Low Nuclear-cytoplasmic Ratio Research Articles

Morphological Analysis of the Hemolymph Cell Composition in the Bivalve Mollusk <i>Anadara</i> <i>broughtonii</i> Schrenck, 1867 (Sea of Japan)

The hemolymph cells of the ark clam Anadara broughtonii were examined using light microscopy, flow cytometry and gradient centrifugation. All three methods of analysis made it possible to identify two main types of cells in the hemolymph of the ark clam Anadara broughtonii – large granular erythrocytes and small agra-nular amebocytes. Erythrocytes accounted for 95.6 ± 0.9% of the total number of hemolymph cells. Erythrocytes were hemoglobin-containing cells with a great number of granules in the cytoplasm, a low nuclear-cytoplasmic ratio (NCR) and a lower intensity of cellular respiration compared to amebocytes. Amebocytes are cells of predominantly irregular shape with a high number of cells that do not contain or contain no more than 10 granular inclusions in the cytoplasm. All types of hemocytes found in the ark clam hemolymph demonstrated the same ability to spontaneously produce reactive oxygen species. For the first time, it has been shown that red blood cells of the ark clam Anadara broughtonii are capable of phagocytosis. At the same time, amebocytes absorbed on the average two times more zymosan particles (10.3 ± 0.7 pcs.), compared to erythrocytes (5.3 ± 0.1 pcs.).

Cytological structure of a vaginal stroke in American mink during estrus

The article presents the data of domestic and foreign authors on the features of the oestrous process of American minks. The results of studies of the cytological structure of the vaginal smear in American minks during estrus are presented. The study was conducted on clinically healthy American mink females of the Standard dark brown (+/+) genotype in 92 animals before the technological rut (February 20-28). A vaginal smear was taken at different periods of changes in the external genital organs - the genital loop, taking into account the scoring of its development (from 0 to 5 points). Microscopic examination of smears taken during this period showed a predominance of superficial, intermediate, and parabasal cells and a small number of basal and spindle cells. The analysis of the nuclear-cytoplasmic ratio made it possible to indicate the specificity of the morphometric parameters of the cells of the vaginal integumentary epithelium. Surface epitheliocytes and intermediate cells have a sizeable cytoplasmic area and a low nuclear-cytoplasmic ratio of 0.034. Parabasal cells have the minimum size of the nucleus and cytoplasm but a high value of the nuclear-cytoplasmic percentage, seven times higher than that of superficial cells and three times intermediate. Quantitative proportions of epithelial cells of the vaginal smear cytogram from February 20 to 28 correspond to the proestrus-estrus stage. The data obtained indicate significant features of the morphological changes in the integumentary epithelium of the vagina and the difference in the cytological dynamics of the oestrous cycle in American minks from other mammals. The cytogram of the vaginal smear of minks with a 4-5 point assessment of the readiness of females for mating does not contain the predominant number of keratinized epithelial cells, which is characteristic of most mammals during the period of ovulation. An important morphological criterion in the analysis of the vaginal smear cytogram in minks is the value of the ratio of superficial and parabasal cells and scales and parabasal cells.

Cytological study of 44 cases with solid papillary carcinoma and a systemic review of solid papillary carcinoma and neuroendocrine tumor of the breast.

Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade in situ and invasive carcinoma but there are only a few of the cytologic studies. We examined 44 cases of SPC of the breast to define the cytologic features. We also made a systemic review of reported cases of SPC and neuroendocrine tumor (NET) of the breast. Both of our and the reviewed cases with SPC were very similar in the cytologic finding. It included hypercellularity, highly discohesive clusters, numerous isolated cells, small nuclei, finely granular chromatin of salt-and-pepper appearance, inconspicuous nucleoli, low nuclear-cytoplasmic ratio, and a plasmacytoid appearance. Moreover, SPC and NET had frequently all of these features in common. Capillary vessels structures and mucinous substance were not frequently seen in our and the reviewed cases with SPC. Rosette and pseudorosette were very rare in the cytologic specimen. The immunocytochemistry with our 9 cases with SPC indicated diffuse positivity for chromogranin A and/or synaptophysin. Many cytologic features are frequently shared by SPC and NET of the breast. However, the vascular structure may not be a precise criterion for SPC. Rosette and pseudorosette are rarely helpful for the cytologic diagnosis.

