Malignant Adnexal Tumors Research Articles

Sonographic prediction of malignancy in adnexal masses using an artificial neural network.

To generate a neural network algorithm which computes a probability of malignancy score for pre-operative discrimination between malignant and benign adnexal tumours. A retrospective analysis of previously collected data. Information from 75% of the study group was used to train an artificial neural network and the remainder was used for validation. The Gynaecological Ultrasound Research Unit at King's College Hospital, London. Sixty-seven women with known adnexal mass who had been examined using transvaginal B-mode ultrasonography and colour Doppler imaging with pulse spectral analysis immediately before surgery. The excised masses were classified histologically as benign (n = 52) or malignant (n = 15), of which three were borderline. The variables that were put into the artificial neural network were: age, menopausal status, maximum tumour diameter, tumour volume, locularity, the presence of papillary projections, the presence of random echogenicity, the presence of analysable blood flow velocity waveforms, the peak systolic velocity, time-averaged maximum velocity, the pulsatility index, and resistance index. Histological classification, categorised as benign or malignant, was the output result. A variant of the back propagation method was selected to train the network. The overall architecture of the network with the best performance contained an input layer with four variables (age, time-averaged maximum velocity, papillary projection score and maximum tumour diameter), a hidden layer with three units and an output layer with one. The sensitivity and specificity at the optimum diagnostic decision value for the artificial neural network output (0.45) were 100% (95% CI 78.2%-100%) and 98.1% (95% CI 89.5%-100%), respectively. These values were significantly better than those obtained from the independent use of the resistance index, pulsatility index, time-averaged maximum velocity or peak systolic velocity at their optimum decision values (P < 0.01). Artificial neural networks may be used on clinical and ultrasound derived end-points to accurately predict ovarian malignancy. There is a need for a prospective evaluation of this technique using a larger number of patients.

Receiver operating characteristic curves of transvaginal Doppler blood flow measurements in benign and malignant adnexal tumors.

The role of receiver operating characteristic curves of transvaginal Doppler velocimetry in predicting malignancy was evaluated in 80 patients with benign and 40 patients with malignant adnexal tumors. The mean values of peak systolic velocity did not differ significantly. Malignant tumors had a significantly higher end diastolic velocity and mean flow velocity than benign tumors. Benign tumors had a significantly higher ratio of peak systolic to end diastolic velocity, pulsatility index, and resistive index than malignant tumors. The diagnostic accuracies in predicting malignancy were as follows: peak systolic velocity, 62%; end diastolic velocity, 79%; ratio of peak systolic to end diastolic velocity, 63%; mean flow velocity, 73%; pulsatility index, 91%; resistive index, RI 92%. Doppler velocimetry analysis allows us to predict the presence of malignancy with limited reliability.

Analysis of blood flow in adnexal tumors by using color doppler imaging and pulsed spectral analysis

Because of various contradictory reports in the literature and an increasingly urgent need for preoperative evaluation of adnexal masses before laparoscopic surgery, our aim was to disclose if examination by means of color Doppler ultrasound is useful in distinguishing benign from malignant adnexal tumors in our population. Prior to surgery, pulsed color Doppler velocimetry of the adnexal blood supply was performed in a prospective study in 80 patients with benign and 40 with malignant adnexal tumors. Vascularization was equally frequent in both groups of tumors. Blood vessels of benign tumors had a diffuse, intraseptal or intraproliferative location significantly more often and malignant tumor vessels more often exhibited a diffuse, intraseptal or intraproliferative location ( p < 0.01). The mean value of RI ± SD was 0.56 ± 0.14 in benign and 0.33 ± 0.13 in malignant tumors. The differences in RI between benign and malignant tumors are statistically significant ( p < 0.01). In detecting malignant adnexal tumors, the sensitivity of RI ≤ 0.40 is 82%, its specificity 97%, positive predictive value 94%, negative predictive value 92% and its accuracy 92%. The analysis of vascularization presence seems not to have any value in predicting the nature of adnexal tumors, and blood vessels arrangement, as well as measured RI ≤ 0.40, allows us to predict the presence of malignancy with limited reliability.

