Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group.

OBJECTIVES: To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result. DESIGN: Prospective temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses. The rules comprised five ultrasonic features (including shape, size, solidity, and results of colour Doppler examination) to predict a malignant tumour (M features) and five to predict a benign tumour (B features). If one or more M features were present in the absence of a B feature, the mass was classified as malignant. If one or more B features were present in the absence of an M feature, it was classified as benign. If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive. SETTING: 19 ultrasound centres in eight countries. PARTICIPANTS: 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a standardised research protocol. Reference standard Histological classification of the excised adnexal mass as benign or malignant. MAIN OUTCOME MEASURES: Diagnostic sensitivity and specificity. RESULTS: Of the 1938 patients with an adnexal mass, 1396 (72%) had benign tumours, 373 (19.2%) had primary invasive tumours, 111 (5.7%) had borderline malignant tumours, and 58 (3%) had metastatic tumours in the ovary. The simple rules yielded a conclusive result in 1501 (77%) masses, for which they resulted in a sensitivity of 92% (95% confidence interval 89% to 94%) and a specificity of 96% (94% to 97%). The corresponding sensitivity and specificity of subjective assessment were 91% (88% to 94%) and 96% (94% to 97%). In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements, the sensitivities were 89% (83% to 93%) for subjective assessment, 50% (42% to 58%) for the risk of malignancy index, 89% (83% to 93%) for logistic regression model 1, and 82% (75% to 87%) for logistic regression model 2; the corresponding specificities were 78% (72% to 83%), 84% (78% to 88%), 44% (38% to 51%), and 48% (42% to 55%). Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91% (88% to 93%) and a specificity of 93% (91% to 94%), compared with a sensitivity of 90% (88% to 93%) and a specificity of 93% (91% to 94%) when subjective assessment was used in all masses. CONCLUSIONS: The use of the simple rules has the potential to improve the management of women with adnexal masses. In adnexal masses for which the rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test; the risk of malignancy index and the two regression models were not useful.

[The use of 2-dimensional and 3-dimensional color and power-Doppler in the diagnosis of blood flow indices of adnexal tumors]. / Zastosowanie ultrasonografii Dopplerowskiej i sonoangiografii trójwymiarowej w badaniu unaczynienia i przeplywu krwi w guzach przydatków macicy u kobiet.

OBJECTIVES: The purpose of this study was to compare 2-dimensional and 3-dimensional color and power-Doppler as measured with blood flow indices for the prediction of malignancy in complex adnexal masses. METHODS: Two hundred eighty women with complex adnexal masses (mean age, 46,3 years (range, 13-83 years) were evaluated by 2-dimensional and 3-dimensional power-Doppler imaging. Complex adnexal mass was defined as the presence of at least one of the following features: solid areas, thick papillary projections, thick septa, or purely solid echogenicity. Tumor volume, sonomorphology and Doppler indices (PI, RI), as well 3-dimensional power-Doppler assessment (VI, FI, VFI) were calculated. All tumors were surgically removed and definitive histological diagnosis was obtained in each case. Diagnostic accuracy and areas under ROC curve (AUROC's) were calculated for each test. RESULTS: Seventy one tumors (25.3%) were proved to be malignant, and 209 tumors (74.7%) were proved to be benign. Statistically significant differences between benign and malignant tumors were found for PI (1.06 vs 0.76; p = 0.001), RI (0.62 vs 0.51; p = 0.002), VI (0.55 vs 1.52; p = 0.002) oraz VFI (0.18 vs 0.49; p = 0.001). However, the highest sensitivity of 3D indices for malignant tumor detection was found for FI (42.9%). Specificity of 2D and 3D indices was between 93.6% for VI to 98.2% for RI. Accuracy and positive and negative predictive values were fund to be between 66.8% to 79.8%, respectively. AUROC's analysis indicated that the most useful test for the discrimination between benign and malignant tumors was VI followed by VFI and PI with RI. CONCLUSION: Three-dimensional power-Doppler imaging has diagnostic potential for the discrimination of benign and malignant complex adnexal masses, but specific, possibly most vascularised areas of each tumor have to be examined in detail to improve not yet satisfactory predictive values of this method.

Female adnexal tumor of probable wolffian origin: morphological, immunohistochemical, and ultrastructural study with c-kit gene analysis.

