Factors associated with outcome in liposarcomas of the extremities and trunk.

PURPOSE: Liposarcomas are malignant tumors that arise from primitive mesenchymal cells rather than mature adipose tissue. We aimed to evaluate the outcomes of patients with extremities and superficial trunk liposarcomas in relation to some clinicopathological factors. METHODS: Sixty-three surgically treated patients with liposarcoma, with mean age 53 years, were included in this study. The 5-and 10-year survival rates were analyzed with respect to local recurrences, distant metastases and death with the Kaplan-Meier method. Cox models estimated univariate and multivariate hazard ratios for each candidate predictor of interest. RESULTS: The 5-year overall survival was 77.8% (95% CI 65.5-87.3) and the 10-year overall survival was 63.5% (95% CI 50.4-75.3). The 5-and 10-year recurrence-free survival were 60% and 57%, respectively. The 5-and 10-year metastasis-free survival were 86% and 84%, respectively. In univariate analysis factors that were significantly associated with outcomes were grade III tumors, amputation procedures, use of chemotherapy and development of local recurrences. No significant association was observed in multivariate analysis. CONCLUSION: Patients with liposarcoma surviving for 5 years, have also a high probability to be alive at 10 years. The development of metastases is observed within the first 5-years from diagnosis. Metastatic disease after that period is rare. The possibility of local recurrence is not negligible after the 5th year of follow up.

Loop electrosurgical excision procedure in Greek patients with vulvar intraepithelial neoplasia.

OBJECTIVE: The aim of our study was to evaluate the therapeutic effectiveness of loop electrosurgical excision procedure (LEEP) in Greek patients with vulvar intraepithelial neoplasia (VIN). MATERIALS AND METHODS: Between January 2002 and January 2009, 55 women with histologically confirmed VIN usual type were included in our study. For the LEEP procedure we used a high frequency electrosurgical unit with at least 80 W output. The tissue was removed to the second surgical plane. Statistical analyses were performed using the SPSS-13 for Windows. RESULTS: Complete response rate at 12-month follow-up was 100%. Complete response rate at 48 months of follow-up was 80%. Recurrence rate at 48 months of follow-up was 20%. CONCLUSION: LEEP may constitute a valuable excisional method for the treatment of VIN. It provides an interpretable specimen of the whole lesion within a few minutes. It needs a short period of training and has low cost.

Expression of E-cadherin, beta-catenin and topoisomerase IIalpha in leiomyosarcomas

INTRODUCTION: The expression of E-cadherin, beta-catenin and topoisomerase II has been associated with clinical outcome of several cancers including sarcomas. We aimed to evaluate the expression of these markers in leiomyosarcomas (LMS). MATERIALS AND METHODS: Paraffin blocks of 19 primary, nonmetastatic LMS were analysed immunohistochemically for the expression of the above-mentioned markers with a cutoff level for positivity of 20% of cell staining. RESULTS: Expression of E-cadherin was negative in all LMS. Nuclear expression of beta-catenin was also negative in all cases, while positive cytoplasmic beta-catenin expression was observed in approximately half of the patients. The majority of LMS had expression of topoisomerase IIalpha, although only in 10 patients was this expression in more than 20% of tumour cells. From the analysed factors, tumour size was statistically significantly correlated with relapse-free survival. CONCLUSIONS: Further evidence with larger series is required in order to determine the implication of these markers in LMS (AU)

Adenoid cystic carcinoma of the Bartholin's gland in a young patient: eight-year follow-up.

Adenoid cystic carcinoma (ACC) of the Bartholin's gland is one of the rarest neoplasms of the female genital tract. Including this report there are 65 cases mentioned in the literature. We report a case of a 36-year-old woman who presented at our hospital after excision of the right Bartholin gland elsewhere which proved to be ACC. The therapy of this rare tumor has many controversial questions and dilemmas, especially in young patients. Our patient underwent surgical treatment only (hemivulvectomy and lymph node dissection) without radiotherapy and is free of disease eight years after.

c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications.

