Ribosome-lamella Complexes Research Articles

Ribosome–Lamella Complexes in the Peripheral Blood of Patients with Chronic Lymphocytic Leukemia are Associated with Serological Immune Deficiency

The ribosome–lamella complex (RLC) is a cylindrical structure composed of different numbers of circular lamellae with associated particles, regarded as ribosomes, around a central core. Structures resembling RLC, but lacking the typical mature appearance of RLC, have been called pre-RLC. The authors have found RLCs and pre-RLCs in peripheral lymphocytes of 3 patients with chronic lymphocytic leukemia (CLL). The fact that CLL patients with RLCs were in early Rai clinical stages, had good clinical prognostic factors, and did not require immediate therapy indicates that RLCs occurred in the early course of some cases of CLL. Moreover, the presence of RLC was associated with hypogammaglobulinemia M.

Ribosome–Lamella Complexes in Injured Podocytes: Description of a Case and Review of the Literature

Ribosome-lamella complexes (RLCs) are mainly observed in a variety of hematological disorders and occasionally in solid neoplasms and in nonneoplastic diseases. These intracytoplasmic organelles are held to arise from rough endoplasmic reticulum, but, in agreement with more recent literature data, their function is still unclear. Ultrastructural analysis of glomeruli from a patient with focal segmental glomerulosclerosis secondary to metabolic syndrome disclosed significant foot process loss and abundant cytoskeletal proteins in major podocyte processes; two of the latter also displayed RLCs. This is the second report of RLCs in human renal glomerulus. Their close association with cytoskeletal proteins and lysosomes suggests a relationship with abnormal protein biosynthesis.

Ribosome–Lamella Complex Precursors in Acute Monocytic Leukemia: A Study of 6 Cases

The ribosome–lamella complex (RLC) is a cylindrical structure composed of annular lamella associated particles, regarded as ribosomes, around a central core, which is best known in hairy cell leukemia. RLC has been presumed to originate from aggregating rER and ribosomes. Incomplete and maturing RLC structures have been called RLC precursors (pre-RLC). The present paper investigates the various architectural aspects of pre-RLC and the ultrastructural characteristics of the blasts in 6 cases of acute monocytic leukemia (M5) in which these structures occur. Blasts bearing pre-RLC contained irregular nuclei with less heterochromatin and a prominent nucleolus, and many cytoplasmic organelles in an abundant cytoplasm. The findings indicate that pre-RLC might result from an asymmetrical differentiation of organelles in blasts associated with expression of CD117 and CD56 but default of CD14 in M5.

