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[Mitochondrial localization of enzymes linked to glycogen metabolism in the snail sperm cell].

The mitochondrial derivative of the sperm cell of the Gastropod Helix is endowed with a compartment loaded with glycogen (Personne et André, 1964). The aim of this work is to establish whether this mitochondrial glycogen is synthesized in the mitochondrial derivative itself or elsewhere in the cell. For this purpose, living sperm were first incubated in a medium containing glucose 1-phosphate, then fixed, sectioned, and stained specifically for polysaccharides by the phosphotungstic acid technique or the periodic acid-thiosemicarbazide-silver proteinate technique. Comparison with controls shows that a synthesis of glycogen occurred during the time of incubation. It can be inferred from this result that an amylophosphorylase system controlling the metabolism of polysaccharides is present in the mitochondrial derivative itself. Results obtained with the iodine technique indicate that the original glycogen molecules are elongated during the experiment. It seems probable that the amylophosphorylase system demonstrated here accounts for at least a part of the proteinaceous coat morphologically detectable around each individual glycogen particle.

Animals↗

Intercellular attachment in the epithelium of Hydra as revealed by electron microscopy.

In Hydra adjacent epithelial cells are bound firmly to each other by desmosomes of a type not described in detail hitherto. The most prominent feature of these desmosomes is the presence of a series of parallel lamellae which bridge the intercellular space and connect the two apposed cell surfaces directly. These structures, here termed intercellular attachment lamellae, display two peaks of density about 50 A apart. These dense lines appear in some instances to be continuous with the outer dense components of the plasma unit membranes of the attached cells. The presence of prominent lamellae in intercellular attachments is sufficiently distinctive to deserve special terminology; accordingly, the term septate desmosome is proposed. It is noted that septate desmosomes may have been seen in other animals in instances where published electron micrographs show cross-striations or prominent connections in regions of intercellular attachment. It is suggested that septate desmosomes in Hydra, in addition to binding cells firmly to each other, form barriers to the movement of water into intercellular spaces and thus help to protect the organism's internal environment. Observations on the use of phosphotungstic acid for improving contrast in materials embedded in epoxy resins are also recorded.

Animals↗

The striated musculature of blood vessels. I. General cell morphology.

The musculature of small lung veins, of the thoracic portion of the inferior vena cava, and of other thoracic veins of the mouse have been studied in the electron microscope. Tissues were fixed in 1 per cent osmium tetroxide buffered with veronal, to which either sodium chloride or sucrose had been added. Methacrylate or araldite served as embedding matrices. Phosphotungstic acid or uranyl acetate was used to stain some of the preparations. Thin sections were examined in a Siemens and Halske Elmiskop Ib electron microscope. The entire musculature of the veins examined was of the striated type. It represents a variety of cardiac muscle, characterized by centrally located nuclei, typical mitochondria, and narrow I bands. Many I bands cannot be recognized at all. H and M bands are likewise indistinct. There is a double array of primary and secondary myofilaments. Mitochondria are large and numerous and contain many cristae. The endoplasmic reticulum consists of longitudinal tubules which run through the whole sarcomeres and bypass Z bands, and of transverse tubules which accompany Z bands. Some "triads," located at Z levels, consist of flattened vacuoles flanked by such transverse tubules. Small vesicles located at Z bands, close to the nucleus, and beneath the plasma membrane may represent still other portions of the reticulum.

Actin Cytoskeleton↗

Synthesis, migration, and release of precursor collagen by odontoblasts as visualized by radioautography after (3H)proline administration.