Female adnexal tumors of probable wolffian origin (FATWO) are rare neoplasms believed to originate from mesonephric (wolffian) remnants. Rarity and variable location of FATWO make the diagnosis difficult. Although most cases follow a benign clinical course, approximately 10% of them either recur or metastasize and are thought to be resistant to chemoradiation therapy. In 2004, imatinib therapy, a tyrosine kinase inhibitor known to be effective against gastrointestinal stromal tumors, was reported to be effective also in a case of KIT-positive FATWO. However, c-kit gene mutations in FATWO have never been studied. Herein is reported the case of a 50-year-old Japanese woman with FATWO arising in the right paratubal site. The tumor had typical characteristics of FATWO in both morphology and immunohistochemistry. KIT protein was diffusely and weakly expressed, but DNA analysis revealed no mutational change in exon 9 or 11 of the c-kit gene. It is believed that accumulation of such genetic data of FATWO are essential from a therapeutic standpoint, although the present case had no mutation. In addition, the cytological features of this rare tumor are presented, which have not been described previously.

Clear-cell epithelioid leiomyoma of the round ligament.

A case of clear-cell epithelioid leiomyoma of the round ligament in a 69-year-old woman is described. The neoplasm presented as a firm left inguinal mass. A preoperative computed tomography (CT) scan demonstrated an enhancing lesion extending extra-abdominally from the region of the external inguinal ring. The surgical resection specimen was tan-white, well-circumscribed, and measured 5.8 cm in maximum dimension. Microscopic examination revealed a well-demarcated neoplasm comprised of polygonal cells with abundant clear cytoplasm arranged in clusters and single files with abundant intervening hyalinized stroma. There was minimal nuclear atypia and mitotic figures were rare. Periodic acid-Schiff with diastase demonstrated intracytoplasmic glycogen. Immunohistochemical stains for pan-actin, smooth muscle actin, desmin, bcl-2, and vimentin were positive in the tumor cells, whereas stains for CD34, carcinoembryonic antigen, cytokeratin, epithelial membrane antigen, S100 protein, and neurofilaments were negative. Electron microscopy demonstrated features of smooth muscle differentiation including longitudinally oriented fine filaments with focal condensations, pinocytotic activity, and subplasmalemmal densities. This case illustrates the ubiquitous distribution of epithelioid smooth muscle neoplasms and highlights the potential pitfalls for diagnosis when they occur in an unusual location.

Adrenal rest tumor of the broad ligament: case report with immunohistochemical study of steroidogenic enzymes.

An adrenal rest tumor of the broad ligament was studied in a 43-year-old woman. The tumor measuring 6 x 3 x 3 cm and appearing as golden-yellow on the cut surface was incidentally discovered during a total hysterectomy due to uterine leiomyoma. The encapsulated tumor was predominantly composed of pale and lipid-rich cells arranged in alveolar clusters or short blunt cords. Electron microscopic examination revealed mitochondria with tubulo-vesicular cristae and abundant lipid droplets. Adrenal 4-binding protein, a transcriptional factor of steroidogenesis, was present in almost all of the tumor cells, suggestive of steroidogenic features in the lesion. Immunoreactivity of steroidogenic enzymes involved in adrenocortical steroid production was detected in the tumor cells, suggesting that tumor cells had the potential to synthesize adrenocortical steroids. A relatively low Ki-67 labelling index (3.20 +/- 1.15 per 100 tumor cells) and an absence of necrosis and vascular and/or capsular invasion suggest benignity of the lesion.

Tumor of the broad ligament in von Hippel-Lindau disease of probable mullerian origin.

A rare neoplasm seen in women with von Hippel-Lindau disease is the papillary cystadenoma of the broad ligament, only three cases of which have been reported. All three exhibited characteristic histologic features identical to those of epididymal tumors that occur in affected patients, and were presumed to be of wolffian origin. This is the case of a broad ligament tumor in a woman with von Hippel-Lindau disease that had features more consistent with a mullerian rather than wolffian origin. This is the first report of a broad ligament tumor of probable mullerian origin in von Hippel-Lindau disease.

The many faces of smooth muscle neoplasms in a gynecological sampling: an ultrastructural study.

