Rapid on-site evaluation during endoscopic ultrasound-guided fine-needle aspiration of lymph nodes does not increase diagnostic yield: A randomized, multicenter trial.

OBJECTIVES: Studies on the impact of rapid on-site evaluation (ROSE) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of lymph nodes are retrospective and have shown conflicting results. We aimed to compare the diagnostic yield of EUS-FNA of lymph nodes with ROSE (ROSE+) and without ROSE (ROSE-). METHODS: This was a multicenter, randomized controlled trial. Consecutive patients who were scheduled to undergo EUS-FNA of mediastinal or abdominal lymph nodes were randomized to ROSE+ or ROSE-. In the ROSE+ group, the number of passes was dictated by the on-site cytotechnician. In the ROSE- group, five passes were performed without interference from the cytotechnician. All samples were reviewed by a single-expert cytopathologist, blinded to group allocation. Primary endpoint was diagnostic yield with and without ROSE. RESULTS: After inclusion of 90 patients, interim analysis showed futility of study continuation since diagnostic yield of ROSE+ and ROSE- were comparable. A total of 91 patients were randomized to ROSE+ (N = 45) or ROSE- (N = 46). Diagnostic yield of ROSE+ and ROSE- and diagnostic accuracy were comparable: 93.3% vs. 95.7% (P = 0.68) and 97.6% vs. 93.2% (P = 0.62), respectively. Two major complications (one per group) occurred (p = 0.99). ROSE- patients more often reported self-limiting post-procedural pain (p < 0.001). Median procedure time for ROSE+ (20 min) and ROSE- (23 min) was comparable (P = 0.06). Median time to review slides in the ROSE- group (12:47 min) was longer than with ROSE+ (7:52 min) (P < 0.001). Mean costs of ROSE- and ROSE+ were comparable: €938.29 (±172.70) vs. €945.98 (±223.38) (P = 0.91), respectively. CONCLUSIONS: Diagnostic yield and accuracy of EUS-FNA of mediastinal and abdominal lymph nodes with and without ROSE are comparable. Time needed to review slides was shorter and post-procedural pain was less often reported in the ROSE+ group. Based on the primary outcome, the implementation of ROSE during EUS-FNA of mediastinal and abdominal lymph nodes cannot be advised. (Dutch Trial Register: NTR4876).

The reliability of the histological diagnosis of endometritis in asymptomatic IVF cases: a multicenter observer study.

BACKGROUND: Chronic endometritis is associated with abnormal uterine bleeding, recurrent abortion and infertility. It is a subtle condition, and therefore is difficult to diagnose. The diagnosis is ultimately based on the presence of plasma cells in the endometrial stroma on histopathological examination. Literature on the reproducibility of the diagnosis of chronic endometritis is lacking. Therefore, the aim of the current study was to assess the interobserver agreement of two pathologists in diagnosing chronic endometritis in asymptomatic, infertile patients. METHODS: In the context of a randomized controlled trial, an endometrial biopsy was taken during a screening hysteroscopy prior to IVF. All endometrial samples were independently examined by two pathologist. The slides diagnosed with chronic endometritis were replenished with a random sample of the remaining slides up to a total of 100, then exchanged between the two pathologists and reassessed. RESULTS: Of the 678 patients who underwent hysteroscopy, 19 patients were diagnosed with at least possible chronic endometritis (2.8%). Perfect agreement between the pathologists, before and after inclusion of 13 slides with additional immunohistochemistry staining, was found in 88 and 86% of reviews, respectively. The interobserver agreement was substantial, with kappa-values of 0.55 and 0.66, respectively. CONCLUSIONS: The interobserver agreement in diagnosing chronic endometritis in asymptomatic infertile patients was found to be substantial. Although the diagnostic reliability is sufficient with the methods in the present study, the low prevalence and unknown clinical significance of endometritis warrants further study.

Progressive derailment of cell cycle regulators in endometrial carcinogenesis.

BACKGROUND: Derailments of the control mechanisms of the cell cycle can initiate carcinogenesis, and play a role in progression to cancer. AIM: To explore the expression of cell cycle proteins in normal, premalignant and malignant endometrial lesions representing the morphologically well defined stepwise model of human endometrial carcinogenesis METHODS: Observational study. Paraffin-embedded specimens from inactive endometrium (n = 16), endometrial hyperplasia (n = 23) and endometrioid endometrial carcinoma (n = 39) were stained immunohistochemically for cyclin A, cyclin B1, cyclin D1, cyclin E, cdk2, p16, p21, p27, p53 and Ki67(MIB-1)). Differences in expression between the tissues, and correlation with classical prognostic factors for the carcinomas were analysed. RESULTS: Expression of cyclin A and Ki67 gradually increased from normal through hyperplasia to carcinoma, indicating that proliferation increases over the carcinogenetic spectrum. cdk2, p16 and p21 gradually increased from normal through hyperplasia to carcinoma, indicating their potential importance in both early and late carcinogenesis. Cyclin D1, cyclin E and p53 especially increased and p27 decreased from hyperplasia to carcinoma, underlining their role in late carcinogenesis. In cancers, expression of cyclin A, p53 and Ki67 was positively correlated to grade, and cyclin A was positively correlated with cdk2, p21, Ki67, cyclin E and p53. CONCLUSION: During (endometrioid) endometrial carcinogenesis, there is increasing proliferation paralleled by progressive derailment of cyclin B1, cyclin D1, cyclin E, p16, p21, p27, p53, and cdk2, indicating the importance of these cell cycle regulators in endometrial carcinogenesis.

p16 is consistently expressed in endometrial tubal metaplasia.

