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H J Ree

Publications and source records attributed to H J Ree.

At least 19 recordsLinked to original sources

Expression of cell adhesion molecules associated with germinal center in Hodgkin's disease: an immunohistochemical study. The germinal center related complex and histologic subtypes.

BACKGROUND: Of the four elements known to be associated with germinal center formation--B-cells, follicular dendritic cells, T-cells, and the cell adhesion molecules--the first three have been well studied in Hodgkin's disease, especially the nodular lymphocytic predominance subtype, established as a tumor of germinal center origin. However, no study has been done on the expression of the cell adhesion molecules associated with germinal center formation in Hodgkin's disease. METHODS: Using the avidin-biodin peroxidase complex method, we studied the staining patterns for CD11a (lymphocyte function-associated antigen 1), CD54 (intercellular cell adhesion molecule 1), and very late antigen 4 (VLA-4) in frozen sections from 24 cases of Hodgkin's disease, along with those for follicular dendritic cell and cell surface markers for lymphocytes. RESULTS: Reed-Sternberg cells and their variants and histiocytic cells stained for CD54. Lymphocytes stained for CD11a. Lymphocytes either formed patchy aggregates or dispersed without forming aggregates. Aggregating lymphocytes expressed CD20 (L-26), whereas dispersed, nonaggregating lymphocytes expressed CD3/CD4, or CD3/CD8. Extracellular matrices of these CD20+ B-cell aggregates stained for CD54, VLA-4, and follicular dendritic cells. CD54 staining revealed four patterns of reaction products deposits: discretely patchy, confluent, predominantly diffuse, and diffuse only. The discrete-patch predominance pattern was seen in the lymphocytic predominance type, both nodular (n = 3) and diffuse (n = 2), and in classic nodular sclerosis with broad collagen bands (n = 4). The confluent pattern was seen in tumors with features of cellular-phase nodular sclerosis versus mixed cellularity type (n = 3). The predominantly diffuse was observed in the remainder of nodular sclerosis type with infrequent, narrow collagen bands (n = 5), in cellular-phase nodular sclerosis (n = 1), in cellular-phase nodular sclerosis versus mixed cellularity type (n = 2), and in mixed cellularity (n = 2). The diffuse-only pattern occurred in mixed cellularity with abundant fibrohistiocytoid stromal cells (n = 2). CONCLUSIONS: The cell adhesion molecules associated with germinal center formation were expressed in the great majority of cases of Hodgkin's disease. The expression was closely associated with the occurrence of distinctive CD20+ B-cell aggregates and follicular dendritic cell networks, forming a germinal center-related complex, and the presence of the complex correlated with nodular sclerosing features.

Antigens, CD

The number of CD1a+ large low-density cells with dendritic cell features is increased in the peripheral blood of HIV+ patients.

Employing a discontinuous Percoll gradient following Ficoll-Hypaque separation of peripheral blood mononuclear cells from normal subjects (n = 14) and patients with HIV-1 infection (n = 50), we separated a population of low-density cells consisting of monocytoid cells, lymphocytes, and some granulocytes. In cytospin preparations, less than 5% of the monocytoid cells were positive for nonspecific esterase and CD14. However, CD1a was positive in 5-20% of these cells. Ultrastructurally, CD1a-labeled immunogold particles were demonstrated on the monocytoid cells which bore some features of dendritic cells. Flow cytometry of the low-density cells identified a subset of buoyant, large cell population, which excluded lymphocytes. This large low-density cell (LLDC) population was significantly expanded in patients with HIV infection and comprised 32.3 +/- 21.3% of low-density cells compared to 7.0 +/- 2.8% in normal subjects (P < 0.0001). Of the LLDC population 45.2 +/- 23.4% were CD1a+ in patients compared to 17.5 +/- 13.3% in normal subjects (P < or = 0.0001). HLA-DR and HLA-DQ were coexpressed in approximately 70 and 50% of these CD1a+ LLDC, respectively. A simple nonculture assay method employed by us facilitates rapid screening of infected blood specimens for the CD1a+ large low-density cells with dendritic cell features, which could be an additional parameter to monitor HIV disease progression.