Smooth muscle neoplasms may have a variety of light microscopic and ultrastructural appearances. On one extreme, a spindle cell mass with a fascicular pattern, located in the myometrium, usually does not need electron microscopy or immunohistochemistry to confirm its smooth muscle nature. However, at the other end of a spectrum is an epithelioid neoplasm of the extrauterine pelvic tissues that could be composed of any of several cell types if routine light microscopy, alone, were used in studying it. In this report, some of these variants of smooth muscle neoplasms are exemplified, including myxomatous, fibroblast-like, nondescript, epithelioid, granular cell, and clear cell types. The main purpose has been to address, in particular, the ultrastructure of these unusual neoplasms, but, at the same time, not to ignore or downplay the contributory role of immunohistochemistry in making a final diagnosis, in some cases. Especially intriguing were the ultrastructural characteristics of leiomyomatous granular cell and clear cell neoplasms. A paucity or absence of filaments and dense bodies in samplings of these lesions makes the reliance on other ultrastructural features extremely useful.

Tissue reconstruction of gynecologic tumor cells in the rotation culture system.

Tissue reconstruction of various kinds of gynecologic malignant tumor cell lines was studied using the rotation-culture system. The reconstructed cell aggregates were examined histologically using both light and electron microscopy. Our established cell lines used in this study were uterine cervical epidermoid carcinoma, endometrial adenocarcinoma, ovarian malignant tumor and uterine sarcoma. All of the reconstructed aggregates from each cell line were very similar to the original tumor tissue. In the case of a well differentiated type of adenocarcinoma derived from the ovarian cancers or the endometrial cancers, papillary cell aggregates (grape-like structures) and/or hollow cell ball (gland alveolus-like) structures were observed. The individual cells were adjoined with by desmosomes and well developed microvilli protruded from the free surface of the cells. On the other hand large cell non-keratinizing squamous cell carcinoma cells formed spherical-shaped aggregates that showed a stratified structure similar to pearl formation. Sarcoma cells formed solid clusters while desmosomes or desmosome-like junctions were not detected. Rotation culture is an excellent method to reveal diagnosis of the original tumor and tumorigenesis by investigating a reconstructed tissue from peritoneal effusions because the reconstructed tissue is similar to the original tumor.

Steroid cell tumor of the broad ligament arising in an accessory ovary.

OBJECTIVE: To determine the histogenesis of an unusual steroid cell tumor that occurred in the broad ligament. PATIENT AND METHODS: The tumor occurred in a 29-year-old woman who had evidence of virilization. The preoperative testosterone level was greater than 700 ng/dL, but it returned to normal after surgery. She was living and well without evidence of recurrent tumor 1 year after operation. The tumor was examined using light and electron microscopy and immunohistochemical stains. RESULTS: The tumor was composed of polygonal cells with prominent eosinophilic cytoplasm. No significant nuclear atypia or mitotic activity was identified; however, the tumor was large, and necrosis and hemorrhage were identified on gross and microscopic examination. A graafian follicle and a primordial follicle were present at the periphery of the tumor within the connective tissue stroma in one section, providing evidence for the presence of an accessory ovary. A separate normal ovary was present on the same side. The tumor mass was connected to the surface of the eutopic ovary by thin membranous tissue. CONCLUSION: To our knowledge, we report the first case in the modern literature of an extraovarian steroid cell tumor arising in the broad ligament, and we present evidence supporting its origin from an accessory ovary.

Adenoid cystic ovarian carcinoma compared with other adenoid cystic carcinomas of the female genital tract.

Adenoid cystic carcinoma (ACC) of the ovary is an extremely rare neoplasm referred to infrequently in the literature. A new case of a pure, primary, ovarian ACC is reported. The patient was a 45-year-old white woman who had a stage IA, well-circumscribed, unilateral, ovarian mass. Histologically, the tumor was composed of small, uniform, and basaloid cells exhibiting predominantly a tubular pattern, as well as demonstrating cribriform and focal solid areas. There was no necrosis and minimal nuclear pleomorphism; the mitotic rate was fewer than three cells per 10 high-power fields. Immunohistochemical examination showed that the tumor cells were strongly positive for cytokeratins CAM 5.2 and AE1/3 and carcinoembryonic antigen. The cells at the periphery of the epithelial aggregates in the cribriform and tubular areas were positive for muscle-specific actin and, occasionally, for S100 protein. Electron microscopic examination revealed that these cells had convoluted nuclei and filamentous structures associated with dense bodies. These findings support a myoepithelial component. A characteristic feature was the production of periodic acid-Schiff stain-positive basement membrane material, which appeared as reduplicated basal lamina by electron microscopic examination. The patient is currently alive, without evidence of recurrence or persistent tumor 7 years after surgical excision. The tumor demonstrated immunohistochemical and ultrastructural findings similar to those of ACCs of salivary gland origin and to other ACCs of the female genital tract. The histogenesis of most ovarian ACCs is through metaplasia of the celomic epithelium, but pure cases might also be of teratomatous origin.