The elaboration of dentin collagen precursors by the odontoblasts in the incisor teeth of 30-40-g rats was investigated by electron microscopy, histochemistry, and radioautography after intravenous injection of tritium-labeled proline. At 2 min after injection, when the labeling of blood proline was high, radioactivity was restricted to the rough endoplasmic reticulum, indicating that it is the site of synthesis of the polypeptide precursors of collagen, the pro-alpha chains. At 10 min, when the labeling of blood proline had already declined, radioactivity was observed in spherical portions of Golgi saccules containing entangled threads, and, at 20 min, radioactivity appeared in cylindrical portions containing aggregates of parallel threads. The parallel threads measured 280-350 nm in length and stained with the low pH-phosphotungstic acid technique for carbohydrate and with the silver methenamine technique for aldehydes (as did extracellular collagen fibrils). The passage of label from spherical to cylindrical Golgi portions is associated with the reorganization of entangled into parallel threads, which is interpreted as the packing of procollagen molecules. Between 20 and 30 min, prosecretory and secretory granules respectively became labeled. These results indicate that the cylindrical portions of Golgi saccules transform into prosecretory and subsequently into secretory granules. Within these granules, the parallel threads, believed to be procollagen molecules, are transported to the odontoblast process. At 90 min and 4 h after injection, label was present in predentin, indicating that the labeled content of secretory granules had been released into predentin. This occurred by exocytosis as evidenced by the presence of secretory granules in fusion with the plasmalemma of the odontoblast process. It is proposed that pro-alpha chains give rise to procollagen molecules which assemble into parallel aggregates in the Golgi apparatus. Procollagen molecules are then transported within secretory granules to the odontoblast process and released by exocytosis. In predentin procollagen molecules would give rise to tropocollagen molecules, which would then polymerize into collagen fibrils.

Animals↗

Isolation of postsynaptic densities from rat brain.

Most synapses in the central nervous system exhibit a prominent electron-opaque specialization of the postsynaptic plasma membrane called the postsynaptic density (PSD). We have developed a procedure for the isolation of PSDs which is based on their buoyant density and their insolubility in N-lauroyl sarcosinate. Treatment of synaptic membranes with this detergent solubilizes most plasma membranes and detaches PSDs from the plasma membrane so that they can be purified on a density gradient. Isolated PSDs appear structurally intact and exhibit those properties which characterize them in tissue. The isolated PSDs are of the size, shape, and electron opacity of those seen in tissue; they stain with both ethanolic phosphotungstic acid and bismuth iodide-uranyl lead and the fraction contains cyclic 3',5'-phosphodiesterase activity. Quantitative electron microscope analysis of the PSD fraction gives an estimated purity of better than 85%. Inasmuch as the PSD is associated primarily with dendritic excitatory synapses, our PSD fraction represents the distinctive plasma membrane specialization of this specific synaptic type in isolation.

Acid Phosphatase↗

Structural and transcriptional features of the mouse spermatid genome.

A whole-mount electron microscope technique has allowed direct visualization of the transcription process in mouse spermatids. Thes observations have been supported by light and electron microscope autoradiographic techniques that employ [3H]uridine and [3H]arginine in attempts to clarify mechanisms of RNA synthesis and their relationship to nuclear histone changes throughout spermiogenesis. Early spermatid genomes are dispersed almost completely, whereas in later spermiogenic steps the posterior or flagellar nuclear region is readily dispersed and the anterior or subacrosomal nuclear region remains compact. Display of genome segments permits identification of regions where transcription complexes, presumably heterogeneous nuclear RNA species, are seen related to chromatin. These complexes appear as ribonucleoprotein chains, some of them of considerable length, decreasing progressively in number in late spermiogenic steps. This decrease coincides with diminishing rates of [3H]uridine incorporation. Two distinct patterns of chromatin have been identified: a beaded chromatin type associated with transcription complexes encounterd in early spermatids; and a smooth chromatin type not involved in transcriptive activity observed in advanced spermiogenic genomes. Protein particles staining densely with phosphotungstic acid become apparent in nuclei of spermatids after [3H]arginine incorporation becomes significant. There is no structural or autoradiographic evidence for the presence of nucleoli during spermiogenesis. From these data and from previous experimental findings, we conclude that: (a) spermatogonia, spermatocytes and Sertoli cells are transcriptionally expressed into heterogeneous nuclear RNA and preribosomal RNA species whereas transcription in spermatids is predominantly heterogeneous nuclear RNA; and (b) the modification of the chromatin patterns in late spermiogenic steps indicates a stabilized genome that restricts transcriptive functions.

