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In order to investigate the possible correlation between p53 and MDM2 co-expression with clinicopathological features of differentiated thyroid cancer (DTC) and its use as diagnostic and/or prognostic markers, we used immunohistochemistry to evaluate 317 thyroid samples including 208 DTC and 94 benign nodules, in addition to 15 normal tissues. MDM2 and p53 expression were highly associated (r = 0.7161; p < 0.0001). The co-expression of p53-MDM2 was observed more frequently in malignant lesions (p < 0.0001) and helped characterize follicular patterned lesions distinguishing FVPTC from FA (p < 0.0001) and FVPTC from FTC (p < 0.0001). In addition, p53-MDM2 co-expression was associated with characteristics of less aggressiveness. It was more frequent in patients ≤45 years old (p = 0.0035), with unique tumors (p = 0.0095), tumors <2 cm (p < 0.0001), tumors without extrathyroid invasion (p = 0.0425), without metastasis at evolution (p = 0.0179), and in patients evolving free of disease after treatment (p = 0.0485). We suggest that p53-MDM2 co-expression profile analysis might help establishing diagnostic and determining prognostic of DTC patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to retrospectively evaluate follicular variant of papillary thyroid carcinoma (FVPTC) and reclassify encapsulated FVPTC as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) according to the criteria proposed by The Endocrine Pathology Society working group in 2015 to correlate with outcome., Materials and Methods: Retrospective review of case records of all patients diagnosed as carcinoma of thyroid between 2015 and 2016 was done for the histologic subtype. Gross and microscopic features on resected specimens of FVPTC were reviewed and subtyped as invasive and encapsulated based on capsular/vascular invasion; the encapsulated forms were further studied for size, number, follicular architecture, nuclear features, presence of psammoma bodies, stromal fibrosis, necrosis, mitoses, and lymph node status., Results: Out of the 383 patients with thyroid carcinomas in the study period, 349 were PTC which included 106 FVPTC. Thirty-three patients fulfilled the criteria to be labeled as NIFTP. Total thyroidectomy was performed in 8 patients and hemithyroidectomy in 25 patients. Lymph node dissection along with total thyroidectomy was done in 3 and completion thyroidectomy following hemithyroidectomy was done in 9. There were 29 single and 4 multiple lesions with size varying from 0.2 to 7 cm including 5 lesions measuring <1 cm. The involvement was confined to one lobe in 31 and both lobes in 2 specimens. Patients are on follow-up with no recurrence till date., Conclusion: Thyroid carcinomas currently diagnosed as FVPTC should be evaluated for criteria of NIFTP to avoid overtreatment as they have an indolent behavior., Competing Interests: There are no conflicts of interest

Background: Multicellular spheroids represent an interesting experimental model with promising applications in the pre-clinical studies on anticancer drugs. We recently demonstrated that thyroid spheroids recapitulate the features of the original tissues, in either the differentiated and "stem-like" components. Here we were aimed to characterize thyroid spheroids and to investigate in vivo the proangiogenic potential of patient-derived xenografts (PDX) of spheroids obtained from papillary thyroid cancer (PTC) and the matched normal tissues., Methods: Spheroids cultures were obtained from 11 PTCs and matched normal tissues and characterized by immunohistochemistry. The expression of p53, involved in the regulation of stem cell homeostasis, was evaluated. The proangiogenic effect of thyroid spheroids was assessed by the injection in zebrafish embryos., Results: Thyroid spheroids are enriched in stem-like cells, as shown by the positivity for the stem cell marker OCT4, and by the low level of p53 expression. Interestingly, PTCs and normal thyroid tissues have a detectable p53 expression, whereas the derived spheroids are mainly constituted by cells that express p53 at a lower level. Finally, we show that PDXs derived from PTC or normal spheroids stimulate the migration and the growth of sprouting vessels toward the implant into the zebrafish embryos., Conclusions: We report the characterization of multicellular spheroids obtained from PTCs and normal thyroid tissues, showing that they are enriched in stem-like cells. Moreover, we established xenografts of spheroids in zebrafish, demonstrating that they stimulate neoangiogenesis. This in vivo model could be considered as a valuable platform to test the effects of anticancer drugs.

Currently, mammary neoplasms in female canines are a serious problem in veterinary clinics. In addition, the canine species is an excellent disease model for human oncology because of the biological and genetic similarities between the species. Cytogenetics has allowed further study of the characterization of neoplasms in canines. We hypothesized that the use of a direct preparation protocol for mitotic chromosome analysis would provide a simple and low cost protocol for use in all laboratories. The objective of this method is to display in a few hours of dividing cells just like the time of collection since cell division in tissue can be obtained. Ten female canines with the spontaneous occurrence of mammary neoplasia were used to test a pioneering direct preparation protocol to obtain mitotic chromosomes. The excised breast tumor tissue fragments were subjected to the protocol consisting of treatment with colchicine, treatment with hypotonic solution, and fixation. Mitotic chromosomes were absent in cell suspensions of only two samples among the 10 materials analyzed, based on the analysis of five blades for each preparation obtained. So, the cell suspension obtained allowed for the observation of eight tissue samples viable for cytogenetic analysis, five of which had excellent numbers of mitotic chromosomes. However, the technique was unsuccessful in producing high-quality cell suspensions because of inadequate condensation and scattering of chromosomes. While adjustments to methodological procedures are needed, this protocol represents a low cost and simplified method to study the cytogenetics of canine tumors.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and constitutes more than 70% of thyroid malignancies. Although TNM staging is the most widely used parameter for determination of therapeutic plans, recent studies have suggested that different histopathologic variants of PTC can also have different clinical courses and patient prognoses. Sonographic criteria for PTC are well established and include a taller-than-wide shape, an irregular margin, microcalcifications, and marked hypoechogenicity. The role of sonography has expanded to enable the characterization of PTC variants based on their sonographic features. Tall cell and diffuse sclerosing variants appear to have more aggressive clinical courses with unfavorable prognoses, whereas the more recently described cribriform-morular and Warthin-like variants have relatively indolent clinical courses. The prognoses of patients with follicular, solid, columnar cell, and oncocytic variants are still controversial and may be similar to the prognosis of conventional PTC. Understanding the sonographic characteristics of PTC variants with clinicopathologic correlation may be helpful for suggesting an appropriate treatment plan., (© 2015 by the American Institute of Ultrasound in Medicine.)

