Lacunar cells of nodular sclerosing Hodgkin's disease: an ultrastructural and immunohistologic study.

Tissues from 22 cases of nodular sclerosing Hodgkin's disease were studied by light and electron microscopy in conjunction with immunohistologic and cytochemical staining. The presence of lipid in the cytoplasm of lacunar cells suggested that this was responsible for the distinctive "lacunar" appearance of the cells. Marked morphologic similarities between "blast cells" resulting from mitogen stimulation of lymphocytes in vi-ro, immunoblasts seen in reactive lymphoid tissues, and mononuclear "Hodgkin's" cells in Hodgkin's disease suggested that all three cell types may result from lymphocyte transformation. It also seemed apparent that there was a developmental sequence from lymphocyte to transformed lymphocyte to the abnormal mononuclear Hodgkin's cell, with further progression, through increasing size and nuclear lobulation, to the lacunar cell or, alternatively, to the diagnostic Reed-Sternberg cell. This proposed sequence was supported by immunoperoxidase studies in which cytoplasmic immunoglobulin was demonstrated in mononuclear Hodgkin's cells, lacunar cells and Reed-Sternberg cells. The proposed relationship between these cells was also supported by the findings of both kappa and lambda chains in the same cells, a pattern not seen in reactive transformed lymphocytes.     

Malignant fibrous histiocytoma, myelomonocytic leukemia, and Hodgkin's disease arising in an elderly man

A 74-year-old man developed a locally invasive malignant fibrous histiocytoma of the scalp with multiple facial recurrences and concomitant hematopoietic dysplasia occurring over a 2-year period. One month prior to his death, his hematologic profile evolved into myelomonocytic leukemia. Mixed cellularity Hodgkin's disease involving mediastinal and periportal lymph nodes, which was not suspected antemortem, was discovered at autopsy. In the experience of the authors, this association of neoplasms is unique and raises the possibility in this case of an unidentified stimulus to neoplastic transformation of cells of histiocyte/monocyte origin.     

Mammary and extramammary Paget's disease. An immunocytochemical and ultrastructural study

Twenty-one cases of Paget's disease have been studied using histochemical, ultrastructural, and immunohistochemical methods. Eight of the tumors involved the nipple, and 13 were extramammary (11 vulvar and two anal). The antibodies used were directed against different classes of cytokeratin proteins, epithelial membrane antigen, carcinoembryonic antigen, gross cystic disease fluid protein-15, and S-100 protein. The findings of this study provide conclusive evidence that Paget's cells, regardless of their location, are adenocarcinoma cells. Intracytoplasmic mucin is scanty in Paget's cells within the nipple, but typically plentiful in the extramammary sites where the cells are frequently signet-ring cells. The common mechanism for the evolution of Paget's disease is extension of cells from an underlying carcinoma, but the possibility that some cases, particularly in the vulva, develop from intraepithelial precursors cannot be excluded.     

Atypical T-cell leukemia terminating Hodgkin's disease.

A case of Hodgkin's disease is described which developed into a terminal illness characterized by a malignant proliferation of T-cells. The leukemic cells, after optical and ultrastructural analysis, were distinct from those of myelomonocytic, acute lymphoblastic, chronic lymphocytic as well as prolymphocytic leukemia. Their relationship with the T-cell lineage seemed to be confirmed by a highly positive E-rosette test and by cytochemistry which showed focal positivity of acid phosphatase. The importance of this T-cell malignant proliferation is discussed, especially with regard to cellular interactions in Hodgkin's disease.     

Treatment-related leukemia in Hodgkin's disease: a multi-institution study on 75 cases

Hematological and cytogenetic characteristics of 75 cases of therapy-related acute non lymphoid leukemia (t-ANLL) occurring in Hodgkin's disease (HD) are analysed in this multi-institution study. Combined radio and chemotherapy had been given in 88 per cent of patients, either as adjuvant (44 per cent) or as salvage modality (44 per cent). Radiotherapy alone and chemotherapy alone had been given in 3 per cent and 9 per cent respectively. Eighty per cent of patients were in remission of HD and 71 per cent off-therapy while developing leukemia. The median latent time from remission of HD to leukemia was 34 months. The myeloblastic variety of leukemia accounted for 43 per cent of total cases; the myelomonocytic and monocytic for 17 per cent and 4 per cent, the promyelocytic and erythroblastic variants for 5 per cent and 7 per cent of t-ANLL. Twenty four per cent of cases were unclassifiable; one of these was TdT-positive. Dysplastic features of erythrocytic line were invariably present with circulating erythroblasts; defects of granulocytes, circulating megathrombocytes and micromegakaryocytes were also present. Bone marrow hypoplasia and marked fibrosis were documented in 47 per cent and 30 per cent of cases. Preleukemia heralded overt leukemia in 73 per cent of cases; 37 per cent had refractory anemia with no excess of blasts; 16 per cent of preleukemias were unclassifiable. Cytogenetics revealed chromosome abnormalities in 83 per cent of cases; 72 per cent presented chromosome 5 and/or 7 monosomy or partial deletion (5q- or 7q-) of the long arm (94 per cent in the combined modality therapy group). In 3 cases, a pure monosomy 7 was observed; in none 5q-alone. Response rate to conventional therapy was 14 per cent; low and high-dose cytarabine were of little benefit. Long-term CR (28 + and 16 + months) was achieved in 2 cases with allogeneic bone marrow transplantation (BMT) as first-line therapy. A better knowledge of t-ANLL in HD and new therapies, including BMT, may improve the prognosis of this late complication of intensive HD treatment.     