Animals↗

The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition.

A postsynaptic density (PSD) fraction, including some adherent subsynaptic web material, has been isolated from dog cerebral cortex by a short-procedure modification of methods of Davis and Bloom (21, 22) and Cotman and Taylor (20), using Triton X-100. The fraction has been visualized by thin-section, replica, and negative (phosphotungstic acid) staining electron microscopy and its proteins separated by high-resoltuion SDS gel electrophoresis. Morphologically, the preparation seems to be quite pure, with very little membrane contamination. The density is composed of protein, no nuclei acids, and very little phospholipids being detectable. The fraction had no ATPase or GTPase activity, but it did have a very small amount of cytochrome c oxidase activity (of a specific activity less than 0.5 percent that of a mitochondrial fraction) and a small amount of 5'- nucleotidase activity (of a specific activity between 6 and 7 percent that of a synaptic membrane fraction). Electron micrographs reveal cup-shaped structures approximately 400nm long and approximately 40nm wide, made up of apparent particles 13-28nm in diameter. However, en face views, and particularly micrographs of replicas and PTA-stained preparations, reveal a disk-shaped structure, outside diameter approximately 400 nm, in which filaments are seen to extend from the central part of the density. High resolution gel electrophoresis studies indicated some 15 major proteins and perhaps 10 or more minor ones; the predominant protein had a mol wt of 51,000, followed by ones at 45,000, 40,000, 31,000, 26,000, and several at 100,000. A comparison by gel electrophoresis of density fraction proteins with those of a lysed synaptosomal membrane fraction containing some adherent densities indicated some comigrating proteins, but the major membrane fraction protein, mol wt 52,000, was not found in the density fraction. Antibodies raised against the density fraction reacted with a preparation of solubilized synaptic membrane proteins. By both these criteria, it was considered that the density and the synaptic membrane have some proteins in common. By separately mixing (125)I-labeled myelin, synaptic vesicle, and mitochondrial fraction proteins with synaptosomes, and then isolating the density fraction from the mixture, it was concluded that a major 26,000 mol wt density fraction protein was common to both mitochondria and density, that none of the proteins of the density were contaminants from the mitochondrial fraction, that a minor approximately 150,000 band was a contaminant from the synaptic vesicle fraction, and that the moderately staining PSD fraction protein of 17,000 mol wt band was the result of contamination by the major basic protein of myelin. On the basis of the marker enzymatic assays and the mixing experiments, it is considered that the density fraction is moderately pure biochemically, and that its protein composition, aside from a few exceptions noted above, reflects its in situ character.

Animals↗

Changes of the cell surface and of the digestive apparatus of Dictyostelium discoideum during the staruation period triggering aggregation.

The effects of starvation on the cell morphology of Dictyostelium discoideum were studied with different cytochemical techniques, and with a morphometric method by which the surface areas of the cell membrane and of the digestive system can be determined. During the first 2 h, the cell membrane becomes very wrinkled and many phagocytic cups and filopods are formed. These changes are in accord with the 40 percent increase in the cell surface area to cytoplasmic volume ratio observed, which is mainly due to a strong decrease in the cytoplasmic volume. At this time of starvation, cells are able to ingest twice as many yeast as during growth. Afterwards, while the phagocytic ability decreases, the phagocytic cups disappear, and all the cells become bristled with many thin filopods. In spite of these morphological changes, no quantitative or topological differences have been observed concerning the polysaccharide content of the plasma membrane, whether it was stained with phosphotungstic acid, silver proteinate, or ruthenium red. During this time, the digestive vacuoles imbricate one into the other. Part of the vacuoles are degraded by this process, thus leading to an atrophy of the digestive apparatus. The digestive apparatus is progressively replaced by an autophagic system. Polysaccharide stainings and morphological observations show that the cytosegresomes seem to originate from the food vacuoles which flatten and sequester portions of cytoplasm. After 5 h of starvation, the digestive system is entirely transformed into an autophagic apparatus. The cell population appears to be homogeneous with respect to these changes. Therefore, potential precursors of prestalk and prespore cells were not observed.

