immunoperoxidase stains on frozen sections showed monotypic lambda staining. Immunoperoxidase stains on paraffin sections showed a predominant population of CD20+, CD10+/-, bcl6+, bcl2+, CD5-, cyclin D1- B cells, with Ki67 ~ 10-15%, and many interfollicular T cells (CD3+). Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Follicular lymphoma, grade 1 of 3, with numerous signet ring cells. Follow-up: Isolated relapses 5 years and 9 years after initial diagnosis, although relapses lacked signet ring cells and contained more large cells. The most recent specimen contained a variant bcl-2 translocation, involving genes for bcl-2 and an immunoglobulin light chain gene, rather than the usual translocation involving the heavy chain gene. Discussion: This case shows a follicular lymphoma with typical features of crowded, ill-defined follicles replacing the lymph node. The atypical follicles are occupied predominantly by centrocytes. The capsule is thickened and reduplicated in areas in which it is infiltrated by neoplastic follicles. The immunophenotype - CD20+, CD5-, bcl6+, bcl2+, Ki67 low - is also typical of follicular lymphoma. The histologic features and the immunophenotype exclude a reactive process. The unusual feature in this case is the prominent component of signet ring cells. Signet ring cell lymphoma is a rare morphologic variant of non-Hodgkin's lymphoma in which some neoplastic cells contain clear cytoplasmic vacuoles or homogeneous eosinophilic globules filling much of the cytoplasm and compressing the nucleus to the periphery of the cell. This entity was first described in 1978, when Kim and co-workers published a series of 7 cases of B-cell lymphoma with signet ring cells [1]. Four cases had clear vacuoles and expressed IgG; 3 cases contained PAS-positive, IgM+ inclusions resembling Russell bodies. Since that first report, a number of other cases of signet ring cell lymphoma have been described, usually in lymph nodes, but occasionally in extranodal sites [2]. Two main types of B-cell lymphomas may have signet ring cells: low-grade B-cell lymphomas with plasmacytic differentiation, such as lymphoplasmacytic lymphoma, and follicular lymphomas. In the former group, the cytoplasmic material is usually thought to be immunoglobulin, resulting in eosinophilic cytoplasm that is often PAS+. Among follicular lymphomas, signet ring cell cytoplasm is more to be clear; ultrastructural studies typically reveal the presence of empty vacuoles. T-cell lymphomas with signet ring cells have also been described [3]. A rare but distinctive subset of cutaneous T-cell lymphoma with signet ring cells has been described; these lymphomas appear to behave in an indolent manner [3]. As seen in our case, loss of the distinctive signet ring cell morphology in relapsed lymphoma has been described [4]. In this case, the diagnosis of follicular lymphoma was not difficult because the specimen consisted of an excisional biopsy of a lymph node, with abnormal follicular architecture readily appreciable. On a small biopsy however, the diagnosis could be difficult, and metastatic signet ring cell carcinoma, fatty tumors and even histiocytic proliferations could be considered in the differential diagnosis. References Kim H, Dorfman R, Rappaport H. Signet ring cell lymphoma. A rare morphologic and functional expression of nodular (follicular) lymphoma. Am J Surg Pathol 1978;2:119-132. Allevato P, Kini S, Rebuck J, Miller J, Hamburger J. Signet ring cell lymphoma of the thyroid: a case report. Hum Pathol 1985;16:1066-1068. Vaillant L, Monegier du Sorbier C, Arbeille B, de Muret A, Lorette G. Cutaneous T-cell lymphoma of signet ring cell type: a specific clinico-pathologic entity. Acta Derm Venereol 1993;73:255-258. Vernon S, Voet R. Transformation of "signet ring cell" lymphoma to typical nodular, poorly differentiated lymphocytic lymphoma: light microscopic, immunohistochemical and electron microscopic observations. Ultrastruc Pathol 1983;4:177-186.