Tropical sprue and multiple myeloma.
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Biomedical subjects
Publications and source records attributed to H J Ree.
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Anti-Leu M1 generally does not stain the lymphocytic and histiocytic (L&H) variants of Reed-Sternberg cells in the lymphocyte predominant type of Hodgkin's disease. However, the authors found that after neuraminidase treatment for removal of sialic acid, the L&H cells in more than half of the cases studied could be stained by anti-Leu M1. This result strongly suggests that L&H cells differ from the Reed-Sternberg cells in other types of Hodgkin's disease in their unique capacity to sialylate the 150-kd Leu M1 antigen.
Ricinus communis agglutinin (RCA) staining of malignant histiocytosis (two cases) and tissue infiltrates of monoblastic leukemia revealed two distinct macrophage-histiocyte types: one with cytoplasmic staining (RCA+), the other without (RCA-). RCA+ cells corresponded to benign-appearing histiocytes without nuclear atypia, whereas RCA-cells were cytologically malignant. In one case of malignant histiocytosis, many RCA-tumor cells were surrounded by a thin cytoplasmic extension of RCA+ cells, which suggested an interaction between the tumor cells and stromal macrophage-histiocytes. These observations support the view that most benign-appearing histiocytes in malignant histiocytosis are reactive in nature and suggest that RCA staining can be useful in distinguishing between benign and malignant disorders of macrophage-histiocytes.
The authors studied the occurrence of Ricinus communis agglutinin (RCA)-binding macrophage-histiocytes in paraffin-embedded tumor tissue of 38 patients with malignant lymphoma, small lymphocytic type, a tumor of low-grade malignancy. Thirty-one patients (82%) had an indolent clinical course and were free of disease for a minimum follow-up period of 24 months. However, seven patients (18%) died within 24 months of biopsy, and six of the seven patients died of rapid progression of their tumor despite intensive treatment. Histologically, the tumors of these six short-term survivors were indistinguishable from those of the long-term survivors. RCA staining of paraffin-embedded tumor tissue of the 38 cases revealed three groups of tumors: (1) tumors with numerous (greater than 10/high-power field [HPF]) stromal macrophage-histiocytes (4 patients); (2) tumors with a moderate number (4-9/HPF) of macrophage-histiocytes (5 patients); (3) tumors with rare or no (0-3/HPF) macrophage-histiocytes, or only thin, anuclear variants (29 patients). Each of the six short-term survivors had readily demonstrable RCA-binding macrophage-histiocytes in their tumor; these were numerous in four and moderate in two. In contrast, macrophage-histiocytes were either rare or absent, or were anuclear variants, in 29 of the 31 patients who had an indolent clinical course. These observations suggest that in small lymphocytic type malignant lymphoma there is a subgroup characterized by an increased number of stromal macrophage-histiocytes and aggressive behavior of the tumor. Tumors of this subgroup can be detected by RCA staining.
The authors studied the occurrence of peanut agglutinin (PNA)-binding cells in paraffin-embedded specimens of 145 patients with Hodgkin's disease (HD). The staining reaction of lymphocytes was consistently negative. A positive staining reaction was observed in two types of cells: macrophage-histiocytes (M-H), and Reed-Sternberg (R-S) cells and their variants. Diffuse or globular cytoplasmic staining was found in M-H, which was easily distinguished from a unique "cell surface and cytoplasmic" staining pattern of R-S and related cells. Thus defined, M-H were numerous in lymphocyte depletion and mixed cellularity, less common in lymphocyte predominance, and least frequent in the nodular sclerosis type. Numerous M-H correlated with B-symptoms and a poor response to therapy. Among the asymptomatic patients with localized disease at presentation, the presence of large numbers of M-H was associated with a high incidence of relapse within 2 years of therapy. These findings suggest that the number of non-neoplastic M-H in HD may be an important determinant in the clinical presentation and course of disease. Peanut agglutinin staining may be useful for the detection of M-H in routine diagnosis and classification of HD, which has not been feasible by conventional methods.
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Patients who require construction of a neovagina provide an opportunity for researchers to study some of the possible factors that cause vaginal neoplasia. Intraepithelial neoplastic changes occurring in the neovagina, remote from the graft margins, cannot be attributed to preexisting disease in the vaginal site. Such changes are unlikely to represent an expression of the oncogenic potential of the transplanted tissue. The most likely cause of these changes is the presence of a local carcinogenic environmental factor. Two cases are presented to demonstrate and support this thesis. The treatment prescribed, local excision in one case and application of topical 5-fluorouracil in the other case, resulted in disease-free intervals in excess of eight years for both patients.
