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Objective: The purpose of this study is to assess the utility of texture analysis of multiple MRI sequences for the differentiation of uterine leiomyomas and leiomyosarcomas., Materials and Methods: Seventeen leiomyosarcomas and 51 leiomyomas undergoing MRI before resection were included. Whole-lesion volumes of interest were placed on T2-weighted images, contrast-enhanced T1-weighted images, and apparent diffusion coefficient (ADC) maps. The diagnostic performance of histogram metrics was assessed., Results: For T2-weighted images, significant differences were observed for mean, skewness, entropy, mean of the bottom 10th percentile (mean 0-10 ), mean of the 10th through 25th percentiles (mean 10-25 ), and mean of the 25th through 50th percentiles (mean 25-50 ) (p ≤ 0.010). For T1-weighted contrast-enhanced images, significant differences were observed for mean 0-10 , mean 10-25 , and mean 25-50 (p ≤ 0.045). For the ADC maps, no metrics showed a significant difference (p ≥ 0.067). Metrics with AUC greater than 0.8 were the mean 0-10 (0.875), mean 10-25 (0.863), mean 25-50 (0.839), and mean (0.802) for T2-weighted imaging. The mean 0-10 , mean 10-25 , and mean 25-50 for T2-weighted imaging all achieved greater AUCs than did the standard mean (p ≤ 0.038). Patients with leiomyosarcoma were significantly older than those with leiomyoma (p < 0.001; AUC = 0.866). At multivariable regression, significant independent predictors of leiomyosarcoma were patient age (p = 0.002) and T2-weighted imaging mean 0-10 (p = 0.004), with a combined AUC of 0.955. Patient age achieved sensitivity of 82.4% and specificity of 92.2%; T2-weighted imaging mean 0-10 achieved sensitivity of 82.4% and specificity of 74.5%., Conclusion: For whole-lesion histogram metrics obtained on various MRI sequences, T2-weighted images provided the highest, and ADC maps the lowest, performance for differentiating uterine leiomyomas and leiomyosarcomas. Metrics reflecting percentiles from the bottom half of the histogram distribution outperformed the standard mean. Models combining the T2-weighted imaging whole-lesion metrics and patient age achieved particularly high diagnostic performance. Although these findings require validation in larger studies, they have implications for facilitating improved treatment selection for these two entities.

Objective: Our study aimed to retrospectively evaluate the utility of volumetric histogram-based diffusion metrics in differentiating benign from malignant endometrial abnormalities., Methods: A total of 54 patients underwent pelvic magnetic resonance imaging with diffusion-weighted imaging before endometrial tissue diagnosis. Two radiologists placed volumes of interest on the apparent diffusion coefficient (ADC) map encompassing the entire endometrium and focal endometrial lesions. The mean ADC, percentile ADC values, kurtosis, skewness, and entropy of ADC were compared between benign and malignant abnormalities., Results: In premenopausal patients, significant independent predictors of malignancy were whole-endometrium analysis for R1, 10th to 25th ADC percentile (P = 0.012); whole-endometrium analysis for R2, mean ADC (P = 0.001) and skewness (P = 0.004); focal lesion analysis for R1, skewness (P = 0.045); focal lesion analysis for R2, 10th to 25th ADC percentile (P ≤ 0.0001). The area under the curve for malignancy was 90.0% to 97.3% and 76.1% to 77.3% for the more and less experienced radiologists, respectively. In postmenopausal patients, the only significant difference was kurtosis using whole-endometrium analysis for R1 (P = 0.042)., Conclusions: Volumetric ADC histogram metrics may help radiologists assess the risk of malignancy in endometrial abnormalities on magnetic resonance imaging in premenopausal patients.

Purpose: Cystadenofibromas are benign ovarian neoplasms. Their most typical features on sonography (US) are unilocular cysts with small, shadowing hyperechoic, solid papillae without internal vascularity. In the past, they were virtually always surgically removed to exclude malignancy. This study was undertaken to review the sonographic appearances of benign cystadenomas., Methods: We retrospectively reviewed the transvaginal US studies of 32 cases of pathologically proven ovarian cystadenofibromas., Results: Twenty-two of the tumors presented as unilocular cystic structures with one or more solid, hyperechoic, shadowing, mural nodules with no discernible blood flow projecting from the inner cyst wall. Ten lesions were multiloculated with multiple small solid areas, with scant or no blood vessels., Conclusions: Cystadenofibromas do not always have a classic appearance on transvaginal US and color Doppler imaging. In our series, however, the majority (69%) presented as unilocular cysts with one or more small solid, avascular projections from the inner cyst wall. These features had 100% reliability for a diagnosis of benign cystadenofibroma in this small series. Further study is necessary to confirm the reliability of this finding for benign cystadenofibroma, thus possibly avoiding or minimizing any surgical exploration., (© 2014 Wiley Periodicals, Inc.)

