Path. Res. Pract. 186, 397-399 (1990)
Tcaching Cases
Proliferation of Marginal Zone Cells Mimicking Malignant Lymphoma l J. H. J. M. van Krieken Department of Pathology of the Leiden University Hospital, The Netherlands
K. Lennert Department of Pathology of the Christian Albrecht University, Kiel, FRG
SUMMARY An enlarged axillary lymph node from a 58-year-old woman showed a proliferation of marginal zone cells in nodules or large band-forming aggregates within the cortex. The marginal zone cells also infiltrated the adjacent fatty tissue. They showed polytypic surface immunoglobulins (IgM++, IgG+, x+, A+). Their immunophenotype (IgD-, CD23-, KiB3-) differed from that of the small lymphocytes of the mantle zone. They were also positive for alkaline phosphatase. The lesion is reactive and must be differentiated from low-grade malignant lymphomas, especially centrocytic lymphoma.
Introduction In lymph nodes the follicular mantle consists mainly of two cell types: small B lymphocytes and somewhat larger ones interpreted as marginal zone cells. The two cell populations can be distinguished morphologically and immunophenotypically4. This report describes a case in which the proliferation of marginal zone cells in a lymph node was morphologically suspicious for malignancy, but was shown by immunophenotyping to be a polyclonal process.
Case Report A 58-year-old woman presented with an enlarged axillar lymph node that was smooth and mobile. There were no
1 Dedicated to Prof. Dr. Buchner on the occasion of his 95th birthday.
© 1990 by Gustav Fischer Verlag, Stuttgart
other complaints, and on physical examination no other enlarged lymph nodes were palpable. The node was extirpated and transported unfixed to the Department of Pathology, Leiden. The diameter of the lymph node was 2 cm. On the cut surface it had a vaguely nodular appearance. The node was sliced and parts were frozen. Other parts were fixed in either formalin or sublimate formalin. One slice was processed for plastic embedding, as described previously2.
Histologic and Immunohistochemical Findings Microscopically, the architecture of the lymph node was, for the most part, intact. Throughout the cortex there was a proliferation of marginal zone lymphocytes arranged in large nodules and band-forming aggregates, but rarely with germinal centers (Fig. 1). These cells also extended outside of the cortex and into the surrounding 0344-0338/90/0186-0397$3.50/0
398 . J. H. J. M. van Krieken and K. Lennert Discussion
In most cases it is not very difficult to distinguish histologically benign processes from malignant ones in a lymph node. The most important criteria for malignancy are disturbance of the lymph node architecture, atypia of the lymphoid cells, and extension beyond the capsule. In some cases the distinction is more difficult, and immunophenotyping is necessary to exclude a clonal B-cell proliferation. The present case is such an example. Due to a large proliferation of lymphocytes in the cortex, the normal architecture was difficult to recognize. The lymphocytes also extended into the fatty tissue. Furthermore, the lymphocytes were larger than the more common small lymphocyte of the follicular mantle, and therefore might be called atypical. However, in fact they represent a proliferation of marginal zone lymphocytes, which are well known in the follicles of the spleen, but which also occur in the follicular mantle of the lymph node 3,4. In "normal" lymph nodes the follicular mantle consists of many smalllymphocytes (IgD +, KiB3 +, alkaline phosphatase -), and there are small numbers of somewhat larger lymphoid cells that
Fig. 1. Cortical area of the lymph node showing rather monotonous follicle-like structures without germinal centers (Paraffin embedding. Hematoxylin-eosin stain; magnification x 53). Inset shows detail of the cells (Magnification x 760).
fatty tissue (Fig. 2). Between the marginal zone cells there were scattered small lymphocytes interpreted as mantle zone lymphocytes. The nuclei of the marginal zone lymphocytes were about 1.5 times the size of the nuclei of the small lymphocytes of the mantle zone. They had a moderate amount of weakly stained cytoplasm (Fig. 1). The paracortical areas were small. The phenotype of the marginal zone cells was as follows: CD3 (Leu-4)-, CDS (Leu-1)-, CD9 (BA-2)-, CD10 (JS)-, CD20 (B1)+, CD21 (B2)+, CD22 (Leu 14)+, CD23 (KiB 1)-, CD24 (BA-1)+, CD2S (a-IL2R)-, KiB3 L . The alkaline phosphatase reaction was positive. Surface immunoglobulin light chains stained in a bitypic pattern. IgD was 'negative. Most cells stained with IgM and a minority with IgG. The scattered small lymphocytes were IgD-positive and also CD23- and KiB3-positive (Fig. 3). It was concluded that this was a reactive lymph node lesion (unspecific lymphadenitis). Seven months later the patient is well and without complaints.
