Vasculogenic mimicry (VM) describes a process by which cancer cells establish an alternative perfusion pathway in an endothelial cell-free manner. Despite its strong correlation with reduced patient survival, controversy still surrounds the existence of an in vitro model of VM. Furthermore, many studies that claim to demonstrate VM fail to provide solid evidence of true hollow channels, raising concerns as to whether actual VM is actually being examined. Herein, we provide a standardized in vitro assay that recreates the formation of functional hollow channels using ovarian cancer cell lines, cancer spheres and primary cultures derived from ovarian cancer ascites. X-ray microtomography 3D-reconstruction, fluorescence confocal microscopy and dye microinjection conclusively confirm the existence of functional glycoprotein-rich lined tubular structures in vitro and demonstrate that many of structures reported in the literature may not represent VM. This assay may be useful to design and test future VM-blocking anticancer therapies.
In 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology published the "LAST" recommendations for histopathology reporting of human papilloma virus-related squamous lesions of the lower anogenital tract, including the use of a 2-tier nomenclature (low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion [LSIL/HSIL]) and expanded use of the biomarker p16 to classify equivocal lesions as either precancer (HSIL) or low-grade lesions (LSIL)/non-human papilloma virus changes. We aimed to determine (1) the frequency with which the poorly reproducible diagnosis of intermediate-grade (-IN 2) lesion in the lower anogenital tract would be downgraded on the basis of p16 results, and (2) whether p16 status was predictive of subsequent higher-grade lesions. A total of 200 specimens diagnosed as an intermediate-grade (-IN 2) lesion of the cervix (168), vagina (2), vulva (2), and anus (28) were reviewed and immunostained for p16. Slides were independently reviewed by 2 pathologists, with discrepant p16 interpretations adjudicated by a third pathologist. Of the 200 cases, 32% were negative for p16. Among the 166 patients with subsequent pathology (including 131 excisions), 26.2% of p16-positive cases versus 4.4% of p16-negative cases were associated with a subsequent diagnosis of HSIL (-IN 3) or worse (P=0.002). Reproducibility of the biopsy diagnosis was fair, with no significant difference with the addition of p16 or using 2 versus 3 tiers. In 11.5% of cases, there was discordance in p16 interpretation (κ 0.735, good agreement). The results indicate that using the Lower Anogenital Squamous Terminology recommendations would result in approximately one third of equivocal (-IN 2) diagnoses being downgraded to LSIL over 1 year in a busy academic practice. The significant association of p16 expression with a higher risk for HSIL on a subsequent specimen suggests that use of p16 to adjudicate equivocal (-IN 2) diagnoses in lower anogenital tract specimens as either LSIL or HSIL would likely predict lesion grade more accurately and avoid unnecessary excisional procedures.
(1) OBJECTIVE: To assess the performance of CA125, HE4, ROMA index and CPH-I index to preoperatively identify epithelial ovarian cancer (EOC) or metastatic cancer in the ovary (MCO). (2) METHODS: single center retrospective study, including women with a diagnosis of adnexal mass. We obtained the AUC, sensitivity, specificity and predictive values were of HE4, CA125, ROMA and CPH-I for the diagnosis of EOC and MCO. Subgroup analysis for women harboring adnexal masses with inconclusive diagnosis of malignancy by ultrasound features and Stage I EOC was performed. (3) RESULTS: 1071 patients were included, 852 (79.6%) presented benign/borderline tumors and 219 (20.4%) presented EOC/MCO. AUC for HE4 was higher than for CA125 (0.91 vs. 0.87). No differences were seen between AUC of ROMA and CPH-I, but they were both higher than HE4 AUC. None of the tumor markers alone achieved a sensitivity of 90%; HE4 was highly specific (93.5%). ROMA showed a sensitivity and specificity of 91.1% and 84.6% respectively, while CPH-I showed a sensitivity of 91.1% with 79.2% specificity. For patients with inconclusive diagnosis of malignancy by ultrasound features and with Stage I EOC, ROMA showed the best diagnostic performance (4) CONCLUSIONS: ROMA and CPH-I perform better than tumor markers alone to identify patients harboring EOC or MCO. They can be helpful to assess the risk of malignancy of adnexal masses, especially in cases where ultrasonographic diagnosis is challenging (stage I EOC, inconclusive diagnosis of malignancy by ultrasound features).
Desmoplastic small round cell tumor (DSRCT) is rare and a highly aggressive neoplasm that typically involves the soft tissues of the abdomen or pelvis in children or young adults, showing a male predilection. Although it can occurs over a wide age range, the peak incidence is in the third decade of life. DSRCT usually shows widespread abdominal serosal involvement, and overall patient survival is poor. On the other hand, extra‐abdominal DSRCT is very rare. DSRCT in major salivary glands has been reported, but it is extremely rare. In the majority of reported series diagnosis is made by the histological analysis of FFPE tissues together with immunohistochemistry (IHC) and molecular analysis, particularly the demonstration of chromosomal translocation involving EWSR1. Very few cases have been diagnosed so far by Fine Needle Aspiration (FNA) cytology. Moreover ancillary studies have been performed in all reported cases in FFPE samples. There is still controversy and lack of consensus regarding the suitability of cytological samples especially smears for immunocytochemical (ICC) and fluorescence in situ hybridization (FISH), what makes its standardization difficult. We report a case of a primary DSRCT of parotid gland in a 17‐year‐old male diagnosed by FNA cytology. The cytomorphological diagnosis was coupled with ICC and FISH analysis performed on stained smears. We emphasize the feasibility and reliability of cytological smears for the application of immunocytochemical and molecular techniques.
Cervical intraepithelial neoplasia (CIN) 2 is an equivocal diagnosis, with p16 immunohistochemical positivity currently recommended for diagnostic confirmation. Biomarkers characteristic of squamocolumnar junction cells were recently found to be positive in almost all CIN 2 and CIN 3. CIN 1 lesions which express squamocolumnar junction markers (in particular cytokeratin 7 [CK7]) are associated with a higher rate of subsequent high-grade squamous intraepithelial lesion, suggesting that CK7 may be a useful prognostic biomarker for CIN 1. We sought to determine the utility of CK7 as a prognostic biomarker in the setting of morphologic CIN 2, and to compare this to the utility of p16 in this setting. We performed CK7 immunohistochemical on 116 cases originally diagnosed as CIN 2. Of these, 68.1% were p16 and 90.5% were CK7. A total of 19.5% of patients had a subsequent diagnosis of CIN 3 on biopsy or excision; the index CIN 2 lesion was CK7 in all of these cases (sensitivity 100%) and p16 in all but 1 (21/22; sensitivity 95.5%). The specificity of p16 (37.4%) and CK7 (8.0%) for predicting subsequent CIN 3 were significantly different (P<0.001). While p16 expression was significantly associated with subsequent CIN 3 (P=0.002), CK7 expression was not (P=0.202). We conclude that CK7, unlike p16, is not useful as a prognostic biomarker in CIN 2. While it is still promising as a prognostic marker in CIN 1, additional studies are needed to determine optimal staining/interpretation criteria.
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