Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors.

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.

Topical testosterone versus clobetasol for vulvar lichen sclerosus.

OBJECTIVE: To compare the effects of topical testosterone and clobetasol treatments on symptoms remission and recurrence rates in patients with vulvar lichen sclerosus (LS). METHODS: A retrospective review of the records showed that, of 140 patients with biopsy-proven vulvar LS, 80 were treated with applications of testosterone propionate 2% in petrolatum and 60 with clobetasol 17-propionate 0.05%. RESULTS: The response rates after 6 months were 77.5% for patients treated with testosterone and 91.7% for those treated with clobetasol (P=0.02). The recurrence rates were 20% and 6.7% in the 2 groups, respectively (P=0.02). Premenopausal patients had higher remission rates and lower recurrence rates than postmenopausal patients (P>0.05). Considering whole patients, low remission rates and high recurrence rates were observed in patients who had had a hysterectomy (P>0.05). CONCLUSION: Treatment of LS with a corticosteroid provided excellent remission rates. In this study, clobetasol 17-propionate 0.05% was superior to testosterone for both remission induction and maintenance therapy.

Triple simultaneous primary gynecological malignancies in a 56-year-old patient.

The occurrence of double simultaneous primary cancers is common. However, the occurrence of synchronous primary triple gynecological malignancies is an extremely rare event. In this report, the clinical and pathologic findings of a 56-year-old female patient with synchronous triple primary gynecological cancers including well-differentiated ovarian mucinous cystadenocarcinoma, well-differentiated endometrial endometrioid adenocarcinoma, and uterine leiomyosarcoma were presented. Synchronous primary, well-differentiated endometrial endometrioid adenocarcinoma and leiomyosarcoma of uterus without any ovarian neoplasm has only been once described in the English literature. To our knowledge, the presented patient is the first case in aspect of accompanying ovarian mucinous adenocarcinoma to endometrial endometrioid adenocarcinoma and leiomyosarcoma of uterus.

Medical treatment of vulvar squamous cell hyperplasia.

OBJECTIVE: To evaluate symptomatic response and recurrence rates of graduated topical fluorinated corticosteroid in patients with vulvar squamous cell hyperplasia. METHODS: Nine hundred seventy-six patients with biopsy-proven vulvar squamous cell hyperplasia from 1990 to 2003 were reviewed in this retrospective study. All patients were treated with graduated topical fluorinated corticosteroid. Data were obtained from hospital records. Symptomatic remission and recurrence rates were noted following six months local therapy. RESULTS: The mean age was 42.55+/-10.93 (15-85). The remission rate was 93.8% in six months. The remission rate was non-significantly higher in postmenopausal patients than that in their premenopausal counterpart (94.9% vs 93.0%, p=0.15). The disease recurred in 6.9% of patients. Of the patients that suffered recurrence 47.5% had persistent disease initially. The patients with following factors older ages (>40 years), postmenopausal period had significantly higher recurrence rates. Four patients with recurrent disease and six patients with persistent disease in the form of vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia, were treated with skinning vulvectomy. CONCLUSION: Corticosteroid in the treatment of vulvar squamous cell hyperplasia yielded excellent response rates. In the evaluation of patients without symptomatic relief, the first step should be a vulvar biopsy to exclude the presence of atypical components.

Predictability of retroperitoneal lymph node metastasis by using clinicopathologic variables in surgically staged endometrial cancer.

