Malignant Mucinous Lesions Research Articles

KRAS Mutations in Mucinous Lesions of the Uterus.

The current study examined the KRAS mutation status in a spectrum of mucinous lesions of the uterus, including mucinous metaplasia (MM), atypical mucinous proliferation (AMP), endocervical mucosa, and microglandular hyperplasia (MGH). Thirty-nine cases, including 15 AMPs, nine MMs, nine MGHs, and six normal endocervical mucosas, were selected from the departmental archive. All AMP cases with follow-up biopsies or hysterectomies were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and KRAS codons 12 and 13 sequence analyzed. KRAS codon 12 and 13 mutations were detected in 10 (67%) of the 15 AMP cases. No KRAS mutations were identified in MMs, MGHs, and endocervical mucosas (P = .002, AMP vs MM or MGH, Fisher exact test). Most women with AMP were postmenopausal (13/15 [86.7%]) and presented with dysfunctional uterine bleeding. Among the 10 cases of AMP harboring KRAS mutations, six (60%) cases were subsequently diagnosed with carcinoma, one with atypical complex hyperplasia, and two with AMP within endometrial polyps. The results suggest a possible association between KRAS mutations and mucinous differentiation in endometrial carcinogenesis. KRAS status can help in assessing benign from precursor or malignant mucinous lesions as well as differentiate endometrial lesions from those of cervical origin.

Mucinous Epithelial Lesions in Endometrial Curettage Material

To evaluate the immunohistochemical expression of several benign or malignant mucinous lesions that can be encountered in endometrial curettage material. Nineteen well-differentiated mucinous endometrial carcinomas, 12 papillary mucinous metaplasias, 11 cervical microglandular hyperplasias, 11 endocervical adenocarcinomas, 2 goblet cell metaplasias, 1 minimal-deviation adenocarcinoma, and 1 lobular endocervical glandular hyperplasia entered the study. Immunohistochemistry was performed with the following antibodies against: estrogen receptors, progesterone receptors, vimentin, p16, p63, carcinoembryonic antigen, and Ki-67. Immunohistochemistry could easily distinguish endocervical adenocarcinoma of usual type from all other lesions under study. A Vim(-)/p16(-)/p63(high) signature was found to favor a cervical microglandular hyperplasia, whereas both mucinous endometrial carcinoma and mucinous papillary metaplasia would be preferentially characterized by a Vim(+)/p16(+)/p63(low) immunophenotype. A high Ki-67 expression would be of help in differentiating the latter 2 conditions. Statistically, the expression of estrogen receptors, progesterone receptors, and carcinoembryonic antigen did not aid in the differential diagnosis of these 3 conditions. For the 4 cases representing goblet cell metaplasia, minimal-deviation adenocarcinoma and lobular endocervical glandular hyperplasia, no results could be drawn. In endometrial curettage material, the differential diagnosis of lesions comprising mucinous epithelium might be rendered by combining the immunohistochemical expression of vimentin, p16, p63, and Ki-67. Of all lesions, endocervical adenocarcinoma of usual type is the most easily identified.

OC23.04: Does spherical sample size affect the performance of 3D power Doppler indexes for predicting malignancy in vascularized adnexal masses?

Methods: Patients with persistent adnexal mass with a risk of major malignancy of 3%, based on ultrasound examination were included in this prospective study. Predefined ultrasound morfological and Doppler characteristics were used by an expert sonologist to determine the nature (benign o malignant) of the mass. Border-line masses were considered as malignant. All patients underwent combined PET/CT with F-fluorodeoxyglucose (FDG). The ultrasound and PET/CT findings were correlated with final hystological diagnosis. Results: Sixty one patients were included in this series. Hystologically there were 25 benign, 27 malignant and 9 border-line masses. All malignant masses were correctly classified at transvaginal sonography, while at PET/CT 25 of those demonstrated metabolic activity and 2 lesions resulted false negative. Among hystologically benign lesions transvaginal ultrasound was accurate in 21 (4 false positive), the same as PET/CT. The borderline tumours were correctly identified at sonography as suspected malignant, though PET/TC was predictive in only 1 of 9. Moreover, 2 malignant and 7 border-line masses revealed silent at PET/CT were mucinous tumours. Conclusions: These data show that PET/CT does not provide additional information compared with expert transvaginal ultrasound. It is likely that some malignant mucinous lesions and especially border-line tumours do not show FDG uptake.

