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PubMedDate not supplied

Microanalytical techniques and image analysis in the evaluation of immunogold-labeled specimens at the ultrastructural level.

Energy-dispersive X-ray microanalysis (EDX) interfaced to a scanning/transmission electron microscope allows direct visualization and photographing of structures analyzed under the electron beam. EDX can perform a point-by-point analysis as it searches for the ion whose X-ray window the computer has been instructed to localize. This technique has been utilized to define ultrastructural immunogold labeling patterns. Once a specimen is immunolabeled with gold, microanalytical techniques can identify the quantity and distribution of detected and labeled antigenic epitopes. Microanalytical techniques add a new objective dimension to ultrastructural gold labeling procedures. Quantitative microanalysis of the gold-labeled antigenic sites provides a way of assessing the specificity of the reactions and permits comparison of the degree of expression of antigenic determinants in different specimens. Image processing allows visual representation of the immunolabeling results. Furthermore, statistical analysis of a large number of parameters is also possible with the digitized images collected. Ultrastructural microanalytical techniques represent a new, unexplored application that may play an important role in the future of ultrastructural pathology and immunologic evaluation of diseased tissues.

Electron Probe Microanalysis↗
PubMedDate not supplied

Heterogeneity of acute myeloblastic leukemia without maturation: an ultrastructural study.

We demonstrated by ultrastructural examination that the leukemic blasts of 13 patients with acute myeloblastic leukemia (AML) without maturation (M1 in the French-American-British classification) showed heterogeneous features. In 7 patients, the leukemic blasts had a high level of light microscopic myeloperoxidase positivity (> 50%). Ultrastructurally, the cells were myeloblast-promyelocytes with 100% myeloperoxidase positivity, and these 7 patients appeared to have typical AML. In contrast, the remaining 6 patients had leukemic blasts with a low myeloperoxidase positivity (< 50%) and heterogeneous features. Three had ultrastructural features of myelomonocytic or monocytic lineage, 1 had myelomonocytic cells associated with megakaryoblasts, and 1 had undifferentiated blasts. The former group had a better prognosis than the latter, indicating that ultrastructural analysis of M1 leukemia may help predict the response to therapy.

Adolescent↗
PubMedDate not supplied

Variability of differentiation patterns in xenotransplanted spindle cell sarcomas: a histomorphological, immunohistochemical, and ultrastructural study.

Three leiomyosarcomas, 3 nerve sheath sarcomas, 1 rhabdomyosarcoma, and 1 sarcoma not otherwise classifiable with 17 of their xenografts, grown on nude mice, were analyzed to assess the degree of concordance between histomorphology, immunohistochemistry, and ultrastructure in spindle cell sarcoma xenograft differentiation. Histomorphology was inconclusive or misleading in 4/8 sarcoma strains and immunohistochemistry in 4/8 originals and in 10/17 xenografts, although specific patterns had been identified ultrastructurally. Electron microscopy was superior to immunohistochemistry and histomorphology in spindle cell sarcoma differential diagnosis. A further purpose of this study was to clarify whether spindle cell sarcoma xenografts retain the morphological characteristics of their primaries. Histomorphological features of the primaries were preserved over all passages, whereas the immunohistochemical marker profiles as well as the ultrastructural phenotypes changed in 14/17 xenografts and in 8/17 xenografts, respectively. Moreover, unusual bidirectional or tridirectional patterns of differentiation were identified ultrastructurally with leiomyomatous as well as Schwann cells occurring side by side and with MFH-like areas in 5/17 xenotransplants. These findings suggest genetic instability of tumor cells and may be important in the consideration of mesenchymal differentiation pathways.

Animals↗
PubMedDate not supplied

The many faces of smooth muscle neoplasms in a gynecological sampling: an ultrastructural study.

Smooth muscle neoplasms may have a variety of light microscopic and ultrastructural appearances. On one extreme, a spindle cell mass with a fascicular pattern, located in the myometrium, usually does not need electron microscopy or immunohistochemistry to confirm its smooth muscle nature. However, at the other end of a spectrum is an epithelioid neoplasm of the extrauterine pelvic tissues that could be composed of any of several cell types if routine light microscopy, alone, were used in studying it. In this report, some of these variants of smooth muscle neoplasms are exemplified, including myxomatous, fibroblast-like, nondescript, epithelioid, granular cell, and clear cell types. The main purpose has been to address, in particular, the ultrastructure of these unusual neoplasms, but, at the same time, not to ignore or downplay the contributory role of immunohistochemistry in making a final diagnosis, in some cases. Especially intriguing were the ultrastructural characteristics of leiomyomatous granular cell and clear cell neoplasms. A paucity or absence of filaments and dense bodies in samplings of these lesions makes the reliance on other ultrastructural features extremely useful.