The purpose of this study was to predict lymphatic involvement in endometrial cancer using clinicopathologic variables of patients treated with surgical staging. Overall, 461 patients treated with an initial surgical staging procedure including complete pelvic-para-aortic lymphadenectomy were included. The mean number of resected lymph nodes was 27 (median 26; range 15-83), and 54 patients (12%) had lymphatic involvement. Of these patients, 32 had only pelvic, 15 had both pelvic and para-aortic, and 7 had isolated para-aortic metastases. In the multivariate analysis, deep myometrial invasion (P= 0.02), lymphvascular space invasion (P= 0.001), positive peritoneal cytology (P= 0.002), and cervical involvement (P= 0.003) predicted retroperitoneal lymph node metastasis (RLN) significantly. Two hundred seventy-four patients (59.4%) had at least one of these poor prognostic factors identified by multivariate analysis. In this patient population, 53 (19.3%) had lymphatic involvement compared to 1 patient in the group of 187 patients with low-risk criteria. Ninety-eight percent of patients with RLN were predicted by this model, and with the advent of accurate diagnostic techniques, 40% of patients could be saved from undergoing lymphadenectomy.

High-grade neuroendocrine carcinoma of the cervix. A case report.

Neuroendocrine tumor of the uterine cervix is a rare and aggressive malignancy. Despite controversial, multimodal treatment methods, prognosis and treatment outcomes are worst in advanced stages. We report an early-stage case treated with the multimodal approach. The nomenclature proposed for this tumor type in 1997 by the College of American Pathologists still has some points of discussion. As in our case some of the tumors cannot be defined exactly into small or large cell types, and this causes confusion at least for nomenclature purposes. A 'mixed' type for this tumor may be appropriate.

Which surgical procedure for patients with atypical endometrial hyperplasia?

OBJECTIVE: To determine the occult coexistence of endometrial carcinoma in patients with atypical endometrial hyperplasia and to compare histological prognostic factors according to lymph node status in occult endometrial carcinoma. MATERIALS AND METHODS: Two hundred and four patients from two referral centers (during the period 1990-2003) who were operated on within 1 month of endometrial biopsy for symptomatic endometrial hyperplasia without receiving any medical treatment were included retrospectively. Patients having preoperative endometrial biopsy results of concomitant endometrial hyperplasia and carcinoma were excluded from the study. Fifty-six patients having atypia in preoperative biopsy (group I) were compared with 148 patients without atypia (group II). Chi-square and Mann-Whitney U-tests were used for statistical analyses. RESULTS: No significant difference was observed between the two groups according to age or menopausal status. Patients in group II had significantly higher parity than patients in group I. In group I, 62.5% of the patients had endometrial carcinoma, 21.4% had endometrial hyperplasia, and 16.1% had normal endometrium in hysterectomy specimens. In group II, the percentages were 5.4, 38.5, and 56.1%, respectively. Complete surgical staging was performed in 20 patients. Four patients had metastatic lymph nodes. All of them had grade 2 tumors with lymphovascular space involvement. Three of them had nonendometrioid tumors. CONCLUSION: Careful intraoperative and preoperative evaluation of the endometrium must be the sine qua non for patients with atypical endometrial hyperplasia. It is reasonable to do frozen section at the time of hysterectomy for atypical endometrial hyperplasia, and if grade 2/3 of nonendometrioid cancer with lymphovascular space involvement is found, complete surgical staging should be performed.

Fibrocystic disease of vulvar ectopic breast tissue. Case report and review of the literature.

INTRODUCTION: Mammary glands located in the vulvar region have been named as ectopic breast tissue or anogenital mammary glands by different authors. Literature on pathologies of ectopic breast tissue located in the vulvar region is rare. Most of the reports are about the malignancies arising from this ectopic tissue. CASE REPORT: We report a case of fibrocystic disease of the mammary glands in the vulva in a 25-year-old pregnant woman. Her disease was exaggerated during pregnancy. CONCLUSION: Ectopic breast tissue in the vulva is a rare entity and fibrocystic disease of this tissue has rarely been reported in the English literature.

Placental site trophoblastic tumor in a patient with brain and lung metastases.

Placental site trophoblastic tumor is a rare neoplasm that arises from intermediate trophoblasts and shows diversity of biological behaviors, resulting in the absence of consistency in treatment modalities. A case of placental site trophoblastic tumor that extended to the cervix, with primary manifestation of amenorrhea and yellow foul-smelling vaginal discharge, is presented. Total abdominal hysterectomy was performed initially, and serial measurements of human chorionic gonadotropin levels were obtained. She was admitted with metastases to brain and lung 1.5 years after surgery. Combination chemotherapy (etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine) and radiotherapy were administered. There was no significant response to chemoradiotherapy. Despite changing chemotherapy regimen, she is still alive with progressive disease.

