Irregular Nuclear Membranes Research Articles

Effect of maternal low protein diet during pregnancy on the fetal liver of rats

Maternal protein restriction plays a critical role in the developmental programming of later disease susceptibility of the fetus. Developmental insults could exert permanent effects on health through alteration of tissue morphology. As the liver has the greatest number of functions among other body organs, this study aimed at evaluating the effects of maternal dietary protein insufficiency on the structure and the proliferative capacity of the liver in rat fetuses. Morphometric histological studies and biochemical analysis were performed. Twenty adult Albino female Wistar rats were divided into two groups after confirmation of pregnancy. Group I (ST), serving as control, was fed a standard diet (20% protein) and group II (LP) a low protein diet (5% protein). Fetuses were extracted on the day 21.5 of pregnancy. Group II morphometric results revealed a significant decrease in the mothers’ weight gain, number and weight of fetuses and weight of fetal livers, but there was also an increase in the mean area of hepatocytes. Histological results showed apoptosis, vacuolization of the hepatocytes, increased positivity of the Oil Red O stained fat droplets and the PAS-positive stained glycogen granules. Liver TUNEL showed increased apoptotic nuclei. Ki-67 immunostaining showed decreased proliferation of the hepatocytes. Ultrastructurally, the nucleus showed peripheral masses of heterochromatin besides irregular nuclear and cell membranes. Mitochondria varied in shape with loss of cristea. Biochemically, there was a significant decrease in the protein concentration and a significant increase in the glycogen concentration in livers of group II. It thus appears that the maternal metabolic condition not only reduced fetal growth in response to protein restriction, but also altered the structure of the liver.

Highlighting nuclear membrane staining in thyroid neoplasms with emerin: Review and diagnostic utility

Immunohistochemical staining (IHC) with emerin, an integral inner nuclear membrane protein, highlights nuclear membrane details in papillary thyroid carcinoma (PTC). We evaluated emerin for highlighting nuclear shape, grooves, inclusions, circumferential nuclear membrane irregularities ("garlands"), deep "stellate" membrane invaginations, and crescents in 34 fine-needle aspiration (FNA) cell blocks, PTC (n = 24) and follicular neoplasms (FN) (n = 10). Tissue microarrays were also examined for 182 cases, PTC (n = 95) and non-PTC (n = 87). Emerin IHC of PTC revealed a predominantly oval nuclear shape in the majority of cases, with FN demonstrating round nuclei and FV of PTC showing a roughly equal distribution of round and oval shapes. In addition to oval nuclear shape, the presence of emerin-positive nuclear grooves, circumferential emerin nuclear "garlands," nuclear crescent shapes, and chromatin clearing on cell block H&E staining were significant predictors of PTC by regression analysis. Emerin IHC of thyroid FNA and surgical specimens serves as a useful adjunct to conventional H&E staining in the diagnosis of PTC and its distinction from FN by delineating diagnostic nuclear membrane irregularities ("garlands" and crescents), nuclear grooves, and a characteristic oval nuclear shape. In diagnostically challenging cases with limited cellularity, emerin staining can help to provide a more definitive diagnosis of PTC.

Non-Hodgkin′s lymphoma: A rare diagnosis on cervicovaginal cytology

Cervicovaginal smear screening is well known to reduce morbidity and mortality rates of invasive cervical carcinoma. Herein, we report a case of 56-year-old woman whose cervicovaginal smear was found to consist of malignant cells characterized by high nuclear/cytoplasmic ratio, scant rim of cytoplasm, coarsely granular nuclear chromatin and irregular nuclear membrane that were all reminiscent of a malignant lymphoma. Histopathological examination of the hysterectomy and unilateral adnexectomy specimen confirmed the presence of a diffuse large B-cell non Hodgkin's lymphoma involving the cervix, endometrium, myometrium, serosa and the right ovary.