Adult

Intercellular adhesion molecule-1 (ICAM-1) staining of reactive and neoplastic follicles. ICAM-1 expression of neoplastic follicle differs from that of reactive germinal center and is independent of follicular dendritic cells.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is expressed on follicular dendritic cells (FDC), and the ICAM-1/LFA-1 pathway is essential for affinity selection of activated B-cells in germinal centers (GC). The expression of ICAM-1 has been studied by immunostaining methods in GC, but not in neoplastic follicles (NF). METHODS: The authors studied the expression of ICAM-1 by the avidin-biotin-peroxidase complex (ABC) method with frozen sections in GC of reactive nodes (n = 22) and NF of follicular lymphomas (n = 19), in comparison with FDC staining. RESULTS: GC stained uniformly for ICAM-1, with staining intensity varying little from node to node, and follicular borders were well demarcated from the surroundings. Endothelial cells within GC did not stain whereas those outside stained strongly. In contrast, NF stained variably from tumor to tumor, and in any given tumor. Characteristically, follicular borders were not demarcated, and stained areas were difficult to define due to the lack of demarcation, with the exception of large cell type with diffuse areas (n = 2). Endothelium of intrafollicular vessels stained prominently (12 of 19), and appeared to contribute to the staining intensity of the follicles. FDC staining revealed a meshwork pattern in GC which was similar to that of ICAM-1. The FDC mesh-work pattern was present in 15 tumors. The pattern was remarkably uniform with sharply defined borders, which contrasted starkly to the variable staining and lack of follicular borders in the ICAM-1 stain of the same tumors. CONCLUSIONS: The staining pattern of follicles for ICAM-1 was similar to that for FDC in reactive nodes, but distinct from the latter in follicular lymphomas. An appropriate expression of ICAM-1 appears to be essential for normal GC, as the alteration of the expression coincides with the malignant transformation of GC. The altered expression of ICAM-1 may be useful in distinguishing NF from reactive GC.

Adolescent

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells.

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.

Adult

The Lewis X antigen. A new paraffin section marker for Reed-Sternberg cells.

Using a monoclonal antibody specific to the Lewis X antigen (anti-Lex), the authors studied 103 cases of Hodgkin's disease (HD) in comparison with 57 cases of non-Hodgkin's lymphoma (NHL); three cases of granulocytic sarcoma (GS); two cases of malignant histiocytosis (MH); one case of monoblastic leukemia (ML); one case of interdigitating reticulum cell sarcoma (IRCS); six cases of histiocytosis X (HX); one case of reticulohistiocytoma (RH); 44 various reactive conditions of the lymph node (LN). Reed-Sternberg and related (R-S) cells stained selectively in 80 of 92 cases of HD (87.0%), excluding 11 cases of lymphocyte predominance type. The stain was better in B-5-fixed specimens than in formalin-fixed specimens, showing a dense deposit of reaction products at a paranuclear site and on the cell surface. The staining results were compared with those of Leu-M1 and found to be superior both qualitatively and quantitatively (detection rate of R-S cells: 87.0% versus 68.5% of Leu-M1). Granulocytes, rare epithelioid histiocytes, and some endothelial and/or erythrocytes also stained with anti-Lex. The stain had positive results in three cases of GS showing a diffuse cytoplasmic staining pattern. Of NHL, two of 29 peripheral T-cell lymphomas stained to show rare paranuclear deposits without cell surface staining. The stain had negative results in MH, ML, IRCS, HX, and RH. Of 45 reactive LN, minute subcapsular collections of Lewis X+, altered-appearing Langerhans'-like cells, were observed in all ten LN from human immunodeficiency virus (HIV)-associated persistent generalized lymphadenopathy (PGL). The stain had negative results in all other various reactive conditions of LN. In conclusion, Lewis X staining is useful as a marker for R-S cells in paraffin sections with staining results superior to those of Leu-M1. Lewis X staining also detects subcapsular clustering of altered-appearing Langerhans'-like cells in PGL, which has not been described previously and warrants additional study.

