L. H. P. M. Rademakers

Primary B‐cell malignant lymphoma of the maxilla with a sarcomatous pattern and multilobated nuclei

Three cases of primary malignant lymphoma of the maxilla are reported. The primary intraosseous origin of these tumors was demonstrated by x‐ray examination and surgical exploration. The initial interpretation as odontogenic infection led to a delay in starting therapy of 9 months in one case. Biopsies of two cases were initially interpreted as sarcoma because of a dense reactive fibrosis between the tumor cells. Subsequently, hemimaxillectomy was performed in one case. Histologically and ultrastructurally the tumor cells showed marked nuclear abnormalities with cleavage, folding, and lobulation. Immune histochemical studies of two cases showed a monoclonal immunoglobulin expression, IgG‐K; T‐lymphocyte‐associated antigens were not detected on the tumor cells. The findings indicate the existence of a primary B‐cell malignant lymphoma of bone with multilobated nuclei. The lymphoid nature may be masked by a dense proliferation of connective tissue. The relation of these tumors to the classifications for malignant lymphoma of lymph node is discussed.

Histiocytic and dendritic reticulum cells in follicular structures of follicular lymphoma and reactive hyperplasia. A quantitative electron microscopical analysis.

SummaryHistiocytic reticulum cells (HRC) and dendritic reticulum cells (DRC) are integral parts of germinal centres. These cell types are also present in follicles of follicular lymphomas, the neoplastic analogues of physiological germinal centres. In this study the distribution and ultrastructural appearances of HRC and DRC present in normal germinal centres and in neoplastic follicles were established by means of morphometric methods.The number of HRC was significantly lower in malignant follicles than in their reactive counterparts. Quantitative analysis of the cytoplasm and phagolysosomes suggest that HRC are smaller and that their activity is lower in malignant follicles. DRC were present in smaller numbers in these structures, as measured by nuclear counts and their relative volume within the follicles. The ultrastructural features indicate that DRC in follicular lymphoma are functionally less active than in reactive lymph nodes.The possibility that differences between the reticulum cells from reactive and neoplastic follicles may be related to the absence of an immune reaction in malignant follicular lymphoma is discussed. The frequency and appearance of HRC and DRC are suitable as additional parameters to differentiate reactive secondary germinal centres from their malignant analogues.

Malignant lymphoma of follicle centre cells with marked nuclear lobation

SummaryFour cases of malignant B-cell lymphoma characterized by a conspicuous component of tumour cells with markedly lobtated nuclei are described. Two exhibited a follicular and two a diffuse growth pattern. The tumour cell population formed a continuous spectrum comprising both cells resembling normal follicle centre cells and multilobated lymphoma cells. Cytomorphological analysis of the multilobated cell group indicated a differentiation series from centroblast-like cells with moderately lobated nuclei to large and medium-sized cells with marked nuclear lobation which revealed features of centrocytes. In three cases (1, 3, and 4) the majority of these multilobated cells showed plasmacytoid differentiation in their cytoplasm in conjunction with the synthesis of monotypical cytoplasmic immunoglobulin. No plasmacytoid features were present in a fourth case (2). In only one case (4) monotypical surface immunoglobulin was detectable on the tumour cells.A close relationship between the multilobated tumour cells and follicle centre cells was further substantiated by the finding of a similar cell variant in the follicle centres of a control group of non-neoplastic lymph nodes. It included cells with plasmacytoid differentiation which synthesized polytypical immunoglobulin.We consider this type of B-cell lymphoma with a conspicuous component of cells with lobated nuclei as a variant of malignant lymphoma, centroblastic/centrocytic.