Liquid-Based Cytology of Villoglandular Adenocarcinoma of the Cervix: A Report of 3 Cases

Villoglandular adenocarcinoma (VGA) is a rare subtype of cervical adenocarcinoma with a more favorable prognosis compared to conventional adenocarcinomas. Although the tumors are usually recognized on colposcopic examination due to the mainly exophytic growth pattern, they may be underdiagnosed as benign lesions by cytology because of their minimal cytologic atypia. We report the liquid-based cytology (LBC) findings of three histologically confirmed VGAs which we have recently identified. They were characterized by hypercellular smears on low-power examination with smooth-bordered three-dimensional papillary fragments. The nuclei were relatively uniform with irregular nuclear membranes. Nucleoli were small but distinct and macronucleoli were also seen. The abnormal architectural patterns such as papillary structures and nuclear overlapping and nuclear hyperchromasia are important clues to the diagnosis of VGA. In addition, nuclear membrane irregularity and prominent nucleoli can be recognized on LBC specimens, further facilitating its diagnosis.

Fine Needle Aspiration Cytology of Metastatic Adenocarcinoma of the Gingiva from the Lung: A Case Report

Metastases of malignant tumors to the oral region from distant sites are uncommon. A 45-year-old man with painless gingival swelling was diagnosed with adenocarcinoma of the lung. On cytology, clusters of tumor cells on mucous background revealed enlarged nuclei, indistinct cell borders, and irregular nuclear membranes. Some cells showed nuclear inclusions, nuclear grooves and small nucleoli. These findings are indicative of metastatic adenocarcinoma. We present a case of gingival metastasis from a lung adenocarcinoma.

Abstract A10: A new in silico physical optical model (iPOM) for the study of cervical intraepithelial neoplasia

Abstract Background: Cervical cancer is the second leading cause of deaths in women worldwide. More than 80% of cervical cancers and deaths occur in the developing world. New optical and imaging technologies (confocal imaging, fluorescence/absorbance spectroscopy, OCT, etc…) are being developed and tested as potential keys components of a necessary global solution to this problem. The success of these new technologies requires a better understanding of the precise interactions between the incident light, the underlying biological events and the physical structure of the cervical tissue. Herein, we present a new platform based on an in silico Physical Optical Model (iPOM), which is designed to simulate, analyze, and quantify the cell-and tissue-level biological changes that are associated with cervical preneoplastic growths. By reproducing these features, iPOM also gives insights into the ways in which dysplastic changes will be detected by different optical technologies being developed for cervical cancer screening, detection, diagnosis or treatment. Methods: The physical module of this platform is based on a database of more than 4000 cervical histological intraepithelial neoplastic specimens, collected from about 1800 women. As part of previous multicenters clinical trials (NIH funded Po1 project), Feulgen-stained sections were quantitatively analyzed by an high-resolution imaging software. Features describing the nuclear phenotype such as shape, size, orientation, nuclear membrane irregularities, DNA amount and DNA chromatin organization (ratio and spatial organization of euchromatin and heterochromatin) were calculated for each nucleus and the position of each of them relatively to the basal membrane automatically recorded. At the tissue level, epithelial thickness, cell density and tissue organization were assessed using sophisticated graph-theory algorithms measuring the intrinsic order/disorder and the loss of differentiation, trademarks of the dysplastic growth process. On a subset of 350 biopsies representing the entire spectrum of dysplastic and non-dysplastic abnormalities, p16 protein and Ki-67 protein expression were precisely evaluated by measuring the spatial distribution of Ki67-positive and p16-positive cells in the each individual epithelial layer. HPV typing and ploidy analysis were also performed for each patient. All these data were extrapolated to build a realistic (real metric dimension) cell-based physical model of the stratified normal cervical epithelium and of epithelium from each pathological grade. In the optical module, we used Finite-Difference Time-Domain (FDTD) modeling to simulate light scattering from normal, hyperplastic, metaplastic, CIN 1, CIN2, and CIS cervical cell nuclei at different epithelial depths and we constructed models of basal, parabasal, and other layers nuclei up to the last superficial layer for computational analysis. Simulation results give significant insights into the depth-dependent scattering profile of cervical epithelium as dysplasia progresses. We also intend to carry out meticulous investigation that will also enable mapping of azimuthal asymmetry in angle-dependent scattering patterns; this may lead to observation of fine pattern changes that can further be linked to precancer progression. Results: We will be presenting this novel conceptual framework illustrated by some preliminary data of our ongoing analyses using iPOM predicted results to guide acquisition of confocal imaging as well as spectroscopy probes from clinical cervical tissues. Ultimately, this strategy will allow us to identify the most robust in vivo macroscopic imaging approaches for detection of cervical neoplasia and aid in determining which image features must be acquired to achieve accurate diagnoses (e.g. variations in excitation and emission wavelength, numerical aperture, polarization, etc.). Citation Information: Cancer Prev Res 2011;4(10 Suppl):A10.