Actins↗
PubMedDate not supplied

Reversible ultrastructural alterations in the myocytic mitochondria of isolated rat hearts induced by oxygen radicals.

The present study focuses on reversible mitochondrial ultrastructural alterations in myocardial myocytes that correspond or accompany reversible metabolic depression observed after oxygen radical exposure. The myocytic mitochondrial membranes and matrix of isolated Langendorff-perfused rat hearts were examined by semiquantitative morphometry using the electron micrograph as unit. The hearts were exposed to either standard perfusion (group A), 10 min of oxygen radicals together with superoxide dismutase and catalase followed by 35 min of recovery (group B), 10 min of oxygen radicals alone (group C), or 10 min of oxygen radicals followed by 35 min of recovery (group D). Mitochondrial ultrastructural alterations were detected in only a few micrographs in groups A and B. The frequency of micrographs with mitochondrial ultrastructural alterations was 69% in group C and 62% in group D. In the group exposed to 10 min of oxygen radicals without recovery (group C) condensed pentalaminar membranous profiles arranged in parallel, interpreted to be closely adhering cristae, were detected in the intracristal compartment of myocytic mitochondria in 50% of the micrographs. The cristal adhesions were associated with other mitochondrial ultrastructural changes. Cristal adhesions were not present in group A or B, and were rarely found in the group exposed to 10 min of oxygen radicals followed by 35 min of recovery (group D). Thus, the cristal adhesions appear to be reversible alterations caused by exposure to oxygen radicals.

Animals↗
PubMed1985

Juvenile granulosa cell tumor of the infant testis: case report with ultrastructural observations.

This report describes the light-microscopic and ultrastructural features of a juvenile granulosa cell tumor of infant testis. Microscopic examination revealed a macrofollicular patterns simulating the preovulatory Graafian follicle and the juvenile granulosa cell tumor of the ovary. Ultrastructure confirmed three cell types: granulosa, theca interna, and externa, with occasional luteinized cells lacking crystalloids of Reinke. Charcot-Bottcher crystalloids were not detected, though rare cells contained a complex arrangement of filaments. An ultrastructural comparison was carried out with infant testes (2 cases), preovulatory Graafian follicle (1 case), juvenile granulosa cell tumor of ovary, adult granulosa cell tumor of ovary, and adult Sertoli cell tumor of testis and ovary. Ultrastructural similarities were noted between the present case and primitive Sertoli cells, preovulatory granulosa cells, and juvenile granulosa cell tumor of ovary. This may reflect the common histogenesis of Sertoli/granulosa cells from the common specialized gonadal stroma.

Epididymis↗
PubMed1986

Ultrastructural criteria in evaluating leukemic infiltration in prepubertal testicular biopsies.

The diagnosis of leukemic infiltration in the testis by routine histology is not always possible. During the past 5 years, 46 bilateral testicular biopsies from prepubertal boys were examined by electron microscopy for the purpose of establishing the presence or absence of leukemic infiltration. The ultrastructure of the cells of acute lymphoblastic leukemia is described from the positive cases and compared with cases from the literature. Variations in ultrastructure between the T-cell, B-cell, and "null cell" types are discussed. The ultrastructure of the normal prepubertal cellular elements, which include immature Leydig cells, primitive fibroblastic cells (intertubular), and attenuated peritubular fibroblasts, is described. Ultrastructural criteria are summarized that enable a definitive evaluation of cases that are equivocal by histologic examination.

Acute Disease↗
PubMed2002

Ultrastructural scoring of graded acute spinal cord injury in the rat.