Fig. 2. Invasion of mainly marginal zone lymphocytes into the fatty tissue (Plastic embedding. Giemsa; magnification x 760).
Marginal Zone Cells of Lymph Node . 399
Fig. 3. Immunohistochemical staining of cortical area. (A) CD22 (Leu 14). (B) KiB3. Marginal zone cells and small lymphocytes of the mantle zone are positive for CD22, whereas marginal zone cells are negative for KiB3 (Magnification x 105).
we interpret as marginal zone cells (IgD -, KiB3 -, alkaline phosphatase +). Therefore a proliferation of lymphocytes larger than the small lymphocytes of the mantle zone is not necessarily atypical. Such proliferations are not rare, especially in axillary or inguinal lymph nodes of older patients. Once we found them in axillary lymph nodes removed from a patient with carcinoma of the breast. In most such cases frozen tissue is not available for immunophenotyping, and since the detection of immunoglobulin in paraffin sections is not reliable in most laboratories, the diagnosis may be very difficult. The lack of IgD and KiB3 (which also stains paraffin sections) can be helpful in such cases.
References 1 Feller AC, Wacker HH, Moldenhauer G, Parwaresh MR (1987) Monoclonal antibody KiB3 detects a formalin resistant antigen on normal and neoplastic B cells. Blood 70: 629-636 2 Te VeideJ, Burckhardt R, Kleiverda K, Leenheers-Binnendijk L, Sommerfeld W (1977) Methyl methacrylate as an embedding medium in histopathology. Histopathology 1: 319-330 3 Van den Oord 11, De Wolf-Peeters C, Desmet VJ (1986) The marginal zone in the human reactive lymph node. Am J Clin Pathol 86: 475-479 4 Van Krieken JHJM, von Schilling C, Kluin PM, Lennert K (1989) Splenic marginal zone lymphocytes and related cells in the lymph node: A morphologic and immunohistochemical study. Hum Pathol 20: 320-325
Received July 14, 1989 . Accepted in revised form December 4, 1989
Key words: Marginal zone cells oflymph node - Centrocytic lymphoma - Reactive lymph node hyperplasia - Malignant lymphoma - Lymphocytic immunophenotypes Dr. J. H. J. M. van Krieken, Department of Pathology, University Hospital, P.O. Box 9603, 2300 RC Leiden, The Netherlands
Tcaching Cases
Proliferation of Marginal Zone Cells Mimicking Malignant Lymphoma l J. H. J. M. van Krieken Department of Pathology of the Leiden University Hospital, The Netherlands
K. Lennert Department of Pathology of the Christian Albrecht University, Kiel, FRG
SUMMARY An enlarged axillary lymph node from a 58-year-old woman showed a proliferation of marginal zone cells in nodules or large band-forming aggregates within the cortex. The marginal zone cells also infiltrated the adjacent fatty tissue. They showed polytypic surface immunoglobulins (IgM++, IgG+, x+, A+). Their immunophenotype (IgD-, CD23-, KiB3-) differed from that of the small lymphocytes of the mantle zone. They were also positive for alkaline phosphatase. The lesion is reactive and must be differentiated from low-grade malignant lymphomas, especially centrocytic lymphoma.
Introduction In lymph nodes the follicular mantle consists mainly of two cell types: small B lymphocytes and somewhat larger ones interpreted as marginal zone cells. The two cell populations can be distinguished morphologically and immunophenotypically4. This report describes a case in which the proliferation of marginal zone cells in a lymph node was morphologically suspicious for malignancy, but was shown by immunophenotyping to be a polyclonal process.
Case Report A 58-year-old woman presented with an enlarged axillar lymph node that was smooth and mobile. There were no
1 Dedicated to Prof. Dr. Buchner on the occasion of his 95th birthday.
© 1990 by Gustav Fischer Verlag, Stuttgart
other complaints, and on physical examination no other enlarged lymph nodes were palpable. The node was extirpated and transported unfixed to the Department of Pathology, Leiden. The diameter of the lymph node was 2 cm. On the cut surface it had a vaguely nodular appearance. The node was sliced and parts were frozen. Other parts were fixed in either formalin or sublimate formalin. One slice was processed for plastic embedding, as described previously2.