Cytologic features of sarcomatoid carcinoma of the urinary bladder: A case report

Sarcomatoid carcinoma of the urinary bladder is a rare entity, whose histogenesis and biological behavior remain controversial. The cytological literature on sarcomatoid carcinoma in voided urine is very scarce. Clinically, the diagnosis of this tumor can be made by computed tomography (CT), magnetic resonance imaging (MRI), cytology, and biopsy material. In this study, cytology, histopathology, and radiological imaging were employed in order to reach a diagnosis of sarcomatoid carcinoma. CT imaging showed increased thickness of the bladder wall associated to a polypoid mass. MRI showed a 4-cm sized, broadly necked polypoid mass with calcification and ulceration at the right side of the bladder wall. T2W1 imaging showed low signal. Voided urinary cytology showed a scattered cellular presentation. The tumor cells had a high nucleo- cytoplasmic ratio, with elongated cytoplasm with faint with indistinct cytoplasm border. The nucleus was oval to round, with large and irregular nucleoli and irregular nuclear membrane. These tumor cells were positive for cytokeratin (CKAE1/AE3), vimentin, p53, carcinoembryonic antigen (CEA), α1-smooth muscle actin (SMA) by the immunoperoxidase staining. Histopathology showed spindle-shaped and clumped large tumor cells with abundant cytoplasm. Mitotic figures were frequently seen and varied from area to area (50% of the tumor cells were positive for MIB1).

Identification of Malignant Cytologic Criteria in Pancreatobiliary Brushings With Corresponding Positive Fluorescence In Situ Hybridization Results

Cytologic evaluation of pancreatobiliary brushings is specific but poorly sensitive for malignancy. Detection of polysomic cells by fluorescence in situ hybridization (FISH) is significantly more sensitive than routine cytology with similar specificity. The purpose of this study was to identify cytologic criteria most associated with malignancy in specimens unaffected by sample failure. Endoscopic brushings were split equally for routine cytologic and FISH analyses per clinical practice. We retrospectively evaluated 16 cytologic criteria on Papanicolaou-stained slides. We assumed that the presence of polysomic cells by FISH indicated successful tumor sampling in specimens from patients with pathologic evidence of malignancy on follow-up. We compared cytologic criteria of malignant brushings with corresponding positive FISH results (positive control, n = 39) with those without evidence of malignancy and corresponding negative FISH results (negative control, n = 30). The presence of single abnormal cells, irregular nuclear membranes, and enlarged nuclei were independent predictors of malignancy by logistic regression (P < .05).

Fine‐needle aspiration biopsy of breast adenomyoepithelioma: A potential false positive pitfall and presence of intranuclear cytoplasmic inclusions

Cytologic diagnosis of adenomyoepithelioma can be very challenging. We report fine needle aspiration cytology (FNAC) findings of a benign adenomyoepithelioma. The cytologic features are characterized by hypercellularity and the presence of numerous atypical dispersed cells with epithelioid morphology and intact cytoplasm. The nuclei showed stippled chromatin, irregular nuclear membrane, and prominent eosinophilic nucleoli. No necrosis or mitoses were seen. The presence of naked nuclei, and extensive intranuclear cytoplasmic inclusions were identified and raised the possibility of adenomyoepithelioma. Immunohistochemically, the atypical cells showed strong positivity for myosin heavy chain, p63, and CK5/6, while the epithelial cells reacted with estrogen receptors. This immunophenotypic pattern supports the myoepithelial origin of the atypical cell proliferation and favors the diagnosis of benign adenomyoepithelioma. However, biopsy was recommended to exclude malignancy. Histologically, the tumor showed prominent myoepithelial cells with significant atypia, intranuclear cytoplasmic inclusions, and dense cytoplasm. No evidence of malignancy was identified. In conclusion, we report a case of adenomyoepithelioma with a significant cytological atypia that may result in confusion with malignant breast tumors. The presence of intranuclear cytoplasmic inclusions, naked nuclei, and expression of myoepithelial markers should provide clues to the right diagnosis and benign nature of this lesion. Cytopathologists should be familiarized with this entity to avoid a misdiagnosis of carcinoma.

