Nuclear Convolution Research Articles

Expanding the Spectrum of NUTM1 -Rearranged Sarcoma : A Clinicopathologic and Molecular Genetic Study of 8 Cases.

Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1 -rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51y; median: 56y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5cm (mean: 6cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12mo after diagnosis). Our study further demonstrated that NUTM1 -rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.

Off-shell effects in bound nucleons and parton distributions from H1 , H2 , H3 , and He3 data

We report the results of a new global QCD analysis including deep-inelastic scattering data off $^{1}\mathrm{H}$, $^{2}\mathrm{H}$, $^{3}\mathrm{H}$, and $^{3}\mathrm{He}$ targets. Nuclear corrections are treated in terms of a nuclear convolution approach with off-shell bound nucleons. The off-shell (OS) corrections responsible for the modification of the structure functions (SFs) of bound nucleons are constrained in a global fit along with the proton parton distribution functions (PDFs) and the higher-twist (HT) terms. We investigate the proton-neutron difference for the OS correction and discuss our predictions for the SF ratio ${F}_{2}^{n}/{F}_{2}^{p}$ and the corresponding PDF ratio $d/u$ in the proton, as well as their correlations with the underlying treatment of the HT terms and of the OS corrections. In particular, we find that the recent MARATHON data are consistent with equal relative OS corrections for both the proton and the neutron.

Nuclear effects in the deuteron and global QCD analyses

We report the results of a new global QCD analysis, which includes deep-inelastic $e/\mu$ scattering data off proton and deuterium, as well as Drell-Yan lepton pair production in proton-proton and proton-deuterium collisions and $W^\pm/Z$ boson production data from $pp$ and $p \bar p$ collisions at the LHC and Tevatron. Nuclear effects in the deuteron are treated in terms of a nuclear convolution approach with bound off-shell nucleons within a weak binding approximation. The off-shell correction is controlled by a universal function of the Bjorken variable $x$ describing the modification of parton distributions in bound nucleons, which is determined in our analysis along with the parton distribution functions of the proton. A number of systematic studies are performed to estimate the uncertainties arising from the use of various deuterium datasets, from the modeling of higher twist contributions to the structure functions, from the treatment of target mass corrections, as well as from the nuclear corrections in the deuteron. We obtain predictions for the ratios $F_2^n/F_2^p$, and $d/u$, focusing on the region of large $x$. We also compare our results with the ones obtained by other QCD analyses, as well as with the recent data from the MARATHON experiment.

Cribriform-Morular Thyroid Carcinoma Is a Distinct Thyroid Malignancy of Uncertain Cytogenesis.

Tumors with papillary cribriform and morular architecture were initially considered to be variants of papillary thyroid carcinoma; however, recent observations have challenged this view. In this study, we reviewed the demographical, histopathological, and immunohistochemical features of the largest case series, consisting of 33 tumors. The age at time of pathological diagnosis ranged from 18 to 59 (mean 33) years, and all patients except one were female. Sixteen patients had multifocal and fifteen had unifocal disease. The status of focality was unavailable in two patients.Tumors were well-circumscribed, ranging in size from 0.1 to 8.0cm. The cribriform component was admixed with morulae in the majority, except seven had a cribriform-predominant architecture and two had predominantly solid growth. Variable degrees of nuclear enlargement, elongation, overlapping, and grooves were seen but florid nuclear convolution, intranuclear pseudoinclusions, and optically clear nuclei due to chromatin margination were not appreciated. There was no or little colloid material within the cribriform spaces. Two solid tumors had high-grade features. Immunohistochemical studies showed beta-catenin nuclear and cytoplasmic positivity in all cases. The cribriform component was positive for TTF1 and negative for thyroglobulin. PAX8 was absent in half of these tumors and focal in the remainder. Morulae were positive for keratin 5 and CD5 and negative for p63, p40, TTF1, and PAX8. Molecular studies revealed germline APC mutations in 12 tumors and were negative in 5 sporadic tumors in a subset of tested tumors. Irrespective of the antibody used in this cohort, all cribriform-morular carcinomas express TTF1; however, PAX8 immunoreactivity is weak, focal or negative, and all tumors lack thyroglobulin reactivity; these findings raise questions about tumor cell origin and may indicate that these are not of thyroid follicular epithelial differentiation. We postulate that morulae may represent divergent thymic/ultimobranchial pouch-related differentiation. Given their unique cytomorphology, immunohistochemical profiles, and genetic features that have little overlap with traditional follicular cell-derived thyroid carcinomas, we propose that these tumors represent a distinct form of thyroid carcinoma unrelated to other neoplasms of thyroid follicular cells.