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., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Ultrasound and prophylactic dissections have facilitated identification of small-volume cervical lymph node (LN) metastases in patients with papillary thyroid carcinoma (PTC). Since most staging systems do not stratify risk based on size or number of LN metastases, even a single-microscopic LN metastasis can upstage a patient with low-risk papillary thyroid microcarcinoma (PMC) to an intermediate risk of recurrence in the American Thyroid Association (ATA) system and to an increased risk of death in the American Joint Committee on Cancer (AJCC) staging system (stage III if the metastatic node is in the central neck or stage IVA if the microscopic LN metastasis is identified in the lateral neck). Such microscopic upstaging may lead to potentially unnecessary or additional treatments and follow-up studies. The goal of this review is to determine if the literature supports the concept that specific characteristics (clinically apparent size, number, and extranodal extension) of LN metastases can be used to stratify the risk of recurrence in PTC., Summary: In patients with pathological proven cervical LN metastases (pathological N1 disease; pN1), the median risk of loco-regional LN recurrence varies markedly by clinical staging, with recurrence rates for patients who are initially clinically N0 (clinical N0 disease; cN0) of 2% (range 0%-9%) versus rates of recurrence for patients who are initially clinically N-positive (clinical N1 disease; cN1) of 22% (range 10%-42%). Furthermore, the median risk of recurrence in pN1 patients varies markedly by the number of positive nodes, <5 nodes (4%, range 3%-8%) vs. >5 nodes (19%, range 7%-21%). Additionally, the presence of extranodal extension was associated with a median risk of recurrence of 24% (range 15%-32%) and possibly a worse disease-specific survival., Conclusion: Our previous paradigm assigned the same magnitude of risk for all patients with N1 disease. However, small-volume subclinical microscopic N1 disease clearly conveys a much smaller risk of recurrence than large-volume, macroscopic clinically apparent loco-regional metastases. Armed with this information, clinicians will be better able to tailor initial treatment and follow-up recommendations. Implications of N1 stratification for PTC into small-volume microscopic disease versus clinically apparent macroscopic disease importantly relate to issues of prophylactic neck dissection utility, need for pathologic nodal size description, and suggest potential modifications to the AJCC TNM (tumor, nodal disease, and distant metastasis) and ATA risk recurrence staging systems.

Understanding the evolution of proliferative breast disease such as atypical hyperplasia and carcinoma in situ is essential for clinical management of women diagnosed with these lesions. Therefore, an animal model that faithfully represents human breast disease in every aspect from spontaneity of dysplasia onset, histopathologic features, and genetics to clinical outcome is needed. Previously, we studied canine spontaneous atypical hyperplasia and ductal carcinoma in situ (low, intermediate, and high grade) and reported their similarities to human lesions in histopathologic and molecular features as well as prevalence. To further validate the resemblance of these lesions to humans, we examined their mammographic and sonographic characteristics in comparison with those of human's as well as the potential of the human Breast Imaging Reporting and Data System (BI-RADS) to predict canine disease. Nonlesional, benign, and malignant mammary glands of dogs presented to Sassari Veterinary Hospital were imaged using mammography and ultrasonography. The images where then analyzed and statistically correlated with histopathologic findings and to their similarities to humans. Our results showed that canine mammary preinvasive lesions, benign, and malignant tumors have mammographic abnormalities, including the presence, pattern, and distribution of macrocalcification and microcalcification, similar to their human counterparts. BI-RADS categorization is an accurate predictor of mammary malignancy in canine, with 90% sensitivity and 82.8% specificity. The similarities of mammographic images and the ability of BI-RADS to predict canine mammary malignances with high specificity and sensitivity further confirm and strengthen the value of dog as a model to study human breast premalignancies for the development of prognostic biomarkers.

Statins show antiproliferative activity in various cancer cells. The aim of this study was to evaluate the effects of rosuvastatin treatment on papillary thyroid carcinoma. The papillary thyroid carcinoma (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines were treated with rosuvastatin at 12.5, 18.5, 25, 50, 100, and 200 μM concentrations. After 48 and 72 h of rosuvastatin treatment, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, Ki-67 immunolabeling, FACS analysis, electron microscopy, caspase-3, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis were performed. Decreased cell viability and G1 phase arrest were detected in papillary thyroid cell line treated with rosuvastatin. Positive immunoreactivity of Ki-67 and dose-dependent increase in S phase on Nthy-ori 3-1 cells were also detected. B-CPAP cells showed intense vacuolisation and autophagosomes with low concentrations and 48 h incubations, while Nthy-ori 3-1 cells showed these changes at higher concentrations. A decrease in the percentage of cells showing autophagy was determined with increasing concentrations of rosuvastatin in B-CPAP cells. Rosuvastatin treatment also caused a dose- and time-dependent increase in caspase-3 activity and apoptotic index by TUNEL assay in B-CPAP cells compared with the Nthy-ori 3-1 cells. Apoptotic cells with nuclear condensation and fragmentation were observed in B-CPAP cell line. Rosuvastatin induced autophagic changes in B-CPAP papillary thyroid cancer cells in lower doses and caused a shift from autophagy to apoptosis. Rosuvastatin may be an alternative treatment for refractory papillary thyroid cancer. Further in vivo studies are necessary to clarify the effects of rosuvastatin in papillary thyroid carcinoma and the clinical implications of rosuvastatin treatment., (© 2011 Society for Endocrinology)

Tall cell variant of papillary thyroid carcinoma is an aggressive form of thyroid cancer with a significant mortality. This review describes the pathology of this variant, compares it to its pathologic mimics and discusses its clinical pathologic features. The literature on this tumor is reviewed. A brief discussion of molecular pathologic correlates is included.

Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, Ukraine, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the "ret-negative" tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

Nuclear irregularities including nuclear pseudoinclusions and nuclear grooves are characteristic of papillary thyroid carcinoma cells and are regarded as important diagnostic clues in histopathology. We observed nuclear features of thyroid carcinoma cell lines (KTC-1 and TPC-1) in various culture conditions and performed immunocytochemical examinations for cytoskeleton molecules to clarify the morphogenesis of thyroid carcinoma nuclei. We found that nuclear irregularities presenting as bean-like nuclei (BLNs) and donut-like nuclei (DLNs) appeared in cells from confluent cultures, but not in cells from sparse cultures. On immunocytofluorescence analyses, clusters of gamma-tubulin, representing a centrosome, frequently localized at the indentation of BLNs or in the hole of DLNs of thyroid carcinoma cells. In conclusion, we suggest that cell-to-cell contact may affect nuclear changes such as BLNs and DLNs in cancer cell lines and that centrosomes may be involved in the morphogenetic process of these nuclear changes.

Nuclear grooves are longitudinal invaginations of the nuclear envelope bilayer, which constitute a characteristic feature of papillary thyroid carcinoma. Their pathogenesis is not yet clear, but there is evidence for the involvement of a signaling pathway downstream of the protooncogene RET. The presence of nuclear grooves is not specific for papillary thyroid carcinoma because it has been documented in other types of thyroid neoplasms, in nonneoplastic thyroid lesions, in ovarian neoplasms (Brenner, adult granulosa cell, and transitional cell tumors), in breast carcinomas, in cervicovaginal and endometrial smears, in papillary neoplasms of several organs (such as papillary transitional cell carcinoma of the bladder, papillary renal cell carcinoma, papillary endometrioid carcinoma of the prostate), in thymic carcinomas, and in nonepithelial tumors.

Objective: To analyze relationships between nuclear features of papillary renal cell carcinoma (PapRCC) subtypes., Study Design: The material for the study consisted of 53 cases, of which 29 were type 1, 17 type 2 and 7 intermediate. At least 100 nuclei per case were segmented from images of 4',6-diamidino-2-phenylindole-stained slides. The geometric and texture features were extracted and used for analysis., Results: In analysis of variance, it was shown that both individual cases and tumor types differ in the majority of the parameters. On nonsupervised expectation-maximization clustering, it was possible to classify the nuclei into separate categories, but PapRCC classes were not reproduced. The neural network classified the nuclei with sensitivity >0.6 and specificity >0.75. Analyzing the results for individual cases, the nuclei of type 1 cases were properly classified in 74-91%, nuclei of type 2 cases in 58-80% and nuclei of intermediate cases in 53-70%., Conclusion: Our findings show that PapRCC subtypes are distinct enough to be reproduced by image analysis.

Background: Solid pseudopapillary neoplasm (SPN) and pancreatic endocrine neoplasm (PEN) are uncommon neoplasms that demonstrate characteristic cytologic features. It is also known that both these tumors may share similar morphologic changes. These features not uncommonly pose significant diagnostic challenge for unsuspecting cytopathologists. In the current study, the authors report that recognition of clear cytoplasmic vacuoles in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from SPN serves as a useful clue that can distinguish this tumor from PEN., Methods: The cytologic features from 5 SPN and 20 PEN cases were evaluated. Both Diff-Quik and Papanicolaou stains from these cases were examined. A Fisher exact test of probability was performed to determine differences in the individual cytologic features noted in these 2 tumor types., Results: The results demonstrated that pseudopapillary groups (P = .004); metachromatic matrix material (P = .004); nuclear membrane irregularity (P = .004); and large, clear cytoplasmic vacuoles (P = .001) are noted significantly more frequently in SPN. The authors also demonstrated that large, clear cytoplasmic vacuoles can serve as a powerful cytologic clue for the suspicion of SPN over PEN when there is a paucity of papillary groups within the smears. Large, clear cytoplasmic vacuoles, however, were noted only in Diff-Quik-stained smears, but not in Papanicolaou-;stained smears., Conclusions: The results of the current study highlight that large, clear cytoplasmic vacuoles can serve as a critical clue with which to distinguish SPN from PEN in diagnostically challenging cases., ((c) 2008 American Cancer Society.)

The paper reviews the data available in the literature and describes the authors' observation of solid pseudopapillary tumor of the pancreas in a 33-year-old woman. Microscopically, the tumor, 2.5 x 2.5 x 2 cm in size, appeared predominantly as solid areas and solitary pseudopapillae comprising monomorphic round and oval cells with a light cytoplasm and round nuclei. Immunohistochemical study revealed diffuse cytoplasmic tumor cell staining in response to vimentin, alpha-antitrypsin, neuronspecific enolase, and cytokeratin 18; focal expression of synaptophysin and CD117; a negative reaction with antibodies to epithelial membrane antigen, S-100 protein, cytokeratins 7, 8, and 19, and CD57. Progesterone receptors were detectable in the nuclei of solitary tumor cells and the reaction with estrogen receptor was negative. The proliferation index (by Ki67) is about 0.2%.

