Dendritic reticulum cells in reactive lymph nodes and tonsils: an immunohistological study

There has recently been much interest in the patterns of follicular dendritic reticulum cells (DRC) in pathological lymph nodes, particularly in relation to the phenomenon of DRC break-up (thought to be pathognomonic of AIDS-related lymphadenopathies) and to progressive transformation of germinal centres (as a possible precursor of lymphocyte predominant Hodgkin's disease). In the present study we have immunostained twenty-nine reactive lymph nodes and five tonsils with monoclonal antibody R4/23 (DAKO-DRC) in order to evaluate the frequency of such changes in lymphoid tissue unaffected by AIDS or Hodgkin's disease. Most of the specimens contained typical secondary follicles with clearly defined germinal centres and mantle zones. There were two variants in lymph nodes showing follicular hyperplasia characterized by (i) progressive transformation of germinal centres and (ii) inclusions of nests of small lymphocytes within germinal centres. In each of these types of follicles the compact evenly-distributed meshwork of DRCs, as previously described, was seen. However there were considerable variations in DRC meshwork in each category (the pattern could not be predicted from the morphology) with examples in all three of the DRC break-up previously considered specific for the AIDS related lymphadenopathy. Since none of the lymph nodes and tonsils studied had any known relationship to either Hodgkin's disease or AIDS it is argued that none of the changes in the DRC meshwork observed are specific for these conditions.     

Study of nuclear sizes in the centres of malignant and benign lymphoid follicles.

The sizes of follicle centre cells in 15 specimens of follicular (centroblastic-centrocytic) non-Hodgkin's lymphoma and 15 specimens of reactive follicular hyperplasia have been measured. The findings differ from previous studies, where nuclei of cells from follicle centres and interfollicular areas were measured and revealed no significant difference between follicular lymphoma and reactive follicular hyperplasia. In the current study, by measuring only follicle centre cell nuclei, it has been found that, in reactive follicular hyperplasia, the mean nuclear maximum diameter (Dmax) and area are significantly greater than in centroblastic-centrocytic follicular lymphoma. In addition, the standard deviation of these data is greater for reactive follicular hyperplasia than follicular lymphoma, implying greater "scatter" or heterogeneity of the nuclear sizes in the follicle centre cells of the former than the latter. Thus, the size of these cells appears to be of value as an histological discriminator between these benign and malignant conditions.     

The chemokines CCL11, CCL20, CCL21, and CCL24 are preferentially expressed in polarized human secondary lymphoid follicles

Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid-tissue chemokine) and CCL24 (eotaxin-2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3-binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra- and extra-follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation.     

Immunoregulatory Leu-7+ and T8+ lymphocytes in B-cell follicular lymphomas

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.     

Selective distribution and quantitation of T-lymphocyte subsets in germinal centers of human tonsils. Definition by use of monoclonal antibodies

The distribution and quantitation of T-lymphocyte subpopulations of human tonsils were studied in situ by the avidinbiotin-peroxidase technique, using monoclonal antibodies to total, helper, and suppressor T cells. Primary follicles contained few T lymphocytes. The germinal centers of secondary follicles contained numerous T cells: in the periphery, 14.2% +/- 1.7% (mean +/- SD), and in the central area, 2.4% +/- 0.7%, of follicular lymphocytes counted were T lymphocytes. The mantle zone had fewer T lymphocytes (7% +/- 0.9%). Most of the T lymphocytes found in the germinal centers had the helper-cell phenotype. There were fewer than 1% of suppressor T lymphocytes in the germinal centers. An occasional secondary follicle could contain up to 10% of suppressor cells (range, 0% to 9.7%). The interfollicular areas contained preponderantly T lymphocytes, a majority of which reacted with monoclonal antibodies to helper cells. The distribution and enumeration of T lymphocytes in normal reactive lymphoid tissue provide a basis for studies of pathological specimens.     

Immunoglobulin idiotype expression in reactive lymphoid tissues and B-cell lymphomas

Summary In an investigation of the immunoglobulin idiotypic expression of non-tumour and neoplastic B lymphocytes in situ, fresh-frozen specimens of reactive tonsils, lymph nodes and B-cell malignant lymphomas (B-MLs) from Japanese patients were studied immuno-histochemically with 39 different anti-idiotype antibodies. In reactive lymphoid tissues, while idiotype-bearing cells were largely distributed sparsely in follicles and perifollicular areas, some were heavily crowded in particular germinal centres (GCs), suggesting the presence of oligoclonal proliferations of B-cells in GCs. Forty-eight out of 100 B-MLs reacted with anti-idiotype antibodies. This proportion was significantly higher than those reported in Western cases (27–36%), indicating that Japanese B-MLs share public idiotypes much frequently than western cases. The idiotypes demonstrated in these lymphomas, in contrast to those not expressed in any B-ML, were found much commonly in non-tumour lymphocytes, suggesting that such public idiotypes as were common in B-MLs were frequently shared by normal B-lymphocytes.     