Mapping ideals of quantum group multipliers

We study the dual relationship between quantum group convolution maps L1(G)→L∞(G) and completely bounded multipliers of Gˆ. For a large class of locally compact quantum groups G, we completely isomorphically identify the mapping ideal of row Hilbert space factorizable convolution maps with Mcb(L1(Gˆ)), yielding a quantum Gilbert representation for completely bounded multipliers. We also identify the mapping ideals of completely integral and completely nuclear convolution maps, the latter coinciding with ℓ1(bGˆ), where bG is the quantum Bohr compactification of G. For quantum groups whose dual has bounded degree, we show that the completely compact convolution maps coincide with C(bG). Our techniques comprise a mixture of operator space theory and abstract harmonic analysis, including Fubini tensor products, the non-commutative Grothendieck inequality, quantum Eberlein compactifications, and a suitable notion of inner co-amenable quantum group, that we introduce and for which we exhibit examples from the bicrossed product construction. Our main results are new even in the setting of group von Neumann algebras VN(G) for quasi-SIN locally compact groups G.

Structure Function of the Bound Proton in the Dressed-quark Exchange Formalism

The idea of the dressed quark scenario, in the context of the quark exchange model has been used to obtain the bound parton distribution functions as well as the bound proton structure function. The Gluck, Reya, and Vogt (GRV)’s parton distribution functions, where they have a good agreement with the experimental data in the whole range of (x, Q2)-region, have been used to extract the amount of the momentum carried by each parton inside the proton; therefore, by using these values, the different parton densities inside the constituent quark have been calculated. To extract the parton distribution functions in the bound proton, the phenomenological constituent quark exchange formalism and the nuclear convolution theorem have been used. By considering these densities, the structure function of the bound proton, ${F_{2}^{P}}(x,Q^{2})$, inside the light nuclei like helium-3 or tritium has been calculated at low- and high-Q2 values. The correctness of the calculations has been tested through computing the difference of the proton-neutron structure functions as well as the ratio of the neutron to the proton structure functions, in which they are well known from experimental data. The results of the present study are in an agreement with both the available and relevant experimental data and the theoretical predictions.

Follicular dendritic cell sarcoma of the large intestine: A rare presentation

Follicular dendritic cell tumors are very rare neoplasms that often occur in lymph nodes. We report here a case in the colon, second in the series to be reported, in a 40 year male. The differentiation from gastrointestinal stromal tumor is emphasized. Tumor was involving the ascending colon without any obstructive feature. Microscopically, tumor cells are arranged in a pattern-less pattern, focal short fascicles. Tumor cells are large cells with varying shaped nuclei and ill defined cytoplasmic outline oval to irregular shaped nuclei with nuclear convolutions and sprinkling of lymphocytes intermingled with the tumor cells noted. The histological appearance resembled gastrointestinal stromal tumor. Immunohistochemically, the tumor is focally positive for CD23; while negative for C-kit, leucocyte common antigen (LCA), CD3, CD20, CD34, DOG-1, Smooth muscle actin (SMA), CD163, desmin, S-100 protein and CD1a. So a final diagnosis of tumor of dendritic-histiocytic cell lineage favoring follicular dendritic cell tumor of malignant potential. So, it is inferred that follicular dendritic cell tumor entity should be considered in the list of differential diagnoses for gastrointestinal stromal tumor.

CD4+, CD56+ Mycosis Fungoides: Case Report and Review of the Literature

This case report details an 85-year-old woman who presented with mycosis fungoides (MF), clinical stage 1A. Bilateral lesions on the upper thighs were responsive to topical steroid therapy. Biopsies showed band-like dermal infiltrates of medium-sized lymphocytes with marked epidermotropism, including large intraepidermal lymphocytes with nuclear convolutions, consistent with MF. Immunohistochemical staining revealed that the lesional cells were CD56+, but unlike the case in previous reports of CD56+ MF, they also expressed CD4 and T-cell intracellular antigen 1 and did not express CD8. To our knowledge, this is the first description of a case of MF with a CD4+, CD8-, CD56+, T-cell intracellular antigen 1-positive immunophenotype. At 85 years of age, the patient is older than all previously described patients with CD56+ MF. Despite an immunophenotype observed more commonly in aggressive forms of cutaneous T-cell lymphoma, the clinical presentation is that of typical MF. The patient presented with limited disease and after 12 months of follow-up has not progressed beyond stage 1A.