Cyst Fluid Cea Concentration, Age and a Diagnosis of Malignancy Are Associated with Increased Mortality: An Update From the Cooperative Pancreatic Cyst (CPS) Study

The natural history of mucinous cystic lesions is unknown. Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) are pre-malignant or malignant lesions that may be associated with a greater mortality rate compared to non-mucinous lesions. We have monitored the outcome of patients in the CPC study to identify risk factors for mortality. Methods: Clinical testing results and patient outcome were prospectively collected in the CPC Study from May 1, 1999 to November 19, 2004. We hypothesized that mortality rate would be determined by type of cystic lesion, presence of malignancy, and cyst fluid CEA concentration (conc). Results: There were 699 EUS-guided aspirations in 625 consecutive patients with a cystic lesion on cross sectional imaging. 209 patients had a diagnosis established by surgical pathology or cytology. The median follow-up period was 1124d (37.5 mo). 125 mucinous lesions (71 IPMN and 54 MCN), 11 serous cystadenomas, 45 inflammatory cysts, 6 neuroendocrine tumors and 20 other cystic lesions were analyzed. Among the mucinous lesions, 46 were benign, 21 had borderline histology and 59 were malignant (carcinoma-in-situ or invasive). During the study period, there were 45 deaths. 30/45 (67%) of these patients had malignant mucinous lesions (8 malignant MCN, 22 malignant IPMN). The mortality rate for patients with malignant mucinous lesions was 51% (30/59) vs. 3% (2/67) for those with benign mucinous lesions (p < 0.001), and 0% for those with serous cystadenomas (p < 0.01). The mortality rate for malignant MCN was 53% (8/15) and 50% (22/44) for malignant IPMN. The mortality rate of patients with a mucinous lesion and who were >70 y old was 38% compared to 15% for <70y old (p < 0.01). The relative risk (RR) of mortality in patients with a malignant mucinous lesion was 34 (95% confidence interval [CI] 4.8-242.2). Age > 70y had a RR of mortality of 2.45 (95% CI 1.29-4.66). Cyst fluid CEA conc. > 500ng/ml was found in 80% of deaths v. 49% in surviving patients (p < 0.01) and had a RR of mortality of 2.95 (95% CI 1.31-6.66). Conclusions: Patients with a malignant mucinous cystic lesion have a significantly higher mortality rate (51%) than those with a benign mucinous cystic lesion (3%). Risk factors for death include increased age and cyst fluid CEA conc >500 ng/ml. The results of cyst fluid aspiration offer prognostic information in the management of patients with a cystic lesion.

Measurement of pS2 protein in pancreatic cyst fluids. Evidence for a potential role of pS2 protein in the pathogenesis of mucinous cystic tumors.

Elevated levels of the growth factor pS2 protein in the cyst fluids of mucinous cystic tumors correlate with earlier observations using immunohistochemical techniques showing that pS2 protein is expressed by these tumors. The markedly elevated levels of pS2 protein compared to normal plasma values suggest that this growth factor may be important in the pathogenesis of pancreatic mucinous cystic tumors. Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies using immunohistochemical techniques have shown that virtually all pancreatic mucinous tumors express pS2 protein. pS2 protein is a growth factor that is believed to be important in the normal process of inflammation and repair. We measured pS2 protein and other growth factors in pancreatic cyst fluids to assess their potential pathophysiologic and diagnostic significance. Levels of pS2 protein were measured in 54 pancreatic cyst fluids by radioimmunoassay. The growth factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factors I and II (IGF-I, IGF-II) were measured in 22 cyst fluids using commercial immunoassays. Mucinous cysts exhibited significantly higher levels of cyst fluid pS2 protein than nonmucinous lesions, including pseudocysts and serous cystadenomas (median: 78,303 pg/mL; range: 218-361,176 pg/mL vs median: 886 pg/mL; range: 0-14,206 pg/mL; p = 0.0001). The level of pS2 in mucinous tumors was markedly higher than plasma values (median: 392 pg/mL). Levels of pS2 protein in malignant mucinous lesions tended to be higher than those in benign mucinous cysts, but this difference was not statistically significant (median: 88,817 vs 64,350 pg/mL; p = 0.159). Levels of other growth factors, including EGF, TGF-alpha, IGF-I, and IGF-II, did not discriminate among the different cyst types, and the values were within normal plasma ranges.