Cluster differentiation antigen expression, proliferative activity and clinical stage in centroblastic centrocytic lymphomas

Using a panel of B-cell antibodies recognizing clusters of leucocyte differentiation antigens, immunostaining patterns of eight reactive lymph nodes and 28 centroblastic/centrocytic and centrocytic lymphomas have been studied. Centroblastic/centrocytic and centrocytic lymphomas retained many of the B-cell differentiation antigens and neoplastic follicles partially recapitulated the staining patterns observed in reactive follicles. Centrocytic lymphomas usually expressed a heavy chain mantle zone-like phenotype. Nearly one-half of follicular lymphomas showed extension of neoplastic cells into interfollicular areas as evidenced by positivity for CD10 (common acute lymphoblastic leukaemia) and/or CD9 (immature B-cell) and CD23 (B-blast cell) antigens. Cases showing interfollicular involvement also manifested considerable phenotypic heterogeneity. Light chain restriction could not be used to determine interfollicular involvement because of the presence of many non-neoplastic cells. Most follicular lymphomas retained a polyclonal mantle around at least some neoplastic follicles and in no case was a monoclonal mantle seen. Most lymphomas (16/21) were diploid when examined by flow cytometry. Diploid tumours exhibiting interfollicular lymphomatous involvement had high proliferation (S + G2) fractions and these lymph nodes were usually derived from patients with widespread disease. Tumours containing a high percentage of cells in the G0/G1 phases displayed fewer B-cell differentiation antigens than tumours with low G0/G1 fractions.     

Immunohistochemical analysis of Mcl-1 and Bcl-2 proteins in normal and neoplastic lymph nodes.

The Bcl-2 protein blocks programmed cell death and becomes overproduced in many follicular non-Hodgkin's lymphomas as the result of t(14; 18) translocations involving the Bcl-2 gene. Mcl-1 is a recently discovered gene whose encoded protein has significant homology with Bcl-2 but whose function remains unknown. In this study, we compared the in vivo patterns of Bcl-2 and Mcl-1 protein production in normal and neoplastic lymph node biopsies by immunohistochemical means using specific polyclonal antisera. Intracellular Mcl-1 immunoreactivity was located primarily in the cytosol in a punctate pattern and was also seen in association with the nuclear envelope in many cases, similar to the results obtained for Bcl-2, which resides in the outer mitochondrial membrane, nuclear envelope, and endoplasmic reticulum. In 4 of 4 reactive tonsils and 28 of 28 nodes with reactive follicular hyperplasia, reciprocal patterns of Bcl-2 and Mcl-1 protein expression were observed. Bcl-2 immunostaining was highest in mantle zone lymphocytes and absent from most germinal center cells, whereas Mcl-1 immunoreactivity was highest in germinal center lymphocytes and absent from mantle zone lymphocytes. Mcl-1 was also expressed in some interfollicular lymphocytes, particularly those that had the appearance of activated lymphocytes. Similar to the patterns of Bcl-2 and mcl-1 expression seen in reactive nodes, Mcl-1 protein was largely absent from the malignant cells in 2 of 2 mantle cell lymphomas, whereas strong Bcl-2 immunostaining was found in these cells. In contrast to normal nodes, however, the neoplastic follicles of t(14;18) containing follicular non-Hodgkin's lymphomas immunostained positively for both Bcl-2 and Mcl-1 in 24 of 27 cases. Intense immunostaining for Mcl-1 was also observed in Reed-Sternberg cells in 2 of 2 cases of Hodgkin's disease but Bcl-2 immunoreactivity was present at much lower levels. These findings demonstrate that the levels of Mcl-1 and Bcl-2 proteins are differentially regulated in normal and neoplastic cells in lymph nodes and thus suggest different roles for these proteins in the control of cell life and death in these tissues.     