AIMS: Disruption of apoptotic cell death has been implicated in tumour aggressiveness in colonic carcinogenesis. The Fas-Fas ligand (FasL) system is involved in the execution of apoptosis induced by the immune system. c-FLIP protein constitutes an inhibitor of Fas and other (TRAIL) death receptor-mediated apoptosis. The aim of this study was to investigate the simultaneous expression of Fas, FasL and c-FLIP in relation to standard clinicopathological parameters and patients' outcome in colorectal cancer. METHODS AND RESULTS: Levels of Fas, FasL and c-FLIP protein expression were quantified immunohistochemically in paraffin-embedded tissues from 90 patients. Immunopositivity was detected for Fas, FasL and c-FLIP in 71%, 35.5% and 68.8% of cases, respectively. Concurrent expression of Fas/FasL was seen in 28 samples (31%), of which 24 (85.7%) also displayed c-FLIP positivity (P = 0.04). c-FLIP overexpression (> 10%) tended to prevail marginally in higher stage tumours (P = 0.09). Additionally, FasL and c-FLIP adversely affected survival on both univariate (P = 0.001 and P = 0.0024, respectively) and multivariate analysis [hazard ratio (HR) 3.491, P = 0.005 and HR 2.960, P = 0.036, respectively]. CONCLUSIONS: The frequent expression and coexpression of Fas, FasL and c-FLIP in colorectal carcinoma implicates c-FLIP as an inhibitor of the Fas-FasL-induced death pathway in these tumours. Moreover, c-FLIP conveys independent prognostic information in the presence of classical prognosticators.

Multiple cutaneous acral metastases in a woman with breast adenocarcinoma treated with pegylated liposomal doxorubicin: incidental or aetiological association?

This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.

First-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer.

The purpose of this study was to evaluate the efficacy and tolerance of combined treatment with docetaxel-cisplatin as first-line chemotherapy in patients with metastatic breast cancer (MBC). Consecutive eligible chemonaive patients received docetaxel 75 mg/m(2) on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks for 6 cycles, with prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on days 4-11. Thirty-two patients (64%) had received prior adjuvant chemotherapy; these included 16 (32%) who had received anthracyclines. In 50 evaluable patients with a median age (range) of 56 (31-72) years, the overall response rate was 68% (95% CI, 55-81%), with 7 (14%) complete and 27 (54%) partial responses. Stable and progressive disease was observed in 10 (20%), and 6 (12%) patients, respectively. The median duration of response was 10 months, and the median time to progression was 39 weeks. Grade 3/4 hematological toxicity included--neutropenia in 9 patients (18%), anemia in 2 (4%) and thrombocytopenia in 1 (2%). One patient (2%) with febrile neutropenia required hospitalization. Grade 3/4 nonhematological toxicities included nausea/vomiting in 18%, nephrotoxicity in 14%, asthenia (4%), and neurotoxicity (2%). Toxicity was common in older patients (>56 years). There were no treatment-related deaths. A combination of docetaxel-cisplatin with rHuG-CSF support is well tolerated and effective as first-line chemotherapy in MBC.

Ameloblastomas of the jaws: clinico-pathological review of 11 patients.

AIMS: The ameloblastoma is an uncommon benign odontogenic neoplasm of the maxillofacial region constituting less than 1% of tumours of the oral cavity. The purpose of this paper is to discuss and evaluate the surgical treatment and the outcome from a series of 11 patients with ameloblastomas. METHODS: Between the years 1995 and 2003, 11 patients (eight female and three male) aged 17-86 years (mean 52.7) suffering from ameloblastomas of the jaws were seen in our Department. RESULTS: Ten patients were treated surgically. In eight of those radical surgery was applied. Patients with maxillary tumours were subjected to hemimaxillectomy and local excision. Radical treatment with segmental resection of the mandible was performed in six patients with multilocular (solid) mandibular ameloblastomas, with immediate reconstruction of the defect. Follow-up ranged from 3 months to 7.5 years. CONCLUSION: Multilocular (solid) type of tumours should be approached with radical surgical treatment. Enucleation and rarely marsupialization can be applied selectively to unilocular ameloblastomas.

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Ovarian fibrothecoma associated with Meigs' syndrome and elevated serum CA 125.

Meigs' syndrome consists of a benign ovarian tumor accompanied by ascites and hydrothorax. Elevated serum CA 125 in postmenopausal women with a solid adnexal mass, ascites and pleural effusion is highly suggestive of a malignant ovarian tumor. We report on an unusual case of a benign fibrothecoma of the ovary associated with Meigs' syndrome and elevated CA 125 level in an 62-year-old white female. Although rarely, a benign ovarian tumor should be considered in the differential diagnosis of an adnexal mass associated with Meigs' syndrome and elevated serum CA 125 levels.

