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To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25-64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25-49 and 50-64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51-0.97); the effect of age >or=50 is 0.29 (95% CI: 0.24-0.35). The CR of CIN2+ is at least eightfold higher in women <50 (CR=2.06, 95% CI: 1.88-2.23) after one previous negative test than in women >or=50 years with four screens (CR=0.23, 95% CI: 0.00-0.46). Over 50 years of age, after four tests at least three false-positive cases are diagnosed for every true positive. Benefits arising from cytological screening is uncertain in well-screened older women. [ABSTRACT FROM AUTHOR]

Background: The accumulation of cyclin-dependent kinase inhibitor 2A (p16 ink4a ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16 ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed., Methods: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists., Results: The overall κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358-0.642] and κ = 0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384-0.866]; second evaluation, κ = 0.403 [95% CI, 0.182-0.643])., Conclusions: Dual staining for p16 ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Human epithelial growth factor receptor 2 (HER2) overexpression and/or amplification is of predictive and prognostic value in infiltrating breast carcinoma (IBC). We evaluated the proportion of HER2-positive cases (score 3 overexpression/score 2 plus fluorescence in situ hybridization (FISH) amplification) in a consecutive series of 2163 patients. According to immunohistochemical analysis of HER2 expression, using Herceptest and FDA criteria, 839 cases had score 0, 476 score 1+, 699 score 2+, and 149 score 3+. Of the 699 scoring 2+ cases, 160 (22.88 %) showed Her2 gene amplification by FISH analysis, making a total of 309 (14.28 %) HER2-positive cases. Grade 1 ductal and special type IBC were never HER2 positive, while only three infiltrating lobular carcinomas but a relevant percentage of small IBC were HER2 positive. Of HER2-positive cases, 52.1 % was pT1 and of these, 38.5 % was pT1b or smaller. Logistic regression analysis revealed that estrogen receptor (ER), progesterone receptor (PgR), grade, and pT were significantly associated with HER2 positivity and that HER2 3+ cases were more frequently of higher grade and pT than HER2 2+/Her2 amplified cases. In addition, HER2 3+ cases were more frequently in ER and PgR negative than HER2 2+/Her2 amplified cases. We conclude that the proportion of HER2 positive cases is lower than that reported in older literature and that pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases.

Objective: Mast cells are bone marrow-derived tissue-homing leukocytes, which have traditionally been regarded as effector cells in allergic disorders, responses against parasites, and regulation of blood flow, but a broader perspective of their functional heterogeneity, such as immunomodulation, angiogenesis, tissue repair, and remodeling after injury, is now emerging. The persistence of mast cells in connective tissues throughout the evolution of vertebrates is evidence of strong selective pressure suggesting that these cells must have multiple beneficial and important roles in normal homeostasis. While mast cells are present within the uveal tract of eutherian mammals, there is little known about their presence in the choroid of other vertebrate classes., Animals Studied: Eye tissues from a range of vertebrate species (fish, amphibian, reptiles, birds, marsupials, monotreme, and eutherian mammals) were investigated. Tissues were fixed in either 2% glutaraldehyde, 2% paraformaldehyde or a mixture of both and processed for resin embedding. Semi-thin sections of the retina and choroid were cut and stained with toluidine blue., Results and Conclusions: Mast cells were identified in the choroid of all classes of vertebrates investigated except sharks. Their morphology, location, and staining characteristics were remarkably similar from teleost fish through to eutherian mammals and bore close morphological resemblance to mammalian connective tissue mast cells. The similar morphology and distribution of mast cells in the choroid of all vertebrate classes studied suggest a basic physiological function that has been retained since the evolution of the vertebrate eye., (© 2013 American College of Veterinary Ophthalmologists.)

Background: The province of Trento has been the target of health campaigns for early diagnosis of cutaneous melanoma for 30 years., Objective: To evaluate incidence and mortality data of skin melanoma in the province from January 1992 to December 2001., Methods: The study is based on the provincial skin cancer registry and the regional mortality registry. Standardized incidence and mortality rates were computed, and time trends were evaluated. Incidence rates were modeled using Poisson regression., Results: Five hundred fifty-four melanomas were diagnosed (226 in males and 328 in females). No period effect was revealed. Incidence rates in females were about 1.24 times those in males. No significant trend in mortality rates was observed., Conclusion: We examined incidence and mortality data of cutaneous melanoma during a 10-year period and failed to find any significant trend. It seems we have reached a plateau after many years of continuous, intensive health campaigns.