Invasive micropapillary carcinoma has recently been reported in various anatomic sites. In this article, we report a case of micropapillary carcinoma of the sigmoid colon. A 70-year-old Japanese woman presented with bloody stool for 2 months. Detailed examination disclosed ulcerative and localized tumor in the sigmoid colon. Histological examination of the colon tumor showed a combination of conventional adenocarcinoma (60%) and micropapillary carcinoma (40%). Immunohistochemically, micropapillary carcinoma cells were positive for cytokeratin (CK) 20, carcinoembryonic antigen, and CA125, but negative for CK7, thyroid transcription factor-1, surfactant apoprotein A, estrogen receptor, and progesterone receptor. Additionally, the immunohistochemistry of epithelial membrane antigen revealed reverse polarity of neoplastic cells. Results of conventional adenocarcinoma were basically identical to those of micropapillary carcinoma. In the stroma of both conventional adenocarcinoma and micropapillary carcinoma, many myofibroblasts were present and CD34-positive stromal cells were absent. Finally, we report the fourth case of micropapillary carcinoma arising in the colon. Immunohistochemical results of CK7(-)/CK20(+) strongly suggest the colon as a primary site of micropapillary carcinoma. Additionally, micropapillary carcinoma of the colon may cause a similar stromal reaction to conventional adenocarcinoma of the colon.

Chromosome territories (CTs) are intranuclear subregions occupied by individual chromosomes in an interphase cell. In this study, we investigated intranuclear CT positionings of chromosomes 10 (CS10), 18 (CS18), and 19 (CS19) in epithelial cells from four normal thyroid tissue (NT), four adenomatous goiters (AGs), six papillary carcinomas (PCs), and two undifferentiated carcinomas (UCs) using the multicolor fluorescence in situ hybridization method. In the NT and AGs, the radial positionings of CS10 and CS18 were detected at the periphery of nuclei in more than 60% and 80% of cells, respectively, whereas the radial positioning of CS19 was in the central region of the nuclei in more than 80% of cells. In the PCs, radial positioning pattern of CS10 and CS18 were similar to that in the NT. The nuclei with centrally located CS19 in PCs were less frequent than those in NT cells (p < 0.01). On the other hand, UCs with cells having DNA amplification demonstrated the locational abnormalities of the CS10, CS18, and CS19 radial positions. These findings indicate that alteration of CT positioning could be related to DNA amplification and, morphologically, may explain the nuclear atypia that accompanies the abnormal chromatin feature.

This study was undertaken to determine the validity of Fuhrman grading in a series of papillary renal cell carcinomas (PRCCs), to examine the interrelationship and prognostic significance of the individual components of the grading system, and further to determine whether any observed predictive value was independent of other prognostic indicators. Ninety cases of PRCC were studied. Fifty-nine tumors were of type 1 and 31 were of type 2. There were 33 TNM stage 1, 26 stage 2, 18 stage 3, and 12 stage 4 tumors, whereas division of cases according to pT category showed 14 pT1a, 20 pT1b, 25 pT2, 15 pT3a, 4 pT3b, and 11 pT4 tumors. Ten tumors were grade 1, 58 grade 2, and 22 grade 3 when predominant Fuhrman grade was assigned, whereas grading according to the high-power field containing the highest grade (focal grade) showed 40 grade 2, 49 grade 3, and 1 grade 4 tumors. Measurements of nuclear size (area, major axis, perimeter) and shape (shape factor, compactness) were undertaken using image analysis. Nuclear area ranged from 27.63 to 116.39 microM, major axis length 6.70 to 14.06 microM, and nuclear perimeter 20.05 to 41.77 microM. Shape factor ranged from 0.805 to 0.878 and compactness from 14.33 to 15.66. Predominant nucleolar grade using the criteria of the Fuhrman classification was nucleolar grade 1 for 13 tumors, nucleolar grade 2 for 56 tumors, and nucleolar grade 3 for 21 tumors. Focal nucleolar grade based on the high-power field showing the greatest degree of nuclear pleomorphism, was grade 2 for 38 tumors and grade 3 for 52 tumors. pT category, TNM stage, focal Fuhrman grade, and PRCC type were significantly associated with survival. Of the various measures of the components of the Fuhrman classification, only focal nucleolar grade was associated with survival, on univariate analysis. On multivariate analysis, focal nucleolar grade and tumor diameter were independently associated with survival, whereas TNM stage retained significance independent of other parameters. It is concluded that assessment of nucleolar prominence rather than Fuhrman grade is applicable for stratification of tumors within TNM stage or pT category for PRCC and that this should be based upon the high-power field showing the greatest degree of nuclear pleomorphism.

Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3-20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site., (2006 Wiley-Liss, Inc.)

Objective: To compare the cytologic features benign and malignant papillary breast lesions., Study Design: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets., Results: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms., Conclusion: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.

Objective: To determine the advantage of examining fine needle aspiration (FNA) smears of papillary thyroid carcinoma (PTC) under a 100 x oil-immersion objective, which is capable of optically sectioning the cells., Study Design: Two hundred neoplastic cells were counted under a high-power (40x) objective as well as oil-immersion (100x) objective in 54 PTC cases classified into variants: 14 follicular neoplasms, 8 Hürthle cell neoplasms, 5 medullary thyroid carcinomas and 9 hyperplastic lesions. The counts of cells with 2 important diagnostic features of PTC, intranuclear cytoplasmic inclusions (INCIs) and grooved nuclei, were compared between various groups and between high-power and oil-immersion objectives in each group., Results: Cytomorphologic features, such as INCI and nuclear grooves, were visible usually under 2 or 3 focal planes under the oil-immersion objective as opposed to a single plane under the high-power objective. In PTC cases, the mean cell count, 10.1 (+/- 1.75 SE) with INCIs, under the oil-immersion objective was significantly higher than the count, 6.1 (+/- 1.32 SE), under the high-power objective (p = 0.023). INCIs were not observed under the high-power objectives in 11 (20.4%) PTC cases, but in 5 (45.5%) of these they were visible under the oil-immersion objective. In PTC the mean cell count, 88.0 (+/- 4.96 SE), with grooved nuclei under the oil-immersion objective was also significantly higher than the count, 69.5 (+/- 4.87 SE), under the high-power objective (p = 0.010). Under the high-power objective, < 20.0% of cells with grooved nuclei were observed in 12 (22.2%) cases of PTC. However, examination under the oil-immersion objective revealed > or = 20.0% cells with grooved nuclei in 9 (75%) of these. In PTC the mean cell counts with INCIs as well as grooved nuclei under the oil-immersion objective were significantly higher than those of follicular neoplasms, Hürthle cell neoplasms, medullary carcinoma and hyperplastic lesions., Conclusion: In PTC, examination of FNA smears for INCIs and grooved nuclei under an oil-immersion objective was diagnostically more useful as compared to a high-power objective.

