Developing indicators for quality assurance in cytopathology. Catalan Society of Cytopathology.

BACKGROUND: Quality control in cytology must be established through reliable and easily measurable indicators. METHODS: From the Catalan Society of Cytopathology a group of experts has been established to write a document with 13 indicators that cover the entire cytological process, based on its Cytopathology Quality Guide. It has been elaborated through guides and documents with scientific evidence and DELPHI methodology in order to reach a structured consensus on the opinions of a group of experts. RESULTS: Thirteen indicators, covering all the cytologic process are expressed in worksheets specifying all their characteristics. CONCLUSION: This document allows the control of all stages of the cytological process.

Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy.

BACKGROUND: Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance. METHODS: Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%. RESULTS: Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm2; P < 0.05). CONCLUSION: The accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.

Underscreened Women Remain Overrepresented in the Pool of Cervical Cancer Cases in Spain: A Need to Rethink the Screening Interventions.

OBJECTIVE: Audit of women with invasive cervical cancer (CC) is critical for quality control within screening activities. We analysed the screening history in the 10 years preceding the study entry in women with and without CC during 2000-2011. METHODS: 323 women with CC from six pathology departments in Catalonia (Spain) and 23,782 women with negative cytology were compared. Age, previous history of cytologies, and histological type and FIGO stage were collected from the pathology registries. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI95%). RESULTS: History of cytology was registered in 26.2% of CC cases and in 78% of the control women (P < 0.0001) and its frequency decreased with increasing age. Compared to women with squamous cell carcinoma, adenocarcinoma cases were significantly more likely to have a cytology within the 3-year interval preceding cancer diagnosis (OR = 2.6 CI 95%: 1.2-5.6) and to have normal cytology results in previous screenings (OR = 2.4 CI 95%: 1.2-4.5). FIGO II-IV cases were more common among older women (older than 60 years). CONCLUSIONS: Absence of prior screening history was extremely common among CC cases compared to controls. Organized actions to reduce underscreened women and use of highly sensitive HPV-based tests could be important to reduce CC burden.

Assessment of methylation status of locoregional lymph nodes in lung cancer using EBUS-NA.

Hypermethylation of the promoter region of tumor suppressor genes is associated with carcinogenesis in lung cancer (LC). Endobronchial ultrasound with needle aspiration (EBUS-NA) is a semi-invasive method for obtaining cell blocks from lymph nodes, which can be used for epigenetic analyses. To establish the relationship between methylation status of p16, DAPK, RASSF1a, APC and CDH13 genes in lymph nodes sampled by EBUS-NA, tumor staging and prognosis. Methylation status of DAPK, p16, RASSF1a, APC and CDH13 genes was assessed in EBUS-NA cell blocks from LC patients and related to stage and survival. Eighty-five consecutive patients [mean age 67 (SD 8)] were included. Methylation of ≥1 gene was found in 43 malignant nodes (67 %). A higher prevalence of RASSF1a methylation was observed in small cell lung cancer patients [9/10 (90 %) vs. 15/53 (28 %); p < 0.001 χ(2) test]. Methylation of APC and/or p16 was related to advanced staging in non-small cell lung cancer (NSCLC) [15/29 (52 %) vs. 6/24 (25 %), p = 0.048, χ(2) test]. Patients with NSCLC showing methylation of APC and/or p16 had also lower 6-month survival (p = 0.019, log rank test), which persisted after adjustment for age and subtyping (HR = 6, 95 % CI [1.8-19.5], p = 0.003, Cox regression). Epigenetic analyses are feasible in EBUS-NA cell blocks and may identify methylation patterns associated with worse prognosis. Methylation of p16 and APC genes in NSCLC patients was associated with advanced staging and lower 6-month survival.

Historia de cribado en mujeres con cáncer infiltrante de cuello uterino / Screening history in women with infiltrating uterine cancer

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Standardized approach for microsatellite instability detection in gastric carcinomas.

Microsatellite instability (MSI) defines a specific type of genetic instability. Although consensus diagnostic criteria for MSI definition in colorectal cancer have been established, their utility in other tumor types remain to be proven. Previously we developed a mathematical model for MSI definition in colorectal cancer. The aim of this study was to establish diagnostic criteria for MSI evaluation in human gastric cancer. We designed an algorithm for the efficient characterization of MSI and used it to analyze data on 7 microsatellite markers in 35 gastric carcinomas. Theoretical models considering 1, 2, or 3 populations were tested against the data collected. Also, hypermethylation of hMLH1 gene promoter and hMLH1 protein expression were studied. The observed frequencies of MSI in our series of samples best fit a 2-population model: stable and unstable, defined by instability in 2 or more of a minimum of 7 markers analyzed. MSI was observed in 29% of the tumors. Misclassification rate was <4% when any 7 loci were analyzed. MSI(+) tumors inversely associated with p53 protein overexpression. A good correlation between hMLH1 status (either protein or promoter hypermethylation) and MSI classification was observed. We have developed a simple, sensitive, and specific approach to assess the presence of MSI in gastric cancer that may have clinical applications.

Fine-needle aspiration cytology diagnosis of metastatic gastrointestinal stromal tumor in the liver: a report of three cases.

Gastrointestinal stromal tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunocytochemically, and genetically differ from leiomyomas, leiomyosarcomas, and schwannomas. GISTs derive from the interstitial cells of Cajal and, in addition to variable expression of smooth muscle and neural markers, they characteristically express CD34 and CD117. The cytological appearance, including immunocytochemical and mutational analysis of c-kit gene in primary GIST has been well described. To our knowledge, only two cases of metastatic GIST diagnosed by fine-needle aspiration (FNA) have been reported. We illustrate three cases of metastatic GIST in the liver. Two cases had no prior history of gastrointestinal tumor and the third case had a 4-yr previous history of duodenal tumor. Consistent immunocytochemistry and ultrastructual studies supported the diagnosis of GIST. We emphasize that in the appropriate clinical and radiological setting, a confident diagnosis of GIST can be established by FNA of metastatic lesions.

Clonally unrelated Hodgkin's disease following autologous stem cell transplant for B-cell lymphoma.

Lymphoproliferative disorders after autologous stem cell transplantation (SCT) are rare. We describe two cases of Hodgkin's disease (HD) as a late secondary neoplasia following autologous SCT for mantle cell lymphoma and B-cell chronic lymphocytic leukaemia respectively. Both HD cases were of mixed cellularity type, showed Epstein-Barr virus (EBV) positivity and followed an aggressive course. Clonal analysis of rearranged immunoglobulin genes from the primary B-cell neoplasm and the secondary HD provided evidence of separate clonal origins of the two tumours in both patients, thus excluding secondary transformation of the original B-cell clone through EBV as the causative event for development of HD.