Acquired Immunodeficiency Syndrome

HIV-associated Hodgkin disease: a clinical study of 18 cases and review of the literature.

Intermediate- and high-grade B-cell non-Hodgkin lymphoma (NHL) occurring in a human immunodeficiency virus (HIV)-infected patient is considered diagnostic of the acquired immunodeficiency syndrome (AIDS). Other neoplasms (both hematopoietic and nonhematopoietic) have also been reported in patients with HIV infection, although none except Kaposi sarcoma carries the same diagnosis of AIDS as B-cell NHL in an HIV-infected host. There have been previous reports in the literature of Hodgkin disease (HD) in HIV-infected patients. We describe our clinical and pathological experience with HD from 1984-1989, in 18 patients with documented HIV infection and also review the literature on HD in HIV-infected patients. Almost all patients described herein presented with advanced disease and mixed cellularity histology and did very poorly despite some good initial responses to therapy. By statistical analysis, we found that the patients with HIV-associated HD had a strong tendency to be outside the age range seen in non-HIV-associated HD (P less than 0.005). We also discuss the possible relationship between HIV and HD and consider whether HIV-associated HD, like B-cell NHL, is a manifestation of AIDS.

Acquired Immunodeficiency Syndrome

Non-Hodgkin's lymphomas of the gastrointestinal tract. An evaluation of paraffin section immunostaining.

Although the gastrointestinal (GI) tract is the most common site of primary extranodal lymphomas, the lineage of these tumors has been controversial. The authors used paraffin-reactive antibodies detecting markers of B-, T-, histiocytic, and epithelial cells to study 34 non-Hodgkin's lymphomas of the GI tract for which unequivocal frozen-section immunophenotypine was available as a control to determine whether these antibodies are reliable in the study of these tumors. Frozen-section studies revealed 31 tumors of B-cell origin and three T-cell tumors. Paraffin-reactive antibodies confirmed B-cell lineage in 28 of the 31 cases, with equivocal results in the remaining three. Only one of the T-cell lymphomas was identified in paraffin studies. Our results indicate that paraffin-reactive antibodies can reliably identify most B-cell lymphomas in the GI tract but may be unreliable in the detection of lymphomas of T-cell origin.

Adult

Paraffin section markers for Reed-Sternberg cells. A comparative study of peanut agglutinin, Leu-M1, LN-2, and Ber-H2.

Hodgkin's disease (HD) is sometimes difficult to distinguish from non-Hodgkin's lymphomas, and a reliable marker for Reed-Sternberg and related (R-S) cells in paraffin sections would be useful. Ninety-one cases of HD with PNA, anti-Leu M1, and LN-2, and 90 cases with Ber-H2 were studied. The staining results were evaluated independently. R-S cells stained positively with one or more of the reagents in all cases. PNA staining was positive in 78 cases (85.7%); Leu M1, 63 (69.2%); LN-2, 71 (78.0%); and Ber-H2, 80 cases (88.9%). Positively stained cells were readily recognized in 71 cases (91.0%) of PNA+, 51 (80.9%) of Leu M1+, and 51 (71.8%) of LN-2+ and 71 (88.7%) of Ber-H2+ cases; the cells were found only after careful search in the remaining cases. Sixteen cases of peripheral T-cell lymphoma (large cell type, ten; mixed, five; unclassifiable, one) were also stained. Tumor cells did not stain with PNA or anti-Leu M1 in any of the 16 cases but did stain positively with LN-2 in four and with Ber-H2 in five. Thus, the detection rate of R-S cells was the highest with Ber-H2, closely followed by PNA. PNA, however, stained the largest number of R-S cells per case, and the results were least affected by the type of fixative employed. Staining of peripheral T-cell lymphoma appeared to be nil or extremely rare with PNA and Leu M1, whereas it was not uncommon with Ber-H2 and LN-2. In conclusion, to facilitate the detection of R-S cells in paraffin sections, the application of a panel of three markers, PNA, Leu M1, and Ber-H2, appears to be necessary at this point in time.