Histologic and Immunohistochemical Findings Microscopically, the architecture of the lymph node was, for the most part, intact. Throughout the cortex there was a proliferation of marginal zone lymphocytes arranged in large nodules and band-forming aggregates, but rarely with germinal centers (Fig. 1). These cells also extended outside of the cortex and into the surrounding 0344-0338/90/0186-0397$3.50/0
398 . J. H. J. M. van Krieken and K. Lennert Discussion
In most cases it is not very difficult to distinguish histologically benign processes from malignant ones in a lymph node. The most important criteria for malignancy are disturbance of the lymph node architecture, atypia of the lymphoid cells, and extension beyond the capsule. In some cases the distinction is more difficult, and immunophenotyping is necessary to exclude a clonal B-cell proliferation. The present case is such an example. Due to a large proliferation of lymphocytes in the cortex, the normal architecture was difficult to recognize. The lymphocytes also extended into the fatty tissue. Furthermore, the lymphocytes were larger than the more common small lymphocyte of the follicular mantle, and therefore might be called atypical. However, in fact they represent a proliferation of marginal zone lymphocytes, which are well known in the follicles of the spleen, but which also occur in the follicular mantle of the lymph node 3,4. In "normal" lymph nodes the follicular mantle consists of many smalllymphocytes (IgD +, KiB3 +, alkaline phosphatase -), and there are small numbers of somewhat larger lymphoid cells that
Fig. 1. Cortical area of the lymph node showing rather monotonous follicle-like structures without germinal centers (Paraffin embedding. Hematoxylin-eosin stain; magnification x 53). Inset shows detail of the cells (Magnification x 760).
fatty tissue (Fig. 2). Between the marginal zone cells there were scattered small lymphocytes interpreted as mantle zone lymphocytes. The nuclei of the marginal zone lymphocytes were about 1.5 times the size of the nuclei of the small lymphocytes of the mantle zone. They had a moderate amount of weakly stained cytoplasm (Fig. 1). The paracortical areas were small. The phenotype of the marginal zone cells was as follows: CD3 (Leu-4)-, CDS (Leu-1)-, CD9 (BA-2)-, CD10 (JS)-, CD20 (B1)+, CD21 (B2)+, CD22 (Leu 14)+, CD23 (KiB 1)-, CD24 (BA-1)+, CD2S (a-IL2R)-, KiB3 L . The alkaline phosphatase reaction was positive. Surface immunoglobulin light chains stained in a bitypic pattern. IgD was 'negative. Most cells stained with IgM and a minority with IgG. The scattered small lymphocytes were IgD-positive and also CD23- and KiB3-positive (Fig. 3). It was concluded that this was a reactive lymph node lesion (unspecific lymphadenitis). Seven months later the patient is well and without complaints.
Fig. 2. Invasion of mainly marginal zone lymphocytes into the fatty tissue (Plastic embedding. Giemsa; magnification x 760).
Marginal Zone Cells of Lymph Node . 399
Fig. 3. Immunohistochemical staining of cortical area. (A) CD22 (Leu 14). (B) KiB3. Marginal zone cells and small lymphocytes of the mantle zone are positive for CD22, whereas marginal zone cells are negative for KiB3 (Magnification x 105).
we interpret as marginal zone cells (IgD -, KiB3 -, alkaline phosphatase +). Therefore a proliferation of lymphocytes larger than the small lymphocytes of the mantle zone is not necessarily atypical. Such proliferations are not rare, especially in axillary or inguinal lymph nodes of older patients. Once we found them in axillary lymph nodes removed from a patient with carcinoma of the breast. In most such cases frozen tissue is not available for immunophenotyping, and since the detection of immunoglobulin in paraffin sections is not reliable in most laboratories, the diagnosis may be very difficult. The lack of IgD and KiB3 (which also stains paraffin sections) can be helpful in such cases.
References 1 Feller AC, Wacker HH, Moldenhauer G, Parwaresh MR (1987) Monoclonal antibody KiB3 detects a formalin resistant antigen on normal and neoplastic B cells. Blood 70: 629-636 2 Te VeideJ, Burckhardt R, Kleiverda K, Leenheers-Binnendijk L, Sommerfeld W (1977) Methyl methacrylate as an embedding medium in histopathology. Histopathology 1: 319-330 3 Van den Oord 11, De Wolf-Peeters C, Desmet VJ (1986) The marginal zone in the human reactive lymph node. Am J Clin Pathol 86: 475-479 4 Van Krieken JHJM, von Schilling C, Kluin PM, Lennert K (1989) Splenic marginal zone lymphocytes and related cells in the lymph node: A morphologic and immunohistochemical study. Hum Pathol 20: 320-325
Received July 14, 1989 . Accepted in revised form December 4, 1989
Key words: Marginal zone cells oflymph node - Centrocytic lymphoma - Reactive lymph node hyperplasia - Malignant lymphoma - Lymphocytic immunophenotypes Dr. J. H. J. M. van Krieken, Department of Pathology, University Hospital, P.O. Box 9603, 2300 RC Leiden, The Netherlands