Topotecan Induces -Apoptosis in the Myelodysplastic Syndromes Cell Line MUTZ-1 That Is Associated with down Regulation of IAP Expression.

Myelodysplastic syndromes (MDS) represent a heterogenous group of clonal stem cell disorders with qualitative and quantitative abnormalities of blood cells and a high probability of evolving to acute leukemia. Intensive induction chemotherapy in order to reduce the malignant clone and reconstruct normal hematopoiesis is a classic therapy of MDS, especially high risk MDS. Topotecan (TPT), a semisynthetic water-soluble derivative of camptothecin, is a potent inhibitor of DNA topoisomerase I and has been extensively studied in hematologic malignances. However, little is known about how TPT acts against neoplastic cells. The aim of this study is to evaluate apoptotic effect of TPT on the MDS cell line MUTZ-1 and its associated changes in the expression of inhibitors of apoptosis protein (IAPs). The effect of TPT on MUTZ-1 growth was determined by using MTT assay. Characteristics associated with apoptosis induced by TPT were evaluated by transmission electron microscope, DNA gel electrophoresis and flow cytometry (FCM). Cell cycle shift were observed by FCM. Semi-quantitative RT-PCR was used to evaluate the mRNA expression of members of IAP gene family, including survivin, XIAP, Bcl-2, Bax, cIAP1 andcIAP2. The potential of mitochondrial membrane potential (MMP) was determined by using JC-1 probe. The results demonstrated that TPT significantly inhibited MUTZ-1 cell growth in a time- and dose-dependent manner with IC50 of 5.011 mmol/L, 1.297mmol/L and 0.483mmol/L at 24h, 48h and 72h respectively. Morphological features associated with TPT-induced apoptosis observed by transmission electron microscopy included cytoplasmic and nuclear shrinkage, karyorrhexis, nuclear convolution, chromatin condensation and margination, cytoplasmic vacuolization, and membrane-bound apoptotic bodies. An ambiguous DNA ladder was observed following treatment with 5mmol/L TPT for 24h, and a typical DNA ladder was observed with 10mmol/L TPT for 24h. The apoptotic rates were 11.69±0.51%, 34.07±1.73%, and 48.59±2.01%, respectively, after 24h culture with TPT as 1, 5, 10 μmol/L, significantly higher than that of the control (3.47%±0.3%; F=31.642, P<0.01). The percentage of MUTZ-1 cells in G2/M phase of the cell cycle decreased while in S and G0/G1 phase increased after treatment with 1mmol/L TPT for 24h,. The majority of the cells were arrested in S phase. After 24h culture with TPT at1, 5, and 10μmol/L, the mRNA levels of survivin, XIAP, cIAP1 and cIAP2 were decreased (P<0.01). This down-regulation was negatively correlated with TPT-induced apoptotic rates(P<0.05). There was no significant change in the Bax and Bcl-2 mRNA levels after TPT treatment (P>0.05). After 24h culture with 1μmol/L TPT, the MMP of TPT treated cells decreased significantly(P<0.01). Together, we conclude TPT can inhibit the growth and induce apoptosis of MUTZ-1 cells in a time- and dose- dependent manner. TPT can also induce the cell cycle changes, with the majoritoy of cells being arrested in S phase. The TPT-induced apoptosis in MUTZ-1 cells is associated with down-regulation of suvivin, XIAP, cIAP1and cIAP2 mRNA expresison. As well, MMP may be play a important role in the apoptotic process of MUTZ-1 cells induced by TPT.

Combined administration of hydrophilic antimitotic desoxyepothilone B and vinorelbine induce PUMA, suppression of microtubule dynamics, development of hypodiploidy and multinucleation, cell cycle perturbation at G2/M and apoptosis in advanced breast carcinoma (ABC) characterised by MDR-1 (Pgp),bcl-2 and mutant b-tubulin