The staining reaction of a panel of lectins in paraffin embedded lymph node specimens of diffuse large cell lymphoma was studied in relation to survival. In 47 of 49 patients, varying degrees of lectin binding were observed with Ricinus communis agglutinin (RCA), crude extract of Arachis hypogaea (c-PNA), Concanavalin ensiformis A (Con A), Triticum vulgaris A (WGA) and Phaseolus vulgaris A (PHA). Binding was either absent or only minimal with Pisum sativum A (PSA) and Lens culinaris A (LCA). Two categories of binding were observed: cell surface and cytoplasmic. Cell surface binding was seen in tumor cells, while cytoplasmic binding was observed in macrophage-histiocytes. Varying numbers of tumor cells were stained with RCA, WGA, c-PNA or PHA; but with Con A virtually no tumor cells were stained. Stromal macrophage-histiocytes were stained with RCA, WGA, or Con A in all but one case, frequently with all three lectins; c-PNA binding macrophage-histiocytes were absent in one third of the cases. With PHA the staining of stromal macrophage-histiocytes was extremely rare. Tumor cells that stained with RCA but not with c-PNA were observed in 9 of 15 patients who survived more than 2 years after diagnosis. In all 15 long-term survivors, stromal macrophage-histiocytes were positive for c-PNA. Tumor cells that reacted with c-PNA but not with RCA were seen in five patients who survived less than two years. All 16 patients whose tumors lacked c-PNA binding stromal macrophage-histiocytes in the presence of RCA binding macrophage-histiocytes were short-term survivors. These observations suggest the heterogeneity of stromal macrophage-histiocytes as well as that of tumor cells. Furthermore, the variation of lectin binding might be useful in assessing prognosis.
The occurrence and staining patterns of Concanavalin A (Con A) binding histiocytes were studied in diagnostic lymph node specimens of 133 patients with Hodgkin's disease. Varying numbers of Con A binding histiocytes were present in all tumors. Two distinct cytoplasmic staining patterns of the Con A binding histiocytes were noted: diffuse, and a pattern termed "globular" which represents a dense, solitary paranuclear aggregate of binding sites. The diffuse binding pattern was seen in the majority of histiocytes with no apparent nuclear atypia, but was also occasionally seen in Reed-Sternberg cells. Globular binding was present in both benign and malignant-looking histiocytes, including rare Reed-Sternberg cells. Based on the number of histiocytes in which globular binding of Con A (G-cells) was observed, tumors were grouped in the following three categories: Group 1: tumors with large numbers of G-cells (42 cases); Group 2: tumors with a small number of G-cells (16); and Group 3: tumors with rare or no G-cells (75). Tumors with large numbers of G-cells were seen more frequently in patients with disseminated disease than in those with localized (69.0% versus 31.0%; P less than or equal to 0.002), and more often in patients with B-symptoms than in those without (73.8% versus 26.2%; P less than or equal to 0.001). Large numbers of G-cells were present in most tumors of the lymphocyte depletion type (14/16), whereas rare or no G-cells were seen in the majority of the nodular sclerosis type (46/59). These observations suggest that the G-cells may represent an abnormal variant of histiocytes, the occurrence of which is associated with unfavorable clinical and pathologic features of Hodgkin's disease.
Peanut agglutinin (PNA) receptors were studied in 37 cases of reactive follicular hyperplasia and 66 follicular lymphomas, using the unlabeled peroxidase-antiperoxidase (PAP) method on paraffin embedded material. Based on the binding sites of the lectin, positively stained cells were easily recognized as either cytoplasmic receptor-positive (CR+) or surface receptor-positive (SR+) cells. In the lymph node specimens, CR+ cells corresponded to macrophage-histiocytes and possibly dendritic reticulum cells; SR+ cells corresponded to lymphoid cells. Three categories of CR+ cells were noted: large, medium, and small. The large CR+ cells were present in most germinal centers from reactive nodes, but were virtually absent in neoplastic follicles. Varying numbers of medium and small CR+ cells were seen in reactive as well as neoplastic follicles. SR+ cells were present in both follicular lymphoma (64%) and follicular hyperplasia (19%). In neoplastic follicles, SR+ cells were distributed uniformly throughout every follicle in the node revealing no relation to the orientation of the node. In reactive follicles, however, the occurrence of SR+ cells was not only infrequent, but also focal, and was often associated with the polarity of the follicles. The uniform distribution of SR+ tumor cells produced a characteristic staining pattern of neoplastic follicles which, along with the disappearance of the large CR+ cells, would provide an additional feature useful in the differential diagnosis of neoplastic from reactive follicles.
