Nucleoli of blood monocytes in malignant lymphoma. A morphometric study.

Morphometric methods were used to study the nucleolar ultrastructure of blood monocytes in 23 patients with Hodgkin's disease, 12 patients with non-Hodgkin's lymphoma, and 20 normal subjects. Nucleolar volume (Vn), surface area (Sn), volume fraction within the nucleus (VVn), surface-to-volume ratio, and number of nucleolar profiles per section were measured. The results were examined with the use of multivariate and univariate analyses of variance, and significant differences between the patient and normal groups were found. Compared with the normals, values for Vn, Sn, VVn and number of profiles per section were 16-20% smaller in the Hodgkin's monocytes and 19-32% smaller in those of the patients with non-Hodgkin's lymphoma. The changes in nucleolar ultrastructure may be related to the known mononuclear phagocyte dysfunction in patients with lymphoma.

Emperipolesis in a case of malignant lymphoma: electron microscopic and immunohistochemical investigation.

In the tissue sections of axillary lymph nodes surgically removed from a case of malignant lymphoma (non-Hodgkin's, diffuse, large cell type), many large cells were observed to contain lymphoma cells in their cytoplasm. From the findings of light microscopy in serial sections and electron microscopy, this phenomenon was confirmed to be "emperipolesis." By immunohistochemistry, the large cells that contained lymphoma cells possessed most of the monocyte/macrophage markers, whereas the lymphoma cells revealed some B-cell markers, suggesting that they were of germinal center cell origin. In a survey of the literature, we found no report describing emperipolesis in the tissue sections of malignant lymphoma. Although the precise mechanisms and biological significance of emperipolesis in the present case are not fully understood, the existence of some interactions between macrophages and lymphoma cells is suggested.

Expression of T-cell antigens on Reed-Sternberg cells in a subset of patients with nodular sclerosing and mixed cellularity Hodgkin's disease.

Expression of T-cell antigens by Reed-Sternberg (RS) cells has not been detected in most studies of Hodgkin's disease (HD). The authors employed an improved method of fixation (paraformaldehyde-lysine-periodate), which sharply defined cell borders and revealed T-cell antigens on RS cells in 8 of 30 (27%) cases of HD. Antigen-specific staining was confirmed by immunoelectron microscopy. RS cells expressed T11 (8/8 cases), Leu-3 or T4 (4/8 cases), Leu-4 or T3 (3/8 cases), but not other T-cell specific antigens (Leu-1, T8, T6, 3A1). RS cells were negative for leukocyte common antigen (LCA/T200), in contrast to positive LCA/T200 staining of RS-like cells in T-cell lymphomas. RS cells in all HD cases were positive for Ki-1 and/or Leu-M1 antigens. The percentage of RS cells expressing T-cell antigens was less than 20% (2 cases), 20-50% (3 cases), or greater than 50% (3 cases). This percentage and the specific T-cell antigens expressed varied in tissues from different sites in each of 2 cases. Expression of T-cell antigens by RS cells was found in nodular sclerosis (6 of 20 cases) and mixed cellularity (2 of 5 cases) but not in lymphocyte predominance (2 cases), lymphocyte depletion (1 case), or unclassified types (2 cases). Two cases of nodular sclerosis contained areas of necrosis surrounded by sheets of lacunar cells (syncytial variant of NSHD). Two other cases were associated with cutaneous lymphoma. One of these cases was mixed cellularity HD, which appeared to be confined to the skin. In a second case, tumor cells of similar phenotype (T4+, Ki-1+) were found in skin and lymph nodes of a patient with coexistent mycosis fungoides and HD. These results are consistent with an origin of RS cells from T cells in some cases of nodular sclerosing and mixed cellularity HD. They also suggest that the same cell type, an activated helper T-cell, is involved in the pathogenesis of both skin lesions and lymphadenopathy of some patients with coexistent mycosis fungoides and HD.

Hodgkin cells in freeze-fracture replicas.