Ribosome-lamella complex in aggressive solitary fibrous tumour of the meninges

Approximately 60 cases of solitary fibrous tumour (SFT) have been reported in the meninges [6]. Only a few cases have been malignant with local recurrences being the most common manifestation [2, 4, 6]. We report the biopsy and autopsy findings of a malignant SFT demonstrating multiple intracranial recurrences over a 17-year period, meningeal spread and invasion into brain tissue. The presence of ribosomelamella complexes (RLC) in an SFT is described for the first time. In 1985 a 59-year-old man presented with dizziness. A left-sided tentorial tumour compressing the cerebellum was completely removed. A recurrent tumour was subjected to surgery 13 years later. The patient died from acute myocardial infarction in 2002, 4 days after surgical resection of a leptomeningeal tumour compressing the cervical portion of the spinal cord (C7 level). Samples from the three tumours removed over the 17year period were fixed and embedded in paraffin wax according to our routine protocol. In addition to routine stainings, immunohistochemical analyses were performed using primary antibodies against the following epitopes: CD34 (Novocastra Laboratories, Newcastle upon Tyne, UK), bcl-2 (Novocastra), desmin (Dako, Glostrup, Denmark), epithelial membrane antigen (EMA, Novocastra), S-100 (Dako), muscle actin (Dako) and Ki67 (Dako). The use of McDowell’s fixative precluded successful Ki67 immunostaining of the oldest biopsy specimen. Electron microscopic examination was performed in all cases. The histological appearances of the three surgical samples were almost identical. The tumours were composed of elongated cells arranged in fascicles between prominent eosinophilic bands of collagen (Fig. 1). No whorls, psammoma bodies, or necroses were observed. Mitoses were absent in the original tumour, whereas the first tentorial recurrence in 1998 demonstrated seven, and the intraspinal tumour from 2002 ten mitoses per ten high-power fields. Immunohistochemical analyses demonstrated strong and uniform expression of CD34 and bcl-2. Scattered cells were positive for desmin. All samples were negative for EMA, S-100 and muscle actin. Approximately 5% of the cells in the recurrence from 1998, and 10% of the cells in the intraspinal tumour from 2002, expressed Ki67. Electron microscopic examination of the tumours from 1998 and 2002 showed cells without basal laminas connected by desmosome-like structures and surrounded by collagen fibres. Interdigitating cytoplasmic processes, typical of meningiomas, were not observed. The cytoplasm of the spindle-shaped tumour cells contained prominent rough endoplasmic reticulum (RER) arranged in concentric, multilaminar structures consistent with RLCs (Fig. 2). The RLCs were numerous and found in more than 50% of the tumour cells. Similar structures were not observed in the original tumour. Autopsy findings demonstrated four tumours in the posterior fossa; a small recurrence of the left-sided tentorial tumour (diameter 0.8 cm) and three leptomeningeal tumours (2.1, 2.0 and 0.3 cm, respectively) outside the original operation field. Two of the latter compressed the brain stem (Fig. 3). A darker area inside the left inferior colliculus was noted. The histopathological findings in all tumours diagnosed at autopsy were identical to those in the surgical specimens described above. Microscopy of the darker area of the left inferior colliculus showed an identical tumour within the brain tissue (Fig. 4). Mitoses were not observed in any tumour. The Ki67-index was less than 1%, but the other immunohistochemical findings were D. Scheie (&) AE F. P. Reinholt AE K. Skullerud Department of Pathology, Rikshospitalet-Radiumhospitalet HF, 0027 Oslo, Norway E-mail: david.scheie@rikshospitalet.no

Ribosome-Lamella Complex of Leukemic Cells in a Patient with Aggressive NK Cell Leukemia

A 36-year-old male was admitted to the hospital with anemia and leukopenia. A bone marrow specimen revealed the proliferation of leukemic cells with flower-like nuclei observed in adult T-cell leukemia. The leukemic cells were positive for HLA-DR, CD2, CD7, and CD56. A diagnosis of aggressive NK cell leukemia was made, the patient was treated with induction chemotherapy and cord blood stem cell transplantation, and he is well now. Seen with electron microscopy, some leukemic cells had ribosome-lamella complexes (RLC). This is the first reported case of leukemic cells with flower-like nuclei seen with light microscopy and RLC seen with electron microscopy.

Stages of Development of the Ribosome—Lamella Complex: An Ultrastructural Study

Ribosome-lamella complexes (RLC) are intracytoplasmic organelles observed in a wide variety of disorders, but mostly in hematologic malignancies. Although their close topographic relationship with rough endoplasmic reticulum (RER) suggests their derivation from it, their development and functional role are unclear. Their maturation phases were studied in 20 cases (19 hematologic neoplasms and 1 parathyroid adenoma) where electron microscopy had evidenced their presence. In 19 of these cases, RLC were in an advanced stage of maturation, whereas in one (acute monoblastic leukemia) they were observed in the early stages of development and appeared to arise from peculiar RER configurations within blast cells, which were rich in both organelles. In this case, the authors observed numerous RER cisternae with distinctive cylindric, concentric and/or whorl configurations, RLC associated and not associated with these configurations, and intermediate structures. The latter were characterized by lamellae devoid of ribosomes oriented parallel to the RER configurations. Reticulum configurations were observed in no other case. The ultrastructural aspects observed in these 20 cases suggest that RLC synthesis proceeds as follows: (1) arrangement of RER in cylindric configurations; (2) synthesis of lamellae oriented parallel to the cylindric configurations (pre-RLC); (3) formation of RLC when ribosomes appear between the lamellae associated with configurations (immature RLC); (4) formation of mature RLC with disappearance of the reticulum.