Hodgkin's disease terminating in a T-cell immunoblastic leukemia.

A patient who developed an immunoblastic leukemia of T-cell type two and one half years after initial diagnosis of mixed cellularity Hodgkin's disease, stage IIIB, is described. The patient's course was characterized by an initial 15-months remission following radiation therapy. A relapse of Hodgkin's disease was treated with intensive chemotherapy. Thirteen months later the patient entered a rapid terminal course with multiple organ infiltrates and a leukemic peripheral blood. The leukemic phase was characterized by a 55,000 WGC with 48% immunoblasts, greater than 90% of which marked as T-cells. Although acute myelogenous leukemia, acute lymphocytic leukemia, lymphosarcoma cell leukemia and other tumors have been described in Hodgkin's disease after intensive therapy, this is the first report of the unusual association of a T-cell immunoblastic leukemia with Hodgkin's disease.     

Ultrastructural and immunocytochemical localization of immunoglobulin synthesis in tumor cells in Hodgkin's disease.

An immunocytochemical and ultrastructural study using the Fab fragment of an anti-human Ig antibody labelled with peroxidase was carried out on affected lymph nodes from five Hodgkin's disease patients. The tumor cells (Reed-Sternberg cells and Hodgkin cells) showed an exclusively hyaloplasmic granular staining. By comparing these grains with ribisome staining. By comparing these grains with ribosome staining of the endoplasmic reticulum of plasma cells it could be suggested that they are free risobomes. This ribosomal Ig synthesis is a major argument for the B lymphocyte nature of Reed-Sternberg and Hodgkin cells. The total absence of vacuole staining allows us to conclude that these cells are not histiocytic or macrophage derivatives.     

Hairy cell leukemia. An immunologic and ultrastructural study.

A case of hairy cell leukemia in a 39-year-old man is reported. Hairy cells from the peripheral blood, spleen, and bone marrow had lambda-type immunoglobulin on their surfaces; those from the peripheral blood and bone marrow also had IgD on their cell membranes. Frozen sections of spleen reacted with IgGEA, but not IgMEA or IgMEAC markers. Transmission electron microscopy revealed ribosome-lamella complexes in cells from the spleen, but not the peripheral blood. Scanning electron microscopy demonstrated a spectrum of cell surface morphology with many cells characterized by ridges and ruffles. The significance of these findings is considered and it is suggested that the hairy cell is a B lymphocyte.     

Extraadrenal paragangliomas. An immunocytochemical and ultrastructural report

Although the majority of extraadrenal paragangliomas are nonfunctional, some of these tumors are associated with hormone production and clinical symptoms, notably hypertension. The authors have investigated 22 paragangliomas, five of which were diagnosed as clinically functional in a light microscopic immunocytochemical and electron microscopic study (nine cases). Histologically, all the paragangliomas exhibited similar features, with a "Zellballen" pattern of polygonal cells. All 22 cases were strongly immunoreactive to protein gene product 9.5 (PGP 9.5) antisera and moderately reactive to antineuron-specific enolase (NSE) sera. Ten cases (five functional) were focally immunoreactive to antichromogranin sera. Seven cases (four functional) were immunoreactive to neuropeptide Y and enkephalin antisera, and six (five functional) to tyrosine hydroxylase antisera. The clinically functional tumors expressed at least two of the antigens, enkephalin, neuropeptide Y, or tyrosine hydroxylase, whereas none of the 17 nonfunctional possessed more than one of these. Electron microscopic study revealed cells from all the nine cases studied to contain secretory granules. Granule sizes ranged from 100 to 280 nm and the morphologic examination of the secretory granules generally showed a dense core with a membrane-bound halo of variable size. Secretory granules were observed in the five functional cases and these were larger (220-280 nm) than those seen in the nonfunctional tumor cells (100-180 nm). Also, tumor cells from the functional cases contained numerous dilated mitochondrial profiles.     

Hodgkin's disease in an elderly patient with B-cell chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia worldwide. It is an indolent disease, almost exclusively of B-cell origin. Some CLLs evolve into a more aggressive lymphoid malignancy. The most common of these is Richter's syndrome. Transformation to acute lymphoblastic leukemia, plasma cell leukemia, multiple myeloma, or Hodgkin's disease (HD) may also occur. CLL patients are also at a significantly increased risk of developing a second malignant neoplasm later in life. One of the most common of these is HD. Herein, we report a case of HD in an elderly man with a history of B-cell CLL.     