Nuclei of papillary thyroid carcinoma (PTC) are characterised by diagnostic morphological features, which include optically clear nuclei, irregular nuclear profile, pseudoinclusions and grooves. In the present study, such nuclear features were analysed by means of confocal microscopy using anti-lamin B antibodies to outline the nuclear membrane. Parallel sections of the nucleus, produced by confocal microscope analysis, showed that the nuclear shape is markedly irregular with profound invaginations, clefts and tunnel-like structures, which correspond to the "grooves" and "holes" detectable using light microscopy, respectively. A tridimensional (3-D) model of the nuclei, obtained by a computer-based reconstruction of confocal microscope images, showed, in the vast majority of PTC cells, nuclei with crateriform areas, clefts and even tunnel-like structures "piercing" the whole nuclear thickness. By rotating these models in space, it became evident that the holes and grooves seen in light microscopy correspond to invaginations and tunnels, depending on the viewpoint. In conclusion, this is the first application of confocal microscopy and tridimensional reconstruction to the study of nuclear morphology of PTC and of tumours in general. The light microscopic appearance of PTC nuclei, so familiar to pathologists, is, therefore, due to profound remodelling of the nuclear shape with invaginations and tunnels, which appear as either grooves or holes, according to the viewpoint.

Cribriform-morular variant of papillary carcinoma is a distinctive histological variant of thyroid cancer, characterized by intermingled cribriform, follicular, papillary, trabecular, and morular architecture. These tumors are known to be associated with familial adenomatous polyposis (FAP), but are also encountered in non-FAP patients. The authors report on ultrastructural and genetic studies of 3 patients with this type of carcinoma-associated FAP. There were numerous microfilaments approximately 100 nm long at the nuclear clearing area of the morular regions. Two of the 3 patients showed germline APC mutations, and 1 had so somatic APC mutation. Both mutations were in previously unreported regions. The study provides new information for understanding the development of this rare tumor.

Objective: To clarify the relationship between biologic behavior and morphologic features of invasive micropapillary carcinoma (IMPC) of the breast., Methods: Two thousand and eighty-eight cases of clinically defined monocentric breast cancer without pre-operative biopsy (except fine needle aspiration procedure) were examined by whole mammary gland serial sectioning. The clinicopathologic and morphologic features (including microscopic and ultrastructural) of IMPC were analyzed., Results: One hundred and seventeen cases of IMPC (6.2%, 117/1 880) were diagnosed during the period of study. The incidence of lymphovascular invasion (54.7%, 58/106) and nodal metastases (76.4%, 81/106) was significantly higher in IMPC, as well as the number of metastatic node (on average 9.6) was significantly more in IMPC, as compared with that of the invasive ductal carcinoma. Microscopically, the tumor was characterized by morula-like clusters and small papillae of malignant cells floating within irregular interstitial spaces and separated by fibrous septa. Ultrastructurally, microvilli were observed on the neoplastic cell surface at the periphery of the micropapillae. There were also numerous fine intermediate filaments in the cytoplasm. Newly formed capillaries were noted in the interstitium and some tumor cells were directly in contact with endothelial cells., Conclusions: A predominant component of IMPC in breast carcinoma is associated with a higher risk of lymphovascular invasion and nodal metastasis. The aggressive behavior of IMPC can be attributed to the proliferative activity of the tumor cells, and its associated angiogenesis.

Human bladder urothelium is able to secrete tissue-type plasminogen activator (tPA). The aim of our study was to analyse localisation of tPA antigen in comparison to differentiation state of cells in samples of histologically normal urothelium and non-invasive tumours of the human urinary bladder. Twenty-five samples of normal urothelium and 31 non-invasive papillary tumours from 36 patients were examined. The presence of tPA antigen was evaluated immunohistochemically. Differentiation of superficial cells was assessed by the presence of urothelial cell differentiation markers, uroplakins (UPs; immunohistochemistry) and cell's apical surface architecture (scanning electron microscopy). All tissue samples stained anti-tPA positive. In normal urothelium, the intensity of anti-tPA staining was the strongest in superficial cells, which were well-differentiated. In tumours, all cell layers stained anti-tPA positive. The intensity of anti-tPA positive reaction in the upper cell layer correlated with the percentage of anti-UP positive superficial cells. Superficial cells showed various differentiation states. The localisation of tPA antigen in human in vivo tissue is not confined to the well-differentiated superficial cells. Our results suggest a positive correlation between tPA secretion and cell differentiation.

The presence of neuroendocrine cells is putative in thyroid hyalinizing trabecular tumor (HTT), although this entity requires a differential diagnosis from paraganglioma or medullary carcinoma of the thyroid, due to similarity of the growth pattern of the cells. Here, we present a case of HTT with a mixture of endocrine cells stained positive for somatostatin, chromogranin A and Grimelius' silver impregnation. The histology and results of other immunostainings were consistent with the features typical for HTT. In the world literature to date, only two cases of HTT with endocrine cells, including the current case, have been reported. Nevertheless, the cases may indicate the diversified differentiation of cells in HTT and may, in part, account for the resemblance of HTT to paraganglioma and medullary carcinoma.