OBJECT: There is a need for an accurate quantitative histological technique that also provides information on neurons, axons, vascular endothelium, and subcellular organelles after spinal cord injury (SCI). In this paper the authors describe an objective, quantifiable technique for determining the severity of SCI. The usefulness of ultrastructural scoring of acute SCI was assessed in a rat model of contusion injury. METHODS: Spinal cords underwent acute contusion injury by using varying weights to produce graded SCI. Adult Wistar rats were divided into five groups. In the first group control animals underwent laminectomy only, after which nontraumatized spinal cord samples were obtained 8 hours postsurgery. The weight-drop technique was used to produce 10-, 25-, 50-, and 100-g/cm injuries. Spinal cord samples were also obtained in the different trauma groups 8 hours after injury. Behavioral assessment and ultrastructural evaluation were performed in all groups. When the intensity of the traumatic injury was increased, behavioral responses showed a decreasing trend. A similar significant negative correlation was observed between trauma-related intensity and ultrastructural scores. CONCLUSIONS: In the present study the authors characterize quantitative ultrastructural scoring of SCI in the acute, early postinjury period. Analysis of these results suggests that this method is useful in evaluating the degree of trauma and the effectiveness of pharmacotherapy in neuroprotection studies.

Animals↗
PubMed1993

Recovery of the ultrastructure of jejunal absorptive cells and absorption of nutrients in starved then re-fed rats.

This study tried to find what fat level of diets would have a good effect on recovery of the ultrastructure and the digestion-absorption function of jejunal absorptive cells in rats which had been subjected to starvation. Fat-free, 5% fat, 10% fat, or 20% fat diet was given for 3 days to the starved rats, and changes in the ultrastructure of the jejunal absorptive cells were observed by transmission electron microscopy. Also, glucose and triolein absorption were studied using an in situ perfusion system. Good recovery of the ultrastructure of jejunal absorptive cells was observed in rats re-fed the 5% fat diet. Glucose absorption did not differ among the groups except in rats given the 20% fat diet. However, triolein absorption in this group was lower than that of the other groups in both the upper and lower jejunum. The best fat level for recovery of the ultrastructure and absorption of glucose and triolein in the jejunal absorptive cells was concluded to be the 5% fat diet.

Animals↗
PubMed2000

Vitamin B6 antagonists alter the function and ultrastructure of mice endothelial cells.

Vitamin B6, is necessary for normal membrane function and stability. Here we studied both the function and ultrastructure of aortic and arterial endothelial cells (ECs) in vitamin B6 deficient mice induced by vitamin B6 antagonists, 4-deoxypyridoxine x HCl (dPN x HCl), and isonicotinylhydrazide (INH). Mice were fed with normal laboratory chow and divided into three groups according to their drinking water. Mice in group I had distilled water and served as a control; group II had 0.1 mg dPN x HCl/mL H2O; and group III had 0.4 mg INH/mL H2O. After 5 mo, plasma concentrations of B6 vitamers pyridoxal-5'-phosphate (PLP) and pyridoxal (PL) were analyzed by HPLC. With the arachidonic acid (AA) as a precursor, prostacyclin (PGI2) production from ECs assayed by thin-layer chromatography (TLC) was used as an indicator of endothelial function. Aorta and arteriole from foot pad were removed, stained with osmium tetraoxide, and examined under transmission electron microscopy (TEM) to study the ultrastructure of ECs. The results showed that plasma concentrations of PLP, PL, and total B6 were the lowest for mice fed with INH. followed by that with dPN x HCl, compared with that of control. PGI2 production was paralleled with the plasma vitamin B6 status, with the lowest level for INH, followed by the dPN-treated group. Abnormalities in the ultrastructure of ECs were found in both dPN x HCl and INH groups, including cells detached from underlying elastic tissue, with prominent pinocytotic vesicles and swelling and/or indistinct cristae of mitochondria. These results suggest that vitamin B6 antagonists induce a deficient status that alters the function and the ultrastructure of ECs detrimental to vascular disease.

Animals↗
PubMed1976

[Sialadenosis of the parotid gland. Ultrastructural, clinical and experimental findings in disturbances of secretion (author's transl)].