Soft tissue sarcomas are a heterogeneous group of tumors associated with poor clinical outcome. Although a subset of soft tissue sarcomas is characterized by simple karyotypes and recurrent chromosomal translocations, the mechanisms driving cytogenetically complex sarcomas are largely unknown. Clinical evidence led us to partially inactivate Pten and Tp53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas, leiomyosarcomas, and carcinosarcomas that widely recapitulate the human disease, including the aberrant karyotype and metastatic behavior. Pten was found haploinsufficient, whereas the wild-type allele of Tp53 invariably gained point mutations. Gene expression profiles showed up-regulated Notch signaling in Pten(Δ/+)Tp53(Δ/+) tumors compared with Pten(+/+)Tp53(Δ/+) tumors. Consistently, Pten silencing exacerbated the clonogenic and invasive potential of Tp53-deficient bone marrow-derived mouse mesenchymal stem cells and tumor cells and activated the Notch pathway. Moreover, the increased oncogenic behavior of Pten(Δ/+)Tp53(Δ/+) and shPten-transduced Pten(+/+)Tp53(Δ/+) tumor cells was counteracted by treatment with a γ-secretase inhibitor, suggesting that the aggressiveness of those tumors can be attributed, at least in part, to enhanced Notch signaling. This study demonstrates a cooperative role for Pten and Tp53 suppression in complex karyotype sarcomas while establishing Notch as an important functional player in the cross talk of these pathways during tumor progression. Our results highlight the importance of molecularly subclassifying patients with high-grade sarcoma for targeted treatments., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Ovarian stromal hyperplasia and ovarian hyperthecosis are non-neoplastic conditions of the ovary associated with clinical manifestations of hyperandrogenism from ovarian production of male hormones. In this article, we present the first published cases of the magnetic resonance imaging appearance of these conditions, which may mimic that of ovarian neoplasm. In contrast to bilateral ovarian vein sampling, magnetic resonance imaging may provide a noninvasive means of suggesting a diagnosis of ovarian stromal hyperplasia/ovarian hyperthecosis when a hormone-secreting ovarian neoplasm is suspected clinically and thereby may assist in identifying patients who may be effectively treated nonsurgically with gonadotrophin-releasing hormone therapy.

Aim: To evaluate the effect of genetic instability and degradation in archived histology samples from cancerous tumors and to investigate the validity of short tandem repeat (STR) typing of these samples and its potential effect on human identification., Methods: Two hundred and twenty eight slides of archival pathology tissues from 13 different types of malignant tumors were compared with healthy tissues from the same individuals. DNA analysis was performed using standard techniques for forensic STR analysis, PowerPlex16 and Identifiler on 2 distinct sample sets. Genetic instability was assessed by comparing reference tissues with cancerous tissues derived from the same individual. Loss of heterozygosity, a > or =50% reduction in heterozygosity ratio between healthy and diseased samples, and microsatellite instability, the presence of an additional allele not present in reference tissue, were assessed. The quality of profiles obtained with respect to completeness among the archived samples and degradation using the 2 platforms were also compared., Results: Profiles obtained using the Identifiler system were generally more complete, but showed 3-fold higher levels of instability (86%) than those obtained using PowerPlex 16 (27%). Instances of genetic instability were distributed throughout all loci in both multiplex STR systems., Conclusion: After having compared 2 widely used forensic chemistries, we suggest individual validation of each kit for use with samples likely to exhibit instability combined with fixation induced degradation or artifact. A "one size fits all" approach for interpretation of these samples among commercially available multiplexes is not recommended.