2087 Introduction: Low aqueous solubility of VRL is a high substrate for ATP dependent drug efflux proteins such as MDR-1(Pgp) and MRP2(ABCC2) inserted in plasma membrane of tumor cells.Furthermore,b-tubulin mutations are cross-resistant to VRL. Methods: We treat with MTC such as VRL and dEpoB advanced mammary carcinoma characterised by overexpression of bcl-2,MDR-1(Pgp),MRP2(ABCC2) and mutant b-tubulin according to PCR,WB and IHC analysis. MT polymerising agent dEpoB is more soluble in aqueous solvents than VRL reducing affinity for Pgp by being a poor substrate. Results: Post-treatment,although VRL and dEpoB are structurally unrelated,they bind to mutually exclusive sites on the tubulin unit.After binding of MTCs to MT,there was synergistic phosphorylation of bcl-2,overexpression of bax,circumvention of expression of altered b-tubulin polypeptides, MDR-1 and MRP-2 due to high hydrophilicity of dEpoB and PUMA. Flow cytometry showed blockage of cell proliferation at the metaphase-anaphase (G2/M) interface of the cell cycle.There was an enhancement in hypodiploid population of tumor cells,multinucleation,aberrant spindle formation,nuclear convolution,suppression of MT-dynamics and formation of MT bundling.Both drugs induced release of cyt-c from isolated mitochondria after interaction of mitochondrial tubulin with the voltage-dept anion channel of the permeability transition pore.There was potent immunosuppression by inhibiting T-cell proliferation.Methylene blue, BrdU and MTT exhibited inhibition of tumor cell proliferation. We observed nuclear factor kB-induced apoptosis displayed by features such as nuclear condensation and fragmentation,Annexin V staining,cleavage of poly(ADP-ribose)polymerase and activation of caspases. Conclusion: We observed synergy between dEpoB and vinorelbine in potentiation of apoptosis in advanced breast carcinoma circumventing chemoresistance. No significant financial relationships to disclose.

Distinct involvement of cAMP-response element-dependent transcriptions in functional and morphological maturation during retinoid-mediated human myeloid differentiation.

We evaluated the involvement of cyclic adenosine monophosphate-response element (CRE)-dependent transcriptions in all-trans retinoic acid (ATRA)-induced myeloid differentiation using human monoblastic U937 cells. ATRA treatment caused an increment in the CRE-dependent transcription activity and induced a wide variety of differentiation phenotypes including functional and morphological maturation. Indeed, ATRA treatment induced the expression of CCAAT/enhancer-binding protein beta (C/EBPbeta), a CRE-dependent transcription factor important in monocytic differentiation, and the inhibition of CRE-enhancer activity by the expression of a dominant-negative CRE-binding protein (dn-CREB) abolished the induction of C/EBPbeta. Functional maturation, such as the enhancement of cell adhesion and respiratory burst activity, was dramatically suppressed by the expression of dn-CREB. In addition, the differentiation-dependent induction of an adhesion molecule (CD11b), the phagocyte oxidase required for respiratory burst, and the transcription factor PU.1 responsible for phagocyte oxidase induction were all abolished by dn-CREB. Surprisingly, morphological maturation, including nuclear convolution and cytoplasmic vacuolar formation, was augmented by dn-CREB. Under the same conditions, the differentiation-associated cell-growth arrest was not affected by the expression of dn-CREB. Our results clearly indicate that CRE-driven transcription plays at least three distinct roles during myeloid differentiation: It stimulates functional maturation but suppresses morphological maturation and has no effects on cell-growth arrest.

Ultrastructural damage in chromium picolinate-treated cells: a TEM study. Transmission electron microscopy.

Chromium picolinate (CrPic) is a human dietary supplement that provides a bioavailable form of chromium(III). Its mechanism of action is unknown, and a number of toxic endpoints have been attributed to its use. Understanding the cellular effects of CrPic is important for confirmation or dismissal of these potential toxic effects. The purpose of this work was to characterize morphological damage caused by CrPic, picolinic acid, and chromic chloride in Chinese hamster ovary AA8 cells. A 48-h exposure to 80 micro g/cm(2) CrPic (0.44 mg/mL CrPic) produced 45% survival by colony formation. Transmission electron microscopy (TEM) showed 83% of analyzed cells having swollen mitochondria with degraded cristae. Apoptosis was identified by nuclear convolution and fragmentation, and cytoplasmic blebbing. Apoptosis was quantified by fluorescence microscopy with acridine orange/ethidium bromide staining. At the 80 micro g/cm(2) dose of CrPic, 37% of the cells were apoptotic cells at 48 h. An equivalent dose of picolinate, 3 mM, was much more cytotoxic and thus there was an inadequate cell number for TEM analysis. However, a lower dose of 1.5 mM induced 49% cell survival, and damaged 86% of the mitochondria, with 51% of the cells undergoing apoptosis. A dose of 1 mM chromic chloride produced 71% cell survival, and damaged 86% of the mitochondria, with 22% of the cells undergoing apoptosis. The amount of apoptosis correlated with overall cell survival by colony formation, but not with the amount of mitochondrial damage. The coordination of Cr(III) by picolinate ligands may alter the cellular chemistry of Cr(III) to make chromium picolinate a toxic form of Cr(III).