Clear-cell (CRCC), papillary (PRCC), and chromophobe (CHRCC) renal-cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well studied in cytopathological materials. Sixty-two fine-needle aspiration biopsy cases of metastatic RCC were studied and correlated with surgical pathology of RCCs with and without metastasis. Special stains for glycogen and immunostaining for cytokeratins, vimentin epithelial membrane antigen (EMA), and carcinoembryonic antigens, and electron microscopic studies were performed. Fifty-nine cases of CRCC and three of PRCC subtypes were retrieved from the cytopathology files at the Ottawa Hospital in a period of 10 years. Of these cases, 10 metastatic CRCC and one metastatic PRCC were diagnosed prior to the diagnosis of the primary tumor. CHRCC and sarcomatoid RCC were not represented in cytopathological specimens. CRCC displayed characteristic filmy cytoplasm and nuclei with prominent nucleoli. PRCC was characterized by dense cytoplasm, large nuclei with prominent nucleoli, and papillary architectures. In addition, all RCCs were characterized by the presence of glycogen and the absence of mucin by using histochemical techniques and electron microscopic studies and positive reactivity for cytokeratins (CK) and vimentin (VIM). In the same period, there were a total of 380 patients with RCC divided into 310 CRCCs, 55 PRCCs, and 15 CHRCCs associated with metastases in 142, 9, and 1 case, respectively. CRCC is by far the most common subtype found in metastases sampled in cytopathology. PRCC, CHRCC, and sarcomatoid RCC were underrepresented. Awareness of this propensity of RCC and the characteristic cytopathological, histochemical, immunohistochemical, and ultrastructural features are helpful in the diagnosis of metastatic RCC., (Copyright 2003 Wiley-Liss, Inc.)

Papillary thyroid carcinoma (PTC) is diagnosed in both cytology and surgical pathology specimens on the basis of distinct nuclear morphology, characterized by nuclear elongation, chromatin clearing, intranuclear grooves, and inclusions. Although these nuclear features are specific to papillary carcinoma, they can be mimicked in some benign conditions. The majority of PTC cases do not pose diagnostic problems. However, a distinct subset of cases has generated controversy among experts. These cases are follicular patterned tumors that show minimal nuclear changes in PTC. Several investigators have explored the role of immunohistochemical markers in the histologic diagnosis of PTC. Somatic rearrangements of the RET protooncogene are the most frequent genetic abnormality found in PTC. The frequency of these rearrangements has varied according to the geographic region, radiation exposure, and methodologies used and histologic variant of PTC. Recent studies have suggested that RET/PTC may be the cause of this specific nuclear change in PTC; however, the role of RET/PTC in tumor progression still needs to be defined.

Abstract. Exophytic tumors of the urinary bladder were examined by means of transmission electron microscopy for the presence of neural tissue because, as yet, there has been hardly any discussion of a neuronal component in the biology of neoplasms. In the stroma and rarely in the epithelium of bladder tumors, fine nerve strands were found to be irregularly distributed. These strands comprised one to a maximum of five axons containing predominantly colocalized clear and dense-core vesicles. Immunohistochemistry revealed some nerve-like structures showing vasoactive intestinal neuropeptide (VIP) reactivity. This response and the combination of vesicle types indicate that parasympathetic cholinergic neurons contribute to the innervation of the tumors. Thus, a morphological basis for neuronal influence on the behavior of such tumors has been demonstrated.

Background: In the works of various authors, performed with the help of morphometry, an assessment of cell changes was carried out, as a rule, by one sign of their atypia (e.g. area of cell nuclei). Moreover, the selective analysis of morphometric data for certain nosologic forms was performed. Such an approach allowed researchers to develop only additional diagnostic criteria of thyroid carcinoma. At the same time, the use of a set of quantitative signs of cell atypia as a criterion for tumor malignancy made it possible to improve oncologic diagnosis. In this study, which is a first step in the development of a quantitative approach to thyroid carcinoma diagnosis, a system of karyometric parameters was developed with the help of morphometry of cytologic material of patients with major nosologic forms of thyroid pathology (papillary and follicular carcinoma, follicular adenoma, autoimmune thyroiditis, and nodular colloid and diffuse toxic goiter). The significance of each parameter in thyroid carcinoma diagnosis was evaluated., Methods: Thyroid cells of autopsy, operative, and aspiration biopsy material were the object of the study. One hundred fifty-two preparations with histologically verified diagnosis were studied. Light morphometry was performed with the help of a semiautomatic computer analyzer of images. One hundred fifty thyroid nuclei were assessed in each preparation., Results: Among many karyometric parameters, six were selected: mean area of thyrocyte nuclei, ratio of frequencies, and number of classes on histograms of distribution of their area, coefficient and a free term of the regression equation to a scattered diagram of perimeter and nuclear area, and the discriminant index. Boundary values of these parameters between the malignant and benign pathology were united into an expert system for thyroid carcinoma diagnosis. Clinical trials of the system were performed. On the basis of the obtained results, the informativity (accuracy, sensitivity, specificity) of its karyometric parameters was assessed. The formula for calculation of the weighting coefficient for each parameter was derived, the diagnostic index being determined by the sum of their values., Conclusions: An expert system was created based on a set of karyometric parameters reflecting the regularities of pathologic changes in thyrocyte nuclei with malignant and benign pathology. The informativity and weighting coefficients included into the system of parameters have been assessed, which made it possible to perform the probabilistic diagnosis of thyroid carcinoma., (Copyright 2001 American Cancer Society.)

Primary pigmented intracranial neoplasms are strikingly uncommon. The differential diagnosis is limited and includes both epithelial and nonepithelial tumors, most of which arise within or near the ventricular system. The authors describe a 42-year-old man who presented with a pigmented papillary epithelial lesion that arose within the sella and exhibited suprasellar extension and bony erosion. Following external beam radiotherapy and multiple surgical resections, tumor growth became rapid, necessitating additional debulking procedures. Pathologic evaluation of subsequent lesional tissue samples revealed an anaplastic lesion with malignant epithelial and spindle cell components. Occasional epithelial cells showed features reminiscent of the original papillary lesion, whereas others exhibited oncocytic morphologic features. This case represents the only report, to our knowledge, of a pigmented papillary epithelial neoplasm arising within the pituitary fossa. Although the histogenesis of this tumor is enigmatic, this appears to be a distinct lesion characterized by aggressive growth and the capacity for anaplastic progression.