Diagnostic Formula for the Differentiation of Adnexal Tumors by Transvaginal Sonography

In Brief Objective To create a strategy for sonographic differentiation of benign and malignant adnexal tumors in premenopausal and postmenopausal patients. Methods Multiple sonomorphologic criteria were analyzed prospectively in 754 tumors. Four hundred were found in premenopausal and 354 in postmenopausal women. In a logistic regression model, relevant criteria were selected, and a diagnostic formula for tumor differentiation was derived. Results There were 165 malignant tumors, of which 37 (9.2%) were found in premenopausal and 128 (36.2%) in postmenopausal women. In both groups, the criteria of solid phase and ascites were the most significant. Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women. These results allowed an estimation of the probability of malignancy. Using a cutoff point of 10% for the probability to classify tumors as malignant, the sensitivity and specificity in premenopausal patients were 86.5% and 92.6%, respectively, with an accuracy of 92%. In postmenopausal women, the sensitivity, specificity, and accuracy were 93%, 82.7%, and 86.6%, respectively. Assuming a prevalence as given in the study, the positive and negative predictive values were 54.4% and 98.5% in premenopausal and 75.3% and 95.4% in postmenopausal women. Conclusions With four binary criteria, a useful diagnostic formula for tumor differentiation was obtained. However, estimates for sensitivity, specificity, and accuracy may be too optimistic because they were derived from the same data that were already used for model selection. A useful diagnostic formula for sonographic tumor differentiation is obtained in premenopausal and postmenopausal women and provides an accurate differentiation between benign and malignant adnexal tumors.

Diagnostic formula for the differentiation of adnexal tumors by transvaginal sonography

To create a strategy for sonographic differentiation of benign and malignant adnexal tumors in premenopausal and postmenopausal patients. Multiple sonomorphologic criteria were analyzed prospectively in 754 tumors. Four hundred were found in premenopausal and 354 in postmenopausal women. In a logistic regression model, relevant criteria were selected, and a diagnostic formula for tumor differentiation was derived. There were 165 malignant tumors, of which 37 (9.2%) were found in premenopausal and 128 (36.2%) in postmenopausal women. In both groups, the criteria of solid phase and ascites were the most significant. Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women. These results allowed an estimation of the probability of malignancy. Using a cutoff point of 10% for the probability to classify tumors as malignant, the sensitivity and specificity in premenopausal patients were 86.5% and 92.6%, respectively, with an accuracy of 92%. In postmenopausal women, the sensitivity, specificity, and accuracy were 93%, 82.7%, and 86.6%, respectively. Assuming a prevalence as given in the study, the positive and negative predictive values were 54.4% and 98.5% in premenopausal and 75.3% and 95.4% in postmenopausal women. With four binary criteria, a useful diagnostic formula for tumor differentiation was obtained. However, estimates for sensitivity, specificity, and accuracy may be too optimistic because they were derived from the same data that were already used for model selection.

DIAGNOSIS AND THERAPY OF ADNEXAL MASSES IN POSTMENOPAUSAL WOMEN: A PROSPECTIVE STUDY

Objectives This prospective study was conducted to examine the safety and efficacy of the operative laparoscopic management of adnexal masses in the postmenopause and to define the limits of this procedure. Main outcome measure The parameter chosen for testing the preoperative diagnostic model was the laparoscopic operation of a malignant ovarian tumour. Design This hospital‐based study included 265 consecutive postmenopausal patients with adnexal masses. After preoperative pelvic examination, transvaginal/abdominal ultrasound and determination of the tumour marker CA 125, primary laparoscopy was performed in 69.4% (group A) and primary laparotomy in 30.6% (group B). In 4.2% the patients were converted to laparotomy following diagnostic endoscopy (group Ab); in 65.2% the operative laparoscopic adnectomy was completed (group Aa). Results In the total sample, 81.1% of the tumours were classified as definitely benign, 3.8% showed borderline changes and 15.1% were malignant. The malignancy rate in group A was 3.8% with 2.2% in group Ab, and in group B it was 53.1%. Complications occured in 1.9% of cases, without statistically significant differences between the two groups. Conclusion By combining pelvic examination, transvaginal/abdominal ultrasound, determination of the tumour marker CA 125, and adequate intraoperative evaluation during laparoscopy, the risk of laparoscopic operation of a malignant adnexal tumour can be reduced to a minimum. After carefully weighing up the benefits and risks, we consider a laparoscopic approach to be justified in a selected patient population in the postmenopause, provided the team has sufficient experience in the preoperative assessment of adnexal masses.