Concanavalin agglutinin (Con A) binding sites were studied in paraffin embedded lymph node specimens of reactive follicular hyperplasia (12 cases) and follicular lymphoma (37) using the avidin-biotin-peroxidase complex method, and the results were compared with those of Peanut agglutinin (PNA) and lysozyme stains. Very similar to the PNA stain, two categories of Con A receptor sites were observed: cytoplasmic and cell surface. In the reactive lymph nodes, the cells showing cytoplasmic receptor sites (CR+ cells) corresponded to macrophage-histiocytes and possibly dendritic reticulum cells in the H & E stained sections, while those showing cell surface receptor sites (SR+) corresponded to lymphoid cells. Unlike the PNA binding, however, the staining reaction of SR+ lymphoid cells was weak, and another staining pattern, a dot-like stain, was observed in some lymphocytes, both SR+ and SR-. In follicular lymphomas, CR+ histiocytes were distinctly displayed within the follicular centers in 25 of 37 cases, including 12 cases in which PNA stains on adjacent or nearby sections were negative for intrafollicular macrophage-histiocytes. Similarly, Con A stains were positive for the intrafollicular CR+ cells in four of the five cases in which lysozyme stains were negative. Many of these intrafollicular CR+ cells contained inclusion-like cytoplasmic globules and/or vacuoles, a hallmark of the large CR+ cells of germinal centers. These observations suggest that macrophage-histiocytes of presumably germinal center origin are retained in neoplastic follicular centers in varying degrees, and Con A might be a useful marker for macrophage-histiocytes in paraffin-embedded routine pathological specimens, in addition to the currently accepted markers, PNA and lysozyme.
Using the avidin-biotin-labeled peroxidase complex (ABC) method, the staining reaction of a panel of 12 biotin-labeled lectins was studied in formalin-fixed, paraffin-embedded reactive lymph nodes and tonsils. Varying degrees of lectin binding were observed in lymphoid cells and macrophage-histiocytes with Concanavalin ensiformis (Con A), Lens culinaris (LCA), Phaseolus vulgaris (PHA), Pisum sativum (PSA), Ricinus communis (RCA), and Triticum vulgaris (WGA) agglutinins, but no evidence of binding was observed with Dolichos biflorus (DBA), Bandieraea simplicifolia (BSA), Arachis Hypogaea (PNA), Glycine soja (SBA), Sophora japonica (SJA), and Ulex europaeus (UEA) agglutinins. Three major patterns of binding were seen: the reaction products occurred along the plasma membranes (membranous), were confined to one pole of the cell membrane (cap-like), or were present diffusely in cytoplasm (cytoplasmic). The cells showing membranous and cap-like staining patterns corresponded to the lymphoid cells, as did the cytoplasmic to plasma cell and macrophage-histiocytes. Cap-like staining was observed on the lymphocytes at B and T cell areas with all six lectins. Thus, the presence of cap-like staining may not be useful for discrimination between B and T cells. Membranous staining, in contrast, was limited to lymphocytes of follicles (B cells) with PSA and LCA, and to germinal center cells with PHA, WGA, Con A, and RCA also reacted with the membrane of T-cell. The cytoplasmic staining reaction of macrophage-histiocytes varied markedly from one lectin to the other. Our study indicates that the carbohydrate moiety of the cells retains their binding sites for lectins through routine processing, providing a means of valid retrospective studies. Furthermore, these observations suggest that each lectin, despite its identical inhibitory sugar, should be tested for its unique reaction pattern, which is not predictable from the data derived from cell suspension studies.
Sclerosis was observed in the lymph node specimens of 26 of 57 (46%) patients with diffuse histiocytic lymphoma. Two major types of sclerosis was observed: "compartmentalizing" (56%), in which the tumor was divided into many small compartments by anastomosing, hyalinized stroma; and "diffuse" (44%), in which the sclerosis occurred without evident partitioning of the tumor. The hyalinized stroma of the compartmentalizing sclerosis was frequently continuous with small vessels accompanied by aggregates of small lymphocytes, suggesting that the sclerosis was related to the occurrence of small lymphocyte-associated postcapillary venules. Compartmentalizing sclerosis was further divided into two groups: The first group (even pattern) was characterized by an orderly occurrence of the stromal network with no evidence of distortion, evenly spaced tumor cells showing no axis in their arrangement, and a sharp demarcation of tumor cells from the stroma. The second group (uneven pattern) was marked by either a disorderly occurrence of the stromal network with distortion of the overall pattern, tumor cells arranged along an axis, or poor demarcation of tumor cells from the stroma with individual envelopment of tumor cells by the stroma. Approximately two-thirds of the patients (9/14) with the compartmentalizing sclerosis survived two years or more after diagnosis; most patients (10/11) with diffuse sclerosis died within two years. Compartmentalizing sclerosis, even pattern, was associated with a consistently favorable prognosis; the uneven pattern was not. This study indicates a marked variation in the survival of patients with diffuse histiocytic lymphoma with sclerosis and demonstrates that prognostic subgroups may be delineated by additional morphologic features.