Among the secretory disturbances ("Dyschylien") of salivary glands the sialadenosis of the parotid gland is a clinic and a morphologic definited entity. The typical clinical symptom is a bilateral, often recurrent, and painless swelling of the parotid gland. The characteristic pathological findings consist in an acinar cell hypertrophy without any inflammatory signs. According to this definition, sialadenosis has to be separated from those diseases of salivary glands, which are primarily altered by inflammation of the salivary tissue with secondary secretory disturbances. From flinical point of view it is possible to distinguish the following kinds of sialadenosis according to the syntropy with various diseases: Endocrine sialadenosis (in diabetes mellitus, dysfunction of gonads, pituitary gland, thyroid gland etc.); dystrophic-metabolic sialadenosis (malnutrition, avitaminosis, alcohilsm, chronic liver diseases etc.), and neurogenic sialadenosis (dysfunction of the vegetative nervous system, drug damages e.g. antihypertensive agents). The question arises, whether all forms of sialadenosis have a common etiology and a coincidental pathogenic factor. The following studies were carried out with the aim to find further details concerning the etiology and pathogenesis of sialadenosis. The study is based on the following material: a) 126 Biopsies of parotid glands from patients with sialadenosis (Register of salivary gland diseases at the Institute of Pathology, University of Hamburg, supported by Deutsche Forschungsgemeinschaft). This material was collected from 1965 to 1973. b) 80 Biopsies of parotid glands from patients with other diseases (parotitis [4]; acinic cell carcinoma [4]; other parotid and oral tumors [72]; for comparison. c) Experimental studies on the parotid salivary glands of Wistar-rats. The biopsies of the parotid glands were studied histologically, morphometrically, and ultrastructurally. The investigations centered on the ultrastruct of sialadenosis. Before interpreting the ultrastructural findings in view of etiology and pathogenesis of sialadenosis, it was primarily necessary to study the normal ultrastructure of the human parotid gland including the vegetative nervous system. Furthermore it was necessary to elucidate details of a functional morphology of the secretory cycle and to integrade the findings into a concept of general pathology of secretory disturbances. The following results were achieved by our investigations: 1. Normal ultrastructure of human parotid gland: The architecture of the acinar cells is identical with these of other animal species (cytoplasm with a basal standing nucleus, rough endoplasmatic reticulum, Golgi-apparatus, secretory granules etc.). Further identical elements are intercalated and striated ducts, myoepithelial cells, and the vegetative nervous system (postganglionic sympathetic and parasympathetic neurites, however no ganglionic cells in the parotid gland)...

Action Potentials↗
PubMed1999

Ultrastructural localization of light-induced lipid peroxides in the rat retina.

PURPOSE: Localization of light-induced lipid peroxides in the rat retina at an ultrastructural level as benzidine-reactive substances. METHODS: Long-Evans rats with nondilated pupils were exposed to intense light of 6000 lux for 12 or 24 hours. Control animals were kept under physiological light conditions. Rats with dilated pupils were exposed to a light intensity of 50 lux or 150,000 lux for 1 hour. For ultrastructural localization the enucleated eyes were fixed in a 0.1-M cacodylate buffer (pH 7.4) containing 2% glutaraldehyde for 2 hours. Pieces of the superior part of the central eyecup were incubated overnight with tetramethylbenzidine (TMB; pH 3.0) at 4 degrees C, postfixed with 1.5% OSO4, and embedded for electron microscopy. RESULTS: In animals exposed to intense light, electron-dense structures appeared exclusively throughout the rod outer segments after an irradiation of 6000 lux for 24 hours or 150,000 lux for 1 hour and were absent in animals with nondilated pupils kept at physiological light conditions. Dilation of the pupils leads to the appearance of electron-dense structures after just 1 hour of 50 lux, whereas rats with nondilated pupils withstand even a 12-hour irradiation with 6000 lux. No electron-dense structures were found when no TMB was used in incubation. CONCLUSIONS: The appearance of electron-dense structures in the rod outer segments depends on the incubation with TMB and intensive light exposure of the rat. Dilation of the pupils lowers the threshold for the emergence of electron-dense structures significantly. This strongly supports the view that light-induced lipid peroxides in the rat retina are localized at an ultrastructural level as benzidine-reactive substances. This protocol presents a tool for the generation and ultrastructural localization of lipid peroxides in rat retinas.

Animals↗
PubMed1998

[The effect of insulin-like growth factor-I on steroidogenesis and ultrastructures of cultured human granulosa cells in vitro].