The distinction of complex atypical endometrial hyperplasia from endometrial adenocarcinoma is often problematic. Foci of back-to-back arrangement of glands or foci of cribriform arrangement of glands smaller than 2.1 mm in diameter are considered insufficient for the diagnosis of endometrial adenocarcinoma by some authors, and sufficient to be diagnosed as endometrial adenocarcinoma by other authors. We refer to these foci as endometrial adenocarcinoma in situ. In this study, we evaluated findings in subsequent hysterectomy in complex atypical endometrial hyperplasia patients with and without adenocarcinoma in situ. Follow-up findings, including the presence or absence of endometrial adenocarcinoma in the hysterectomy specimen, the grade of the carcinoma and the depth of myometrial invasion were analyzed. Of the total 87 patients with complex atypical endometrial hyperplasia, 33 patients had adenocarcinoma in situ and 54 lacked adenocarcinoma in situ. Of 33 patients 22 (66%) with adenocarcinoma in situ had endometrial adenocarcinoma on subsequent hysterectomy vs 13 of 54 (24%) patients without adenocarcinoma in situ (P=0.0001). Myoinvasive endometrial adenocarcinoma was present in 20 of 33 (61%) patients with adenocarcinoma in situ vs 8 of the 54 (15%) patients without adenocarcinoma in situ (P< or =0.0001). The depth of myometrial invasion in cases with myoinvasion was 24.5+19.4% in patients with adenocarcinoma in situ and 12.8+8.5% in patients without adenocarcinoma in situ (P=0.05). Among patients younger than age of 50, 5 of the 7 (71%) with adenocarcinoma in situ had myoinvasive carcinoma vs 2 of the 13 (15%) without adenocarcinoma in situ (P=0.02). The likelihood of finding endometrial adenocarcinoma in subsequent hysterectomy in patients with complex atypical endometrial hyperplasia is significantly increased if adenocarcinoma in situ is present in prior endometrial sampling. Endometrial adenocarcinomas in patients with adenocarcinoma in situ are far more frequently myoinvasive, and invade to a greater depth than endometrial adenocarcinomas seen in patients without adenocarcinoma in situ. Use of adenocarcinoma in situ terminology could lead to improved management of patients with complex atypical endometrial hyperplasia.

Objective: The purpose of this study was to evaluate the usefulness of virtual spherical tissue sampling using 3-dimensional (3D) ultrasound power Doppler angiography to enhance differentiation between normal and pathologic ovaries., Methods: Twenty-seven cases with ovarian tumors were analyzed: 14 with invasive cancers and 13 with borderline tumors confirmed by surgery. The control subjects consisted of 53 healthy ovulating women. Ultrasound scans were done, and 3D volumes were analyzed with 3-/4-dimensional software for personal computers based on 3D vascularity indices: the vascularization index, flow index, and vascularization-flow index. A virtual spherical tissue sample of 1 cm3 was taken from the place of the highest vessel density contained completely within the contours of the ovary. Calculations for the whole solid volume were done for comparison., Results: Vascularity indices for both 1-cm3 spherical samples and whole dense parts of the ovaries were compared in the following groups: (1) ovarian tumors versus controls, (2) normal ovaries in the proliferative versus secretory phase, (3) invasive cancers versus borderline tumors, (4) invasive cancers versus normal ovaries, and (5) borderline tumors versus normal ovaries. Spherical 1-cm3 sampling achieved a higher degree of discrimination between the groups compared with the whole solid-part approach., Conclusions: Spherical 1-cm3 sampling of ovarian tissue with 3D ultrasound power Doppler angiography is a sensitive and promising approach to differentiate between ovarian tumors and normal ovaries. It opens the possibility to implement objective computerized positioning, standardized comparison, and analysis of ovarian tumors.