Light and electron microscopic characterization of the evolution of cellular pathology in HdhQ92 Huntington's disease knock-in mice

Huntington's disease (HD) is a fatally progressive neurodegenerative disease that is characterized anatomically by the abnormal accumulation of fragments of mutant huntingtin protein, within the glia and neurons of the brain. Several genetic (transgenic and knock-in) animal models have been established to mimic human HD. None of these models represent all of the elements of the human disease, but they provide an opportunity to understand the processes of the disease and aid in the development of therapeutic strategies. In this study, the Hdh(Q92) mouse model of Huntington's disease was analysed at different time points across the lifespan of the animal. At 4 months of age, Hdh(Q92/Q92) mice showed dense nuclear staining and nuclear inclusions in the olfactory tubercle and striatum with the mutant N-terminal antibody S830. Widespread formation of mutant huntingtin aggregates in the neuronal nuclei and cytosol increased in number with age and disease progression. Electron microscopy revealed that at 14 and at 21 months of age neurons showed the features of both necrotic and apoptotic cell death, such as irregular nuclear and cytoplasmic membranes, dark condensed nuclei, vacuolated cytoplasm, and swollen mitochondria. The spatial spread of NIIs progressed along the anterior-posterior and ventral-dorsal planes. Our detailed analyses of the Hdh(Q92) mouse line demonstrated a progressive and marked early focal striatal pathology with later widespread neuronal changes, including cellular degeneration, mutant protein aggregation and inclusion formation. We have demonstrated that the distribution of intra- and extra nuclear inclusions in this animal model expresses many features similar to the human pathology.

Spindle shaped pigmented cells in a vitreous fluid cytology

Choroidal melanoma is a rare tumor, but it is the most common primary malignancy of the eye in adults. 3 Here, cytomorphological features corresponding to a cytological smear from a vitreous fluid, obtained by means of a vitrectomy, are described. A dark liquid from a 72-year-old male with an intraocular mass at the back end of the right ocular globe, and diagnosed by magnetic resonance, was sent to the laboratory. Cytospin smears for Papanicolaou staining and cell block for immunohistochemistry (IHC) were made. The Papanicolaou smear (Fig. C-1A) showed a high cellularity consisting of numerous spindle-shaped neoplastic cells which can be found isolated or arranged in clusters. These cells have elongated acidophilic cytoplasms containing brown pigment and enlarged nuclei (round-oval in shape) with anisokaryosis, binucleations, coarse chromatin, and prominent nucleoli. A careful observation, under oil immersion magnification, showed irregular nuclear membranes with indentations and oval nuclei with longitudinal nuclear grooves (Fig. C-1B). Moreover, in a very few cells, the presence of nuclear inclusions was observed (Fig. C-1C). IHC techniques were positive to S-100 and Melan-A. A cytological diagnosis of suspected choroidal melanoma was given. Subsequently, the histopathological examination of the enucleated eye confirmed the existence of a spindle cell choroidal melanoma.

Interobserver Variability in the Diagnosis of Crypt Dysplasia in Barrett Esophagus

Recent morphologic and molecular evidence suggests that dysplasia in Barrett esophagus (BE) begins in the bases of the crypts [crypt dysplasia (CD)] and progresses with time to involve the upper portions of the crypts and surface epithelium. The aim of this study was to evaluate the criteria and reproducibility of diagnosing CD among 6 gastrointestinal pathologists, all with research interest in BE. Six gastrointestinal pathologists evaluated 2 clinical study sets, the first consisting of 40 BE cases [BE: 10, CD: 9, low-grade dysplasia (LGD): 10, high-grade dysplasia (HGD); 9, and intramucosal adenocarcinoma; 2] and the second consisting of 63 cases (BE: 16, CD: 15, LGD: 15, HGD: 15, and intramucosal adenocarcinoma: 2), at least 4 months apart. In between evaluations, all of the pathologists met at 1 hospital (consensus conference) to review the areas of disagreement and establish more objective criteria. Overall, the level of agreement for all cases was moderate (κ=0.44), and the level of agreement did not change significantly after evaluation of the second study set. The highest levels of agreement were obtained for lesions at the low and high end of the spectrum (BE without dysplasia and HGD). Overall, the degree of agreement for CD was moderate after both the first and second study set review (κ=0.44 and 0.46, respectively). However, the degree of agreement for CD was higher than that obtained for LGD in both study sets. In the first study set, 4 or more pathologists agreed with the original CD diagnosis in 78% of cases, and this value did not change significantly after review of the second study set. The observers agreed that characteristic features of CD include the presence of unequivocal dysplastic cells, similar in appearance to traditional LGD, involving any part, or all of the length, of the crypt in the absence of intercrypt surface epithelial involvement. Rare cases of CD may show high-grade cytologic features composed of markedly enlarged nuclei with increased nuclear/cytoplasmic ratio, eosinophilic cytoplasm, irregular nuclear membranes, and loss of polarity. The findings in this study suggest that CD can be diagnosed reliably with a moderate level of interobserver agreement. Long-term and multi-institutional studies should be carried out to further determine the biological and clinical significance and natural history of CD in patients with BE.