Ultrastructural Features of Pleomorphic Xanthoastrocytoma: A Comparative Study with Glioblastoma Multiforme

Eighteen tumors (15 cases) were ultrastructurally examined and compared to 11 examples of glioblastoma multiforme (GBM) [to determine the cellular nature of pleomorphic xanthoastrocytoma (PXA).] PXA, as well as GBM, were principally composed of pleomorphic astrocytes containing numerous intermediate filaments. Lipid droplets, lysosomes, and basal laminas were more numerous and fully developed in PXA, but were not specific to the tumor. Aggregates of secondary lysosomes, light microscopically evident as eosinophilic granular bodies, and ribosome-lamella complexes were exclusively seen in PXA. Also noted in PXA were centrioles, occasional Rosenthal fibers, hemidesmosomes in small number, rudimentary cell junctions, and interstitial calcifications. In addition to astrocytic constituents, 20% of PXA contained cells with neuronal features, as evidenced by the presence of dense-core granules, microtubules, and clear vesicles. In contrast, GBMs consisted solely of astrocytic cells. In the present study, the salient ultrastructural findings of PXA were largely degenerative in nature, including numerous lipid droplets and secondary lysosomes, as well as basal laminas, ribosome-lamella complexes, and occasional neuronal differentiation. The presence of basal lamina does not necessarily imply a histogenetic derivation from subpial astrocytes, in that it is also a common feature of GBM. Given the occurrence of biphenotypic, glioneuronal differentiation in some cases, PXA may be derived from a neuroepithelial stem cell. The authors conclude that PXA is fundamentally an astrocytic tumor, albeit one with a significant tendency to undergo neuronal differentiation.

As You Like It, Part 2: A Critique and Historical Review of the Electron Microscopy Literature

As You Like It, Part 2, is a continuation of the lecture given at UltraPath VIII in 1996. It is meant to be a critical historical review of some topics of interest to electron microscopists that will show what went wrong and perhaps also why. Topics are presented under the following headings : (1) Amianthoid Fibers and Giant Collagen Fibrils, (2) Ribosome-Lamella Complex, (3) Globular Filamentous Bodies, and (4) Siderosomes, Hemosiderin vs. Ferritin.

Ribosome-lamella complexes in a case of transitional cell carcinoma involving the prostate

We report ribosome-lamella complexes (RLC) in cancer cells of transitional cell carcinoma (TCC) of the prostate in a 52-year-old Caucasian man. Histopathologically, cancer cells were proliferated in various-sized nests, mostly associated with central necrosis. Some invaded into the surrounding normal glandular space and the stroma, with occasional lymphatic invasion. Fine structural study of cancer cells revealed that cross-sectioned RLC as well as densely aggregated ribosomes were detected in their cytoplasm, situated close to, but not directly connected with, dilated rough endoplasmic reticulum. These were composed of a concentric alternative arrangement of both lamellae and ribosomes. In the central and surrounding parts of the RLC, ribosomes were observed, revealing a smooth transition to the ribosomal component of RLC in size and shape. The presence of both RLC and dense aggregation of ribosomes close to the rough endoplasmic reticulum suggests that their functions might be related to specific or aberrant protein synthesis under unknown conditions. Although RLC have been often reported in hematopoietic malignancies, their occurrence in the malignant epithelial component has been only reported in a case of pulmonary adenocarcinoma. This is the first report of RLC in TCC in the literature.

Ribosome-lamella complexes in the perineurial cells of neurofibromatosis.

Ribosome-lamella complexes are occasionally seen in neoplastic disorders of the hematopoietic system, particularly in hairy cell leukemia. However, these structures are rare in epithelial and mesenchymal cells. In this report three tumors from a patient with neuro-fibromatosis (von Recklinghausen's disease) are examined by electron microscopy. Ribosome-lamella complexes were seen in the perineurial cells. This may be the first report of these complexes in nerve sheath tumors.

