Pearls and Pitfalls in Lymph Node Diagnosis
Case 1 -
Follicular Lymphoma, Grade 1 of 3, with Numerous Signet Ring Cells
Massachusetts General Hospital
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
Follicular lymphoma, grade 1 of 3, with numerous signet ring
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.
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 . 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 . 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
. 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 . As seen in our case, loss of the
distinctive signet ring cell morphology in relapsed lymphoma has been described .
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.
- 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.