Lymph nodes from six patients with Hodgkin's disease (three with the nodular sclerosing subtype, one with mixed cellularity and two with the lymphocyte-predominant subtype) were analysed by electron microscopy in freeze-fracture replicas and thin sections. Two main variants of Hodgkin cell could be identified in the nodular sclerosing and mixed cellularity subtypes. (1) Hodgkin cells with wide cytoplasm and short, smooth- and rough-surfaced tubular profiles of endoplasmic reticulum (ER) unevenly scattered in the cytoplasm. (2) Hodgkin cells with well developed rough ER. In freeze-fracture replicas the ER was seen to consist of both short and long tubules, some of the latter forming anastomoses with each other. Both cell types possessed branching cytoplasmic processes. A P-face rich in intramembrane particles (IMP) and an E-face with few IMP were common to both Hodgkin cell types. These cells do not, therefore, possess the membrane features characteristic of interdigitating reticulum cells, thus refuting the previously held belief that Hodgkin cells, in particular lacunar cells, are related to interdigitating reticulum cells. The cytoplasmic structures and membrane characteristics of Hodgkin cells in the lymphocyte-predominant subtype (L & H cells) are similar to other Hodgkin cells in that they may show a high content of rER, and the P-face of these cells contains more IMP than the E-face. Both characteristics support the theory put forward in the literature (based on immunohistochemical findings) that these are lymphoid cells (immunoblasts or immature plasma cells).

Hodgkin's disease accompanied with thymoma.

An autopsy case of Hodgkin's disease accompanied with thymoma is reported. The patient died of acute interstitial pneumonitis 9 years after the development of lymphadenopathy. On post-mortem examination thymoma was recognized. We believe that the present case is a very rare Hodgkin's disease complicating thymoma. The occurrence of second neoplasia in Hodgkin's disease is also discussed.

Ultrastructural localization of Leu M1 in Reed-Sternberg cells and normal myeloid cells.

An antigen Leu M1 has been localized to myelomonocytic cells and Reed-Sternberg cells by light microscopic immunocytochemical studies. We used both pre- and post-embedding immunoelectron microscopy to define the ultrastructural distribution of this antigen. Post-embedding techniques heavily labeled the granules of polymorphonuclear leukocytes and the nonspecific granules of eosinophils. At high concentrations there was labeling of the specific granules of the eosinophil. The antibody consistently labeled the perinuclear granules and vesicles of Reed-Sternberg cells. Some Reed-Sternberg cells also exhibited labeling of the endoplasmic reticulum, suggesting that these cells have the capacity to synthesize this antigen. Although plasma membranes were labeled with the post-embedding technique, these structures were most heavily labeled with the pre-embedding method. These results indicate that Leu M1 is synthesized and packaged by Reed-Sternberg cells and represents an integral structural component of these cells.

Hodgkin's disease presenting with superficial lymph nodes and tumors of the scalp.

Invasion of the skin by malignant cells in Hodgkin's disease is a rare occurrence and less common than skin involvement in non-Hodgkin's lymphoma. We describe a 36-year-old man with Hodgkin's disease who presented with superficial lymph nodes and tumors on the scalp as initial clinical findings. Biopsy of a tumor of the scalp showed a diffuse dermal infiltrate composed of polynuclear neutrophils and eosinophils, large lymphocytes, and Sternberg-Reed cells. Ultrastructural examination of the skin biopsy specimens demonstrated the characteristic morphology of the Sternberg-Reed cells.

[Cytological verification of histological variants of lymphogranulomatosis]. / O tsitologicheskoi verifikatsii gistologicheskikh variantov limfogranulematoza.

Punch biopsies of the affected lymph nodes from 60 patients with lymphogranulomatosis were examined in order to verify cytologically the histological variants of the disease. It was established by a correlation between the cytological picture and histological diagnosis that the morphological structure of Berezovsky--Sternberg cells is the basis for the cytological verification of the lymphogranulomatosis histological type. Cells with polymorphic nuclei containing large nucleoli are characteristic of a mixed-cell variant of the tumour, So-called lacunar cells with a clear cytoplasm and multiple small monomorphic nuclei with small nucleoli are specific for a nodular variant. Pronounced cell polymorphism is characteristic of the so-called reticular type with suppression of lymphoid tissue; this type of lymphogranulomatosis is verified tentatively if an essential number of lymphoid cells are present in smears.

[Ultrastructural study of 36 lymph node sites of Hodgkin's disease]. / Etude ultrastructurale de 36 localisations ganglionnaires de maladie de Hodgkin.