Ultrastructural investigation of circulating villous lymphoid cells: A tool in the differential diagnosis of splenic lymphoma with villous lymphocytes

Ultrastructural examination of circulating lymphoid cells was performed in three cases of splenic lymphoma with circulating lymphocytes (SLVL) in order to define morphological features helpful to distinguish this lymphoma from hairy cell leukemia (HCL). The samples for ultrastructural investigation were obtained by Ficoll sedimentation from peripheral blood and routinely processed for electron microscopy. The ultrastructural features examined were: morphology of villi, morphology of nuclei, presence of nucleoli, distribution of heterochromatin, type of cytoplasmic organelles, presence of specific intracytoplasmic structures such as the ribosome-lamella complex, lysosome-like bodies and perinuclear microfibrils. Our results and a careful review of the literature seemed to confirm that SLVL has electron microscopic features typical enough to be relevant in the differential diagnosis with HCL.

Hairy cell leukemia: an ultrastructural study of hairy cells before and after interferon therapy.

To test the diagnostic relevance of the presence of ribosome-lamellae complexes (RLC) in 18 hairy cell leukemia (HCL) cases, and to correlate clinical response to interferon (IFN) therapy with hairy cell ultrastructural modifications in 5 of these cases. Peripheral blood samples of 18 HCL patients were studied by transmission electron microscopy. Five of these patients received IFN treatment and subsequently were evaluated at different intervals for ultrastructural modifications of the peripheral blood. RLC were observed in 66.66% of our 18 HCL patients, but in less than 1% of all the cases contained in the files (consisting of over 8,000 cases) of our Electron Microscopy Unit. The microvilli disappeared after IFN therapy in the patients who did not display RLC before therapy (2 cases), whereas they were fewer, shortened and blunted, but still evident, in the cases where RLC had been observed before therapy (3 cases). Moreover, in the HCL cases with pretherapy RLC, neoplastic cells still synthesized RLC after IFN treatment, but their morphologic aspect was immature. Our study suggests that: 1) the presence of RLC, when associated to the hairy aspect of the cells, has considerable diagnostic value even though RLC are observed in other rare neoplastic and non-neoplastic conditions; 2) HCL cases with pre-therapy RLC exhibited a morphologic response to IFN therapy different from that of cases without pre-therapy RLC; 3) the quantitative and qualitative modifications of RLC following IFN treatment, as yet unexplained, are probably related to IFN action, in line with a previous report.

Immunogold labelling of leukemic hairy cells with the B-ly7 monoclonal antibody: An SEM and TEM study

Two cases of hairy cell leukemia have been studied by immuno-TEM and immuno-SEM after immunogold labelling of the cell surface antigen recognized by the B-ly7 monoclonal antibody. Most hairy cells appeared significantly labeled, although the density of the expression of the antigen, as demonstrated by immunogold labelling, seems variable from cell to cell. Moreover, some cells with the morphology of hairy cells and which could not be identified as monocytes were not labeled. Labelling for the antigen identified by the B-ly7 mAb does not seem to correlate with the presence of ribosome lamellae complexes which were present only in one of the two cases studied. Rare lymphocytes of unidentified lineage were labeled. Monocytes were significantly absent from the samples of peripheral blood of the two patients studied. In one normal control sample, monocytes were observed unlabelled. The results are discussed in reference to the pathogenesis of hairy cell leukemia, its surprisingly low mitotic rate, and its distinct response to chemotherapy.

Hairy Cell Leukemia, an Ultrastructural Study with Double Immunogold Labeling

Two cases of hairy cell leukemia were studied using a novel method of sequential double immunogold labeling for both scanning and transmission electron microscopy. Characteristic ribosome lamellae complexes were observed in one case only. The antigens expressed on the surface of hairy cells were those recognized by anti-CD 11c and anti-CD20 murine monoclonal antibodies. All hairy cells, in both cases, co-labeled for the corresponding antigens, as demonstrated by recognizing colloidal gold markers of distinct sizes (5 and 20 nm, or 15 and 40 nm) under SEM and TEM. The specificity of the double labeling method seems to be most satisfactory. Immuno-electron microscopy enables us to characterize the integrated ultrastructural and antigenic phenotype of hairy cells at the single cell level. This represents an unique analytical approach which may contribute significantly in further studies aimed at a better understanding of the pathogenesis of hairy cell leukemia.

