Leiomiosarcoma cutáneo: características clínicas, histopatológicas y correlación pronóstica en 12 pacientes / Clinical and Histopathologic Findings of Cutaneous Leiomyosarcoma: Correlation with Prognosis in 12 Patients

INTRODUCCIÓN: El leiomiosarcoma de piel es una neoplasia maligna de estirpe muscular cuya baja incidencia dificulta el desarrollo de protocolos específicos de diagnóstico y manejo terapéutico. OBJETIVOS: Describir las características clínicas e histopatológicas de una serie de leiomiosarcomas cutáneos primarios y secundarios, junto con su correlación pronóstica. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y observacional. Se seleccionaron 17 casos de leiomiosarcoma cutáneo en 12 pacientes, diagnosticados entre el 1 de enero de 2000 y el 31 de diciembre de 2015. Se recogieron sus datos demográficos, características clínicas e histopatológicas, evolución y respuesta al tratamiento. RESULTADOS: Se reclutaron 5 varones y 7 mujeres, todos ellos mayores de 50 años al diagnóstico. Se recogieron 4 leiomiosarcomas dérmicos (4/17, 23%) en 4 pacientes, 2 leiomiosarcomas hipodérmicos (2/17, 11,5%) en 2 pacientes, y 11 metástasis cutáneas de leiomiosarcoma (11/17, 65%) en 6 pacientes. Las localizaciones más frecuentes fueron cuero cabelludo (7/17, 41%), miembros inferiores (3/17, 17%) y tronco (3/17, 17%). Durante el seguimiento, un 50% de leiomiosarcomas dérmicos recidivaron, un 50% de leiomiosarcomas hipodérmicos presentaron metástasis a distancia y 5/6 pacientes con metástasis cutáneas de leiomiosarcoma (83%) fallecieron a causa de su enfermedad. Limitaciones: Este estudio es una revisión retrospectiva de una serie de casos de tamaño limitado en un centro único. CONCLUSIONES: El leiomiosarcoma cutáneo es una neoplasia maligna poco frecuente. A la hora de adoptar una actitud diagnóstico-terapéutica en estos pacientes debemos tener en cuenta la marcada heterogeneidad pronóstica entre sus diferentes subtipos

INTRODUCTION: Cutaneous leiomyosarcoma is a malignant neoplasm derived from smooth muscle cells. Its low incidence hampers the development of specific protocols for diagnosis and treatment. OBJECTIVES: To describe the clinical and histopathologic characteristics of a series of primary and secondary cutaneous leiomyosarcomas and to determine how these characteristics correlate with prognosis. MATERIAL AND METHODS: We performed an observational, descriptive, retrospective study based on 17 cutaneous leiomyosarcomas in 12 patients diagnosed between January 1, 2000 and December 31, 2015. We recorded demographic data, clinical and histopathologic characteristics, outcome, and response to treatment. RESULTS: We included 5 men and 7 women, all aged more than 50 years at diagnosis. There were 4 cutaneous leiomyosarcomas (23%) in 4 patients, 2 subcutaneous leiomyosarcomas (11.5%) in 2 patients, and 11 skin metastases of leiomyosarcoma (65%) in 6 patients. The most frequently affected sites were the scalp (41%), lower limbs (17%), and trunk (17%). During follow-up, 50% of the cutaneous leiomyosarcomas recurred, 50% of the subcutaneous leiomyosarcomas presented distant metastases, and 83% of the patients with skin metastases of leiomyosarcoma died of their disease. Limitations: Ours was a retrospective review of a small case series at a single center. CONCLUSIONS: Cutaneous leiomyosarcoma is an uncommon malignant neoplasm. Our approach to diagnosis and therapy must take into account the marked heterogeneity in the prognosis of the various subtypes

Indications for morcellation in gynecologic surgery.