Urine cytology of micropapillary carcinoma of the urinary bladder

A case of micropapillary carcinoma (MPC) of urinary bladder is presented, in which the urine smear was studied in detail in an attempt to better characterize the cytologic findings of MPC. When the voided urine was examined in low power, cancer cells were scattered in the specimens as compact papillary/spheroidal clusters composed of pleomorphic cancer cells. Solitary carcinoma cells were occasionally observed. High power view of the smear revealed that the papillae/spheroids consisted of high-grade urothelial carcinoma cells. The cancer cells had pleomorphic nuclei with coarsely granular chromatin and thickened, irregular nuclear membrane, and thick cytoplasm. Histologically, the tumor in the resected bladder appeared as small nests with surrounding hallo both in the luminal surface and in the site of wall involvement. These tightly bound papillary/spheroidal clusters comprised of highly atypical cancer cells were the most specific cytologic finding in the urine of MPC, which were considered as a key diagnostic clue of MPC. The background of the urine smear showed numerous granulocytes and bacilli compatible with cystitis, which is a previously known complication of MPC. Differential diagnoses of MPC from those with pertinent cytologic findings such as conventional UC (including glandular differentiation), and primary/secondary adenocarcinoma of urinary bladder are discussed with a brief review of literature.

Minimizing the diagnosis of “follicular lesion of undetermined significance” and identifying predictive features for neoplasia

We used proposed standard morphologic criteria as a guideline to conduct a 10-year retrospective review of thyroid fine-needle aspiration specimens that were originally interpreted as "follicular lesion of undetermined significance" and followed by surgical intervention. We sought to investigate whether the indeterminate diagnosis could be minimized by assessing various cytomorphologic features and identifying the features predictive of neoplasia. Using the standard morphologic criteria, we semi-quantitatively assessed a total of 24 cytomorphologic features in 123 aspirates and recorded an overall interpretation on completion of the review. Cyto-histologic correlation was evaluated and logistic regression model was performed to identify cytomorphologic features predictive of neoplasia. Although 32 of 123 aspirates remained in the indeterminate category, the retrospective review reclassified 64 aspirates as non-neoplasia and 27 aspirates as neoplasia. Histologic confirmation was achieved in 47 (73.4%) non-neoplastic and 15 (55.6%) neoplastic aspirates with a diagnostic accuracy of 68.1%. Furthermore, our analysis demonstrated that neoplasia is positively associated with the presence of syncytial tissue fragments, isolated microfollicles, follicles with scalloped borders, scant cytoplasm, irregular nuclear membranes, nuclear overlapping, coarse chromatin, and increased cellularity. On the contrary, the presence of honeycombing tissue fragments, background colloid, and histiocytes inversely correlated with neoplasia. Overall, using proposed standard morphological criteria can minimize the diagnosis of "follicular lesion of undetermined significance," and allow for more accurate cyto-histologic correlation, and thereby playing a substantial role in reducing unnecessary surgical intervention.