OBJECTIVE: To observe the effect of insulin-like growth factor-I (IGF-I) on steroidogenesis and ultrastructures of cultured human granulosa cells in vitro and the synergetic influence of follicle stimulating hormone (FSH) on this process. METHODS: Human granulosa cells were cultured in serum-free 1640 medium. After stimulated with various concentrations of IGF-I or IGF-I + FSH for 24 hours, estradiol (E2) and progesterone (P) levels in the media were measured by radioimmunoassay, and the ultrastructure changes of granulosa cells were observed under electronic microscope. RESULTS: When stimulated with different concentrations of IGF-I for 24 hours, E2 and P levels produced by granulosa cells were in a dose-dependent manner and significantly higher than those of controls (P < 0.01). The E2 and P levels in the media under the stimulation of IGF-I + FSH were 3.5 times and 14.5 times respectively higher than those of FSH alone. The main ultrastructureal appearances of granulosa cells stimulated with IGF-I were abundance of enlarged smooth enodplasmic reticulum, mitochondria and lipid droplets in cytoplasm. CONCLUSIONS: IGF-I possesses a positive effect on the steroidogenesis of cultured human granulosa cells in dose-dependent fashion which could be enhanced by combination of IGF-I and FSH. The ultrastructures of granulosa cells showed a tendency toward activation of steroidogenesis under the stimulation of IGF-I.

Cells, Cultured↗
PubMedDate not supplied

Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure.

A variety of active diterpene epoxides, including the triptolide (isolated from Tripterygium wilfordii) have been reported to cause infertility in male rats. Previously, we showed that oral administration of triptolide at a dosage of 100 microg/kg per body weight for 70 days completely inhibited fertility in male rats, with little or no demonstrable detrimental effect on spermatogenesis and Leydig cell function as determined by testicular light microscopic appearance and serum and intratesticular testosterone levels. Despite the apparent absence of effects on the testes, cauda epididymal sperm were abnormal, with complete cessation of sperm motility and some reduction in sperm numbers. This study was undertaken to provide additional insight into the subcellular sites and possible mechanisms of action of this compound using ultrastructural analysis of the testes and epididymidis. The most striking effect of triptolide treatment was observed in sperm in the epididymis. In rats rendered infertile with 100 microg/kg per body weight of triptolide daily for 70 days, virtually all cauda epididymal sperm exhibited complete absence of plasma membrane over the entire middle and principal piece, premature decondensation of the nuclei, and disorganization of the mitochondrial sheath with many vacuolated mitochondria. No ultrastructural differences in the epididymal epithelium were observed between control and triptolide-treated rats. The testes appeared to be mildly affected after triptolide treatment but exhibited only subtle ultrastructural defects in the germ cells. The findings of severe impairment of cauda epididymal sperm ultrastructure, along with minimal discernible abnormalities in the fine structural cytology of the testes, further suggest that the site of action of this compound is posttesticular and may be confined to the cauda epididymal sperm. However, we cannot rule out an effect of triptolide that occurs during germ cell maturation but is delayed in its manifestation or triggered at the rete testis and epididymal level.

Animals↗
PubMed1999

Ultrastructural study of the effects of 6-hydroxydopamine on the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis).

The present study examined the ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after 6-hydroxydopamine (6-OHDA) at survival times of 1, 3, 5, 7 and 14 days. Changes ranged from dissolution of the cytoplasm to amorphous appearance and darkening of the nodal cells. Initially, the ultrastructural changes were quite similar in both sinuatrial (SA) and atrioventricular (AV) nodal cells but in the later stage, especially at fourteen days, affected SA nodal cells showed empty-looking appearance while affected AV nodal cells displayed a darkened appearance. The cardiac neurons also showed ultrastructural changes such as diffuse accumulation of glycogen particles, distended cisternae of the rough endoplasmic reticulum and increased lipofuscin granules. Some of the vacuolated axonal profiles containing large dense-cored vesicles were in close association with the somata of the cardiac neurons. There were also changes in the non-neuronal cells such as darkening and vacuolation of the cells capping the neurons. Macrophages and Schwann cells were activated to engulf the degenerating nodal cells and axonal profiles. The ultrastructural changes in the nodal cells and the cardiac neurons reflect a disturbance in the cell metabolism presumably brought about by the impairment of the sympathetic nervous system.

