Primary vaginal leiomyosarcoma, a rare tumour: case report and review

Primary vaginal leiomyosarcomas (pvLMS) are rare, recurrent tumours accounting for ca. 2% of all vaginal cancers. The etiology is still unknown, the prognosis is poor and there is no consensus guideline on its management. Diagnosis is usually made during the 5th decade due to the presence of a vaginal mass or nodule [1-2]. Current medical literature reports about 200 cases (PubMed®); only 3 studies have considered the ultrastructure [2-4]. Herein a pvLMS is presented and discussed. A nodular, 25 x 23 x 28 mm-mass, infiltrating the urethra but not the rectovaginal septum, was widely excised from the superior vaginal wall of a 58-year-old previously hysterectomized woman. Macroscopic images and MRI were performed. Iliac lymph nodes and HMB45 were negative. The sample was fixed and prepared for light microscopy, transmission (TEM) and scanning (SEM) electron microscopy. Semithin sections showed a storiform pattern of spindle shaped cells with blunt-ended nuclei. Cells arranged in interwoven fascicles within a dense and richly vascularised stroma (neoangiogenesis). Some atypic mitotic figures and focal necrosis were seen. SEM evidenced a dense collagenous stroma with numerous microvessels. TEM showed neoplastic and pleomorphic cells with complex cytoplasm projections containing paranuclear crowds of dilated mitochondria, free ribosomes and a well-developed rough endoplasmic reticulum. Nuclei were large, mostly hyperchromatic, usually indented, with prominent nucleoli and nucleolonema. The dense intercellular space contained dense bundles of collagen fibers. A high and reactive endothelium lined blood vessels. After 4 follow-ups, the patient is fine and without recurrence. Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as it was for this case. As there are different kinds of LMS, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice. References [1] Umeadi et al. (2008) Vaginal leiomyosarcoma. J Obstet Gynaecol 28(5): 553-554. [2] Tobon et al. (1973) Primary leiomyosarcoma of the vagina. Light and electron microscopic observations. Cancer 32(2): 450-457. [3] Akhtar et al. (1978) Primary leiomyosarcoma of the vagina: light and electron microscopic study of a case with review of literature. Tex Med 74(9): 67-71. [4] Rastogi et al. (1984) Primary leiomyosarcoma of the vagina: a study of five cases. Gynecol Oncol 18(1): 77-86

Personalized Treatment of Vulvar Cancer

Vulvar cancer (VC) accounts for 5% of all gynecologic cancer and the most common histological type is squamous cell carcinoma (up to 90%

Primary vaginal leiomyosarcoma: A case report with complete morphological, immunohistochemical and ultrastructural study

Objective: Primary vaginal leiomyosarcomas (LMS) are rare, easily recurrent tumours with an unknown etiology; the prognosis is poor and there is no consensus guideline on their management. Case report: A nodular, 25 × 23 x 28 mm-mass, infiltrating the urethra, was found in a 58-year-old woman. A biopsy showed a LMS of the vagina that was positive for vimentin, alpha-smooth muscle actin, caldesmon, desmin, p16 and p53. An anterior pelvic exenteration was performed. The sample was fixed and prepared for light microscopy, transmission and scanning electron microscopy, confirming the diagnosis of LMS. Conclusions: Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as in this case. As there are different kinds of malignant mesenchymal tumours, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice and surgical resection is generally the gold standard in these cases. Keywords: Electron microscopy, Immunohistochemistry, Leiomyosarcoma, Light microscopy, Vagin

Ultrastructural changes of the extracellular matrix in human uterine leiomyoma and squamocellular cervical carcinoma

Leiomyomata are the most common benign uterine tumors and are a major cause of gynecological morbidity and infertility. Squamocellular cervical carcinoma, in turn, is a common gynecologic malignancy. However, their etiopathogenesis remains poorly understood. The aim of this study was to characterize from an ultrastructural point of view the changes occurring in the extracellular matrix (ECM) of human uterine cervices with leiomyoma or squamocellular carcinoma. Eight women, aged 45-58, underwent laparoscopic myomectomy (n=5) or vaginal hysterectomy (endometrial carcinoma, n=3). Samples were processed for transmission electron microscopy, and digital images were obtained from either semithin and thin resin-embedded sections. The lamina propria of the uterine cervix with leiomyoma was generally filled by a dense and disarranged ECM, wherein twisted collagen fibers with a regular banding and diameter, predominated. Collagen tended to be closely-packed and compartmentalized into large lacunar-like spaces by very thin (ca. 0,25 μm) and long (> 10 μm) cytoplasmic processes originating from myofibroblastic, smooth muscle or interstitial Cajal-like cells. Fibril-forming channels or fibripositors (Birk et al., 1989; Starborg et al., 2008), were sometimes identified and consisted of isolated collagen fibrils surrounded by plasma membrane. Very electron dense core-like aggregates (1-2 μm length x 1-1,5 μm width) scattered within the lacunar-like spaces. Cores consisted of structures whose diameter was similar to that of collagen (ca. 71 nm) but showing a gradient of decreasing electron density from the core itself towards peripheral mature collagen fibers; in between these fibers, intermediate electron dense ones laid (fibrillin microfibrils?). Leiomyoma showed more and denser ECM with respect to carcinoma, the latter evidencing numerous and heterogeneous, actively proliferating cancer cells, leaving few and small intercellular spaces wherein macrophages, mast cells and plasma cells, were sometimes observed. The abnormal orientation of collagen fibers in leiomyoma contributes to the fibrotic and stable ECM and may also facilitate local tumor invasion. Therapy in these cases should target ECM dissolution, rather than solely inhibiting cell proliferation