La telorrea como manifestación del carcinoma intraductal de mama

Introduction Nipple discharge is an innocuous and accessible diagnostic method that, in practice, is considered to have low sensitivity and specificity. Case A 45-year-old woman presented with bloody right nipple discharge and burning sensation. Imaging tests revealed a 1-mm dilatation as the only finding of interest. In one of the examinations, a sample of the secretion was obtained that showed a bloody background and some clusters of epithelial cells, with slight cellular overlapping, and contour that was smooth in parts and dented in others. The cells showed an increase in the nucleus/cytoplasm ratio, hyperchromatic nuclei, irregular nuclear membrane and images of cannibalism. Because a papillary lesion was suspected, excisional biopsy was performed, revealing intermediate-grade ductal carcinoma in situ with comedo-like necrosis. Conclusion Though the ductal carcinoma of the breast, whether in situ or invasive, is rare expresses nipple discharge, if there are epithelial clusters with cytologic atypia we have not forget this possibility besides papillary lesions.

Encapsulated apocrine papillary carcinoma of the breast: Case report with clinicopathologic and immunohistochemical study

We describe a case of encapsulated papillary carcinoma (EPC), apocrine variant in a 50-year-old woman. The patient presented a cystic lesion in her right breast, measuring 8 cm in diameter, containing three solid papillary nodules. A fine-needle aspiration showed isolated apocrine cells containing round nuclei, irregular nuclear membranes, fine chromatin, and prominent macronucleoli. The lesion was excised and showed a pure papillary apocrine carcinoma, which stained diffusely with GCDFP-15 and androgen receptors. The lesion was totally devoid of myoepithelial cells (smooth muscle actyn, p63, calponin, and collagen IV stains were negative). With MIB1 the proliferative activity was 10%. To the best of our knowledge, this is the first report of EPC apocrine variant with cytologic and immunohistochemical study. This lesion must be included in the list of apocrine lesions of the breast.

Novel amelanotic and melanotic cell lines NM78-AM and NM78-MM derived from a human oral malignant melanoma

Abstract Novel cell lines, designated NM78-AM and NM78-MM, have been established from a malignant melanoma of the cheek oral mucosa. NM78-AM cells were spherical, grew in suspension as clusters, and produced no melanin. In contrast, NM78-MM cells were adherent and produced melanin granules. Initially, NM78-AM cells were grown on fibroblast feeder cells or in growth media supplemented with 10% conditioned medium from fibroblasts, but eventually grew in standard growth media alone. NM78-AM cells had interdigitating microvilli and formed cell clusters. They had large nucleoli, desmosomes, lipid droplets, and well-developed Golgi apparatuses. In contrast, NM78-MM cells grew as adherent neuron-like cells. They had large prominent nucleoli, irregular nuclear membranes, a number of mitochondria, well-developed Golgi apparatuses, melanosomes at various stages of development in the cytoplasm, and the cells secreted melanin granules. Projections from these melanotic cells formed anastomoses with each other. NM78-MM cells stained immunofluorescently for internexin, neuron specific enolase, NF-200, and glial fibrillary acidic protein. These cells were severely aneuploid, approximating to triploidy, and had many marker chromosomes. We used a real-time monitoring system to evaluate oxygen concentrations in culture medium to investigate the susceptibility of both cell lines to various anti-cancer drugs. NM78-AM cells were slightly sensitive to actinomycin D, but not to cisplatin, irinotecan, the irinotecan metabolite SN-38, taxol, taxotere, bleomycin and methotrexate; NM78-MM cells were sensitive to cisplatin, and not to taxol, taxotere, carboplatin, and irinotecan. These new cell lines, NM78-AM and NM78-MM, will be very important for the development of new chemotherapeutics for oral malignant melanoma.

Effects of Ultraviolet B Radiation on the Cornea of Adult Male Albino Rats and the Possible Role of Lornoxicam