Localized and diffuse mesotheliomas of the genital tract and peritoneum in women. A clinicopathologic study of nineteen true mesothelial neoplasms, other than adenomatoid tumors, multicystic mesotheliomas, and localized fibrous tumors.

Peritoneal mesotheliomas are rare in women, compared to serous epithelial neoplasms with which they are often confused. We evaluated the clinicopathologic features of 19 true mesothelial neoplasms affecting the genital tract or peritoneum of women (other than adenomatoid tumors, benign multicystic mesotheliomas, and localized fibrous tumors) to characterize their clinicopathologic features and to determine their clinical behavior. Six tumors were localized to one anatomic site at presentation, and 13 involved more than one anatomic site. The six localized tumors were solitary, small (0.8-2.0 cm), polypoid or nodular lesions, five of which were incidental findings. All had a predominantly tubulopapillary pattern, either pure or mixed with adenomatoid-like or small solid foci. Nuclear grade ranged from 0 to 2. Mitotic figures (MF) were absent in two tumors. The mitosis count in the other four tumors was < 1 MF/10 high-power microscopic fields (HPF) (average method) and ranged from 1 to 3 MF/10 HPF (highest count method). Five patients were alive without recurrence after postoperative intervals ranging from 19 months to 9 years (median, 5 years); one patient died of metastatic gastric carcinoma at 14 months. Thirteen tumors involved more than one anatomic site and were classified as diffuse mesothelioma. Typically, these tumors were symptomatic and accompanied by ascites. The tumors had either a plaque-like or endophytic configuration. Eleven were purely epithelial mesotheliomas, and two had a minor sarcomatoid component. Tubulopapillary patterns were present in 10 tumors, usually admixed with focal adenomatoid-like or solid patterns, and three had a purely solid pattern. All 13 tumors had grade 3 nuclei. The mitosis count ranged from < 1 to 2 MF/10 HPF (average count method) with a range of 1-4 MF/10 HPF by the highest count method. Immunohistochemically, 13/13 tumors stained for cytokeratin (AE1/AE3). None were immunoreactive for polyclonal carcinoembryonic antigen (CEA), Leu-M1, or B72.3. One diffuse mesothelioma stained focally for Ber-EP4, and electron microscopy confirmed the mesothelial nature of this tumor. Nine patients died of tumor after postoperative intervals ranging from 1 month to 6 years. Eleven patients had received postoperative adjuvant intraperitoneal or systemic chemotherapy. One patient died with increased abdominal girth 8 years after operation and one course of intraperitoneal chemotherapy, though the role of mesothelioma in her death was uncertain. One patient was alive with diffuse tumor and persistent ascites 25 months after six courses of intraperitoneal chemotherapy. One patient was alive without evidence of disease 4 months after two courses of systemic chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of progesterone receptor form A and B mRNAs in gynecologic malignant tumors.

This study was designed to examine the biological implication of progesterone receptor (PR) forms A and B mRNA expressions in gynecologic cancers. The ratio of PR form A to form B in mRNA expression was approximately 1:1 in all endometria studied. The predominant expressions of form B transcript occurred in 6 out of 7 cases of advanced stages (stages III and IV) in ovarian cancers, in 5 out of 9 cases of cervical cancers, and in 5 out of 11 cases of endometrial cancers. In conclusions, the dominancy of PR form B mRNA expression might be associated with the expression of a malignant phenotype in gynecologic cancers, and advanced clinical stage in ovarian cancers, suggesting a biological marker of malignant phenotype in these three types of cancer cell.

Growth factor expression in normal peritoneum of patients with gynecologic carcinoma.

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.

Glomus tumor of the female external genitalia: a report of two cases.