Controversies in assessment of ovarian tumors with transvaginal color Doppler ultrasound.

The observations made in the late 1980s indicated that the transvaginal color Doppler ultrasound can be used in the detection of ovarian cancer. This has generated a stream of clinical trials. The conflicting results of numerous publications, however, have led to a major controversy. The aim of this communication is to review the literature and our own observations in order to provide more insight into the subject. The performance characteristics of the 32 previous transvaginal color Doppler ultrasound studies showed a considerable heterogeneity: the sensitivity was 25%-100%, the specificity was 46%-100%, the positive predictive value was 28.6%-100% and the negative predictive value was 63%-100%. The accuracy varied between 57% and 100%. An indisputable overlap was found between the ranges of pulsatility index (PI) and resistance index (RI) values from the benign and malignant adnexal tumors. The RI was <0.40 in 43% of benign tumors and in 25% of the normal vascular ovaries. The current cut-off levels for PI or RI values should not be used in clinical decision making due to their poor specificity.

A comparison of intratumoural indices of blood flow velocity and impedance for the diagnosis of ovarian cancer

The aim was to assess the value of blood flow velocity indices in an ultrasound-based test to discriminate between malignant and benign adnexal tumours. Fifty-one women (35 premenopausal and 16 postmenopausal) with persistent adnexal masses were scanned prior to surgery using transvaginal sonography with colour Doppler imaging. Intratumoural flow velocity waveforms obtained by pulsed Doppler sonography were used to determine the time averaged maximum velocity (TAMXV), peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI). The tumours were classified by histologic criteria (42 benign, 1 borderline and 8 malignant tumours). Two of the malignant and the single borderline tumour were stage I, five were stage III and one was stage IV. Detectable blood flow signals were found in all malignant and borderline tumours and in 33 of 42 (78.6%) of the benign tumours. TAMXV was the best parameter for discrimination of benign and malignant adnexal pathology and at a cut-off value of TAMXV ≥12 cm/s to indicate malignancy, the sensitivity and specificity were 88.9% and 81.0%, respectively. At the same sensitivity level, this gave a better specificity than the PI ≤0.90 (specificity 61.9%, P = 0.036), RI ≤ 0.60 (specificity 54.8%, P = 0.010) and PSV ≥ 16 cm/s (specificity 71.4%, P = 0.121). Discrimination between benign and malignant tumours was improved further by using two criteria rather than one. When the two criteria of a TAMXV of ≥12 cm/s and a PI ≤ 1.0 were applied simultaneously, the tumours could be characterised with a sensitivity of 88.9% and a specificity of 88.1%. Therefore, intratumoural PSV and TAMXV could be used to discriminate between benign and malignant adnexal tumours better than values for PI and RI. The best discrimination was achieved by using a combination of cut-off values for velocity and impedance parameters as two criteria to define malignancy.

Intratumoral peak systolic velocity as a new possible predictor for detection of adnexal malignancy

OBJECTIVE: Our purpose was to evaluate whether intratumoral blood flow velocity measured by transvaginal Doppler ultrasonography would afford better discrimination between benign and malignant adnexal tumors. STUDY DESIGN: One hundred two patients with adnexal tumors (72 benign, 30 malignant) were studied with transvaginal B-mode, color, and pulsed Doppler ultrasonography before surgery. RESULTS: Sixty-five benign tumors (90.3%) had abnormal morphologic features suggesting malignancy, and blood flow was detected in 29 (40.3%). The peak systolic velocity was 13.1 ± 9.1 cm/sec and the resistance index was 0.563 ± 0.177. All malignant tumors had abnormal morphologic features and blood flow was detectable in all cases. The peak cystolic velocity was 23.9 ± 11.5 cm/sec and the resistance index was 0.488 ± 0.118. When 16 cm/sec was considered as the cutoff value of peak systolic velocity, the sensitivity and specificity of peak systolic velocity in detecting malignant adnexal tumors were 83.3% and 91.6%, respectively. The sensitivity and specificity of the resistance index (cutoff value 0.72) was 93.3% and 68.1%, respectively. There was no significant difference in sensitivity between peak systolic velocity and resistance index. The specificity of the peak systolic velocity was significantly higher than that of the resistance index ( p < 0.05). Moreover, the sensitivity of the peak systolic velocity did not significantly differ from that with transvaginal ultrasonography diagnosis (86.7%), and the specificity of the peak systolic velocity was significantly higher than that of transvaginal ultrasonography (69.4%). CONCLUSION: These results suggest that peak systolic velocity obtained from intratumoral abnormal morphologic features provides a superior means for differentiating malignant from benign adnexal tumors.