Diffuse large cell lymphoma is frequently localized at the time of presentation, but the aggressive natural history of the disease in most patients has suggested that extensive and intensive radiation and/or chemotherapy is necessary to control this disease. We describe a patient who has remained free of disease for 20 years after simple excision of a diffuse large cell lymphoma localized to the right cervical region. Review of the biopsy material showed characteristic histological features suggestive of an orderly growth pattern of tumor cells as well as sclerosis. The clinical course of this patient after minimal therapy emphasizes the possibility of long survival with localized large cell lymphoma and suggests that the characteristic morphologic features observed in this case should be sought in other cases, since it may imply a favourable prognosis.
A factor inhibitory to PHA-induced lymphocyte blastogenesis was found to be present in the serum of a patient with advanced Hodgkin's disease and nephrotic syndrome. The inhibitory activity for both syngeneic and allogeneic lymphocytes was dependent on the presence of peripheral blood monocytes. The Raji-cell serum assay, as well as immunofluorescence and light and electron microscopy of the renal biopsy, showed no evidence of immune complexes. Nevertheless, a high serum IgE level as well as the finding that ultracentrifugation and heating at 56 degrees C significantly reduced the inhibitory activity (P less than 0.01) suggested the possibility that an immune complex might have mediated the suppressive activity. Treatment of the Hodgkin's disease with combined chemotherapy caused a marked reduction in the monocyte-dependent serum inhibitory activity which in turn coincided with a prompt remission of the nephrotic syndrome and marked regression of disease.
The clinical presentation of 71 untreated patients with Hodgkin's disease was studied in relation to immunohistochemically demonstrable lysozyme in the lymph node biopsy material. Sixty-one patients (86%) showed a positive staining reaction of varying degree, while ten (14%) showed no demonstrable lysozyme. The clinical features of lysozyme-positive patients differed markedly from those of lysozyme-negative patients. Stain-positive patients were younger (29 vs. 46), were more often in clinical Stage I or II disease (69% vs. 10%, P less than 0.001), and less frequently had constitutional symptoms (34% vs. 70%, P less than 0.02). Moreover, within the stain-positive group, patients who had the most intense staining reaction (mottling pattern) also had the most favorable clinical and histopathologic features at the time of diagnosis. The observations suggest that in Hodgkin's disease the lysozyme secretory activity of macrophage-histiocytes may be an important element of host resistance to neoplasia and that a depression of this secretory activity corresponds with disseminated disease.
The occurrence and pattern of cytoplasmic muramidase containing histiocytes were studied by the unlabeled antibody peroxidase-antiperoxidase method in biopsy material from patients with Hodgkin's disease, non-Hodgkin's lymphomas, and reactive hyperplasia. The majority of lymph nodes from patients with Hodgkin's disease, nodular lymphoma, and reactive hyperplasia gave positive staining reactions when tested in this manner. Differences in the staining pattern were observed for the different conditions studied. In general, stain positive cells occurred in one of the following four patterns: nodular, dispersed, aggregating without background stain, or aggregating with background stain (mottling pattern). The nodular and aggregating without background stain patterns were not specific and were seen in various conditions. The dispersed pattern, however, was observed only in some cases of non-Hodgkin's diffuse lymphomas, suggesting a subgroup of tumors characterized by active participation of reactive histiocytes. The mottling pattern was virtually limited to Hodgkin's disease. Since the mottling pattern appeared to be produced by virtue of a large amount of extracellular muramidase, the elevation of the serum muramidase level in Hodgkin's disease may be related to enzymatically active secretory histiocytes. Moreover, the mottling staining pattern was observed frequently in the lymphocytic predominance and nodular sclerosis type of Hodgkin's disease, but relatively infrequently in the mixed cellularity or lymphocytic depletion types, suggesting that the variation in histiocytic activity may be related to the course of the disease. The decreased staining reaction observed in the latter two categories could not be accounted for by a decrease in the numbers of histiocytic cells in hematoxylin and eosin stained sections, suggesting that release or synthesis may be defective in those unfavorable types of Hodgkin's disease.
Radionuclide ventriculography was used to diagnose the presence of a left-ventricular mural thrombus in a patient with left-ventricular aneurysm. Diagnostic features of the radionuclide study are described and correlated with postmortem findings.