Nuclear Convolution Research Articles

A Case of Adult T-Cell Leukemia Initiated with Central Nervous System Symptoms

We treated a 52-year-old Japanese woman with adult T-cell leukemia (ATL) initiated with central nervous system (CNS) symptoms. Her chief complaints were paraplegia and left facial palsy. CNS-ATL was diagnosed because of the following three features. 1) Various sized lymphoid cells with marked nuclear convolution were numerous in her cerebrospinal fluid. 2) These cells were a monoclonal proliferation of T lymphocytes with OKT 4 marker. 3) The patient's serum was positive for anti-ATL associated antigen (ATLA). Although the neurological signs and symptoms improved markedly after intrathecal administration of combined chemotherapy (methotrexate, cytarabine and corticosteroid), these ATL cells were highly resistant to radiation therapy. The abdominal mass which developed in the course of the disease was diagnosed as a tumor formed of ATL cells, and VEPA (vincristine, endoxan, prednisolone and adriamycin) was administered with marked success.

Quantitative electron microscopy in the diagnosis of mycosis fungoides. A simple analysis of lymphocytic nuclear convolutions

• In the present study we compared the accuracy of three different ultrastructural methods used to confirm clinically proved cases of mycosis fungoides (MF) from skin biopsy specimens. Method 1 is a qualitative method and confirmed the diagnosis of MF in only 44% of the patients with MF. Method 2 involved image analysis of lymphocytic nuclei and confirmed the diagnosis of MF in only 67% of the patients with MF. The most sensitive ultrastructural method for confirming the diagnosis of MF was a simple scoring of the number of sharply angled nuclear invaginations in 100 lymphocytes (method 3). Control biopsy specimens had many more lymphocytes (19% to 55%) with no sharply angled nuclear invaginations compared with those from patients with MF (3% to 15%). The clinical diagnosis of MF was confirmed in 100% of our patients with MF using method 3. (<i>Arch Dermatol</i>1984;120:63-75)

Immunoelectron microscopy related to T-cell monoclonal surface antigen in mycosis fungoides.

For the purpose of diagnosing and staging cutaneous T-cell lymphoma, the nuclear contour index and subsets of T-cells in the lesions were studied. Nuclear contour index measured in T-cells identified precisely with monoclonal pan-T antibody was found to be higher than nuclear contour index measured in T-cell-like cells with significant nuclear convolution. Nuclear contour index increased as the disease progressed from erythematous to tumor stage or to the Sézary syndrome. The relative ratio of suppressor cytotoxic T-cells to helper T-cells was higher in the early rather than late stage of cutaneous T-cell lymphoma.

Proton-Beam Irradiated Epithelioid Cell Melanoma of the Ciliary Body

A malignant ciliary body melanoma received proton-beam irradiation. After an apparent failure of the tumor to respond, the eye was enucleated. A predominantly epithelioid cell tumor appeared viable by light microscopy, and a low degree of mitotic activity persisted, despite therapy. The tumor cells, however, displayed degenerative changes ultrastructural ly, presumably results of the radiotherapy. These consisted of numerous cytoskeletal filaments, lipid vacuoles, prominent phagolysosomes, and nuclear convolutions and fragmentations. The mitochondria were fewer in number in the present tumor than typically encountered in epithelioid cells. A rare leptomeric structure was discovered, probably an organizational modification of the cytoplasmic filaments. The tumor’s capillaries showed radiation-induced changes in terms of thickened basement membranes and perivascular fibrin deposition. The foregoing features are indicative of cellular and metabolic injury from the radiotherapy, but these were evidently not sufficiently injurious to sterilize the tumor.

Characterization of surface markers and cytoplasmic organelle in benign and malignant lymphoid lesions of skin; immunohistochemical and electron microscopic evaluation.

In order to characterize the benign and malignant proliferation of lymphoid cells in skin, we compared surface markers and cytoplasmic organelles of cells in cutaneous lymphoid hyperplasia (CLH), lymphomatoid papulosis (LP), mycosis fungoides (MF), Sézary's syndrome (SS) and primary cutaneous malignant lymphoma (ML). The immunohistochemical study showed cells with both T - and B-cell markers in CLH,LP and early MF, whereas cells with only the T-cell marker were seen in late MF, SS and ML. T-cells in all cutaneous lesions possessed the surface marker common to T-cells of peripheral lymph nodes, and not that of central thymus cells. Cutaneous T-cells contained clustered or scattered dense core granules. Although no specific organelles indicative of benign or malignant lymphoid proliferation were found, there were several ultrastructural features that could help identifying each form of cutaneous lymphoid lesions. These included clustered or scattered dense-core granules, the variable degree of nuclear convolutions as well as dendritic arborization, and the presence or absence of 10 nm filaments.