The prognostic value of nuclear grading and the revised FIGO grading of endometrial adenocarcinoma.

The purpose of this study was to determine a convenient method for the modification of architectural grade by nuclear features and to evaluate the prognostic significance of the new International Federation of Gynecology and Obstetrics (FIGO) grading system by studying 288 patients with endometrioid endometrial carcinoma. All patients were subjected to initial surgical exploration and staging by 1988 FIGO guidelines. Three different grading systems were evaluated for their prognostic value: architectural, nuclear, and FIGO combined systems. All three grading systems significantly predicted poor survival, but only the FIGO grade (p < 0.001), stage (p < 0.001), and cervical involvement (p = 0.04) remained significant in multivariate analysis. In the architectural grade 2 group, the 5-year survival rate for 39 patients with grade 1 or 2 nuclei was 87%, compared with 66% for 35 patients with grade 3 nuclei (p = 0.03). In the architectural grade 1 group, the 5-year survival rate for 84 patients with grade 2 nuclei was 93% without significant difference from the original group (96%). FIGO grade 3 tumor predicted 70% of deaths (29/41), whereas architectural grade 3 tumor detected 41% (17/41) of deaths (p = 0.001). In conclusion, in determining the FIGO grade, upgrading of architectural grade 1 or 2 tumors by grade 3 nuclei was the most reliable method. The new FIGO grading system was prognostically superior to the previously used architectural grading system.

The influence of cytoreductive surgery on survival and morbidity in stage IVB endometrial cancer.

The purpose of this study was to detect possible survival advantages of surgical cytoreduction and different adjuvant treatment regimens for stage IVB endometrial cancer patients, and also to evaluate the prognostic importance of surgico-pathological risk factors and surgical morbidity rates. Thirty-seven FIGO stage IVB endometrial cancer patients treated at the Hacettepe University Hospital between 1977 and 1998 were included in this study. Clinical data were obtained from the private oncology files and all specimens were re-evaluated by the co-author pathologist. Optimal cytoreduction was defined as a surgical procedure leaving the patient with < or =1 cm residual disease in maximal diameter. All patients were subjected to initial cytoreductive surgery, but it had been achieved for 22 (60%) patients. Fourteen (38%) patients received both radiotherapy and chemotherapy, 10 (27%) patients received only radiotherapy and the other 10 (27%) patients received only chemotherapy. Three patients refused any type of adjuvant therapy. The median survival of the suboptimally cytoreduced patients was 10 months, while the median survival in the optimal group was 25 months (P = 0.001). In optimal cytoreduction group, the median survival for 12 (55%) patients without visible tumor was 48 months compared to 13 months in 10 (45%) patients with visible tumor. As an adjuvant treatment, concomitant cisplatin and radiotherapy revealed 54 months median survival compared to 15 and 13 months in patients treated with only radiotherapy and only chemotherapy, respectively. By univariate analysis, extra-abdominal metastases, suboptimal cytoreduction, visible tumoral mass after cytoreduction, pelvic-para-aortic lymphatic metastases, and cervical invasion were found to be significant predictors of poor survival. In multivariate analysis, optimal cytoreduction, concomitant cisplatin-radiotherapy treatment, and extra-abdominal metastases were significant. Morbidity was mild in six (16%), and severe in nine (24%) patients. We conclude that optimal cytoreduction achieved significant survival benefit for stage IVB endometrial cancer patients with a reasonable surgical morbidity rate. As an adjuvant treatment, concomitant cisplatin and radiotherapy was the best choice.

Ovarian lymphomas. A clinicopathological analysis of 10 cases.

Analysis of 10 cases of Non-Hodgkin's lymphoma with initial manifestation in the ovaries is presented with the histologic and immunohistochemical findings.