Antigens, Differentiation

Expression of sialylated Leu-M1 antigen in histiocytosis X.

The purpose of this study is to determine the versatility of the monoclonal antibody anti-Leu-M1 in histiocytosis X diagnosis. This antibody recognizes an unsialylated lacto-N-fucopentaose III (hapen X) carbohydrate moiety that is linked to the cell membrane protein in interdigitating reticulum cells and Langerhans' cells. Previously, the authors have shown that anti-Leu-M1 can be used to stain Reed-Sternberg cells, which are likely related to interdigitating reticulum cells. In this study, the authors tested the usefulness of anti-Leu-M1 in staining formalin-fixed and paraffin-embedded tissue sections from eight patients with histiocytosis X. For staining of histiocytosis X cells, unlike Reed-Sternberg cells in Hodgkin's disease, neuraminidase treatment was required for removal of sialic acid residues from the Leu-M1 antigen. The staining characteristics of anti-Leu-M1 in histiocytosis X cells resembled those of normal Langerhans' cells and lymphocyte and histiocyte variants (L & H cells) in the lymphocyte-predominant type of Hodgkin's disease. The significance of sialylation of Leu-M1 antigen in histiocytosis X cells has yet to be determined in order to correlate the prognosis of the disease. The authors suggest that anti-Leu-M1 used together with neuraminidase treatment is a valuable tool in the diagnosis of histiocytosis X when electron microscopy or frozen sections for OKT6 immunostaining are not available.

Adult

Inflammation and/or necrosis of tumors cannot account for fever in most febrile patients with Hodgkin's disease.

Inflammation and/or necrosis (I/N) of the tumor are generally believed to be a cause of fever in patients with Hodgkin's disease. However, there have been few studies in the literature which can corroborate this common belief. Inflammation and/or necrosis were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (57 febrile and 83 afebrile). In 37 of the 140 tumors I/N were readily observed; 18 were from febrile patients, and 19 from afebrile. Thus, it is evident that I/N cannot account for fever in the majority of febrile patients, necessitating an alternative explanation. Among the patients with I/N of their tumor, fever occurred most often in male patients and in virtually all patients who had histologic types other than nodular sclerosis. However, it was peculiarly absent in the great majority of patients whose tumors were of the nodular sclerosis type. This paradoxic inverse correlation of fever with I/N of tumors in patients with the nodular sclerosing histologic type has not been described previously.

Biopsy

Stromal macrophage-histiocytes in Hodgkin's disease. Their relation to fever.

Morphologic variations of Concanavalin A-binding histiocytes were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (72 asymptomatic, and 68 with constitutional symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Three morphologic types of stromal histiocytes were recognized: medium-sized cells similar to those seen in reactive follicles, characterized by distinct cytoplasm and cell borders, and uniform nuclei (Type A); damaged-appearing Type A cells marked by rarefied or ragged cytoplasm, disrupted or indistinct cell borders, and varying sized nuclei (Type B); and large spindling or stellate cells (Type C). Type A cells were predominant in 52 patients; Type B cells in 51; Type C cells in seven; and Type A cells were mixed with Type B in 30. Fever was present in one of 52 patients (1.9%) with Type A predominance; 43 of 51 (84.3%) with Type B cell predominance; none of seven (0%) with Type C predominance; and 13 of 30 (43.3%) with mixed Type A and B cells. Logistic regression analysis of the data showed that the association of fever with Type B cell predominance was highly significant, and was not attributable to the known association of fever with other variables. Morphologic evidence suggests that fever in Hodgkin's disease may be a clinical manifestation of damaged macrophage-histiocytes rather than an acute-phase response of inflammatory or immune reaction.

Adolescent

Anti-interleukin-1 reactive cells in Hodgkin's disease.