Background: Primary papillary serous carcinoma of the peritoneum is a well-known entity in women. The tumour is derived from the extraovarian mesothelium and the pelvis and lower abdomen mesothelia. The treatment strategies are similar to ovarian serous papillary carcinoma., Patients and Methods: A case of primary serous papillary carcinoma of the peritoneum in a man is presented. The patient, 53 years old, died 2 months after diagnosis., Results: The histologic and immunohistochemical studies of the tumour will be presented. These studies, made during lifetime and at autopsy of the patient, confirm a diagnosis of primary serous papillary carcinoma of the peritoneum., Conclusions: primary serous papillary carcinoma of the peritoneum can occur in men, and should be considered in the differential diagnosis in cases of abdominal carcinomatosis of unknown origin. Treatment options remain to be determined.

Two cases of solid papillary carcinoma of the breast were pathologically studied. Subjects included two female patients: a 76-year-old (Case 1) and a 43-year-old (Case 2). Both cases showed solid and papillary proliferation of spindle cells in expanded ducts, perivascular pseudorosettes, eosinophilic fine granules in an abundant cytoplasm, intracellular mucin production, and positivity for chromogranin A. Case 1 showed an aggregation form involving multiple ducts, admixture of signet-ring like cells, mucin pools, and small and large electron-dense granules and flocculent granules in electron microscopy. Case 2 showed a solitary and compact form in a dilated duct and an interlacing bundle pattern.

Objective: To study the significance of nuclear grooves in thyroid and extrathyroid benign and malignant lesions., Study Design: In this retrospective study, 26 cases were selected randomly, consisting of papillary carcinoma of the thyroid (7), papillary adenocarcinoma (9), normal cervical smear (5) and benign bronchioalveolar lavage (BAL) (5). In all cases hematoxylin and eosin- and Papanicolaou-stained smears were studied for nuclear grooves., Results: Except for one case of papillary adenocarcinoma, nuclear grooves were discernible in all cases. The highest number of nuclear grooves was seen in normal cervical smears, followed by papillary carcinoma of the thyroid, papillary adenocarcinoma and BAL smears., Conclusion: The number of grooves did not correlate with either benign or malignant conditions. These findings cast serious doubt about the diagnostic significance of nuclear grooves. Probably nuclear grooves are nonspecific findings and should be considered only in association with other diagnostic features.

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.

Nitric oxide (NO) is generated by a family of enzymes, nitric oxide synthases (NOS), in a wide range of mammalian cells. NO produced by the inducible NOS isoform (iNOS) has been suggested to play an important role in tumor biology with both tumor promoter and anti-tumor activity. Here, the cellular localization of iNOS in tissue of 100 cases of urinary bladder cancer was assessed immunohistologically using a commercially available antiserum. Positive iNOS immunostaining was detected in all samples of tumor tissue, whereas nonmalignant tissue adjacent to malignant areas did not show any iNOS positivity. The tumor tissue revealed a highly inhomogeneous staining pattern. In addition to uniformly stained tumor specimens, we also found markedly iNOS-positive tumor islets in the midst of unstained tumor tissue and scattered individual tumor cells expressing marked staining. In some cases, the tumor tissue showed no or only weak staining intensity. In some instances, the superficial epithelial layer of papillary carcinomas was extremely immunoreactive, in other cases it was not. Thus we were unable to show a clear correlation to tumor grade or stage. Further studies with a diversity of tumor markers including molecular genetics techniques will be necessary to elucidate how and to what extent NO and bladder cancer of different grades and stages are functionally interrelated.

Septate cytoplasmic vacuoles, which are one of the cytologic findings characteristic of papillary thyroid carcinoma, are small, uniform, and well-defined vacuoles, with defined strands of cytoplasm separating them. We report on a case with histologic and ultrastructural findings corresponding to septate cytoplasmic vacuoles, which have not been previously described. The patient was a 51-yr-old man with a mass in the left anterior of the neck, measuring 4.0 x 3.5 cm in diameter. Aspiration cytology smears revealed findings typical of papillary thyroid carcinoma, including papillary tissue fragments, intranuclear inclusions, nuclear grooves, powdery chromatin, and psammoma bodies. The tumor cells which were located at the periphery of small three-dimensional clusters, and others which showed a sheet-like arrangement, demonstrated uniform, small vacuoles in relatively abundant, dense cytoplasm. Histologically, a small number of papillary thyroid carcinoma cells with multiple vacuoles were observed, which were limited to the hobnail-shaped cells located at papillary configurations or floating tumor cells within the papillary lumen. Ultrastructurally, the hobnail-shaped tumor cells demonstrated various-sized dilated rough endoplasmic reticulum and rich heterochromatin. We emphasize that septate cytoplasmic vacuoles correspond to dilated rough endoplasmic vacuoles and are probably related to degenerative changes., (Copyright 2000 Wiley-Liss, Inc.)

A new human thyroid carcinoma cell line, KTC-1, was established from the malignant pleural effusion of a recurrent thyroid carcinoma patient. Cytogenetic analysis revealed a normal karyotype, and no p53 mutation in exons 5-9 was detected. This cell line is tumorigenic in athymic nude mice. Histological findings by light and electron microscopy, such as the absence of follicular structures and the existence of intranuclear cytoplasmic inclusions and psammoma bodies, indicated transplanted tumors to be a poorly differentiated papillary thyroid carcinoma. A low expression level of thyroglobulin was detected by immunocytochemistry and RT-PCR. Messenger ribonucleic acid (mRNA) expression of thyroid transcription factor-1 and PAX-8 was also detected. No mRNA expression of TSH receptors, thyroid peroxidase, or Na+/I- symporter was detected. Interleukin-6 and leukemia inhibitory factor were secreted into the medium. These findings suggest this cell line to be functionally poorly differentiated. Moreover, all-trans-retinoic acid increased the mRNA expression of thyroglobulin and decreased both the mRNA expression and secretion of interleukin-6 and leukemia inhibitory factor while significantly stimulating growth. RT-PCR analysis of retinoic acid receptors (RARs) revealed that KTC-1 cells express a moderate level of RARalpha and -gamma, but a low level of RARbeta. This cell line may be useful for studying redifferentiation therapy for thyroid carcinoma.