Interphase-arrestedDrosophilaembryos activate zygotic gene expression and initiate mid-blastula transition events at a low nuclear-cytoplasmic ratio.

Externally deposited eggs begin development with an immense cytoplasm and a single overwhelmed nucleus. Rapid mitotic cycles restore normality as the ratio of nuclei to cytoplasm (N/C) increases. A threshold N/C has been widely proposed to activate zygotic genome transcription and onset of morphogenesis at the mid-blastula transition (MBT). To test whether a threshold N/C is required for these events, we blocked N/C increase by down-regulating cyclin/Cdk1 to arrest early cell cycles in Drosophila. Embryos that were arrested two cell cycles prior to the normal MBT activated widespread transcription of the zygotic genome including genes previously described as N/C dependent. Zygotic transcription of these genes largely retained features of their regulation in space and time. Furthermore, zygotically regulated post-MBT events such as cellularization and gastrulation movements occurred in these cell cycle–arrested embryos. These results are not compatible with models suggesting that these MBT events are directly coupled to N/C. Cyclin/Cdk1 activity normally declines in tight association with increasing N/C and is regulated by N/C. By experimentally promoting the decrease in cyclin/Cdk1, we uncoupled MBT from N/C increase, arguing that N/C-guided down-regulation of cyclin/Cdk1 is sufficient for genome activation and MBT.

Apocrine lesions of the breast: part 1 of a two-part review: benign, atypical and in situ apocrine proliferations of the breast

Apocrine morphology is a common phenomenon encountered in everyday breast pathology practice, and is defined as cuboidal or columnar cells exhibiting abundant eosinophilic granular cytoplasm, prominent apical granules, a low...

Morphological and functional characteristics of cell culture derived from the mouse nail unit

Nail unit is a complex anatomical structure that is capable of rapid growth and regeneration throughout the life. Such significant reparative potential is associated with the presence different types of stem and progenitor cells, whose biology remains one of the fundamental issues today. Taking into account the active search for new stem cell sources for cell therapy, the view of the nail unit as a potential site for the localization of undifferentiated cells with stem potency is topical problem.Purpose. The study was conducted with an objective to establish the morphological, morphometric and proliferative characteristics of cultured cells isolated from the mouse nail unit.Materials and methods. Primary cultures of cells were obtained from tissue sampling, which included areas of the proximal nail fold, nail matrix and onychodermis of the FVB mouse nail organ. Cells were cultured in DMEM:F12 medium with 15 % fetal bovine serum during 6 passages. We determined the colony-forming activity, the population growth rate and doubling time, measured the area of cells, nuclei, and calculated the nuclear-cytoplasmic ratio. For cell morphology analysis, we used staining with Bemer’s hematoxylin and eosin, Heidenhain’s iron hematoxylin and May-Grünwald stain.Results. According to the morphological analysis in vitro the cells from mouse nail unit are heterogeneous with high synthetic activity and a low nuclear-cytoplasmic ratio – the features characteristic of the low-differentiated cells. The population doubling time of the culture was 80 ± 6.5 hours on average, the fastest growing cells were at the 4th passage (63 ± 7 hours). The specific growth rate for cell culture is low (0.01 ± 0.0007).The colony forming efficiency at the 5th passage was only 4 %. A significant number of colonies was small with large poorly proliferative cells, which may indicate a production of large numbers of transitional progenitor cells.Conclusion. The obtained cell culture from the mouse nail unit according to the analysis of their morphology, morphometry and proliferative potential is heterogeneous and requires the further development of pure culture technologies for the detailed characterization of separate subpopulations of cells.

Cytodiagnosis of distant metastases from follicular thyroid carcinoma.