Constitutional symptoms (or B-symptoms) of Hodgkin's disease may be mediated by interleukin 1 (IL-1), a product of macrophage-histiocytes. To further study this relation, the authors examined the cells that reacted with anti-human IL-1 antibody in biopsy specimens from 140 untreated patients with Hodgkin's disease (72 asymptomatic patients and 68 with B-symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Anti-IL-1 reactive cells were observed in 62 cases. A positive staining reaction was observed in three types of cells: Reed-Sternberg and related (R-S) cells (33 cases); small to medium cells of undetermined origin (18); and granulocytes (11). The staining was negative in 78 cases, including 42 with B-symptoms. The majority of tumors (27/33) with positively stained R-S cells were from asymptomatic patients. Most tumors (14/18) with positively stained small to medium sized cells were from patients with B-symptoms. Large numbers of granulocytes were positively stained in five asymptomatic patients and six with B-symptoms. The immunohistochemical demonstration of IL-1-bearing cells in tumors does not correlate with the manifestation of constitutional symptoms in Hodgkin's disease.

Histocytochemistry

Concanavalin A-binding histiocytes in Hodgkin's disease. A predictor of early relapse.

Staining with Concanavalin agglutinin (Con A) reveals a far greater number of macrophage-histiocytes (M-H) in paraffin sections than any other staining method. With Con A staining, the shapes of stromal M-H are clearly visualized, thus enabling a study of their morphologic variations. Con A staining patterns were also unchanged in specimens left at room temperature for 24 to 28 hours before fixation. The appearance of Con A-binding histiocytes was studied in tumors, recurrent as well as original, of 18 patients with biopsy-proven early relapse (within 26 months of diagnosis), and compared with those of 26 patients who were in complete remission (lasting 48 months at the minimum). The early-relapse patients were diagnosed from 1977 through 1984, and all received intensive combination chemotherapy. The relapse-free patients were treated in various manners, and included six patients diagnosed in the 1960s who were treated with radiation alone. Three forms of Con A-binding histiocytes were easily recognized: medium-sized cells similar to those seen in reactive follicles, characterized by uniform nuclei and distinct, abundant cytoplasm (Type A); cells of varying size and shape with altered cytoplasm, rarefied and ragged with indistinct cell borders, or globular (Type B); and large cells, stellate or spindling (Type C). Large numbers of Type A cells were present in all tumors of the relapse-free patients but were virtually absent in the original and recurrent tumors of the early-relapse group. Conversely, Type B cells were rare in the relapse-free group, but were the most common type in the patients with early relapse. Type C cells were not seen in the former group, but were present in the latter. These observations suggest that the morphologic variations of Con A-binding histiocytes in Hodgkin's disease are associated with tumor behavior. Con A staining, which can best depict stromal histiocytes in paraffin sections, may be used to identify patients at a high risk of early relapse.

Adult

Peanut agglutinin. A useful marker for histiocytosis X and interdigitating reticulum cells.

We studied the peanut agglutinin (PNA) staining patterns of histiocytosis X (H-X) (three cases, including one case of Letterer-Siwe disease) and well-characterized cases of malignant histiocytosis (two cases) and monoblastic leukemia (one case) in paraffin-embedded specimens. H-X cells showed staining identical to that of interdigitating reticulum cells, with unique paranuclear and cell surface deposits of reaction products. Thus, H-X cells were easily distinguished from benign macrophage-histiocytes, which show diffuse cytoplasmic staining, and malignant cells of malignant histiocytosis and monoblastic leukemia, which did not stain with PNA, PNA staining proved more useful than Leu-M1 antibody for this purpose, since neither interdigitating reticulum cells in ten reactive lymph nodes nor Langerhans'-type cells in three cases of H-X were stained with Leu-M1 antibody. These observations support a close relationship between H-X cells and interdigitating reticulum cells, and demonstrate the usefulness of PNA for the identification of these cells in paraffin-embedded material.

Adult