Venous endotelin-1 (ET-1) and brain natriuretic peptide (BNP) plasma levels during 6-month bosentan treatment for pulmonary arterial hypertension

Objective: Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan. Setting and patients: Twenty-five patients with PAH (idiopathic n = 16, CTD n = 9) in WHO functional class II-III were included in this study. After initial evaluation, patients' WHO class, 6-minute walking-test (6MWT), ET-1 and BNP venous plasma levels were assessed at baseline and after 6-month bosentan therapy. To evaluate whether the ET-1 levels could influence the clinical response to bosentan, data were analyzed for the whole population which was stratified according to high and low ET-1 plasma levels (on the basis of the baseline median value of ET-1 plasma: Gr.1 18.7 pg/ml). Results: Study population included patients with moderate-severe PAH. After 6-month of treatment we observed a significant increase in 6MWT distance (from 435 ± 85) m to 467 ± 77 m, p > 0.001) and an improvement in WHO class (from 2.4 ± 0.5 to 2 ± 0.6 p > 0.01), with a significant decrease in BNP (from 87 ± 33 pg/ml to 67 ± 41 pg/ml, p = 0.006) and a trend towards lower ET-1 plasma levels (from 17.7 ± 5 pg/ml to 16 ± 6 pg/ml, p = ns). Improvement in effort tolerance (Δ distance) was not correlated to modification in ET-1 (ΔET-1) and BNP (ΔBNP) plasma levels, while we found a significant correlation between ΔET-1 and ΔBNP (r = 0.63, p = 0.0006). Analyzing the subpopulation, Gr.2 patients were older (Gr.1: 41 ± 10 years vs Gr.2: 50 ± 9 years, p = 0.04), had less effort capacity (6MWT distance, Gr.1: 469 ± 76 m, vs Gr.2: 398 ± 82 m, p = 0.03), and showed a trend towards higher BNP values (Gr.1: 82 ± 41 pg/ml vs Gr.2: 92 ± 23 pg/ml, p = 0.051), but no significant differences in pulmonary hemodynamics. After the 6-month treatment both groups showed a significant improvement in 6MWT (Gr.1: + 32 ± 24 m, Gr.2: + 32 ± 21 m p = 0.05) without differences between groups. WHO class had a trend towards lower class (Gr.1: - 0.5 ± 0.5, Gr.2: - 0.3 ± 0.4 p = 0.15) in both groups. BNP plasma levels showed a significant decrease only in Gr.2 (Gr.1: - 6 ± 41 pg/ml, Gr.2: - 34 ± 19 pg/ml p = 0.02); similarly ET-1 plasma levels showed a trend towards a decrease only in Gr.2 (Gr.1: 0.2 ± 4.6 pg/ml, Gr.2: - 3.8 ± 6.6 pg/ml p = 0.09). Conclusions: Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy. © 2008 Elsevier B.V. All rights reserved

Prevention, Screening, Treatment and Follow-Up of Gynecological Cancers: State of Art and Future Perspectives