Etoposide-induced apoptosis in lymphoblastoid leukaemic MOLT-4 cells: evidence that chromatin condensation, loss of phosphatidylserine asymmetry and apoptotic body formation can occur independently.

Apoptosis is characterised by a series of typical morphological features, such as nuclear and cellular convolution, chromatin condensation and the final disintegration of the cell into membrane-bound apoptotic bodies, which are phagocytosed, by neighbouring cells. Relocation of phosphatidylserine residues from the inner leaflet of the cellular membrane to being exposed on the cell surface is a necessary event for the phagocytic elimination of apoptotic cell debris. Using the MOLT-4 lymphoblastoid leukaemic cell line we investigated whether the formation of apoptotic bodies and loss of phosphatidylserine asymmetry were causally related. We have previously demonstrated that classical apoptotic morphology, including production of apoptotic bodies, was only possible in etoposide-treated MOLT-4 cells when administered in the presence of non-cytotoxic doses (200 microM) of aurin tricarboxylic acid (ATA). Electron microscopic analysis, followed by the quantitation of the ultrastructural morphological features of apoptotic MOLT-4 cells, demonstrated that the etoposide and ATA co-treatment, which caused the cellular fragmentation into apoptotic bodies, was closely associated with extensive chromatin condensation in individual cells. In this model however, the addition of ATA to frank cytotoxic doses of etoposide (50 microM), which we confirmed lead to formation of apoptotic bodies, caused no further increase in externalisation of phosphatidylserine moieties as determined by staining with fluorescence labelled annexin V. Consequently, in MOLT-4 cells undergoing etoposide-induced apoptosis, the mole-cular mechanisms leading to loss of phosphatidylserine asymmetry and the formation of apoptotic bodies are not causally related.

Cutaneous type of adult T cell leukemia/lymphoma in a French West Indian woman: Clonal rearrangement of T-cell receptor β and γ genes and monoclonal integration of HTLV-I proviral DNA in the skin infiltrate

A 45-year-old woman, a native of the French West Indies who had lived in France since 1973, developed multiple cutaneous plaques and nodules in 1987. Histopathologic studies revealed dermal infiltration with mature activated T cells (CD4 +, CD25 +, DR +) with nuclear convolutions and epidermatotropism. High titers of specific human T lymphotropic virus (HTLV)-I antibodies were detected in the serum. Molecular analysis of DNA extracted from the skin tumor biopsy specimen showed a clonal integration of an HTLV-I provirus and a T-cell clonal population as demonstrated by T-cell receptor β and γ gene rearrangement studies. Neither HTLV-I provirus nor T-cell receptor rearrangements were detected in peripheral blood mononuclear cells DNA despite the presence of rare adult T cell leukemia cells (< 1 %) and a small excess of DR-expressing cells, and detection of HTLV-I Pol and Px sequences by in vitro gene amplification. In this case only gene analysis of the skin lesions made possible an early diagnosis of a cutaneous adult T cell leukemia. This illustrates the need for such molecular studies to differentiate, in HTLV-I seropositive patients from endemic areas, a HTLV-I—induced T cell lymphoma from HTLV-I—nonrelated cutaneous T cell lymphomas.

Arthritis in a human T lymphotropic virus type I (HTLV-I) carrier.

The case is described of a 57 year old woman with polyarthritis fulfilling the 1987 revised criteria of the American Rheumatism Association for rheumatoid arthritis, accompanied by clinical carrier state infection of HTLV-I. Anti-HTLV-I IgM antibodies were detected by western blot analysis in her synovial fluid and serum. Atypical lymphocytes with nuclear convolutions were found in synovial fluid and synovial tissue obtained from the affected knee joint, suggesting in situ activation of HTLV-I infected lymphocytes in the affected synovial compartment. The HTLV-I antigens were detected (1.2%) in short term cultured synovial fluid lymphocytes, by indirect immunofluorescence. These findings supported the possibility that HTLV-I has a role in triggering or modifying inflammation in the synovial compartment.