A total of 570 cases with thyroid papillary cancer are analyzed. Eight cytologic variants of the tumor were distinguished: typical (classical), 240 (42.1%) cases; follicular, 225 (39.5%); cystic, 70 (12.3%); with squamous-cell metaplasia, 16 (2.8%); with B-cell transformation, 10 (1.7%); from high cells, 6 (1.0%); anaplastic, 2 (0.4%); and sclerosing, 1 (0.2%) cases. Cytometric analysis of tumor smears from 103 patients was carried out. Four parameters were acknowledged as the most valuable for verification of thyroid papillary cancer variants: cell perimeter, cell area, nuclear area, and nucleus/cytoplasm ratio. Cytologic and cytometric findings allow the clinical cytologist verify the variant of thyroid papillary cancer in the majority of cases.

This study identified that the carcinogenesis of hamster buccal pouch (HBP) induced by 7,12-dimethylbenz[a]anthracene (DMBA) was greatly enhanced (18 folds) by a combination treatment with Taiwanese betel quid (BQ) extract. A new cell line, HCDB-1, has been established from induced carcinomas. The cultured monolayer cells were epithelioid in shape with irregular nuclei. They demonstrated abundant cytokeratin and tonofilaments; however, ultrastructural well-organized desmosomes were lacking. The HCDB-1 cell exhibited population doubling in 19 h and was highly tumorigenic in nude mice. A C-->T transition at codon 141 (Ala to Val) of the p53 gene was detected in this cell. This mutation is equivalent to a specific temperature-sensitive mouse p53Ala135Val mutant that causes transformation by shifting to 37.5 degrees C. HCDB-1 is the first cell line established from the HBP model of oral carcinogenesis induced by DMBA/Taiwanese BQ extract. It might be valuable for exploring the molecular pathogenesis of oral cancer.

We report 2 cases of solid and pseudopapillary tumors of the pancreas occurring in female children. Lesions were made of uniform small cells arranged in solid areas associated with pseudopapillary and cystic patterns. Immunohistochemistry study was positive for neuron-specific enolase, alpha-1 anti-trypsin and vimentin. Ultrastructural study showed an abundant cytoplasm, rich in mitochondria, containing a lot of granules of variable sizes, often disintegrated, and some lipid droplets. The differential diagnosis of this lesion included endocrine tumor, pancreatoblastoma and acinar cell carcinoma. It is a rare tumor of the pancreas with a favorable prognosis after complete resection.

Solid-pseudopapillary tumors are uncommon neoplasms of low malignant potential generally occurring in young women. They often cause few symptoms and may reach a large size by the time they are detected. Degenerative cystic changes are common, and the clinical presentation is often that of a cystic pancreatic tumor. Pathological features include solid, cellular, hypervascular regions without gland formation, and degenerative pseudopapillae. The cells contain eosinophilic granules rich in alpha-1-antitrypsin and the nuclei are typically grooved. Despite its characteristic microscopic appearance, the immunophenotype (positive for vimentin, alpha-1-antitrypsin, and neuron specific enolase) is not specific and does not define a line of differentiation corresponding to any normal pancreatic cell type. Ultrastructural studies have also failed to identify specific differentiated features. Nonetheless, the biological behavior of solid-pseudopapillary tumor is well established. The tumor is indolent, with infrequent metastases to liver or peritoneum and usually long survival, even in the presence of disseminated disease.

The aim of this study was to investigate the possibility of identifying urothelial neoplasia by nuclear chromatin texture feature analysis using high resolution image cytometry to improve the diagnostic accuracy of cytologic examination in the detection and monitoring of bladder cancer. Touch imprints of transurethral resection material of 56 control group (CG) cases of nonmalignant urothelium and 94 tumor group (TG) cases of bladder cancer were analyzed. The specimen collection was divided randomly into a training set and a test set. Cells were stained specifically for DNA by the Feulgen method. Only diploid cell nuclei were analyzed from both groups. A discriminator comprised of three nuclear texture features was derived from the training set of cases to separate CG from TG cases. This discriminator was then applied to the independent test set. CG cases were separated from TG cases with a sensitivity of 97% and a specificity of 95% on the independent test set of cases. When dividing TG cases into high-risk and low-risk groups, sensitivity in the low-risk group was 93%. None of the high-risk cases was misclassified (sensitivity, 100%). This retrospective investigation demonstrates that by high-resolution image cytometry it is possible to distinguish between urothelial neoplasia and normal urothelium with high reliability when examining diploid cell nuclei only. This method is superior to DNA ploidy analysis using image or flow cytometry and may become clinically relevant as a supplement to conventional cytologic examination. These promising results should be confirmed on cytologic preparations derived from bladder washings or voided urine.

Cytologic smears from fine-needle aspirates of three histologically and ultrastructurally confirmed hyalinizing trabecular adenomas of the thyroid (HTAT) were reviewed. In two cases a cytodiagnosis of HTAT was suggested, and in one patient a diagnosis of trabecular epithelial neoplasm was made. In all three cases, small clusters and sheets of epithelial cells with abundant, filamentous, vacuolated, and ill-defined cytoplasm were present. The nuclei were slightly pleomorphic and showed nuclear overlapping, nuclear grooves, and intranuclear cytoplasmic inclusions. Small and irregular fragments of acellular hyalinized material (AHM) were noted within the tumor cell clusters in the first two cases. In the third patient, large syncytial sheets and anastomotic cords of epithelial cells showing ill-defined, filamentous cytoplasm, slightly pleomorphic nuclei, nuclear overlapping, intranuclear cytoplasmic inclusions, and nuclear grooves were present. Fragments of AHM were not observed within clusters and syncytial sheets of tumor cells.