Objective: This study aims to analyze the available data on prevention and early diagnosis in gynecological cancers. Mechanism: A comprehensive search was performed in the PubMed (MEDLINE), EMBASE, SCOPUS and Web of Science databases. Findings in Brief: To date the prevention programmes of all degrees exist exclusively for cervical cancer. Human Papilloma Virus (HPV) vaccination prevents from infection and development of precancerous lesions and contributes significantly to the deflection of the incidence of cervical cancer. Screening for HPV-related lesions is worldwide performed by cervical smear (Pap-test) and HPV test. Finally, tertiary prevention is aimed at the treatment of previously diagnosticated lesions with the aid of surgery, chemotherapy, radiotherapy and immunotherapy. Unfortunately, to date the prevention programmes of other gynecological tumors have not reached a good performance; indeed, the primum movens that leads to the development of such neoplasms has not been identified yet. Actually, no screening programs for the early diagnosis of endometrial cancer are available, however, it is recommended the adoption of a healthy lifestyle and a balanced diet. Diagnostic biomarkers would be helpful for screening asymptomatic high-risk women, but histopatological examinations remain the gold standard for diagnosis of endometrial cancer. Similarly, there are no screening tests for the diagnosis of ovarian cancer. In recent years many steps forward have been made in this field and new perspectives have been presented, however, additional investigation is needed to optimize the duration and timing of treatment, examine its cost-effectiveness, and identify potential tumor or host biologic factors predictive of the efficacy and adverse events. Finally, there are no primary and secondary prevention for vulvar cancer so patients should be invited to self-examination and pay attention to the presence of symptoms. Conclusions: Are the available screening programs for the diagnosis of gynecological carcinomas sufficient? The prevention and the diagnosis of precancerous lesions is the goal to be achieved for all gynecological cancers in order to improve patient outcomes, reduce the costs for managing the disease and prolonged follow up

Cyclophosphamide "metronomic" chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer

BACKGROUND: Evaluation of the clinical efficacy and tolerance of metronomic chemotherapy as salvage therapy in a young patient with advanced, platinum resistant, ovarian carcinoma and bad performance status. CASE PRESENTATION: We tried palliative chemotherapy with daily low dose oral cyclophosphamide with a patient suffering from stage IIIC ovarian cancer that responded to daily cyclophosphamide (CTX) after no response to chemotherapy with paclitaxel and carboplatin as first line and progression after second line with topotecan. The progression-free survival time on daily low dose oral cyclophosphamide treatment was 65 months without side effects. She was well during the chemotherapy and lived a normal working and social life. CONCLUSION: We think that use of low dose of oral CTX should be investigated further as a strategy against tumour progression after standard chemotherapy in patients who are platinum resistant with poor performance status

Prognostic factors in uterine adenosarcoma: subanalysis of the SARCUT study

ObjectiveThe purpose of the study was to analyse the role of prognostic factors on the risk of recurrence and overall survival of patients with uterine adenosarcoma.MethodsA retrospective international multicentre study involving 46 centres collected 32 cases of uterine adenosarcoma, and these cases were included in the present subanalysis. Clinical and demographic features and tumour characteristics were gathered, as well as information on treatment and relapse. Disease-free and overall survival were analysed.ResultsThe 5-year disease-free survival (DFS) was 85.3% and the 5-year overall survival (OS) rate was 89.5%. The risk factors significantly associated with overall survival were age (HR 1.09, 95% CI 1.03–1.15; p = 0.004) and FIGO stage II–III (HR 17.75, 95% CI 2.87–109.93; p = 0.002). Patients who experienced early relapse (within 12 months) had a tumour size >30 mm and advanced stage. The majority of recurred cases were treated with radiotherapy or surgery and obtained a good response rate.ConclusionThe most significant prognostic factors in uterine adenosarcoma were age and FIGO stage and, indirectly, tumour size at diagnosis. The use of secondary surgery and/or radiotherapy could help in prolonging the disease-free status of the patients

Human Papilloma Virus prevalence and type-specific relative contribution in invasive cervical cancer specimens from Italy

Background: Cervical cancer represents an important global public health problem. It is the 2(nd) most common cancer among women worldwide. Human Papillomavirus (HPV) infection is now well-established as a necessary cause of invasive cervical cancer (ICC) development. Only a few studies on HPV prevalence and type-specific distribution in ICC have been conducted in Italy. Aim: To describe the prevalence of HPV and the HPV type-specific distribution in ICC cases identified in Rome, Italy. Methods: 140 paraffin embedded tissue blocks of primary ICC diagnosed between 2001 and 2006 were identified at the Regina Elena Cancer Institute in Rome (Italy). HPV was detected through amplification of HPV DNA using SPF-10 HPV broad-spectrum primers followed by DEIA and then genotyping by LiPA(25) (version 1). Results: 134 cases were considered suitable for HPV DNA detection after histological evaluation; and overall, 90.3% (121/134) HPV prevalence was detected. 111 cases had a single HPV type, 4 cases had an uncharacterized type (HPVX) and 6 cases had multiple HPV infections. The five most common single HPV types among positive cases were: HPV16 (71/121; 58.7%), HPV18 (12/121; 9.9%), HPV31, HPV45 and HPV58 (5/121; 4.1% each). 2 (1.5%) of the single infections and 2 (1.5%) of the multiple infections contained low risk types. Statistically significant differences in the relative contribution of HPV18 were found when comparing squamous cell carcinomas with adenocarcinomas. Conclusions: HPV16 and HPV18 accounted for almost 70% of all the HPV positive ICC cases. The study provides baseline information for further evaluation on the impact of recently introduced HPV vaccines in Italy