Aim: To report on the successful use of Laser Capture Microdissection (LCM) as a tool for isolation of human chorionic villi from admixed maternal tissue. Subsequent DNA isolation for forensic short tandem repeat (STR) analysis for parentage testing was performed in two cases of alleged sexual assault of female victims. We also performed validation of the LCM instrument platform, using archival formalin-fixed human fetal products of conception (POC), for which microdissection was utilized to separate maternal (decidua) and fetal (chorionic villus) components., Methods: To isolate DNA from placental chorionic villi admixed with maternal decidua recovered after spontaneous or therapeutic abortion, LCM was used to separate fetal from maternal cells. In contrast to the relatively crude conventional microdissection performed using a narrow pipette, needle, or scalpel blade, LCM allows cell- or tissue-specific isolation of placental chorionic villi from archival paraffin-embedded tissue sections, leaving the maternal tissue intact., Results: After polymerase chain reaction (PCR) amplification of villi after LCM of 9-15 STR loci, the quantity and quality of DNA yielded from fetal cells isolated by LCM was sufficient for PCR analysis and successful forensic parentage testing. The validation data obtained on two sets of formalin-fixed archival POC tissues from anonymous donors demonstrated the encouraging reproducibility of these protocols and procedures., Conclusion: We demonstrated the reliability and utility of LCM for forensic applications when high specificity of a particular analyzed cell population or tissue is required. Care must be taken during routine pathology procedures to avoid contamination of tissues with admixture of extraneous DNA.

Well-differentiated endometrial adenocarcinoma can be difficult to distinguish from complex atypical hyperplasia (CAH) in a curettage or biopsy specimen. When a focus of back-to-back glands or cribriforming smaller than 2.1 mm is seen in a biopsy, we make a diagnosis of adenocarcinoma in situ (AIS). Whether this diagnosis translates into a more frequent diagnosis of carcinoma on the hysterectomy specimen is unknown. The objective of this study was to compare follow-up hysterectomy findings in biopsies showing AIS in CAH with biopsies showing only CAH without AIS. Twelve biopsy/curettage cases diagnosed as endometrial AIS in CAH and 12 biopsy/curettage cases diagnosed as CAH only were reviewed and correlated with corresponding hysterectomy material. A diagnosis of AIS was designated on biopsy/curettings when a focus of back-to-back glands or cribriforming less than 2.1 mm was present. Hysterectomy specimens showed endometrial carcinoma in 6 (50%) of 12 cases of CAH with AIS, and in 2 (17%) of 12 cases diagnosed as CAH only. Endometrial carcinoma with myometrial invasion was identified in 5 (42%) of the cases showing AIS on biopsy, but in none of the 12 cases diagnosed as CAH only on biopsy. Identification of AIS in CAH cases provides useful prognostic information.

The management of cervical dysplasia is determined by the grade of SIL (LSIL, conservative management; HSIL, ablative/excisional therapy). The grading, however, is subjective and its reproducibility is low. This study evaluates if quantitative differences in mitotic activity and MIB-1 expression (ME) in LSIL and HSIL are helpful in their discrimination. Twenty-seven cervical biopsies with LSIL and 16 with HSIL were immunostained for MIB-1. ME was evaluated in 100 contiguous cells of lesional squamous epithelium in basal layer, lower-third, middle-third, and upper-third, in areas with highest staining. Mitoses were counted in 10 contiguous high power fields in areas with the highest mitotic activity (mitotic index, MI). MI was significantly increased in HSIL (mean 27.5) as compared to LSIL (mean 14.3). MI at cut-off values < or =10 and > or =25, favored a diagnosis of LSIL, and HSIL, respectively. ME, in all four layers, was significantly greater in HSIL vs. LSIL. ME in the basal and the upper-third layer proved useful in grading SIL with equivocal MI: all LSIL cases with MI >10 had <30% of ME in the basal layer; and all, except one, had <30% of ME in the upper-third; all, except one HSIL cases with MI <25 had >30% of ME in either the basal or the upper-third layer. MI and ME (percentage) appear helpful in grading equivocal SIL cases.

Objective: Immunohistochemical analysis of MIB1, p53, estrogen, and progesterone receptors can provide prognostic information in endometrial adenocarcinoma. Since predictors of recurrence for low-grade endometrial stromal sarcoma (LESS) are still unknown, a battery of immunostains was performed to find markers, which might be useful to predict prognosis., Methods: Eleven patients with an average age of 43.8 years (range 27-76) were identified with stage I LESS. Immunostains, including MIB1, p53, ER, and PR, were evaluated by two pathologists, independently., Results: All tumors were positive for ER and PR; 1/11 was positive for p53; MIB1 ranged from 0 to 20% positive tumor nuclei. Mitotic counts ranged from 0 to 7/10 hpf. Two patients developed recurrences. One had a pelvic recurrence 7 years after diagnosis. This tumor had a mitotic count of 1/10 hpf, MIB1 expression in 10% of nuclei, and focal p53 expression. A second patient developed pulmonary metastases 10.8 years after diagnosis; the tumor showed a mitotic count of 7/10 hpf and MIB1 expression in 20% of nuclei, but was negative for p53. There was a significant difference in MIB1 reactivity scores between patients who did or did not develop recurrence (P = 0.0303). A marginally significant association was detected between MIB1 (P = 0.0896) or p53 (P = 0.0833) positivity and length of recurrence-free survival., Conclusion: Although MIB1 and p53 appear to be useful prognostic markers, a larger study would be necessary to confirm their validity.