Follicular carcinoma of the thyroid is second most common primary malignancy of the thyroid gland after papillary carcinoma and metastasis is uncommonly seen in these patients. To describe the cytomorphologic features for the accurate diagnosis of distant metastases from follicular carcinoma of thyroid. A total of 10 aspirates reported as metastatic follicular carcinoma of thyroid were reviewed for the available clinical and radiological details. All the patients were females. Six of these patients presented with subcutaneous and soft tissue swellings, one presented with a lung mass, one with right breast swelling, one with lumbar vertebral lesion and one with left iliac bone involvement. The cytology smears revealed tumour cells predominantly arranged in a repetitive microfollicular pattern with some scattered individually and in sheets. The tumour cells were small, had mild nuclear pleomorphism, round nuclei, low nuclear-cytoplasmic ratio, fine chromatin, inconspicuous nucleoli, and scanty to moderate amount of cytoplasm with some showing marginal vacuoles with "fire-flare" appearance. Occasional microfollicles showed scanty eosinophilic colloid in the center. Identification and establishment of a correct clinical diagnosis of a distant metastasis from a follicular thyroid carcinoma is a challenging task. We believe that with prior knowledge of characteristic cytologic features, such metastases can be rapidly and accurately diagnosed by fine needle aspiration cytology.

Cytological study of 20 cases of solid‐papillary carcinoma of the breast

Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade intraductal carcinoma but there are few cytological studies. We examined 20 cases of SPC of the breast, aged 31-80 (mean age 66.0 yr), to define the cytological features. In each of the cytological specimens, we could find both malignant and benign cytological features; the former were characterized by hypercellularity, highly discohesive clusters, numerous isolated cells, and severe overcrowding cells, while the latter were marked by small and bland nuclei, a low nuclear-cytoplasmic ratio, and inconspicuous nucleoli. Neither abnormal naked nuclei of tumor cell origin nor oval naked nuclei of myoepithelial cell origin were seen. We also reviewed the cytological findings of SPC as well as neuroendocrine carcinomas with intraductal components that had been reported and we concluded that the coexistence of malignant and benign features was the most characteristic cytological feature of SPC.

Distinguishing Primary and Metastatic Conventional Renal Cell Carcinoma From Other Malignant Neoplasms in Fine-Needle Aspiration Biopsy Specimens

Differentiation of conventional renal cell carcinoma from other malignant neoplasms can be difficult, particularly with the limited sampling in fine-needle aspiration biopsies. Many studies have discussed the features of renal cell carcinoma in fine-needle aspiration biopsy specimens, but the significance of the cytologic features is not known. To define the significant cytologic findings that aid in differentiating renal cell carcinoma from other malignant neoplasms in fine-needle aspiration biopsy specimens. Fine-needle aspiration biopsies from 35 patients with proven primary or metastatic conventional renal cell carcinoma and from 145 patients with proven primary or metastatic non-renal cell carcinoma malignant neoplasms were assessed for the presence or absence of the following cytologic features: the heterogeneous cell population, hemosiderin deposits, small cytoplasmic vacuoles, large cytoplasmic vacuoles, low nuclear-cytoplasmic ratio, prominent nucleoli, intranuclear inclusions, irregular nuclear membranes, and smooth nuclear membranes. Statistical analysis was performed to identify the features significant in distinguishing conventional renal cell carcinoma from non-renal cell carcinoma malignancies. The presence of the heterogeneous cell population, hemosiderin deposits, small cytoplasmic vacuoles, and low nuclear-cytoplasmic ratio were each highly significant in conventional renal cell carcinoma when compared with non-renal cell carcinoma malignant neoplasms (P < .001) using univariate exact analysis. Features that were identified as being predictive of conventional renal cell carcinoma using multivariable logistic regression analysis included heterogeneous cell population, small cytoplasmic vacuoles, and hemosiderin deposits (P < .05). The presence of the heterogeneous cell population, small cytoplasmic vacuoles, hemosiderin deposits, and a low nuclear-cytoplasmic ratio aids in differentiating conventional renal cell carcinoma from other malignant neoplasms, including morphologically similar entities such as hepatocellular carcinoma, in fine-needle aspiration biopsy specimens.

