Proliferative Brenner tumor of the ovary. clinicopathological study of two cases and review of the literature.

BACKGROUND: Ovarian Brenner tumors are rare epithelial tumors that account for 1%-2% of all ovarian neoplasms. They can be subdivided into benign, borderline or proliferative, and malignant neoplasms. In the vast majority of cases, these lesions are benign. Tumors of borderline malignancy are less frequent and only about 1% of Brenner tumors are malignant. We present two cases of Brenner tumors with borderline malignancy which were treated in our Department together with a review of the literature. CASES: A 50-year-old, gravida 1, para 1, patient was admitted for abnormal vaginal bleeding. Clinical examination, abdominal ultrasound (US), and computed tomography (CT) revealed a cystic multilobulated tumor of the right ovary with solid elements measuring 20 x 19 x 15 cm in diameter. In the other case a 70-year-old, gravida 2, para 2, patient presented with severe urinary difficulties. Palpation revealed a mobile abdominopelvic tumor 10 x 15 in diameter. US and CT exhibited a cystic tumor with multiple solid elements and calcifications of the left ovary. Both patients underwent exploratory laparotomy. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and total omentectomy were performed in both cases, while pelvic lymphadenectomy was decided only in the second case. Histologically, in both cases the diagnosis confirmed borderline Brenner tumor. CONCLUSION: Although Brenner tumors are rare and the majority of them are benign, the correct histological diagnosis at frozen section with identification of the small proportion of malignant tumors, allows the extent of the operation to be adapted if needed.

Preoperative work-up of early cervical cancer (stages Ib-IIa).

OBJECTIVE: To determine the effectiveness of preoperative investigations in early cervical cancer. MATERIALS: We retrospectively reviewed the medical records of 309 patients with previously untreated early cervical carcinoma who completed pretreatment evaluation at "St. Savas" Cancer Hospital of Athens and "Metaxas" Memorial Hospital of Peireas between January 1986 and September 1, 2000. Ages ranged from 18-77 years old with a mean age of 48 and S.D. of 12.25. FIGO staging was Ib (200 pts.), IIa (105 pts.), IV (4 pts.). Histologic type was squamous (267 pts.), adenoid (35 pts.), adenosquamous (7 pts.). The patients were clinically examined and routinely evaluated with blood work-up, chest X-ray, IVP, abdominal CT scan, barium enema, sigmoidoscopy, cystoscopy, and/or urine cytology. Patients with early stage cervical carcinoma were treated with Wertheim-Meigs radical hysterectomy and pelvic lymphadenectomy, while those with advanced stage cervical carcinoma were treated with radiotherapy and chemotherapy. RESULTS: In urinary tract investigation, CT showed a sensitivity of 100% and a specificity of 99.67%. In gastrointestinal tract investigation CT showed a sensitivity of 50% and a specificity of 99.67%. When we compared the histologic findings of the pelvic lymph nodes that were extracted in surgically treated patients with the preoperative CT findings, we found that CT had a sensitivity of 63.33% and a specificity of 88.57%. CONCLUSION: In our series of patients with early stage cervical carcinoma, imaging and endoscopic tests added limited information over pelvic examination and altered in four cases (1.29%) the choice of the appropriate treatment modality. CT scans proved adequate in this series of patients in the evaluation of the bladder and colon. All other tests could have been performed only when CT was suspicious of invasion. Moreover, CT served as a baseline examination for future comparative studies in the follow-up of patients.

Tamoxifen associated uterine pathology in breast cancer patients with abnormal bleeding.

The purpose of this study was to evaluate the underlying pathology in breast cancer patients treated with tamoxifen who present with abnormal bleeding. A total of 56 cases were studied and the histopathologic features of 50 curettage and 18 laparotomy specimens were reviewed. All patients were under tamoxifen treatment (10-40 mg daily) for a period ranging from 5 months to 15 years. Cervical and endometrial polyps were the most common finding in the D and C material (44%). Hyperplasia was the most frequent feature identified at hysterectomy, often combined with leiomyomas, adenomyosis and ovarian tumors. Five primary adenocarcinomas of the endometrium, most of them Stage I beta, Grade I minimally invading, were found as well. These data support the hypothesis that tamoxifen exerts a proliferative estrogen-like effect on the uterus. Abnormal bleeding in women under TAM treatment warrants prompt investigation and careful follow up of the patients.

Malignant ovarian neoplasms. The place of conservative surgery.

Even though radical surgery is the treatment of choice in malignant neoplasms, a conservative approach may be considered in young patients who wish to preserve fertility, provided well-defined criteria are met and survival is not jeopardized. Unilateral, stage I, borderline (BT), germ cell (OGCT), sex cord stromal tumors, and grade I epithelial cancer can be treated with unilateral salpingoophorectomy (USO). If bilateral ovarian involvement is present, bilateral salpingoophorectomy (BSO) and preservation of the uterus can be considered. Cystectomy is rarely practiced, because of published contraindications, in borderline tumors. Complete surgical staging is mandatory in all cases regardless of the type of surgery (USO or BSO). Conservative management of more advanced disease is considered in a few BT and OGCT cases, provided it can be combined with successful cytoreduction. Adjuvant chemotherapy is necessary in almost all OGCT and epithelial cancers, although its role in BT and sex cord tumors is unspecified yet. Current knowledge suggests that conception is possible after conservative management for malignant ovarian neoplasms and chemotherapy does not cause obvious genetic malformations in the newborn.