A quantitative study of histiocytic reticulum cells in diffuse and follicular non-Hodgkin''s lymphomas

Histiocytic reticulum cells have been counted in 160 lymph nodes, comprising 50 high grade non-Hodgkin's lymphomas, 90 lymphomas of low grade histology, and 20 specimens exhibiting reactive follicular hyperplasia. The histiocytes were shown immunohistochemically by virtue of their content of the cysteine proteinase cathepsin B. A consistent and striking finding was that high grade lymphomas contain many more histiocytes than low grade lymphomas. Immunoblastic neoplasms contain up to 24.2% of these cells, whereas low grade diffuse lymphomas possess only up to 3.6% histiocytes. Histiocytic reticulum cells were also counted in benign or malignant follicular lesions in standard areas from follicle centres only. No significant differences were found between low grade lymphomas and hyperplastic nodes. These findings are discussed in relation to previous, more limited studies.     

Correlation between apoptosis microarray gene expression profiling and histopathological lymph node lesions.

AIMS: Microarray technology has recently led to the identification of molecular prognostic subgroups in non-Hodgkin's lymphomas. To determine the usefulness of ready made macroarrays as routine diagnostic tools in haematopathology, lymph node biopsies were analysed using a cDNA macroarray containing genes involved in apoptosis, including caspases. METHODS: Nine biopsy specimens were analysed using total frozen tissues: four samples of B cell follicular lymphoma, two of B cell diffuse large cell lymphoma, and three of non-neoplastic lymph nodes from benign lymphadenitis. Nine cell populations were sorted from fresh tissues: malignant B cells from two patients with follicular lymphoma and two with diffuse large cell lymphoma, reactive B cells from two benign lymph nodes, reactive T cells from one benign lymph node, and virgin (mantle zone) B cells and germinal centre B cells from benign tonsils. Immunohistochemistry (IHC) on paraffin wax sections was performed for the localisation of caspases 2, 3, 4, 7, 8, and 9. RESULTS: In the clustered array data, sorted cells from samples sharing common histological lesions were grouped together, whereas the array/histology correlation was less satisfactory for tissues. The expression profiles of both the array and IHC methods correlated for most caspases and samples. CONCLUSIONS: Variations in array profiles of sorted cell populations can be associated with specific histological features, suggesting a possible diagnostic application of ready made apoptosis macroarrays in haematopathology.     

The immunohistology of non-T cells in the acquired immunodeficiency syndrome.

The authors employed a panel of monoclonal antibodies to characterize B cells, histiocytes, and natural killer cells in lymph node biopsies obtained from 7 homosexual men with the acquired immune deficiency syndrome (AIDS) and 5 heterosexual controls. Six of the AIDS patients, each with cutaneous and/or nodal Kaposi's sarcoma, exhibited reactive follicular hyperplasia, as did the 5 controls. The seventh AIDS patient had opportunistic infections and exhibited a lymphocyte depletion pattern in lymph nodes. In AIDS patients, reactive B-cell follicles often exhibited attenuation of their mantle zones. Many were regressively transformed and composed predominantly of dendritic reticulum cells. Occasional germinal center dendritic reticulum cell networks exhibited fragmentation reminiscent of the "follicle lysis" described previously in the persistent generalized lymphadenopathy syndrome. In the 1 AIDS patient with the lymphocyte depletion pattern of lymph node histology, germinal center elements, including dendritic reticulum cells, were totally absent. In all cases, the mononuclear-cell subsets exhibited normal patterns of antigen expression. Quantitative studies, however, revealed a significant increase (P less than or equal to 0.01) in natural killer cells and histiocytes within the paracortical T-cell domain of lymph nodes obtained from patients with AIDS. There was no significant difference in the number of natural killer cells within the mantle or germinal center B-cell domains. While there was no significant difference in the absolute number of paracortical B cells, they were relatively increased due to an absolute decrease in T cells. It is concluded that quantitative alterations in mononuclear-cell subsets in patients with AIDS are not restricted to T cells and that these alterations are microenvironmentally specific.     

Leu 7+(HNK-l+) Cells

In the present immunohistochemical studies, Leu 7+ (HNK-1+, human natural killer and killer) cells were found to occupy preferentially germinal centres of follicles in lymph nodes and tonsils. Leu 7+ cells were also present in germinal-like zones of spleen follicles and in mantle zones of hyperplastic thymus follicles and varied in localization in lymph nodes involved in different types of follicular centre cell-derived malignant lymphomas. Most of the Leu 7+ cells in the follicles expressed the Leu 3 (helper/inducer) marker. Double staining studies of tonsil sheep erythrocyte-rosetting and peripheral blood mononuclear cell suspensions showed that two main, mutually complementary, subpopulations of Leu 7+ cells could be distinguished in both cases, namely Leu 7+/Leu 4+ (subdivided into Leu 2+ (suppressor/cytotoxic) and Leu 3+) and Leu 7+/Leu 4-, including mostly cells with OKM 1 (myelomonocytic) characteristics. Thus, in the tonsil cell suspension the cells with Leu 7+ Leu 3+/OKM 1- immunophenotype strongly predominated, whereas among peripheral blood mononuclear cells Leu 7+Leu 2+/OKM 1- and Leu 7+/OKM 1+ immunophenotypes were mostly observed.     