Acid Phosphatase↗

Isolation and characterization of the membrane envelope enclosing the bacteroids in soybean root nodules.

The membrane envelope enclosing the bacteroids in soybean root nodules is shown by ultrastructural and biochemical studies to be derived from, and to retain the characteristics of, the host cell plasma membrane. During the early stages of the infection process, which occurs through an invagination, Rhizobium becomes surrounded by the host cell wall and plasma membrane, forming the infection thread. The cell wall of the infection thread is degraded by cellulolytic enzyme(s), leaving behind the enclosed plasma membrane, the membrane envelope. Cellulase activity in young nodules increases two- to threefold as compared to uninfected roots, and this activity is localized in the cell wall matrix of the infection threads. Membrane envelopes were isolated by first preparing bacteroids enclosed in the envelopes on a discontinuous sucrose gradient followed by passage through a hypodermic needle, which released the bacteroids from the membranes. This membrane then sedimented at the interface of 34--45% sucrose (mean density of 1.14 g/cm3). Membranes were characterized by phosphotungstic acid (PTA)-chromic acid staining. ATPase activity, and localization, sensitivity to nonionic detergent Nonidet P-40 (NP-40) and sodium dodecyl sulfate (SDS) gel electrophoresis. These analyses revealed a close similarity between plasma membrane and the membrane envelope. Incorporation of radioactive amino acids into the membrane envelope proteins was sensitive to cycloheximide, suggesting that the biosynthesis of these proteins is primarily under host-cell control. No immunoreactive material to leghemoglobin antibodies was found inside or associated with the isolated bacteroids enclosed in the membrane envelope, and its location is confined to the host cell cytoplasmic matrix.

Adenosine Triphosphatases↗

The striated musculature of blood vessels. II. Cell interconnections and cell surface.

The interconnections and the surfaces of the striated muscle cells which occur in thoracic and in lung veins of the mouse were studied with the electron microscope. The osmium-fixed tissues were embedded in methacrylate or in araldite and sectioned with a Porter-Blum microtome. Many preparations were stained before embedding with phosphotungstic acid or after sectioning with uranyl acetate. Typical intercalated discs are observed in this muscle. They are similar to the discs found in heart muscle. These intercalated discs represent boundaries between separate muscle cells. Along the discs, cells are joined in planes normal to their myofilaments. The same cells are also joined in planes parallel to the myofilaments by means of lateral interconnections. These lateral cell boundaries are in continuity with the intercalated discs. Three morphologically distinct parts occur within the lateral cell interconnections: One is characterized by small vesicles along the plasma membrane, the second part has the structure of desmosomes, and a third part represents an external compound membrane (formed by the two plasma membranes of the adjoining cells) and is termed "quintuple-layered cell interconnection." Small vesicles and plasma membrane enfoldings along the free surface of muscle cells are interpreted as products of a pinocytosis (phagocytosis) process. Some of them are seen to contain small membrane-bounded bodies or granules. The free cell surface shows a characteristic outer dense layer ("basement membrane") which accompanies the plasma membrane. The topographic relation of this dense layer with the plasma membrane seems to vary in different preparations. The significance of this variation is not well understood. On two occasions a typical arrangement o vesicles and tubules was observed at Z band levels, just beneath the plasma membrane. These structures are believed to represent endoplasmic reticulum. Their possible significance for the conduction of excitation is discussed.