The authors report their ultrastructural findings of 36 involved lymph-nodes in Hodgkin's disease (HD), before any treatment. More than 400 tumour cells were studied. An analytical study was carried out on the different aspects presented by the nuclei (uni or multi-lobated); the nucleoli (compact, reticulate or dispersed); and the cytoplasm (immunoblastic, complex, intermediate). No cellular structure evoking phagocytic activity with digestion, and consequently an eventual histiomonocytic origin, could be detected even on serial sections. The presence of lipid inclusions, sometimes of glycogen, as well as certain peculiar structures are described and discussed. The ultrastructural aspects could be easily correlated with the different types of tumour cell described in HD using light microscopy. The various kinds of cells which could could be detected in the same lymph node, may correspond to a real tumour cell lineage, consisting, firstly, of a cell of immunoblastic type with a mono- or bilobated nucleus, then an intermediate type with a bilobated or multisegmented nucleus, and finally a complex cell type with a multisegmented nucleus. The lacunar cells are characterised by a fragile hyaloplasm, without cellular organelles at their periphery, these being concentrated around the nucleus. This special organisation explains the aspects observed in light microscopy. However, no explanation could be offered to understand this particular aspect of the cytoplasm. The ultrastructural characteristics of the Reed-Sternberg cells and their variants did not allow a precise cellular origin to be proposed. The absence of phagolysosomes pleads against a histiocytic origin. However their similarity of the interdigitated reticular cells did not seem sufficient to propose this origin. The likeliness of the cytoplasm of cells with mono- or bilobated nuclei with that of immunoblasts, constitutes the most interesting morphological feature. This fact, associated with the appearance of immunoblasts similar to Reed-Sternberg cells of infectious mononucleosis, suggests a lymphoid origin. The study of the reactive cells around the tumor cells did not allow any consequences to be drawn. One could simply note that the Reed-Sternberg cells and their variants were surrounded by lymphocytes, forming a kind of crown. No etiological agent could be detected. These data are compared to those of other publications, and discussed. This ultrastructural study, therefore, does not offer the solution to most of the questions which still remain to be answered as to the origin of the Reed-Sternberg cells.(ABSTRACT TRUNCATED AT 400 WORDS)

The reactivity of Reed-Sternberg cells with monoclonal antisera at thin section and ultrastructural levels.

In an attempt to improve the morphology of Reed-Sternberg cells after immunochemical procedures, the biotin-avidin technique has been used. Satisfactory morphology was obtained at the level of both light and electron microscopy. Reed-Sternberg cells failed to react with a monoclonal antimonocyte serum but gave positive results with anti-1a and FMC7, a monoclonal anti-B cell serum. Positive results were also obtained with FMC1 and B1 both of which are monoclonal B cell antisera.

The ultrastructural heterogeneity of the Reed-Sternberg cell and its resemblance to monocyte-macrophage differentiation in vivo.

Hodgkin's disease is a malignant neoplasm that shares many histologic features with granulomatous diseases. We have examined 11 cases of Hodgkin's disease, representing the spectrum of histologic types, using transmission electron microscopy and have compared the morphology of Reed-Sternberg cells to that of the developmental stages described for monocyte-macrophage differentiation in vivo. Ultrastructurally, a close parallelism exists between the cells that typify granulomatous inflammation and Reed-Sternberg cells. It is our contention that the heterogeniety among Reed-Sternberg cells in all types of Hodgkin's disease parallels the diversity of the monocyte-macrophage system.

Reed-Sternberg cells cultured from morphologically unidentifiable precursors in the blood of patients with Hodgkin's disease.

In order to examine whether morphologically unidentifiable precursors of Reed-Sternberg cells (RSC) may circulate in the blood of patients with untreated Hodgkin's Disease (HD), mononuclear leukocytes were isolated from the blood of 33 consecutive patients and cultured in soft agar. Abnormal colonies containing multinucleated giant cells developed in the specimens of 12 patients. These cells had the light and electron microscopic appearance of RSC. They were positive for alpha-naphthyl acetate and alpha-naphthyl butyrate esterases, acid phosphatase and lysozyme, bespeaking their monocyte/macrophage lineage. The observations suggest that unidentifiable precursors of RSC could be responsible for hematogenous spread of the disease in some cases. Moreover, since RS-like cells developed in the specimens of 8 patients with stage I and II HD, it may be useful to evaluate whether soft agar colony culture would yield data of prognostic significance in patients with early disease.