Vimentin immunostaining in fibroblastic reticulum cells within human reactive and neoplastic lymphoid follicles

We analyzed the distribution of fibroblastic reticulum cells (FRCs), stationary cells of lymphoid tissues, as visualized by the anti-vimentin (V9) monoclonal antibody in human reactive and neoplastic lymphoid follicles, by using immunoenzymatic and immunofluorescence methods on fixed and paraffin-embedded tissue sections from 37 lymphoid specimens with reactive disorders and 10 specimens with nodular/follicular non-Hodgkin's lymphomas (NHLs). The pattern of distribution of the vimentin-positive (VIM+) FRCs was compared with that of follicular dendritic reticulum cells (DRCs) as visualized by anti-S-100 protein antibody. Elongate VIM+ FRCs intimately attached to reticulum fibers were randomly distributed in the paracortical and interfollicular areas of lymph nodes, whereas they were recognized specifically in the mantle zones of the secondary follicles, mostly in the outer margins. Germinal centers were consistently devoid of VIM+ FRCs. Comparative analysis on serial sections as well as paired immunoperoxidase and double immunofluorescence studies demonstrated that there was a sharp difference between the patterns of intrafollicular distribution of VIM+ FRCs and S-100 protein-positive (S-100+) DRCs without juxtaposition, the FRCs being confined to the mantle zones. In the 10 nodular/follicular NHLs VIM+ FRCs could be observed in the thinned mantles of neoplastic nodules displaying a corona-like pattern that accentuated the boundaries of the nodules. The results of this study support the view that the intrafollicular distribution of VIM+ FRCs is specific for the mantle zone. The different microenvironmental organization within the follicles of VIM+ FRCs and S-100+ DRCs suggests that FRCs or at least VIM+ FRCs are stationary cells strictly related to the mantle zone microenvironment, where they may play a role in supposed sustentacular and immunologic functions similar to that of DRCs in the germinal center microenvironment.     

Immunoarchitecture of the "pseudofollicles" of well-differentiated (small) lymphocytic lymphoma: a comparison with true follicles

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.     

Early lymph node involvement by mantle cell lymphoma limited to the germinal center: report of a case with a novel "follicular in situ" growth pattern

Recently, several reports have described cases of "in situ" mantle cell lymphoma (MCL) in which scattered cyclin D1+ cells were present within the mantle zones of reactive-appearing lymphoid follicles. In this report, we describe an unusual histologic pattern of in situ MCL that was identified in a staging lymph node for colonic adenocarcinoma resected 4 years before a diagnosis of symptomatic MCL. Retrospective immunohistochemical studies showed scattered cyclin D1-expressing cells within otherwise reactive germinal centers but not in the surrounding mantle zones. The presence of early MCL cells limited to reactive germinal centers represents a novel "follicular in situ" growth pattern for MCL, which overlaps morphologically with reactive follicular hyperplasia and follicular lymphoma and which could have implications for MCL pathogenesis.     

Heterogeneous immunostaining patterns of follicular dendritic reticulum cells in human lymphoid tissue with selected antibodies reactive with different cell lineages

A comparative immunohistologic study of the cell density and distribution pattern of follicular dendritic reticulum cells (DRCs) within their follicular microenvironments (germinal centers and mantle zones) was performed by immunoperoxidase technique with a selected panel of antibodies either operationally specific for DRCs (DRC-1) or reported as having additional immunoreactivity with DRCs (antibodies to B- and T-cells, leukocytes, monocytes/macrophages, desmosomal components, and S-100 protein). Twenty-five biopsy specimens, including reactive lymph nodes and tonsils as well as normal spleen tissue, were analyzed. Serial frozen sections were tested either with single antibodies or paired monoclonal reagents in double-labeling procedures. Our results consistently indicated that DRCs positive for Leu M3 and BA-2 antibodies were confined to the central portion of germinal centers, whereas DRCs immunoreactive for S-100 protein and desmoplakin 1 and 2 were localized mostly in the central and pericentral portion of germinal centers. All the DRCs extending from the central portion of germinal centers to the mantle zones were labeled with DRC-1 and, unexpectedly, with OKB7 antibodies. Other immunostainings, such as those for HLA-DR antigens, common leukocyte antigen, and Leu 3a, were not contributory in defining topographic differences of DRCs within the follicle. The consistent heterogeneity of the labeling patterns appears to suggest a possible in situ immunophenotypic grouping of DRCs, and the concept of their possible heterogeneity appears to be corroborated.     