Monocytic differentiation induced by 1,25 dihydroxyvitamin D3 in myeloid cells: an ultrastructural immunocytochemical study

We have studied, by ultrastructural morphology and immunocytochemistry, the alterations that occur in cells from the HL60 leukaemia cell line and from patients with CGL following incubation in vitro with 1,25(OH)2D3 for 2-5 days. The main morphological changes observed were in the nuclear shape, the development of autophagic vacuoles and the appearance of a population of small granules in the cytoplasm. These changes were associated with a significant reduction in MPO activity and increased expression of membrane antigens detected by the monocyte-specific McAb FMC17 and FMC32, as shown by the IGM at EM level, and a decrease in granulocyte-specific antigens demonstrated by the McAb FMC10. These observations suggest that promyelocytes and myelocytes could transform into monocyte-like cells and that this remodelling of cells was associated with autophagic digestion of cellular structures.     

Hodgkin's disease in siblings: a family study.

Hodgkin's disease may sporadically occur in more than one member of a family. A family in which two siblings were documented to have the nodular sclerosing form of the disease was studied for immunological competency, distribution of HL-A antigens, and Epstein-Barr virus (EBV) antibody titers. All family members examined, except the living individual with HD, had no significant abnormality in humoral and cellular immunity. HL-A antigens previously reported to appear in Hodgkin's disease with increased frequency were not found. Antibody titers to the viral capsid antigen of EBV were normal. Therefore, none of the genetically associated laboratory tests related to cancer (particularly Hodgkin's disease) were found in this family. The evidence from this family thus supports the probable importance of environmental factors in the etiology of Hodgkin's disease, particularly in the nodular sclerosis group.     

Characteristics of Sternberg-Reed, and related cells in Hodgkin's disease: an immunohistological study.

A panel of monoclonal antileucocyte antibodies was used in a study of Hodgkin''s disease (HD) to explore the phenotypic characteristics of Sternberg-Reed and related cells (collectively termed HD cells). Cryostat preparations of 31 lymph nodes and 2 spleens were obtained from 30 patients with active HD. The histological diagnoses were: lymphocyte predominance (LP), 4 patients; nodular sclerosis (NS), 22; mixed cellularity (MC), 2; lymphocyte depletion (LD), 2. The monoclonal antibodies used were: OKT3, T11, Leu-1 (pan T cell specific); Leu-3A (T "helper" specific); Leu-2A, OKT8 (T "suppressor" specific); immunoglobulin (Ig) antibodies: anti kappa and lambda light chains, anti mu and delta heavy chains; B1 (anti B lymphocyte); CA2-11 (anti HLA-DR); OKM1, Mo-2 (anti myeloid/monocyte); OKT9 (anti transferrin receptor); Leu-7 (anti "NK" cell) and J5 (anti common ALL antigen). Reactions with peanut lectin (PNL) were also studied. The reactions were developed using a modified "ABC" immunoperoxidase technique. Specific attention was paid to the cell surface phenotype and anatomical localisation of HD cells in relation to surrounding T and B lymphocytes. HD cells formed distinct "rosettes" with T cells of "helper" phenotype although in 3 cases (1: LP, 2: NS) Leu-7 positive cells formed a prominent component of these interactions. In partially involved lymph node and spleen, HD cells were prominently distributed in a perifollicular distribution. In addition follicular mantle zones were frequently infiltrated by HD cells, the degree of ensuing destruction being related to the extent of lymph node effacement by HD. In 2 cases (1: NS, 1: LD) HD cells expressed clear, positive reactions with B1 although in neither of these cases nor in any other instance, was surface Ig expressed on the HD cell surface. The great majority of HD cells reacted positively with both OKT9 and, as previously reported, with anti HLA-DR antibody. In addition, HD cells demonstrated intense surface and cytoplasmic staining with PNL. HD cells were negative with all other antibodies. On the basis of these findings, no lineage specificity can confidently be attributed to the HD cell. However, the pattern of immunohistological reactions suggest that it is related to a cell of B follicular origins.     

Leukocytic fibrinolysis in myelomonocytic leukemia.

A case of myelomonocytic leukemia is described in which an increase in primary fibrinolytic activity produced a severe hemorrhagic diathesis. The leukemic cells were demonstrated to be the source of the fibrinolytic activity. Utilizing a fibrin coated slide technique, the intact leukemic cells were shown to release their fibrinolytic activity and to induce local lysis. Intact leukocytes from normal subjects and other patients with acute leukemia of varied cell types were unable to release fibrinolytic activity although in some of the leukemic preparations, increased fibrinolytic activity was demonstrated after in vitro disruption of the cells.