To evaluate the effectiveness of a cytological screening to prevent invasive cervical cancer in the province of Trento, a northern Italian area where a population-based cancer registry is active. The history of Pap test was evaluated through a case-control study in 61 population-based invasive cervical cancer patients, incident during 1995-2000, and in 244 age-matched (between 25 and 75 years old) controls. Women who had at least one Pap test had a reduced risk of invasive carcinoma of 80% (odds ratio=0.20; 95% confidence intervals 0.10-0.40). The protection of a previous Pap test for both squamous cell carcinoma (odds ratio=0.23; 95% confidence intervals 0.09-0.58) and adenocarcinoma (odds ratio=0.24; 95% confidence intervals 0.07-0.78) was similar. The overall protective effect of the Pap test was not seen among younger women (<40 years). The protective effect of the Pap test seems to be stronger for shorter intervals. Our study confirms that Pap-test screening, particularly in middle-aged and older women, is an effective public health intervention with encouraging results also for the prevention of cervical adenocarcinoma.

In the experimental arm of a randomised trial, women were tested both for liquid-based cytology and human papillomavirus (HPV) DNA and referred for colposcopy if cytology was ASCUS (atypical cells of undetermined significance) or more severe. We considered those with ASCUS (757) or LSIL (low-grade squamous intraepithelial lesions) (485) and a valid HPV test who received colposcopy. We computed sensitivity, specificity and ROC curves with different values of relative light units (RLU, that are related to viral load) as cut off, using cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) at blind histology review as the endpoint. The area under the receiver operating characteristic (ROC) curve was significantly less among women aged 25-34 years than in those older, both considering ASCUS/AGUS (atypical glandular cells of undetermined significance) (p=0.0355) and LSIL (p=0.0009). At age 35-60 the curves for ASCUS and LSIL were similar, while at age 25-34 the area under the curve for LSIL was significantly less than for ASCUS (p=0.0084). With LSIL cytology, specificity of Hybrid Capture 2 with 2 RLU cut-off was 35.0% (95%CI 28.4-42.1) at age 25-34 and 64.5% (95%CI 58.3-70.3) at age 35-60. In conclusion, triaging by HPV testing performed better in women aged over 35 years than those younger. For older women, HPV triaging should also be considered for managing those with LSIL cytology.

Background: A Skin Cancer Registry was established in the province of Trento in northeast Italy in 1992 with the aim of collecting data on all cutaneous tumors affecting residents. These neoplasms are responsible for considerable morbidity and utilization of the Health Service because of their high frequency and, therefore, knowledge of the exact incidence is very important in planning health policies. Registry data are also very helpful in performing studies of analytical and descriptive epidemiology., Methods: For each patient, we collected personal data, phenotypical characteristics, professional history, concurrent diseases, previous therapy or trauma, and all data regarding the tumors. Patients were interviewed in person or, less frequently, by phone. All data were verified and put in a computerized file, in a protected room. The Statistics Institute of Trento University analyzed the data. Comparison among means was performed using the analysis of variance and differences among proportions were tested by chi-squared analysis. Poisson regression and the likelihood ratio test were used to compare incidence rates. We analyze here the data regarding epiteliomas and melanoma., Results: During the study period we registered 3435 primary skin tumors in 2868 individuals. Crude incidence rates, calculated using the number of subjects (not the number of tumors), were 87.9 for basal cell carcinoma (BCC), 28.9 for squamous cell carcinoma (SCC), and 14.2 for cutaneous melanoma (CM), per 100,000 per annum. We also calculated the same figures in females and males and specific incidence rates in both sexes and evaluated the distribution of skin cancer according to sex and anatomical site., Conclusion: We report the analysis of the data collected by the Skin Cancer registry in a 6 year period and compare the data with published data in literature and with data of a previously registered melanoma file. Our results confirm the high incidence of nonmelanoma skin cancers and the variation in the histological patterns of CM.