Monocytoid B lymphocytes: their relation to the patterns of the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy

It was shown recently that monocytoid cells express B-cell-restricted antigens and polyclonal surface immunoglobulins, and the term monocytoid B lymphocytes (MBL) has thus been offered as a more appropriate designation. Although most commonly seen in toxoplasmic lymphadenitis, MBL have been observed in a variety of reactive and neoplastic conditions involving lymph nodes. In the present study MBL were found in 17 of 22 lymph nodes from 20 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy. In all 17 samples, the MBL were found in lymph nodes with florid reactive follicular hyperplasia, and they were geographically close to the hyperplastic lymphoid follicles. However, MBL were not detected in lymph nodes showing involuted follicles or lymphocyte depletion. The disappearance of MBL apparently parallels the progressive involution of secondary follicles. Leu-3+/Leu-2+ (T-helper/T-suppressor) ratios were studied in 14 lymph node cell suspension samples and ten peripheral blood samples. The lymph node Leu-3+/Leu-2+ ratios were significantly lower in AIDS-related lymphadenopathy than in non-AIDS-related reactive follicular hyperplasia (P less than 0.001); the peripheral blood ratios were decreased in nine of the ten cases. The diminished T-helper status in patients with AIDS and AIDS-related lymphadenopathy may be relevant to the immunopathogenesis of follicular involution and, indirectly, to the disappearance of MBL.     

An immunohistochemical study of branchial cysts.

Twenty five specimens of branchial cyst from the same number of patients have been examined. On staining with haematoxylin and eosin a consistent finding was that the mural lymphoid follicles were always aligned with their mantle zones towards the luminal epithelium. With conventional staining lymphatic sinuses were noted in 17 of the specimens, but with immunohistochemical staining these structures were apparent in 23 cysts. Their frequent occurrence in branchial cysts supports the theory that these lesions are derived from epithelial inclusions in lymph nodes. Immunohistochemical techniques for a range of other markers, using polyclonal and monoclonal antisera, showed a distribution of lymphoid and non-lymphoid tissue elements, as seen in lymph nodes and, for example, palatine tonsils. The lining luminal epithelium also shared many features in common with the crypt epithelium of tonsils.     

Report of an unusual lymphoma arising from parafollicular B-lymphocytes (PBLs) or so-called "monocytoid" lymphocytes

A distinctive B-cell has been recognized recently in reactive lymph nodes, especially those of toxoplasmic lymphadenitis. Previously designated as "immature sinus histiocytes" or "monocytoid" cells, these B-lymphocytes proliferate in subcapsular and parenchymal sinuses and the parafollicular area of nodes. The authors now report a 55-year-old male who developed a malignant lymphoma composed of cells with light microscopic, immunologic, and ultrastructural characteristics identical with these newly described B-cells. The term parafollicular B-lymphocytes (PBLs) is recommended herein to emphasize their morphologic and immunologic features. An unusual feature of this PBL lymphoma is the numerous benign-appearing hyperplastic follicles surrounded by the neoplastic infiltrate, mimicking the cytologic appearance and distribution of PBLs seen in toxoplasmic lymphadenitis. The function of these recently recognized B-cells is unknown; their anatomic relationship with hyperplastic follicular centers in reactive states and the lymphoma herein described suggests a role in follicular function.     

Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations.

Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma. A dendritic staining pattern within germinal centers was present in 25 of 26 routinely processed lymph nodes with reactive follicular hyperplasia. In contrast, dendritic staining with anti-NGFR was present within neoplastic follicles in only three of 28 follicular lymphomas. Staining of benign, residual germinal centers with anti-NGFR was present in mantle zone lymphoma and Hodgkin's disease. These findings suggest a possible role for the NGFR in the maturation and/or activation of normal DRCs. The loss of NGFR expression in most follicular lymphomas indicates that DRCs are altered as part of the neoplastic process. The possibility that DRCs may play a role in the pathogenesis of follicular lymphoma is suggested.