Ribosome‐lamella complexes observed in an epstein‐barr virus‐producing B‐cell line, infected with human T‐lymphotropic virus type I

Co-cultivation of peripheral blood mononuclear cells, from a 4-year-old boy with infectious mononucleosis, with a human T lymphotrophic virus type I (HTLV-I)-producing T-cell line resulted in the establishment of an HTLV-I infected Epstein-Barr virus (EBV)-producing B-cell line. Ultrastructural examination revealed the presence of ribosome-lamella complexes (RLCs), in a small proportion of long-term cultured cells. Evidence is presented of continuity between RLC and the rough endoplasmic reticulum, and in some instances there was also an intimate relationship with tubuloreticular structures. The findings support the view that RLC is derived from the rough endoplasmic reticulum and also provide further evidence of the non-specific nature of RLC in relation to cell type.

Secretion of Mucoid Material by Lymphokine-Activated Killer Cells: Study by Light and Electron Microscopy

When lymph node cells from nude mice were grown on embryonic fibroblast monolayers together with rat interleukin-2, only one type of colonies developed. These colonies were composed of cytotoxic cells termed "granular/lymphokine-activated killer/mucus-secreting cells" (LAK-GM). An extensive differentiation course, in which all the cellular components were involved, ended with a population of short-lived, mature, nondividing large cells that apparently synthesized and deposited a flowing mucoid material (FMM) that stained distinctly blue with periodic acid-Schiff/alcian blue (PAS-Ab) at pH 1 and distinctly red by the naphthol AS-D-chloracetate method for specific esterase. So far, the best monolayers to trigger the FMM synthesis were those prepared from 16- to 18-day-old whole embryos. These cells were compared with LAK cells that developed on monolayers (such as embryonic skin or adult kidney) that did not trigger FMM synthesis. They were also compared with other cell types that differentiated in colonies on the fibroblast monolayers: histiocytes (fixed macrophages), mixed granulocytes/monocytes, mucosal mast cells; and with populations of mature rat T-killer cells developed on same mouse monolayers. Features distinctive to the secreting LAK-GM cells were presence of masses of membrane-limited vesicles that were strictly confined to the surface of the cells in FMM-containing colonies. All transitional forms of budding activity could be seen on the cell surface facing the masses. Within the same cells, many granules displayed varying degrees of degradation, the granular material being transformed into flocculent material that formed small pools facing each degraded surface. Other characteristics of the LAK-GM lineage were the accumulation of glycogen prior to the appearance of the FMM, the presence of several structures of a ribosome-lamella complex in the LAK-GM in colonies that did not accumulate FMM, and filopodia commonly emerging from the pole proximal to the nucleus. Of various fixation methods tried, only after treatment with absolute alcohol and subsequent drying was the FMM stained with PAS-Ab. By subsequent wetting, the capacity to be stained was irreversibly lost. After incubation of the living cultures with the enzymes hyaluronidase or chondroitinases AC or ABC, the FMM disappeared. These observations suggest a triggering mechanism by the embryonic mesenchymal fibroblastoid cells for synthesis and secretion of mucous material that is a proteoglycan of the chondroitin sulfate group.

Hairy cell leukemia. Ultrastructural and cytochemical evaluation of leukemic colonies grown in a semi-solid medium

We examined the fine structure and enzymatic activity of cells composing colonies grown from blood and/or spleen of eight patients with hairy cell leukemia. Mononuclear cells (MNC) were plated over an agar layer in a medium containing methylcellulose and leukocyte-conditioned medium. After 7–10 days incubation colonies were harvested for cytologic study. Colony cells possessed a euchromatic nucleus with an occasional nucleolus. Their cytoplasm contained a prominent Golgi region, numerous mitochondria and small vesicles, many short strands of rough endoplasmic reticulum (RER) and an infrequent phagosome. Well-developed ribosome-lamella complexes and what may have been their intermediate forms appeared in colony cells from three patients. Strong activity for tartrate-resistant acid phosphatase, localized in the RER, nuclear envelope and some Golgi vesicles, was evident in 50–95% of all colony cells. Our results indicate that a high proportion of MNC forming colonies in this culture system maintain the characteristic morphology and cytochemical activity of hairy cells.

Stereologic analysis of the ultrastructure of isolated human T and non-T lymphoid cells. III. Studies in chronic lymphoid leukemias, hairy cell leukemia and some malignant lymphomas.