Animals↗

Putative 51,000-Mr protein marker for postsynaptic densities is virtually absent in cerebellum.

Cerebrum and cerebellum contain numerous asymmetric synapses characterized by the presence of a postsynaptic thickening prominently stained by phosphotungstic acid and other electron-dense stains suitable for electron microscopy. A 51,000-Mr protein, copurified in postsynaptic density-enriched fractions from cerebrum, is considered to be a well established marker for the postsynaptic density. On the basis of two criteria, our studies demonstrate that the 51,000-Mr protein marker for postsynaptic densities is virtually absent in cerebellum, First, it is present in negligible amounts in deoxycholate-insoluble fractions from cerebellum but abundant in parallel fractions from cerebrum. Secondly, the 51,000-Mr protein, which binds 125I-calmodulin after SDS PAGE is readily visualized in membrane samples from cerebrum but is virtually undetectable in cerebellar samples. It is apparent that these results require reexamination of the role of the 51,000-Mr protein in postsynaptic density structures.

Calmodulin↗

THE ENTRY AND DISTRIBUTION OF HERPES VIRUS AND COLLOIDAL GOLD IN HELA CELLS AFTER CONTACT IN SUSPENSION.

The way in which herpes virus of a well adapted strain penetrates susceptible HeLa cells has been investigated using thin sectioning techniques for electron microscopy. Mature virus particles and cells were mixed together in suspension cultures for 15, 30, 60, or 120 minutes so that the stages in virus uptake could be followed in sequence. The ingestion of particles of colloidal gold by HeLa cells under similar conditions was studied for comparison in parallel experiments. After 15 minutes' contact, the mature virus was found adsorbed on the surface of the cells but separated from them by a narrow gap in which phosphotungstic acid staining was sometimes able to reveal an extraneous coat which appeared as an amorphous layer on the outer aspect of the plasma membrane. When mixing continued for longer the particles were present in deep invaginations or actual cytoplasmic vacuoles, with their outer layers in various stages of stripping and digestion. The stripped, naked, central portion of the virus was occasionally found in these vacuoles but was more commonly free in the cytoplasmic matrix; the mode of transition between these sites could not be determined. Where contact continued for 2 hours these phenomena were much less frequently observed. The larger particles of colloidal gold were ingested in the same way as the virus, but smaller ones were taken up in micropinocytosis vesicles. The gold passed through membrane-bounded cytoplasmic spaces to accumulate in vacuoles from which, in contrast to herpes particles, it did not escape. These findings are discussed, and considered with particular reference to their bearing on the initiation of infection, the uptake and disposal of particles by cells, and the influence on the latter of virus morphology.

Cytoplasm↗

Evaluation of a rapid homogeneous method for direct measurement of high-density lipoprotein cholesterol.

We evaluated the performance of a direct Liquid N-geneous HDL-C assay (N-HDL; Genzyme Diagnostics, Cambridge, Mass) and compared it with a Centers for Disease Control and Prevention (CDC) modified reference procedure (M-REF) and phosphotungstic acid (PTA) precipitation method in patients with normotriglyceridemia (triglyceride level, <400 mg/dL) and hypertriglyceridemia (triglyceride level, > or =400 mg/dL). Excellent intra-assay and interassay coefficients of variation were obtained (<2.0%) using the N-HDL assay. The N-HDL and PTA assays correlated well with M-REF in normotriglyceridemic samples. In hypertriglyceridemic samples, however, the N-HDL method exhibited better correlation with M-REF than the PTA assay. In addition, compared with M-REF, the mean absolute percentage bias of N-HDL was lower than the PTA assay in normotriglyceridemic (4.9% vs 5.8%) and hypertriglyceridemic (5.4% vs 12.9%) samples. Hemolysis, ascorbic acid, and bilirubin did not interfere with the N-HDL assay. On the basis of these findings, the N-HDL assay compares favorably with the modified CDC reference method and seems superior to the PTA assay. It also has the advantage of being suited for complete automation and, thus, would prove useful in large clinical laboratories.