Human papillomaviruses in cervical cancer I. HPV-16 and 18 predominate in the Greek population.

Human papillomaviruses (HPV) and their role in carcinogenesis have been the subject of extensive investigation Specific types of HPV have been associated with cervical carcinoma HPV 16 and 18 are mainly associated with malignant progression and considered "high risk" viruses Using Southern blot analysis and in situ hybridization we investigated the presence of papilloma viruses in cervical carcinoma patients as well as appropriate controls. The results presented here support the aetiological role of HPV 16 and 18 in cervical carcinoma and demonstrate the prevalence of these viruses in Greek women. The role of viruses in carcinogenesis in well established in almost all species from fishes, to birds, to mammals. Although not well circumstantiated, viruses probably play as-great a role in human cancer as in other species. The role of human papillomaviruses (HPV) not only in benign proliferations, but also in a number of malignancies has long been postulated (1,2). Presently over 20 HPV types have been identified and there is evidence now associating specific types with certain human anogenital cancers, notably cervical cancer (3,4). Advance neoplasias such as squamous cell carcinomas are associated with types, 16,18 and 31, with type 16 prevailing in these lesions (5,6). In this paper we shall present evidence which extends and confirms that previously reported on the prevalence of HPV 16 and 18 in Greek women.

Human papillomaviruses in cervical cancer: II. Application of PCR and in situ hybridization and HPV significance.

Human papillomaviruses especially type 16 and 18 are associated with cervical cancer. These viruses encode transforming proteins which are capable of binding and form complexes with p53 protein. Tumour-tissue samples from women with cervical cancer as well as normal controls were analysed for the presence of HPV and the expression of p53 by in situ hybridization and PCR analysis. The results showed that HPV 16 and 18 predominated in all pathological conditions and that p53 expression was related to the presence of certain types of HPV. The significance of HPV in cervical carcinoma is well demonstrated.

"Butterfly" operation vs triple incision technique in vulvar cancer. a comparison of morbidity and clinical outcome.

Two groups (group A = 25 cases and group B = 34 cases) of vulvar cancer patients, treated with a modified "butterfly" operation (MBO = group A) and a triple incision (TI = group B) technique, were evaluated retrospectively. The aim was to compare the two operative methods, regarding perioperative morbidity and clinical outcome. The histopathologic and clinical characteristics of the patients were comparable, in the two groups. The hospitalization period was significantly shorter in group B (TI), both when primary (22 vs 34 days, p < 0.01) or secondary (41 vs 55 days, p < 0.05) healing occurred. Local recurrences were quite similar in number (A = 5/25, B = 6/34) and were successfully treated. No relapses in the remaining skin bridges were observed in group B. The overall survival was similar in the two groups (A = 64%, B = 63%). However, LN positive cases had a better (p < 0.05) survival when treated by MBO (48% vs 23%).

Cytogenetic findings in uterine epithelioid leiomyomas.

Epithelioid leiomyomas of the uterus, unlike ordinary leiomyomas, show substantial epithelial differentiation. No chromosome abnormalities have been reported in uterine epithelioid leiomyomas before. We analyzed short-term cultures from five such tumors and detected abnormal karyotypes in four. A del(7) (q21.2q31.2) was found in two tumors, in one as the only change and in the other as a secondary aberration acquired during clonal evolution. Rearrangement of chromosomal band 12q15, another of the cytogenetic hallmarks of ordinary uterine leiomyomas, was seen in the form of a t(10;12) in one tumor. Band 17q21 was involved in structural aberrations in two cases. The data we present indicate that epithelioid leiomyomas are fundamentally similar cytogenetically, and hence presumably also pathogenetically, to the much more common smooth muscle-differentiated uterine myomas. The only differences hinted at are that epithelioid tumors may be karyotypically more complex and more often have rearrangements of 17q21.

Chromosome analysis of uterine adenomyosis. Detection of the leiomyoma-associated del(7q) in three cases.

Adenomyosis is a uterine disease whose defining characteristic is the presence deep in the myometrium of endometrial glands and stroma. The condition is believed to arise from inordinate downward growth by contiguity from the endometrium rather than from in situ metaplasia or neoplasia. No acquired chromosome abnormalities have been associated with adenomyosis before. We analyzed short-term cultures from three cases and detected in all of them a del(7) (q21.2q31.2), a karyotypic anomaly that has hitherto been found repeatedly only in uterine leiomyomas. The cytogenetic similarity to leiomyoma suggests that the del(7q) was present in the mesenchymal or, more precisely, smooth muscle cells of the adenomyosis lesions. The very fact that clonal chromosome abnormalities were present questions whether the prevailing understanding of adenomyosis pathogenesis is adequate; the cytogenetic data would better fit a model of the disease envisioning the intramyometrial endometrial foci as having arisen through a neoplastic process.