The role of cytology in 44 cases of renal adenocarcinoma was evaluated. The diagnosis of neoplasia was made with radiographic means in all cases; urinary cytology was positive in only 19 patients (43.18%) and is therefore considered unsatisfactory in the detection of renal adenocarcinoma. The cytologic presentation of this disease was characterized by four different malignant cellular types. Multinucleated cells with distinct nucleoli as well as large vacuolated cells with hyperchromatic, eccentric nuclei showed the same cellular morphology seen in the corresponding histologic pictures. Granular eosinophilic cells, with pyknotic nuclei and distinct and/or ill-defined cytoplasmic borders, are believed to be the result of degenerative changes caused by the urinary environment. The multinucleated cell type was almost benign in appearance and could be confused with benign urothelial cells. The malignancy and the renal origin of such cells were confirmed by the observation of strikingly similar cells in the parent neoplasms.

Aspiration biopsy cytology is an accurate, safe, innocuous alternative to excisional biopsy in diagnosing the nature of concomitant superficial nodules or lymphadenopathy in patients with known cutaneous malignancy. In patients with penile cancer, aspiration biopsy cytology may avoid the morbidity (30-50%) and mortality (3%) of groin dissection staging. A positive aspirate is conclusive of Stage III tumor and, in patients with occult nodal metastases, may lead to early curative lymphadenectomy. In the present study of 28 patients with known cutaneous malignant melanoma, the aspiration biopsy cytology of 31 superficial nodules resulted in a cytologic diagnosis of metastasis in 29 nodules from 26 patients. In the management of patients with known melanoma, the positive cytology of superficial nodules is conclusive of metastatic disease and requires an accurate radiologic study to establish or exclude disseminated disease. Surgical removal of a metastatic superficial nodule is indicated when the lesion is considered localized disease and the patient, having been accurately examined, is determined to be apparently free of disease in other sites and organs. When systemic diffuse melanoma is found, the excision of metastatic superficial nodules is unnecessary. Positive aspiration cytology may avoid risk from ill-judged surgical procedures and indicate appropriate palliative treatment of the disease.

A retrospective study of patients at the Trento S. Chiara Hospital in the period 1982-86 showed up 8 cases of malignant mesothelioma (7 pleural and 1 peritoneal). The histology was re-examined for each case and clinical records was also looked at so as to identify onset symptomatology, diagnostic procedures and treatment. A standard questionnaire given to patients or close relations revealed previous exposure to asbestos in 2 of 3 males and in none of the 5 females. There was also a significant delay in formulation of correct diagnosis, attributable on the hand to the nonspecificity of the symptomatology of onset and on the other to the inadequacy of currently available clinical and radiological procedures. Only histology with the aid of immunocytochemical procedures was able to pinpoint correct diagnosis, in life. The ineffectiveness of conventional therapies and the poor overall prognosis for these patients is confirmed.

The cytologic findings in the urinary sediment of 13 patients with tuberculosis (TB) of the bladder were compared with the histologic findings. TB was cytologically recognized in 11 patients because of the presence of epithelioid and/or Langhans' giant cells. The morphologic deviations of the urothelial cells and the urothelium were classified according to the criteria of Koss. The type I atypical urothelial cells found in ten patients were correlated to the urothelial hyperplasia found at histology; the follow-up data documented the benign reversible nature of the urothelial hyperplasia as the focal expression of the reactive potential of urothelium to various forms of inflammatory processes. The presence of type II atypical urothelial cells reflected moderate and severe atypia of the urothelium at biopsy. In order to assess the reactive, reversible or precancerous nature of these forms of atypia associated with TB, an accurate follow-up is necessary. Since TB of the bladder may cause the presence of atypical cells in the urine, this lesion is of special interest in the differential diagnosis between inflammatory processes and carcinoma.

Renal adenocarcinoma shows an unpredictable clinical course. At autopsy, metastases are present in as many as 95 percent of patients with renal adenocarcinoma. The percentage of metastases from renal adenocarcinoma is greater than would be expected from the frequency of this carcinoma among all carcinomas. The breast is an exceptional site of metastasis, that is not described in literature. In the present report the metastasis in the breast represented the early symptom of renal adenocarcinoma.

An unusual cytologic presentation of spermatic hydrocele fluid is reported. The aspirate contained highly atypical cells, exhibiting marked anisocytosis and nuclear abnormalities strongly suggestive of cancer. On histologic examination the lesion displayed pseudosarcomatous fasciitis in the cyst wall and foci of atypical reactive mesothelial hyperplasia in the lining. This case illustrates a potential pitfall in the cytology of spermatic hydrocele fluid.

We describe a patient with a cytologic diagnosis of ureteral metastasis from breast carcinoma with peripelvic extravasation, representing the beginning of metastatic spread of malignant disease.