Glomus tumors occurring in the external genitalia of two women aged 53 and 46 years, respectively, are reported. One of the tumors was clitoral and the other arose in the periurethral area of the vulva. The diagnosis in one case was supported by immunocytochemical analysis. Electron microscopy was performed on both tumors. Only two glomus tumors involving the female external genitalia have been reported in the literature. The tumors we describe appeared to be morphologically similar to the glomus tumors that typically arise in the distal extremities.

Immunohistochemical localization of insulin-like growth factor 1 receptors in benign and malignant tissues of the female genital tract.

The distribution of insulin-like growth factor I (IGF-1) receptors in the female genital tract was examined by immunohistochemistry. The monoclonal antibody alpha-IR-3, which binds to the alpha-subunits of the IGF-1 receptor, was used for specific binding and the peroxidase-antiperoxidase method was used for staining. IGF-1 receptors were consistently detected in the epithelium of cervix, endometrium and the fallopian tube. Furthermore, high expression of the IGF-1 receptors was found in ovarian cancer tissue, where predominantly the stromal cells around the vessels gave an intense staining. Since the expression of the IGF-1 receptors in tumor epithelium was only weak and inconsistent, it is tempting to speculate that the stromal compartment in ovarian cancer is the target tissue for the effects of IGF-1.

Submicrostructure and typing of female genital condylomata.

Thirty biopsies from female genital condylomata were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to study structural characteristics and typing of condylomata. It was found that cytoplasmic clearing was marked in acuminate condylomata, diffuse interstitial and epithelial proliferation in nodular condylomata (flat condylomata), and invagination of the lesions into the interstitial tissue or glandular ducts in endophytic condylomata. In nodular condylomata, SEM also showed some structural features similar to those of intra-epithelial neoplasia. Microridges on the surface of squamous cells had villiform of granular changes. On the surface of a percentage of squamous or columnar cells, there were holes with a diameter of about 3 to 5 microns. A number of giant cells were seen among other cells. The cervical squamatization zone contained groups of special cells covered with dense microvilli. TEM of nodular condylomata revealed some pictures resembling active proliferation of tumor cells, such as enlarged or irregular nuclei (large N/C ratio), evaginated or invaginated nuclear membranes, condensed chromatin attached to the inner part of the nuclear membrane, transparent nucleoplasm, and frequent nucleosomes and karyokinesis. Virus particles with the morphological characteristics of HPV (naked hexagon-like particles with an average diameter of 45-50 nm) were seen in some nuclei with markedly condensed chromatin. It is suggested that HPV-induced genital condylomata, especially nodular one (flat condylomata), entail a potential progression to malignancy.

Female adnexal tumor of wolffian origin.

We describe a female adnexal tumor of probable wolffian origin with stage 2B disease. The presence of peritoneal implants suggests a more aggressive clinical course than is usually expected. We present the findings of light microscopic and ultrastructural evaluation as well as those of immunohistochemical and DNA ploidy analysis, which, to our knowledge, have not been previously described for this type of tumor.

Elastin in adenomatoid tumor. Light microscopic and electron microscopic study.

Elastin distribution was examined in adenomatoid tumors of the human genital tract. Two distinct patterns were identified: strongly positive or completely negative for elastin in the stroma, according to the case. Even in cases appearing to have very similar histologic features, the stroma was rich in elastin in some cases and was almost devoid of elastin in others. Electron microscopic examination with tannic acid staining revealed that the elastin in the stroma was composed mainly of amorphous material surrounded by a small amount of microfibrils and abundant collagen fibers. Fibroblasts were sparsely distributed in the stroma. Tumor cells displayed mesothelial cell-like features, such as abundant microvilli on the surface, numerous cytoplasmic organelles, several well-developed basal lamina. In some areas, elastin seemed to be formed by mesothelial cells. In some adenomatoid tumor cases, elastogenesis would be enhanced by activated mesothelial tumor cells as well as stromal fibroblasts.

Peritoneal washing cytology in women: diagnostic pitfalls and clues for correct diagnosis.

The significance of peritoneal washing cytology in the management of patients with gynecologic cancer is well established. Its microscopic evaluation, however, is not always straightforward. Previous studies have identified some of the conditions that may result in misinterpretation of cytologic results. This report reviews the literature and describes other sources of diagnostic difficulties and clues for correct diagnosis. In addition, an outline for distinguishing endosalpingiosis from borderline and well-differentiated serous carcinoma is proposed.