Cholesterol, HDL↗

Embryonal rhabdomyosarcoma presenting in an adult: a case report and discussion of immunohistochemical staining.

Embryonal rhabdomyosarcoma is the most common soft tissue sarcoma of childhood but is rarely seen in adults. We report an embryonal rhabdomyosarcoma of the cheek in a 21-year-old Filipino man presenting as a rapidly enlarging mass. An incisional biopsy was consistent with embryonal rhabdomyosarcoma. The patient failed to respond to one cycle of chemotherapy after initial diagnosis and workup for metastatic disease. Wide local excision of the tumor was then completed with the use of the Mohs technique to clear the glabrous cutaneous margins during surgery. A Mohs surgeon and dermatopathologist were involved in interpretation of the Mohs sections. Subsequent immunohistochemical staining revealed a poorly differentiated spindled and epithelioid cell tumor, which stained diffusely positive for vimentin, S-100, and MyoD1. Rare rhabdomyoblasts were present and stained positively for desmin, muscle-specific actin, and phosphotungstic acid hematoxylin. The patient subsequently underwent radiation therapy for a total of 6,000 cGy, followed by two cycles of chemotherapy. The patient continues to be disease-free at 22 months after his wide local excision.

Adult↗

Evaluation of agonal artifacts in the myocardium using a combination of histological stains and immunohistochemistry.

The problem of discrimination between agonal artifacts and intravital ischemic myocardial lesions was studied with four histochemical stains [hematoxylin-eosin, Mallory's phosphotungstic acid hematoxylin (PTAH), modified luxol fast blue, and Lie's hematoxylin basic fuchsin picric acid (HBFP)] and with immunohistochemistry using two antibodies (antimyoglobin and anti-C5b-9). Seventy-five forensic autopsy cases were divided into six groups designed to represent successively shorter periods of agonal myocardial ischemia: (a) sudden deaths with coronary artery disease, macroscopically visible myocardial infarction, and/or fresh coronary thrombus; (b) unexplained sudden deaths without coronary artery disease; (c) accidental CO poisoning; (d) suicidal CO poisoning in cars; (e) suicidal hangings; and (f) instant traumatic deaths, i.e., total brainstem laceration or rupture of the thoracic aorta. From each heart, five pieces were removed from standardized locations, and six parallel sections were stained with each method (i.e., 30 sections from each heart). Hematoxylin-eosin and anti-C5b-9 were only positive in the first three groups, thus indicating specificity for intravital necrotic changes. The other staining methods were "positive" in one or more cases in all six groups, thus implicating a high degree of sensitivity for artifactual, agonal ischemic changes. The latter methods cannot be used alone in the diagnosis of myocardial infarction. By staining parallel sections with different stains and antibodies, it seems possible to estimate the relative length of the agonal period in cardiac and noncardiac deaths.

Adult↗

Microcystic variant of meningioma: a light-microscopic and ultrastructural study.

Meningiomas occasionally show small areas in which the cells are stellate with slender processes surrounding microscopic spaces, giving a lace-like appearance to the tissue. In the case of a 52-year-old woman with a tumor rising from the falx, virtually the entire tumor was composed of lacy reticulated tissue. Most of the tumor cells had processes that stained blue with phosphotungstic acid hematoxylin, suggesting the appearance of a glioma. However, electron microscopy showed that the extracellular space was extensive, and the tumor cells had long cytoplasmic processes which formed interdigitations with one another. Desmosomes were numerous. The immunoperoxidase method for glial fibrillary acidic protein gave negative results. On the basis of these histologic features, we suggest that this tumor was a microcystic variant of meningioma.

Female↗

Use of anti-skeletal muscle antibody from myasthenic patients in the diagnosis of childhood rhabdomyosarcomas.