Sclerosing stromal tumor (SST) is a rare benign ovarian neoplasm of stromal origin with less than 100 cases reported in the literature. Unlike the other stromal tumors, thecomas and fibromas, which tend to occur in the fifth and sixth decades, sclerosing stromal tumors predominantly affect females in the second and third decades. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound findings have been described, but have not been reported previously in the pediatric literature. We present a case of SST of the ovary in a 10-year-old premenarchal female, the youngest patient to our knowledge reported in the literature, and describe the ultrasound and CT findings with pathologic correlation.

Objective: Endometrial polyps are relatively common in all groups of women. More polyps are being diagnosed with the widespread use of transvaginal ultrasound scanning and sonohysterography. The reported incidence of malignancy is low. The potential benefit of a noninvasive technique to distinguish benign from malignant polyps is obvious. This study was undertaken to evaluate endometrial polyps by color flow Doppler ultrasound scanning and histopathologic examination., Study Design: This was an observational study of patients with an endometrial polyp on sonohysterography who underwent interrogation of their polyp with color Doppler ultrasound scanning and subsequently polypectomy. Polyp volume, resistive index, pulsatility index, indication for scan (bleeding vs incidental), and patient age were correlated with histopathologic type of the polyp (nonfunctional, proliferative, secretory, hyperplastic, or malignant)., Results: Of 61 patients studied, 42 patients (68.9%) were scanned for abnormal bleeding, and 19 patients (31.1%) had their polyps discovered incidentally. There were no statistically significant differences between histologic categories and the resistive index, pulsatility index, or size of the polyp. The age of patients with nonfunctional polyps was significantly greater than any other group (P <.001). Ninety-four percent of the functional polyps were discovered because of abnormal bleeding; 38% of the nonfunctional polyps were discovered incidentally (P <.001)., Conclusion: The data suggest that the objective assessment of blood flow impedance (resistive index, pulsatility index) in endometrial polyps and the size of these polyps cannot replace surgical removal and pathologic evaluation to predict histologic type. Patients with nonfunctional polyps were older and less likely to have vaginal bleeding.

Background: Pancreatic acinar tissue (PAT) at the gastroesophageal junction (GEJ) has been reported in 3% of adults with Barrett esophagus (BE) and in 24% of healthy subjects. The pathogenesis of this ectopic tissue is controversial. Both an acquired metaplastic process in the setting of BE and a congenital abnormality have been suggested in adults., Objective: To clarify the origin of PAT at the GEJ., Methods: We reviewed material obtained from the GEJ in 69 children and young adults. Each specimen was evaluated by 3 levels stained with hematoxylin-eosin for the presence of PAT, BE, esophagitis, and gastritis. Selected cases were also examined with immunohistochemical stains for lipase, trypsin, and amylase., Results: In 16% of the study population, PAT was present at the GEJ and was not associated with BE. The prevalence of esophagitis and/or gastritis did not vary significantly between patients with and without PAT., Conclusions: Our data suggest that PAT at the GEJ develops independently of inflammation and is, therefore, likely to be congenital.

We report the first case of synchronous Paget's disease of the vulva and breast diagnosed within a period of 7 months. This is the fourth case of mammary Paget's disease associated with either preceding or following vulvar Paget's disease documented in the literature. With consideration of increasing age of the population, and the fact that vulvar Paget's disease affects elderly women and that breast cancer is the most common malignancy of women in the United States, one can anticipate the occurrence of these two conditions to be more prevalent in the future., (Copyright 1998 Academic Press.)

Pseudopolyps constitute a relatively common finding in inflammatory bowel disease and have well-defined microscopic appearances. We report a new, unusual morphologic feature of colonic pseudopolyps in a patient with Crohn's disease, nodular neuronal hyperplasia.