Disseminated peritoneal leiomyomatosis. A benign entity mimicking carcinomatosis.

Disseminated peritoneal leiomyomatosis (DPL) is a rare entity, occurring primarily in premenopausal women. The lesion is characterized by numerous subperitoneal nodules of benign smooth muscle proliferations which usually mimics the macroscopic appearance of the peritoneal carcinomatosis. We report a case of DPL and multiple uterine leiomyomas, occurring in a 50 year old premenopausal woman who was on oral contraceptives for the last three years. In order to diagnose this entity clinicians and pathologists have to be alert and collaborative during the intraoperative frozen section consultation.

Search for problem areas in endometrial biopsies to achieve quality assurance.

The aim of this study was to underline the frequently seen problems in diagnosing the lesions seen in the hyperplasia-carcinoma sequence by evaluating the variances between the observers. Four pathologists re-evaluated 137 endometrial biopsies and grouped them into diagnostic categories. The results were analyzed by Kappa statistics. Full agreement was reached in 89 cases (64.96%), with Kappa values ranging between 0.63-0.74. Three observers rendered the same diagnosis in 34 (24.81%) cases, and only one pathologist disagreed. Two or more observers held different views in 16 cases (10.95%). The problem areas were as follows: criteria distinguishing simple hyperplasia from other benign lesions, discrimination between atypical hyperplasia and carcinoma, and decision-making regarding the presence of atypia. There was a tendency towards overdiagnosis of hyperplasia in our department. Since the progression to carcinoma is a sequential event, borderline cases will exist if categories based on simple and clear cut off points are not defined.

Fibroadenoma of the vulva.

A well-circumscribed mass was excised from the vulva of a 37-year-old woman. Histological and immunohistochemical findings showed the characteristic features of fibroadenoma of breast. The concepts about the histogenesis of this lesion were discussed.

A case of late infantile neuronal ceroid lipofuscinosis associated with precocious puberty.

Neuronal ceroid lipofuscinosis is one of the hereoffegenerative diseases for which clinical and neuropathologic findings are well documented. We present a patient with late infantile neuronal ceroid lipofuscinosis with true precocious puberty; to our knowledge, this association has not been reported before. The association could be due to an underlying disturbance of hypothalamic-pituitary gonadal function, or to coincidence.

Skinning vulvectomy for the treatment of vulvar intraepithelial neoplasia 2-3: a study of 21 cases.

Twenty-one cases of patients with vulvar intraepithelial neoplasia (VIN) 2-3 were reviewed. The mean age at diagnosis was 45.4 years. All of the patients presented with vulvar pruritus. Five of the patients had hypertension, two had coronary heart disease and two had diabetes mellitus as complicating medical illnesses. None of the patients had history or evidence of vaginal intraepithelial neoplasia (VAIN) or cervical intraepithelial neoplasia (CIN), and only one patient had invasive cervical cancer at diagnosis. Provided the histology confirmed VIN, the patients were subjected to a skinning vulvectomy procedure. Of the patients, 15 (71.4%) had VIN 2, and the remaining 6 (28.6%) had VIN 3 at preoperative evaluation. Histologic analysis of skinning vulvectomy specimens revealed no evidence of neoplasia in three patients (14.2%). Multifocality was observed in only three patients (14.2%). The areas involved were the perineum in four patients, labia in 15 and clitoris in two patients. Associated vulvar pathologies were condyloma acuminata in one, squamous vulvar hyperplasia in three and lichen sclerosus with squamous hyperplasia in one patient. The complications of the procedure included febrile morbidity in three patients and minor wound break-down in one patient. None of the patients in this series experienced recurrence. Skinning vulvectomy seems to have a high success rate in treatment of VIN 2-3 with minimal postoperative complications and satisfactory cosmetic results. However, observation of only three patients with multifocal lesions as well as no patient with invasive cancer adds credence to an ablative procedure after appropriate evaluation under colposcopy.