Clear cell eccrine carcinomas of the skin. A clinicopathologic study of nine patients.

Sweat gland carcinomas with clear cell features are extremely rare neoplasms, with few well documented cases reported in the literature. Data on nine patients with malignant eccrine adnexal neoplasms characterized by a prominent clear cell neoplastic component were studied. Immunohistochemical stains with a panel of antibodies against epithelial, stromal, and neural antigens were performed on five tumors and electron microscopic examination of one. The tumors showed a spectrum of histologic features and growth patterns that ranged from well differentiated, low grade malignant neoplasms to poorly differentiated, highly aggressive, recurrent, and metastasizing tumors. All tumors contained a varied proportion of cells with abundant clear cytoplasm, similar to those seen in a group of benign eccrine adnexal neoplasms that have been variously designated as clear cell hidradenoma, nodular hidradenoma, clear cell myoepithelioma, and eccrine acrospiroma. Immunohistochemical stains on five tumors and ultrastructural examination in one were consistent with eccrine differentiation. Clinical follow-up of eight patients showed local recurrence in six, followed by metastases in three, despite local excision, radiation, and chemotherapy. Criteria for differentiating these tumors from their benign counterparts and from other types of malignant adnexal neoplasms and metastatic lesions are presented. The findings indicate that clear cell eccrine carcinomas comprise a heterogeneous group of lesions that may range from locally recurring, low grade well differentiated tumors to highly aggressive, high grade tumors with a definite potential for uncontrollable local recurrence and metastasis. Wide surgical excision is recommended as the primary treatment for such neoplasms.

Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas

Ninety-eight different malignant adnexal tumors were analyzed for the presence of epidermal growth factor (EGF)-specific binding sites and binding parameters were calculated by Scatchard plot analysis [G. Scatchard, Ann. N.Y. Acad. Sci. 51, 660–672 (1949)]. Thirty-four biopsies were EGF receptor (EGF-R) positive with dissociation constants ( K D ) of 0.5–12 × 10 −9 M and binding capacities ( B max) of 2–250 fmol/mg. One tumor had a K D of 60 × 10 −9 M and a B max of 1660 fmol/mg. The correlation of EGF-R status with clinical parameters showed no significant differences in primary, metastatic, or recurrent tumors, histological subtype, tumor differentiation, and tumor residual after primary surgery. As an inverse correlation, EGF-R-positive tumors are 39% and EGF-R-negative tumors 60% progesterone receptor positive. A response to chemotherapy was noticed in 50% of EGF-R-positive ovarian carcinomas with a mean survival time of patients of 28 months. The response rate of EGF-R negative ovarian carcinomas was 12% with a mean survival time of 16 months. Regarding the treatment schedule the major differences were noticed in the cis-platinum plus cyclophosphamide treatment group. These results suggest that the biology of ovarian carcinomas is influenced by growth factors and their receptors, which can be used as prognostic factors.

Hair Matrix Differentiation

The formation of structures resembling hair matrices is the least common form of follicular differentiation and only occurs with any frequency in pilomatricoma. Rarely, follicular cysts and both benign and malignant adnexal tumors can show areas of pilomatricoma-like change, or hair matrix differentiation. Examples of focal hair matrix differentiation in a follicular cyst, a cutaneous mixed tumor, and an adnexal carcinoma are presented. Each of these cases also demonstrates the presence of limited differentiation toward structures of the inner root sheath.