Adrenergic Agents↗
PubMed1975

Experimental glomerulonephritis in the guinea pig. II. Ultrastructural lesions of the basement membrane associated with proteinuria.

Humoral immune processes mediate alterations in glomerular basement membrane (GBM) permeability by two mechanisms. One requires complement and polymorphonuclear leukocytes and the second is complement- and polymorphonuclear leukocyte-independent. The structural basis for enhanced GBM permeability induced by anti-GBM antibody is not clear. Experimental anti-GBM glomerulopathy was induced in guinea pigs by immunization with human GBM in complete Freund's adjuvant. Control animals received injections of complete Freund's adjuvant alone. Light, immunofluorescent, and electron microscopic studies were done on eight heavily proteinuric animals, four immunized nonproteinuric animals, three controls, and two normal animals. All animals that received injections of GBM had intense linear deposits of gamma2 anti-GBM antibody. Complement deposition was not demonstrable in vivo, and anti-GBM antibody deposits did not fix complement in vitro. Histologic abnormalities in proteinuric animals were confined to the GBM, which was of variable density and had a characteristic beaded thickening, with numerous areas of electron lucency most prominent in the outer aspect of GBM in peripheral portions of capillary loops. The inner margin and endothelium were normal. Ultrastructural tracer studies with ferritin demonstrated increased permeability confined to portions of GBM demonstrating ultrastructural lesions. The urine protein excreted by animals with ultrastructural GBM lesions was largely albumin. The absence of complement deposition accompanying anti-GBM antibody deposits in vivo and the unique GBM lesion in this model differ from the findings in nephritis induced by most heterologous nephrotoxic antibodies and suggest that GBM injury in this model is mediated by autologous antibody through complement-independent mechanisms. The selective proteinuria and ultrastructural lesions suggest a derangement in glomerular permeability functionally localized to the epithelial side of the GBM and could reflect an antibody-mediated abnormality in GBM biosynthesis.

Animals↗
PubMed2000

Preimplant ultrastructure and calcification tendency of various biological aortic valves.

BACKGROUND AND AIM OF THE STUDY: In recent years a number of fixation and anti-calcification methods have been developed, but little is yet known about the calcification process of biological valves. The aims of this study were to: (i) perform a systematic ultrastructural investigation on various biological valves; and (ii) determine the extent of calcification of these valves in a subcutaneous rat model. METHODS: The following porcine aortic prostheses were investigated: Toronto-SPV, Intact, Freestyle, Mosaic and Hancock-II. Samples taken from the valve leaflets, and in the case of the Freestyle and Toronto-SPV valves also from the aortic wall, were examined ultrastructurally using scanning and transmission electron microscopy. Other samples were implanted subcutaneously in Wistar rats for 12 weeks. The calcium content of the samples was measured using atomic absorption spectrophotometry. RESULTS: All valves examined showed a considerable loss of the endothelial cover. Significant changes in valve ultrastructure were also detected. With regard to calcium content, two valve groups could be distinguished (p <0.05): (i) those with high calcium content, e.g. Toronto-SPV and Intact (>40 mg/g dry tissue); and (ii) those with low calcium content, e.g. Mosaic, Freestyle and Hancock-II (<5 mg/g). CONCLUSION: Fixation methods have pronounced effects on the ultrastructural integrity of bioprostheses. The degenerative calcification of bioprostheses can be effectively inhibited by glutaraldehyde-free fixation and anti-calcification treatments.

Animals↗
PubMedDate not supplied

[Ultrastructural phenotypes of tumor cells of endocrine-cellular neoplasms of hepatopancreatoduodenal organs and their role in determining the degree of malignancy and prognosis of these diseases].

78 tumors of the hepatopancreoduodenal system were studied clinically, cytologically and ultrastructurally. Hormonal disturbances were observed in 36% of the patients. The 5-year survival after radical surgery did not depend on the tumor size, tumor cell atypia or metastases to the regional lymph nodes. The prognosis was worse when the tumor was located in the liver. Ultrastructural features of the tumor cells were reliable criteria of the malignancy degree and tumor prognosis. The prognosis, recurrence-free interval and survival improve with an increase in the number of ultrastructurally differentiated cells and organoids in cytoplasm, and with a reduction in nuclear polymorphism and number of dark cells. The degree of histologic and ultrastructural differentiation of tumor cells may not coincide.

Adult↗