Introduction: Ultraviolet Radiation (UVR) represents a significant environmental and occupational hazard to human beings especially after the ozone hole. Lornoxicam is a strong non-steroidal anti-inflammatory drug (NSAID) with few side effects. Aim of the Work: This work aimed to clarify effects of UVBR on the cornea of adult male albino rats and the possible role of lornoxicam. Materials and Methods: Thirty adult male albino rats were used. They were divided into three main groups: Control; Lornoxicam treated and UV irradiated which was further subdivided into 3 subgroups. On sacrifice, cornea was processed for histological, immunohistochemical and morphometrical studies. Results: Cornea of UV irradiated rats revealed epithelial thinning with cellular degeneration, exfoliation and metaplasia. Bowman's membrane was focally interrupted or absent. Stroma showed irregularly arranged widely separated collagen fibers, degenerated few keratocytes with neovascularization, interstitial hemorrhage and cellular infiltration. Ultrastructurally, epithelial cells showed nuclear membrane irregularities, chromatin condensation, mitochondrial degeneration and loss of rER. Immunohistochemically, epithelial cells and keratocytes showed marked expression of caspase-3 protein in their cytoplasm. Morphometrically, there was a highly significant decrease in epithelial thickness, area % of stroma and number of keratocytes. Rats left to recover without treatment showed mild improvement, while treatment of irradiated rats with lornoxicam for one week after exposure showed nearly normal histological, ultrastructural, and immunohistochemical pictures. Conclusion: Lornoxicam (a cheap, available tolerable NSAID) could ameliorate UVB induced corneal changes. So it could be considered as a curative measure of the cornea against UVB.

Cytomorphological criteria, subclassifications of endocervical glandular cell abnormalities, and histopathological outcome: A frequency study

The objective of this study was to evaluate the frequency and the significance of cytomorphological criteria defined in studies as being predictive of neoplasia in cervical smears of women with a cytological diagnosis of atypical glandular cells (AGC) or adenocarcinoma in situ (AIS). Women (n = 103) with cytological findings suggestive of AGC or AIS, whose diagnoses were later established by histopathology, were included in the study. The criteria analyzed and classified as present or absent in cervical smears previously classified as AGC-NOS (not otherwise specified), AGC-FN (favor neoplasia), or AIS were as follows: irregular nuclear membranes; scanty cytoplasm; dyskeratotic cells; increased nuclear/cytoplasmic ratio; nucleoli; overlapping; papillary clusters, feathering; loss of polarity; nuclear enlargement; coarsely granular chromatin; and pseudostratified strips. Histopathology resulted in neoplastic diagnoses in 55 cases (53.3%) and nonneoplastic diagnoses in 48 cases (46.6%). Coarsely granular chromatin was observed in 62.5% of cases with a diagnosis of neoplasia. Feathering was present in 80% of cases of histopathological AIS. Loss of polarity and coarsely granular chromatin were significantly associated with neoplastic diagnosis considering all subcategories of glandular abnormalities diagnosis. In AGC-SOE subclassification, coarsely granular chromatin was significantly associated with neoplastic diagnosis. The presence of nucleoli was significantly associated with neoplastic diagnosis in cervical smears qualified as AGC-FN and AIS. Nuclear enlargement, increased nuclear/cytoplasmic ratio, coarsely granular chromatin and overlapping cells were found in all the subclassifications of glandular cell abnormalities irrespective of the histopathological results. Chromatin aspects, polarity, and presence of nucleoli can predict neoplasia.

Diagnostic significance of atypical category in the voided urine samples: A retrospective study in a tertiary care center

Background:Voided urine samples continue to play an important role in the surveillance of urothelial malignancy and also as a screening mode for high risk patients. In some cases, it is difficult to reliably distinguish changes induced by inflammation, stone or other reactive condition from neoplasm, and these cases are categorized as atypical. The aim of our study is to evaluate the prevalence and the significance of atypical diagnosis in the voided urine samples and also to identify the cytomorphologic features that are seen more frequently in the atypical malignant urine samples.Materials and Methods:All voided urine cytology samples with a diagnosis of atypical urothelial cells, between the period of 2000 and 2009, were obtained from the cytology database. Only those cases with histologic follow-up were included in the study. The cytology and the histology slides were retrieved and reviewed. The following parameters were evaluated: cellularity, cell clusters, nuclear membrane irregularities, hyperchromasia and India-ink type nuclei, the presence of spindle cells and the cytoplasmic characteristics.Results:Out of 72 voided urine samples included in the study, 49 cases (68%) had a positive histologic diagnosis of urothelial malignancy in the follow-up histology; of these (55%) were high-grade urothelial carcinoma. Increased cellularity, papillary cell clusters, nuclear membrane irregularity, hyperchromasia and India-ink type nuclei were observed more frequently in the atypical malignant urine samples, while cytoplasmic vacuolization were seen more in the negative reactive urine samples.Conclusion:The atypical category diagnosis is associated with a significant proportion of urothelial carcinoma. It should be used by the pathologist to convey concern to the clinician in difficult cases that may require close follow-up.