Pelvic lymphocysts after radical hysterectomy and lymphadenectomy.

Five cases (5.5%) of lymphocysts were diagnosed and treated, among 80 type III modified radical hysterectomies performed for cervical cancer St. Ia2-IIa, in the last 6 years. Identification was initially made by palpation and confirmed by CT or US, in 4/5 cases in the first 2 postoperative months. Pelvic pain, fever and pressure symptoms were the most common clinical findings. A conservative approach was successful in 4/5 cases. Spontaneous regression was observed in one, while needle aspiration under radiologic guidance with (1/3) or without (2/3) tube insertion was applied in the rest. Conservative treatment failed in the last case presenting with a 12 cm cyst. An intestinal fistula developed, necessitating partial resection of the ileus and marsipulization. The complicated course of this patient's disease may indicate that a more aggressive treatment is warranted for large persisting cysts located in the irradiated field.

Chromosome aberrations and expression of ras and myc oncogenes in leiomyomas and a leiomyosarcoma of the uterus.

Twenty eight leiomyomas and one leiomyosarcoma were cytogenetically analysed and also examined for ras and myc oncoprotein expression. Chromosome alterations were found in seven leiomyoma cases. In four of them 12q14-15 was involved. P21 product of H-ras and P62 product of c-myc genes were detected in paraffin embedded parallel tissue sections. A high expression of H-ras was apparent in most tumors. C-myc expression was weak or negative in most leiomyomas with normal karyotype while on the contrary in three out of seven cases with abnormal cytogenetic findings the gene product stained moderately positive. Considerable chromosome abnormalities and oncogene overexpression were also identified in the leiomyosarcoma.

Evaluation of lactate dehydrogenase activity as an index of cervical malignancy.

The diagnostic accuracy of an investigational test for cervix cancer screening is studied. The method involves a vaginal tampon that changes colour in relation to LDH activity and can detect preinvasive and invasive cervical lesions. The test was applied in 50 women with CIN, 50 women with histologically proved cervical cancer and in 500 women with no history of malignancy. The test was positive in 54% of CINs and 86% of cervix cancer patients, while it was not specific in 16% and 4% respectively. Among 268 healthy controls the test results were negative in 77.99% and false positive in 12.31%. The test can be performed any day of the menstrual cycle apart from the time of menstruation. It can also be performed, without any serious problem of misinterpretation in women suffering from myomas, vaginal relaxation or menstrual disorders. On the contrary, the test should be avoided if vaginitis or cervicitis are present, since false positive conclusions might be drawn. The test results suggest that the sensitivity of this method was 77% and the specificity 86% if we exclude the benign conditions that influence or possibly influence the colour indication of the tampon.

Complex chromosome rearrangements involving 12q14 in two uterine leiomyomas.

Cytogenetic analysis of short-term cultures from 10 uterine leiomyomas revealed normal karyotypes in 8 and clonal complex chromosome rearrangements in 2 tumors. In both leiomyomas with clonal abnormalities, 12q14, but not 14q22-24, was involved in translocations with 1q43 in one tumor and with 12q24 in the other. Additional chromosome abnormalities were found in both cases: 1-5 rings and monosomy of chromosome 9 in case 1, and complex numerical and structural abnormalities of chromosomes 1, 6-8, 11, 13, 16, 17, and 22 in case 2. The consistent cytogenetic rearrangement of 12q14 in uterine leiomyomas, sometimes without concomitant 14q changes, indicates that a gene of critical importance for leiomyoma development may be found in this band.

Therapeutic effect of bovine albumin in the experimental fat embolism syndrome.

The toxic effects of the free fatty acids (FFA) are responsible for the initiation and the clinical manifestations of the fat embolism syndrome (FES). Serum albumin binds to the FFA and by producing atoxic compounds it has a therapeutic effect on the syndrome. In this study we applied bovine albumin to 48 Sprague-Dawley rats which were previously submitted to intravenous infusions of FFA solutions (oleic, palmitic, stearic). The histopathologic lesions observed in their lungs were compared to those of 50 control animals suffering from the FES. The administration of 0.5% bovine albumin solution intravenously and 0.2% intraperitoneally, especially when it was synchronous to the FFA infusion and not metachronous, resulted in substantial and statistically significant therapeutic effects.

Monoclonal antibodies in ovarian tumor imaging.

Immunoscintigraphy of ovarian tumors by intraperitoneal administration of I131 HMFG2 monoclonal antibodies (mabs) was used in this study. The purpose was to evaluate the diagnostic potential of this non-operative imaging technique in detecting ovarian tumor nature and spread. Sixteen patients that received 500-1000 microCi of I131 labelled HMFG2 mabs were evaluated. The scans obtained were compared mainly with the macro and microscopic operative findings of the subsequent laparotomy. Immunoscintigraphy accurately scanned tumor spread in 7 out of 9 patients with known ovarian cancer. It also successfully revealed the malignant or benign nature of pelvic masses in 6 out of 7 patients examined.