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

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.

Treatment of malignant colonic obstructions with metal stents and laser.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and safety of combined endoscopic therapy with self-expanding metallic endoprostheses and laser application in the management of malignant colonic obstruction. METHODOLOGY: Between March 1998 and September 2000, obstruction of the distal colon was diagnosed in a total of 11 patients (6 M, 5 F, age range: 67-87 years, mean: 73). The site of obstruction was located in the rectosigmoid colon (n = 6), in the sigmoid colon (n = 4) and in the descending colon (n = 1). The etiology of stenosis was colorectal adenocarcinoma (n = 8), ovarian cancer (n = 2) and infiltrating bladder carcinoma (n = 1). In all patients the tumor was considered non-resectable. Six patients had confirmed metastases, one refused colostomy and 4 were unable to undergo surgery. After radiological visualization of the proximal extent of the stricture, the stenosis was dilated with Savary-like (10 patients) and pneumatic balloon dilators (1 patient-descending colon). RESULTS: Stents were placed successfully in 10 patients. Prostheses migration distal to lesion, into the sigmoid colon, was observed in one patient (bladder cancer). A mild autoresolved bleeding was observed in 8 patients. Five patients remained free of clinical colonic obstruction until their death, which occurred 6-16 weeks (mean: 10) after stent placement. A moderate non-occlusive ingrowth of tumor into the stent lumen was documented in the other 5 cases. These patients were treated with introspective application of Diomed laser in a total of 16 sessions (4120-12,476 Joules each session, mean: 6258, power 10-14 W, interval between 2 sessions 6 weeks) and died of progressive disease without clinical signs and endoscopic findings of reobstruction 22-56 weeks (mean: 32) after stent placement. CONCLUSIONS: Metallic stent placement is an adequate palliative and cost-effective option, effective and save, in advanced colonic obstruction due to non-resectable tumors. It circumvents the need for colostomy and allows the patient a better quality of life. Delayed stent occlusion with tumor ingrowth requires a regular follow-up and can be treated with introspective laser ablation.

Unusual spread of liposarcoma.

BACKGROUND: The aim of our study was to investigate the unusual pattern of metastatic spread of liposarcoma. MATERIALS AND METHODS: We retrospectively studied thirty-two patients with liposarcoma (in seventeen located in the retroperitoneum and in fifteen in the extremities) who were managed at our institution over a ten-year period. Six patients with extremity liposarcoma developed local recurrence and or distal metastases and in three the site of the distal spread was other than the lungs. In only one patient with retroperitoneal liposarcoma we observed extra-pulmonary spread. The histologic type of all four cases with unusual spread was myxoid, with small areas of round cell differentiation in two cases. RESULTS: The survival of the patients after the initial recurrence was relatively prolonged (6, 1.5, 8 and 3 years with the last patient alive and well). CONCLUSION: Physicians should maintain a low threshold for initiating evaluation of relatively minor symptoms in patients with liposarcoma, as these symptoms may reflect the first manifestation of an extrapulmonary metastasis. Such an approach should result in earlier detection and hopefully improve survival for patients with liposarcoma.

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Long-term tamoxifen treatment: a possible aetiological factor in the development of uterine carcinosarcoma: two case-reports and review of the literature.

Two cases of uterine carcinosarcoma developing after long-term tamoxifen (TAM) treatment are presented. The patients, 67 and 72 years old, were treated with TAM for 6 and 7 years, continuously. They both developed an heterologous malignant mixed Mullerian tumor (mmMt). At laparotomy, an advanced stage of disease was found with peritoneal spread. In spite of the surgical and the postoperative treatment, they both died of disease, 3 and 10 months later. There are only 10, well documented, similar cases reported. Another 7 were identified in series of uterine malignancies developing after TAM treatment. Considerable evidence suggests that mmMt represents an epithelial cancer with sarcomatous dedifferentiation. Prolonged (> 5 years) TAM treatment may represent a causative factor in the development of this highly lethal disease (80% of the reported patients had a dismal prognosis). Large uterine polyps with special histological features, may represent an intermediate step in the tumor formation. Close follow-up of the patients is warranted.