Malignant Lymphomas of Thymus Origin in Two Sows

Two cases of swine thymic lymphoma were investigated by electron microscopy and the immunoperoxidase method for terminal deoxynucleotidyl transferase (TdT), and furthermore sheep erythrocyte rosette assay was applied to one case. In case 1, immunoblastoid cells predominated and smaller cells were admixed with them. Many neoplastic cells were TdT-positive and formed rosettes with sheep erythrocytes at 4 degrees C, but about half of them formed rosettes at 37 degrees C. Ultrastructurally the neoplastic cells were characterized by highly irregular nuclei, poorly developed organelles and clustered dense bodies. The neoplasm in case 2 was composed of medium-sized to large cells and the latter predominated. A few of the neoplastic cells stained positively with anti-TdT serum. Ultrastructurally the neoplastic cells were characterized by nuclear convolution, narrow cytoplasmic bands and clustered dense bodies. The morphological features of thymic lymphomas were discussed in comparison with those of other swine lymphomas and lymphomas of other animals. Histological and immunological progression into T-immunoblastoid cells in case 1 was also discussed.

ＨＴＬＶ‐１感染と滑膜炎 滑膜組識の病理組織学的検討

Histopathological analysis of the synovial tissues from 7 cases of HTLV-1 carriers who had chronic arthritis was performed. Synovial tissues showed villous proliferation to a various degree. Proliferation of synovial stromal cells associated with interstitial edema and proliferation of small blood vessels was observed. Lymphocytic infiltration was rather diffuse without evident lymph-follicle like structures. The most characteristic feature was the presence of atypical lymphocytes with nuclear convolution in the synovial tissues. Immunohistochemical analysis of the synovial tissues revealed infiltration both of CD4 and CD8 positive lymphocytes, accompanied with the expression of HLA-DR antigens on the synovial cells.These findings suggest that HTLV-1 infection might play an important role in the pathogenesis of the arthritis. Further examination of the function of HTLV-1 infected cells in the arthropathy is necessary.

Multiple myeloma associated with multilobated plasma cell nuclei.

Ten cases of multiple myeloma are reported in which there were a large number of plasma cells with excessively convoluted or lobulated nuclei. These cases represent 3% of the 297 evaluable multiple myeloma patients treated at our institution over a 22-year period. All 10 had intermediate or advanced stage disease at the time of diagnosis, and all have died after a mean survival of 19.5 months. Ultrastructural features of 2 cases are described. When found in abundance, such cells can cause difficulty in establishing a morphologic diagnosis of multiple myeloma because of their resemblance to other cell types. Therefore, it may be necessary to perform immunoperoxidase staining and/or electron microscopy to confirm the plasmacytic identity of these cells. The findings add further support to the contention that the presence of excessive nuclear convolutions is not a completely reliable indication of T-cell, as opposed to B-cell, lineage.

Malignant lymphoma of convoluted lymphocytes: diagnosis by fine-needle aspiration cytology and cytochemistry.

The technique of fine-needle aspiration cytology (FNAC) was utilized in the diagnosis of 31 cases of malignant lymphoma of convoluted lymphocytes. The age of the patients ranged from 5 to 70 yr (median, 24 yr). Clinical history was available in 29 cases. All patients had peripheral lymphadenopathy. There was radiological evidence of mediastinal adenopathy in 62% of the cases, and 41% had pleural effusion; 52% of the patients presented with mediastinal compression syndrome. The diagnostically crucial convoluted cells comprised 47.3 +/- 23.73% of all lymphoid cells. Nuclear convolutions were appreciated in a significant number of cells in paraffin sections of 17 of 21 cases (85.7%) having subsequent histopathology. Cytochemical and E-rosette tests performed in 17 cases confirmed the T cell nature of the neoplasms. On an average, 72.3% of cells showed focal positive reaction for acid phosphatase, and 73.8% of cells formed E-rosettes.

Immunological and ultrastructural observations on swine thymic lymphoma

A case of swine thymic lymphoma is described. A young pig had a mediastinal mass and bone marrow involvement and the microscopic findings showed peripheral blood involvement. The tumour was composed of small to medium sized lymphoid cells which formed rosettes with sheep erythrocytes and were characterized by narrow cytoplasmic bands, nuclear convolution and clustered dense bodies. Such structural and immunological features resembled those of human thymic lymphomas derived from thymic T-cells.