Lymphoblastic lymphoma in adults.

Clinical and cytogenetic studied were done on 12 patients with lymphoblastic lymphoma. The ages of the patients ranged from 17 to 58 years (median, 24.5 years). Males predominated by a ration of 5:1. Ten of the 12 patients had a mediastinal mass at diagnosis; two thirds of the patients had involvement of the bone marrow (3 of 12 patients initially were in a leukemic phase), and 5 of 12 patients had involvement of the central nervous system (CNS) with lymphoma. In all patients, the malignant cells were characterized by nuclear convolutions. Cytogenetic studies done on four patients showed clonal chromosome abnormalities in two cases. Six of the 12 patients were treated with the combination chemotherapy regimen COPA and received CNS prophylaxis; their survival was slightly longer than that of the other patients, who were treated with a variety of treatment regimens. Two of the 12 patients achieved a complete remission. The median survival of all patients was 11.5 months but was shorter in patients with initial CNS involvement or leukemia. The poor results achieved thus far in the treatment of this disease demand a new therapeutic approach.

Primary histiocytic lymphoma of bone: a light and ultrastructural study of four cases.

The light and ultrastructural features of primary histiocytic lymphoma of bone are indistinguishable from similar studies of respective cell types of nodular and diffuse large cell nodular and extranodal lymphomas. These ultrastructural features add further support to their lymphocytic histogenesis. There was no relationship between increasing nuclear clefts and convolutions in individual cases and the ultrastructural presence of increasing "histiocytic" features. Primary histiocytic lymphoma of bone is not a completely uniform monomorphic tumor cell population, but may vary in percentage of large noncleaved, large cleaved, large convoluted lymphocytic, histiocytic, and small atypical lymohocytic cells. Detailed study of four cases enabled division into two primary subgroups: Type I, consisting of a predominance of large noncleaved cells; and Type II, consisting of a mixture of cleaved, noncleaved, and convoluted cells. Further cases are being studied to determine whether these two groups are distinct or merely represent part of a continuous spectrum of cellular pleomorphism. In contrast to nodal lymphomas, there is no evidence at this time that proportional variations in the tumor cell population bear any relationship to biologic behavior or survival. Glycogen may be present in histiocytic lymphomas but was very rare (less than 1% total cells). Therefore, this feature as an isolated observation will not differentiate histiocytic lymphoma from Ewing's sarcoma.

Fluorine concentration profile determination in MAGNOX reactor fuel canning material

The role of fluorine, as a corrosion inhibitant was investigated by determining fluorine concentration profiles in corroded MAGNOX reactor fuel cladding material. A nuclear convolution method was employed, based on the19F(p, αγ)16O resonant reaction and prompt gamma detection. The investigation was carried out for scale thicknesses of 3.5 and 4.5 μm as determined using 4.5 MeV protons and a broad resonance in16O(p, p)16O back-scattering cross-section. The results indicate the presence of thin fluorine concentration layers near to the scale surface on both etched and pre-oxidized magnesium alloy samples. Furthermore, an additional lower concentration distribution was also observed throughout the scale of the pre-oxidized sample.

Acute lymphoblastic leukemia.The significance of nuclear convolutions

Because of the significance attributed by some investigators to the presence of cells with convoluted nuclei in lymphoblastic lymphoma, and the absence of any information on the presence and significance of such cells in acute lymphoblastic leukemia (ALL), we reviewed the blood, bone marrow films, and clinical records of 101 children with ALL. We attempted to determine whether leukemic cells with convoluted nuclei can be recognized in such films, and if so, whether this observation has clinical significance. In fifty-seven of the patients the leukemic cells had convoluted nuclei. For the purposes of this study, our patients were divided into three groups: Group I, 44 patients without cells having convoluted nuclei: Group II, 30 patients with 10% or fewer convoluted nucleus cells (CNC); and Group III, 27 patients with more than 10% CNC. Clinical comparison of the three groups with respect to age and sex distribution, physical and hematologic findings at presentation, response to therapy and survival showed no significant differences. Patients with a mediastinal mass had a significantly shorter survival compared to those without a mediastinal mass, regardless of the presence or absence of CNC (p = 0.0001). Our results indicate that the nuclear convolutions can easily be recognized in blood or bone marrow films of patients with ALL, and that their presence has no provable clinical significance.