Rhabdomyosarcoma (RMS), a common soft tissue tumor in children, may often be difficult to distinguish from Ewing's sarcoma, neuroblastoma, and malignant lymphomas. Confirmation of the skeletal muscle origin of RMS depends partly on the demonstration of striations in tumor cells that are usually undetectable in poorly differentiated tumors. A number of tissue markers (e.g., myoglobin and desmin) are currently being used to establish the origin of RMS. However, most of these markers lack specificity and have relatively low sensitivity. We have investigated the specificity and sensitivity of anti-skeletal muscle antibody (ASMA) from patients with myasthenia gravis in the diagnosis of childhood RMS. Out of eight cases of childhood RMS (four embryonal and four alveolar) examined, two showed striations with hematoxylin and eosin and four with phosphotungstic acid hematoxylin. Myoglobin was detected in five tumors; only well-differentiated tumor cells contained myoglobin. Anti-desmin antibody and ASMA reacted with cells in all the eight tumors whether or not the tumor cells were well differentiated. Anti-skeletal muscle antibody did not react with nine lymphomas, four Ewing's sarcomas, four neuroblastomas, four osteogenic sarcomas, four lipomas, eight duct carcinomas of the breast, and eight squamous cell carcinomas of the lung. Eight leiomyomas and four leiomyosarcomas of the uterus were compared for their reactivity with anti-desmin antibody and ASMA. All the tumors stained with anti-desmin antibody and none with ASMA. The results show that ASMA is useful in the diagnosis of childhood RMS and is a more sensitive reagent than anti-myoglobin antibody. Unlike anti-desmin antibody, it can distinguish skeletal muscle tumors from smooth muscle tumors.

Antigens, Neoplasm↗

Intraductal oncocytic papillary neoplasms of the pancreas.

We describe the clinical and pathologic features of 11 intraductal oncocytic papillary neoplasms of the pancreas, a hitherto unrecognized tumor. The patients were six men and five women, and most of the tumors were in the head (head: body/tail = 8:3). The mean patient age was 62 (range, 39-78), and the average tumor size was 6 cm. Grossly the tumors exhibited mucin-filled cysts containing nodular papillary projections. Dilated ducts communicating with the main tumor were sometimes noted. Microscopically the cystic structures appeared to represent dilated ducts containing intraductal tumor. The tumors were characterized by variably complex, arborizing papillary structures. The papillae had thin, delicate fibrovascular cores with focal myxoid changes and were lined by stratified oncocytic cells. Goblet cells and intra-epithelial mucin-containing lumina were present, the latter resulting in a characteristic cribriform pattern. The exuberance of the epithelial proliferation varied from case to case and between different regions within individual tumors; solid sheets of cells were often identified. Although the degree of cytologic atypia was not generally severe, the complexity of the architecture justified a designation of intraductal oncocytic papillary carcinoma in 10 of the 11 cases. In nine cases the tumor was entirely intraductal; one case exhibited focal microinvasion and another showed widespread invasive carcinoma, the invasive elements appearing cytologically similar to the intraductal papillary components. The oncocytic cells stained positively with phosphotungstic acid hematoxylin and Novelli stains. Immunohistochemically, all cases stained positively for B72.3, and five cases showed focal, weak luminal membrane staining for carcinoembryonic antigen. Ultrastructurally many of the cells were packed with mitochondria, and mucin was also identified. Seven patients were alive and free of tumor from 1 month to 3 years (average, 1 year) after resection. Two patients died postoperatively. The remaining two patients died with no evidence of disease at 2.5 and 5 years, the latter following a recurrence at 2.5 years. We conclude that intraductal oncocytic papillary neoplasm is a distinctive pancreatic tumor that is usually intraductal but may develop invasive carcinoma and should be treated with complete resection.

Adenocarcinoma, Mucinous↗