BACKGROUND: Cell cycle proteins and HIF-1alpha with downstream factors are often abberrantly expressed in (pre)neoplastic tissue. METHODS: Paraffin-embedded specimens of inactive endometrium with TM (n=15), ovarian inclusion cysts (n=6), cervix with TM (tubal metaplasia) (n=3), Fallopian tubes (n=7), cycling endometrium (n=9) and a ciliated cell tumor of the ovary were stained for p16 and LhS28. 39 Endometrioid endometrial carcinomas and 5 serous endometrial carcinomas were stained for p16. Additionally, inactive endometrium (n=15) was immunohistochemically stained for p21, p27, p53, cyclin A, cyclin D1, cyclin E, HIF-1alpha, CAIX, Glut-1 and MIB-1. RESULTS: A mosaic pattern of expression of p16 was seen throughout in all cases of endometrial TM (15/15), in 2/6 of the ovarian inclusion cysts with TM, in all (3/3) cervical TM and focal in 5/7 of Fallopian tube cases. Mosaic expression was also seen in a ciliated cell tumor of the ovary and in 18/39 of endometrioid endometrial carcinomas, and diffuse p16 expression was seen in 5/5 serous carcinomas. In comparison with normal endometrium, TM areas in the endometrium showed significantly increased expression of HIF-1alpha, cyclin E, p21 and cyclin A, and decreased expression of p27. Membranous expression of CAIX and Glut-1 was only seen in TM areas, pointing to functional HIF-1alpha. CONCLUSION: As p16 is consistently expressed in TM, less and only patchy expressed in the normal Fallopian tube, is paralleled by aberrant expression of cell cycle proteins, HIF-1alpha, CAIX and Glut-1 and resembles the pattern of p16 expression frequently seen in endometrial carcinomas, we propose endometrial TM to be a potential premalignant endometrial lesion.

Lymph node recurrence following stage IA vulvar carcinoma: two cases and a short overview of literature.

Stage IA vulvar carcinoma is not supposed to metastasize to the lymph nodes. Therefore, it is assumed that these lesions can be safely treated by less aggressive methods than macroinvasive carcinomas. However, in this case report, two patients are described who had vulvar lesions with a depth of invasion of less than 1 mm and developed lymph node metastases in the groin despite radical wide local excision of their lesions. Both the patients underwent lymphadenectomy and received postoperative radiation therapy on the groins. Neither of the two patients died of vulvar carcinoma. Thus, we conclude that vigilance for the occurrence of lymph node metastases remains necessary after radical, local excision in stage IA vulvar cancer. However, this case report also shows that adequate treatment of groin node metastases can result in a very good long-term survival.

Irregularly shaped inclusion cysts display increased expression of Ki67, Fas, Fas ligand, and procaspase-3 but relatively little active caspase-3.

Human ovarian cancers are thought to arise from sequestered ovarian surface epithelial (OSE) cells that line the wall of inclusion cysts. Nevertheless, the early events toward neoplasia are not well understood. In this study, immunoreactivity for apoptotic proteins in human OSE of control and tumor ovarian sections was examined. Ki67, a marker for cell proliferation, was generally absent in the flat-to-cuboidal OSE cells on the ovarian surface and in regularly shaped inclusion cysts. Fas, Fas ligand, and caspase-3, components of the apoptotic pathway, were also largely absent. Ki67, Fas, Fas ligand, and procaspase-3 expression, though not active caspase-3 expression, was more frequently observed in epithelial cells lining irregularly shaped inclusion cysts, particularly in the columnar and Müllerian-like OSE cell types that resembled ovarian tumor OSE cells. Immunoreactivity for these factors as well as active caspase-3 was found frequently in ovarian tumors. We postulate that the appearance of the Fas system and its related proteins in sequestered columnar OSE cells of irregularly shaped inclusion cysts may contribute to balance cell growth with cell death, although little active caspase-3 expression was observed. Further studies are required to identify whether inhibition of apoptosis in inclusion cysts is an early event in ovarian carcinogenesis.

Sclerosing polycystic adenosis: a case report.

About 70 to 80 percent of all salivary gland neoplasms, the majority of which are benign, arise in the parotid gland. Sclerosing Polycystic Adenosis (SPA) is a relatively unknown and newly described entity that is considered to be benign in nature. A 55-year-old patient was treated for SPA in our hospital. The diagnostic work-up consisted of Magnetic Resonance Imaging (MRI), Fine Needle Aspiration Cytology (FNAC) and histological examination. However, in our case, both the cytological appearance, which usually has a high accuracy in discriminating benign from malignant lesions, and the appearance on MR images, mimicked a malignant tumour. This case report illustrates the importance of an adequate histological confirmation of the work-up diagnosis.