Eccrine sweat gland carcinoma: an histologic and immunohistochemical study of 32 cases*

In an attempt to characterize the immunocytochemical attributes of eccrine sweat gland carcinoma, we studied 32 examples of this tumor with antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), carcinoembryonic antigen, S100 protein, alpha-lactalbumin, salivary amylase, blood group isoantigens, beta-2-microglobulin, and Leu M1. All cases expressed EMA and CK, and 28 of 32 cases also displayed at least 2 of the 6 remaining antigens. No significant variations were noted in the immunophenotypes of histologic subtypes of eccrine carcinoma. These results provide an objective means of diagnostic separation between sweat gland carcinoma and other primary malignant cutaneous tumors. However, they do not appear to correlate with the degree of tumoral differentiation, and are of no assistance in the separation of benign and malignant sudoriferous neoplasms. The ability of immunocytochemical techniques to distinguish between primary malignant adnexal cutaneous tumors and metastases to the skin appears unlikely, but remains to be studied further. Also, the use of immunostaining panels is advised in the study of adnexal carcinomas, since no single determinant in isolation is specific for these neoplasms.

Basement membrane Laminin and Type IV Collagen in Various Benign and Malignant Adnexal Tumors of the Skin: An Immunohistochemical Study

Thirty benign and seven malignant adnexal tumors of the skin and one lymph node metastasis were stained for laminin and type IV collagen with rabbit antibodies against the human basement membrane (BM) proteins using the immunoperoxidase technique. Fifteen of the benign sweat gland, sebaceous gland, and hair follicle tumors showed a continuous and distinct BM around the tumor aggregates. The cylindromas and eccrine spiradenomas seemed to produce excessive amounts of BM material, part of which was seen as amorphic patches within the tumor cell clusters, whereas the trichofolliculomas, trichoepitheliomas, and pilomatrixomas showed an absence of BM from many areas. In syringomas, in addition to the tubular structures surrounded by a continuous BM, undifferentiated cell nests containing granular BM material were present. They probably represent primitive structures obtaining during early development into tubules. The seven malignant tumors and the only metastasis studied here all contained small, narrow strips of BM material extracellularly between the infiltrating tumor clusters. Only in two cases was faint staining for laminin found within the cells. The pepsin pretreatment of the formalin-fixed, paraffin-embedded samples had most probably degraded the intracytoplasmic BM material in most cases. The BM defects were found to be associated with malignancy and low differentiation of the adnexal skin tumors, as reported previously for other tumor types, but a partial loss of BM was also associated with high differentiation in some benign adnexal tumors.

Beta-2-microglobulin in benign and malignant adnexal skin tumors and metastasizing basocellular carcinomas.

Immunostaining for beta-2-microglobulin (beta-2m) was performed on various benign and malignant adnexal skin tumors and 3 cases of metastasizing basocellular carcinomas. All the tumors and their metastases, with the exception of 2 basocellular carcinomas gave evidence of beta-2m. Most tumors contained both stained and unstained cells. The stained cells showed differentiation, the unstained ones appeared to be undifferentiated and basal-like in character. The staining of cutaneous tumors for beta-2m may offer a tool for investigating tumor differentiation, but seems not to be of much value in distinguishing malignant from benign lesions.

Pseudomelanoma in Nevus Sebaceus of Jadassohn

Nevus sebaceus of Jadassohn is an organoid nevus composed of varying admixtures of sebaceous glands, hair follicles, and apocrine glands. The degree of differentiation of these appendages can be related to age. Clinically this nevus appears as a yellow, hairless plaque on the scalp or face of infants, but it may occasionally arise in adult life or in unusual locations such as the back or the inguinal or pubic regions. Cerebriform, linear, irregular, zosteriform, and multiple lesions have all been described. 1,2 Development of various malignant or benign adnexal tumors often occurs with advancing age but can be seen in young adults. 3 Recently, Fellner and Katz 4 emphasized the occasional close clinical resemblance of pigmented basal cell carcinoma to superficial spreading melanoma. The following case of pseudomelanoma arising in a patient with nevus sebaceus is another example of the diagnostic dilemma these lesions can cause. Report of a Case