Identification of Alkaline Phosphatase Positive Cells in Human Germinal Centres as Follicular Dendritic Cells

Follicular dendritic cells (FDC) are exclusively found in germinal centers, where they form an extensive meshwork between the lymfoid cells. Many controversies exist about their origin. Ultrastructural studies on their ontogeny (1–3) suggest that FDC transform from fibroblastic reticulum cells. Marker studies have shown that FDC have antigens which are common to macrophages (4,5) and a monocyte-macrophage lineage has been suggested (6,7). Humphrey and Sundaram (8), however, excluded in their chimaera studies a bone marrow derivation of FDC. In a previous enzyme-cytochemical study on FDC isolated from human tonsils (9) we have shown that FDC have an enzyme pattern that is different from macrophages. At least a proportion of FDC is alkaline phosphatase-positive (AF+). Thus far it is unclear whether the alkaline phosphatase activity of FDC is an expression of a specialized activity of FDC or a “rudimental marker” of precursor cells of FDC. To study the nature and “in situ” localization of AF+ FDC we examined AF+ cells in germinal centers at the light and electron microscopical level.

Distribution of dendritic reticulum cells in follicular lymphoma and reactive hyperplasia. Light microscopic identification and general morphology.

SummaryReactive and neoplastic follicles in lymph nodes showing changes of (1) follicular hyperplasia and (2) follicular lymphoma were examined for the presence of dendritic reticulum cells (DRC). These cells could be identified under the light microscope after comparing electron microscopical sections with subsequent 1 ώm sections of reactive germinal centres. Quantitative light microscopical evaluation showed that DRC, both mononuclear and binuclear forms, were less numerous in neoplastic follicular structures than in reactive follicles.Before determining the frequency of binucleated DRC in follicular tissue their morphology was studied first in cell suspensions. DRC isolated by enzymatic treatment of tonsils and reactive lymph nodes were morphologically identical and contained one, or at most two, nuclei arranged in a typical doublet formation. Stereological calculations —made on three dimensional models of nuclear complexes prepared from serial tissue sections — indicated that 51 to 68% of DRC in reactive germinal centres were binucleated, whereas in neoplastic follicles this figure is 18 to 23%. The multinucleated giant cell forms of DRC described by others result from complex formation with other DRC or lymphoid cells.The smaller number of DRC and the lower frequency of binucleated DRC in follicular lymphomas suggest that differentiation of DRC from stromal cells is less complete in these neoplasms.The ability to identify DRC reliably by light microscopy offers a new means to define the difference in frequency of DRC. This may be of practical value in distinguishing reactive germinal centres from neoplastic follicles.

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients

Abstract Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 μm 2 . The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 μm 2 ; P = 0.02), as did the values of P75NA (20.7 vs 27.9 μm 2 ; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.

Tumor growth stimulatory macrophages induced by a subclinical bacterial infection in vivo.

Nonelicited peritoneal macrophages obtained from normal mice from our animal house unexpectedly expressed a strong tumor growth stimulatory effect in vitro. Macrophages expressing this stimulatory effect had an aberrant morphology compared to the morphology of normal macrophages as observed by electron microscopy.

Non-Hodgkin’s lymphoma with multilobated nuclei is not a distinct pathologic entity

T-cell non-Hodgkin’s lymphoma (NHL) of large multilobated cell type was originally described by Pinkus et al. in 1979 [1]. The 4 cases mainly presented in extranodal sites and were associated with a favorable clinical course. Consecutively T-lymphocyte derived tumors with multilobated cells have been reported to occur in lymph nodes [2–5] and in the skin [6, 7]. A separate entity may comprise human T-cell leukemia virus (HTLV) related adult T-cell leukemia/lymphoma in which multilobated cells are frequent [2, 8], especially in the pleiomorphic subtype. Clinical studies reveal a poor survival [9].

Follicular Dendritic Cells in Human Germinal Centres and Lymphomatous Follicles; A Morphological Comparison

Follicular Dendritic Cells (FDC) are non-lymphoid cells which are able to trap immune-complexes. FDC are exclusively present in germinal centres of lymphoid organs and form a meshwork with their extensions within reactive germinal centres. Though their precise function is unknown it is assumed that FDC are involved in the regulation of the germinal centre reaction. FDC are also a constituent of the follicles of follicular lymphomas, the neoplastic counter part of germinal centres (1).