Unusual Cytologic Findings in Low Grade Papillary Transitional Cell Carcinoma

To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. We defined the following unusual cytologic findings as "isolated, single cell pattern": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. Some LG-pTCCs show many single, atypical transitional cells.

Atypical acinar cell foci in human pancreas. Morphological and morphometric analysis.

The morphological and quantitative findings of the present study suggest that atypical acinar cell foci are not neoplastic in nature. Atypical acinar cell foci (AACF) are rare and unusual lesions in the human pancreas. The biological nature of AACF is poorly understood, and is not clear whether they represent neoplastic or degenerative changes in the acinar cells. To further characterize and understand the significance of AACF in relation to acinar cell tumor development, we have examined these lesions by light and electron microscopy and evaluated the growth pattern by measuring cell proliferation and the size of the foci in the pancreas of a 16-yr-old male. The pancreas was grossly unremarkable. AACF were randomly distributed throughout the pancreas, well delineated, and showed minimal variation in sizes. The constituent cells contained uniform nuclei, pale vacuolated cytoplasm, and exhibited low nuclear-cytoplasmic ratio. Electron microscopic examination showed a few zymogen granules and markedly dilated rough endoplasmic reticulum. Proliferative index in AACF (13%) was less than in adjacent uninvolved acinar tissue (19%). Quantitative stereological analysis showed the pancreas to contain approximately 1800 AACF/cm3 with a mean focal diameter of 360 microns.

Structure-activity relationships in corpora allata of the cockroach Diploptera punctata: roles of mating and the ovary.

Morphometric studies were made on corpora allata of the cockroach Diploptera punctata from animals in which increasing gland size is not coupled to hormone synthesis (ovariectomized mated females; last-instar larvae) and in which gland size is coupled to hormone synthesis (normal mated and virgin females; penultimate-instar larvae). Cell number, gland volume, and juvenile hormone synthesis were measured. From electron micrographs, nuclear, cytoplasmic, and extracellular volumes; and cell membrane area were calculated; and fine structure described. Low-activity glands of ovariectomized mated females resembled high-activity glands from mated females in high cell number, large overall and cytoplasmic volume, and low nuclear-cytoplasmic ratio; they differed in having organelles typical of low-activity glands, mitochondria with dense matrices and large whorls of smooth endoplasmic reticulum. Inactive last-instar larval glands resembled mated ovariectomized female glands in increased cell number and organelles characteristic of inactive glands; however, their nuclear-cytoplasmic volume ratio was much higher. Penultimate larval glands with high activity per cell resembled active glands of normal mated females. Ovariectomy did not change morphometric parameters of virgin female glands; thus mating results in increase in size of adult female glands whereas the growing ovary is needed for changes in mitochondria and endoplasmic reticulum associated with high juvenile hormone synthesis.

Neuroendocrine Tumors of the Lung With Proposed Criteria for Large-Cell Neuroendocrine Carcinoma

Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.

Unusual Melanocytic Nevi of the Conjunctiva

In one patient, an epithelioid cell nevus of the conjunctiva contained numerous large, unpigmented, mononucleated, binucleated, and multinucleated benign-appearing nevus cells with abundant cytoplasm and frequent intranuclear vacuoles. Despite their overall size, the cells manifested a low nuclear-cytoplasmic ratio. After a partial excision of the lesion, the remainder spontaneously regressed during a two-year period. Another patient's lesion was dominated by a proliferation of spindle nevus cells developing in a long-standing epibulbar nevus. The spindle cells were moderately pigmented, frequently located within walls of epithelial inclusion cysts, and had benign cytologic features. Finally, in a third patient with the cutaneous B-K mole syndrome, a dysplastic conjunctival nevus developed that featured intraepithelial, atypical melanocytic proliferation with superficial colonization of the substantia propria. This portion coexisted with a deeper, preexistent lesion in the substantia propria that was comprised of orderly nests of unpigmented cuboidal nevus cells surrounded by pigmented, spindle-shaped blue nevus cells--a so-called "mixed nevus."