Malignant cells from 9 cases of chronic lymphocytic leukemia (CLL), 4 cases of prolymphocytic leukemia (PLL), 4 cases of hairy cell leukemia (HCL), 4 cases of malignant lymphoma of centrocytic type and 3 cases of malignant lymphoma of lymphoblastic type (Kiel classification), all examined for T and B markers, were analysed by electron microscopy. Stereological methods were applied to assess relative and absolute values concerning the whole cell and nuclear and cytoplasmic components of the average cell in each population, and comparisons were made between the morphologically and immunologically defined subsets. The CLL-lymphocyte possessed the smallest cell volume, a high nucleo-cytoplasmic volume ratio, densely packed heterochromatin, a small nucleolar volume and a sparse Golgi complex. The 7 B-derived cases were characterized by a larger volume of rough ER and a more irregular plasma membrane than the two T-derived cases, which typically displayed dense granules in paranuclear aggregations. The prolymphocyte could be distinguished from the CLL-cell by its larger cell volume, lower nucleo-cytoplasmic volume ratio, proportionally lesser heterochromatin, typically condensed at the periphery and around a prominent nucleolus. All 4 cases of PLL were of B-nature and shared the features of B-CLL regarding increased rough ER and low content of granules. The hairy cell exhibited the largest cell volume, the lowest nucleo-cytoplasmic volume ratio, an indented nucleus and a remarkable irregular cellular surface with long "hairy" processes. The cytoplasmic inclusions of ribosome-lamella complexes were recorded exclusively in hairy cells, in half of the patients. The centrocyte was characterized by a cell volume of intermediate size, a high nucleo-cytoplasmic volume ratio and the highest degree of nuclear irregularity recorded. The amount of rough ER was considerably less than in B-CLL and B-PLL. Finally, the blast from the cases of lymphoblastic lymphoma, all of T-nature, displayed a smooth plasma membrane, a high euchromatin-heterochromatin volume ratio and dense granules, characteristically clustered in the vicinity of the Golgi complex. Stereology on the ultrastructure of malignant lymphoid cells provides a more accurate characterization and may be helpful in classification.

The Coexistence of Ribosome-Lamella Complex and Annulate Lamellae in Chronic Lymphocytic Leukemia

An electron microscopic study of peripheral blood and lymph node from a patient with chronic lymphocytic leukemia revealed ribosome-lamella complexes in 11-16% of the peripheral lymphocytes and in 14% of the nodal lymphocytes. Annulate lamellae were seen in 2-8% of the peripheral lymphocytes and in 8% of the nodal lymphocytes. One peripheral blood specimen revealed coexistence annulate lamellae and ribosome-lamella complexes within the same cells in an additional 4% of the lymphocytes. The two structures were connected by continuous strands of apparent endoplasmic reticulum. Although annulate lamellae and ribosome-lamella complex have each been described in chronic lymphocytic leukemia, albeit uncommonly, their unusual association with one another has not previously been documented and might offer a clue as to the origin and role of these interesting structure. The possible ramifications of these observations include relationship of the structures to endoplasmic reticulum and protein synthesis, to in vitro and possible clinical induction by drugs including "antitubulins," and to induction in vitro by viral infection.

Lysosomal granules in leukemic monocytes and their relation to maturation stages.

Material from 11 patients with acute monocytic leukaemia (M5), including two with monoblasts transformation of chronic granulocytic leukaemia, were studied by light and transmission electron microscopy (TEM) cytochemical techniques. Conventional TEM examination revealed typical ribosome-lamella complexes in two cases. Acid phosphatase (AP) and myeloperoxidase (MPO) at TEM level helped to demonstrate three types of lysosomal granules: 1) primary, small (0.05 – 0.2 µm) were AP positive and MPO negative; 2) secondary, medium size (0.2 – 0.4 µm) were MPO and AP positive; 3) tertiary, of variable size (0.05 – 0.6 µm) were both AP and MPO negative. Primary granules were the only ones seen in monoblasts, secondary granules appeared during the promonocyte stage and tertiary granules were seen in more mature monocytic cells. These studies have helped us in the characterisation of leukaemia cells and to understand the sequential development of lysosomal enzymes during monocytic differentiation.