Convoluted lymphocytic lymphoma in adults: a clinicopathologic entity.

Twelve adults had a distinct clinicopathologic type of malignant lymphoma that closely resembles the mediastinal lymphomas of childhood. Nine patients presented with mediastinal masses, and seven had symptoms related to intrathoracic compression. Seven patients presented with or developed leukemia, and in four of these patients the central nervous system (CNS) became involved. Structurally, the tumor cells had a distinctive stippled chromatin pattern, in addition to the characteristic nuclear convolutions. Tumor cells from five patients were studied immunologically, and, in each case, the tumor cells formed rosettes with sheep erythrocytes. The response to combination chemotherapy was rapid and dramatic, but usually transient, with relapse in the CNS or previously involved sites. The above data strongly suggest that these cases represent a distinct clinicopathologic entity that should be treated similarly to childhood leukemia and lymphoma, with intensive multiple agent induction, CNS prophylaxis, possibly radiation therapy to initially involved sites, and prolonged maintenance.

Multiparameter geometric and densitometric analysis of the G0-G1 transition of WI-38 cells.

Automated image analyses were performed using Feulgen stained smears of WI-38 cells that were either confluent, or that had received a nutritional stimulus to proliferate 3 hr before collection. These experiments show that it is possible to observe changes in morphometric and densitometric parameters of nuclei that correlate with structural and functional differences in isolated chromatins from quiescent G0 and proliferation G1 cells that have been demonstrated by other means. Scatter plot analyses of the data indicated the presence of nuclear images from the stimulated G1 population that had the same deoxyribonucleic acid content as the confluent G0 cells, but had greater areas, perimeters and horizontal projections and smaller mean free paths, form factors, and average optical densities. Multiparameter cluster analysis permits, even minimally, an objective, model-independent identification of G0 from G1 cells that present an increased nuclear dispersion (i.e., lower average optical density) systematically accompanied by increased nuclear convolution (i.e., lower form factor), both compatible with the reported increase in available binding sites with respect to G0 cells.

Malignant lymphoma, lymphoblastic.

Among the malignant lymphomas of the diffuse, poorly differentiated lymphocytic type, a cytologically distinctive form can be recognized. It is composed of immature lymphoid cells that are indistinguishable from the cells of acute lymphoblastic leukemia (ALL). Although these neoplasms usually have been classified as malignant lymphoma, lymphoblastic type, they contain, in addition to lymphoblasts, prolymphocytes in varying proportions. On the basis of the nuclear morphology, malignant lymphoma of the lymphoblastic type, (MLLB) can be further divided into those with and those without convoluted nuclei. In our series both groups had the following clinical features in common: 1) frequent occurrence in children and adolescents; 2) clinical presentation with mediastinal masses in 50% of cases; 3) a high incidence of bone marrow and perpheral blood involvement during the course of the disease; and 4) rapid progression of the disease with a median survival of 8 months. Our observations indicate that nuclear convolutions are helpful but not essential for the recognition of a clinicopathologic entity which is histologically and cytologically characterized by 1) the immaturity of the lymphoid cells indistinguishable from the lymphoblasts and prolymphocytes of ALL and 2) a high mitotic index. Because of the frequency with which MLLB progresses into ALL, systemic therapy may be indicated even before this progression is hematologically evident. This indicates the need for morphologic recognition of this malignant lymphoma regardless of the presence of nuclear convolution, age of the patient, and site of presentation.

Identification of Promonocytes and Monocytoid Precursors in Acute Leukaemia of Adults: Ultrastructural and Cytochemical Observations

Summary. Examination of 25 cases of adult non‐lymphoid acute leukaemia by electron microscopy and esterase cytochemistry revealed that most cases contained a majority of classifiable cells, however undifferentiated they may have appeared by routine light microscopy. The major proliferating cell in most cases (72%) was found to be a promonocyte or monocytoid precursor cell, characterized by extreme nuclear convolution, large cytoplasmic bundles of microfilaments, and numerous small electron‐dense lysosomal granules, which strongly stained for alpha‐naphthyl acetate esterase. Pure granulocytic cases, representing a minority (24%), were composed of blasts and typical promyelocytes and myelocytes, staining for Naphthol‐AS‐D chloroacetate esterase. Only one case was totally composed of undifferentiated, unclassifiable blasts. These results show that electron microscopy and cytochemistry increase the accuracy of classification of leukaemia and that the true incidence of monocytic leukaemia may be much higher than generally recognized.