PURPOSE OF REVIEW: Minimally invasive gynecologic procedures, in particular laparoscopic hysterectomy and myomectomy, often require tissue morcellation. RECENT FINDINGS: Whether morcellated or not, myometrial cells can be found in the abdomen and pelvis after either laparoscopic or open myomectomy. Following morcellation, careful inspection for and removal of tissue fragments and copious irrigation and suctioning of fluid can remove residual tissue and cells without the use of containment bags. The dogma of not 'cutting-through' cancer is not correct for many surgical specialties and irrelevant with regards to leiomyosarcoma (LMS) and minimally invasive gynecologic surgery. Eliminating residual disease in the pelvis and abdomen should be the goal of myomectomy or hysterectomy. SUMMARY: Morcellation of excised tissue is necessary for many women with symptomatic fibroids who choose to undergo laparoscopic myomectomy or hysterectomy. LMS is an uncommon disease, with a poor prognosis due to early hematogenous metastasis to lung, bone and liver. Preoperatively, it is often difficult to differentiate from benign fibroids. LMS has a high propensity for local recurrence despite performance of total hysterectomy. Efforts to remove all tissue and cells from the pelvis and abdomen should be the goal of minimally invasive surgery with morcellation.

Tumour-inducing viruses.

Virus infections are an important factor in the global burden of human cancer. The discovery and mode of action of human tumour viruses is briefly reviewed together with the promise of prevention through vaccination.

Updates in uterine fibroid tissue extraction.

PURPOSE OF REVIEW: Safety concerns regarding morcellation of presumed benign fibroid disease have led to an increase in recent research activity on this topic, as well as advances in surgical technique. RECENT FINDINGS: The prevalence of occult leiomyosarcoma is debated; however, estimates from a robust meta-analysis suggest it may be in the range of 1 case per 1960-8300 fibroid surgeries. Advancing age is an important clinical risk factor for occult malignancy. The impact of tumor morcellation may vary by mode of tissue removal, though tissue fragmentation is consistently associated with poorer outcomes. Decision and cost analyses continue to support laparoscopic hysterectomy as a low-morbidity and cost-effective approach. The increased scrutiny on fibroid procedures in the past few years may lead to changes in surgical approach; however, alternative tissue extraction options are evolving, including incorporation of contained morcellation. SUMMARY: Although the incidence of occult leiomyosarcoma is low, outcomes are poor and may be worsened by morcellation. By addressing risk factors for malignancy and incorporating evolving surgical techniques into practice, gynecologists can continue to offer patients a minimally invasive approach for fibroid management.

The importance of surgical margins in retroperitoneal sarcoma.

Surgery is the "gold-standard" treatment for retroperitoneal sarcomas, but local recurrence is common, and can cause disease-related death. Complete gross resection is associated with improved survival, but debate exists as to whether resection of adjacent organs to improve margins or prescription of neoadjuvant radiation leads to better outcomes. This review summarizes data addressing prognostic value of margin, extent of surgery necessary to optimize treatment of retroperitoneal sarcomas, and role of histology in optimizing therapy.

Positive surgical margins in soft tissue sarcoma treated with preoperative radiation: is a postoperative boost necessary?

PURPOSE: For patients with an extremity soft tissue sarcoma (STS) treated with preoperative radiotherapy and surgically excised with positive margins, we retrospectively reviewed whether a postoperative radiation boost reduced the risk of local recurrence (LR). METHODS AND MATERIALS: A total of 216 patients with positive margins after resection of an extremity STS treated between 1986 and 2003 were identified from our institution's prospectively collected database. Patient demographics, radiation therapy parameters including timing and dose, classification of positive margin status, reasons for not administering a postoperative boost, and oncologic outcome were collected and evaluated. RESULTS: Of the 216 patients with a positive surgical margin, 52 patients were treated with preoperative radiation therapy alone (50 Gy), whereas 41 received preoperative radiation therapy plus a postoperative boost (80% received 16 Gy postoperatively for a total of 66 Gy). There was no difference in baseline tumor characteristics between the two groups. Six of 52 patients in the group receiving preoperative radiation alone developed a LR compared with 9 of 41 in the boost group. Five-year estimated LR-free survivals were 90.4% and 73.8%, respectively (p = 0.13). CONCLUSIONS: We found that including the postoperative radiation boost after preoperative radiation and a margin-positive excision did not provide an advantage in preventing LR for patients treated with external beam radiotherapy. Given that higher radiation doses placed patients at greater risk for late complications such as fracture, fibrosis, edema, and joint stiffness, judicious avoidance of the postoperative boost while maintaining an equivalent rate of local control can reduce the risk of these difficult-to-treat morbidities.

Anticarcinogenic and antiplatelet effects of carvacrol.

AIM: To investigate the effect of carvacrol on chemical carcinogenesis, cancer cell proliferation and platelet aggregation, and to find possible correlation between all these processes and the antioxidant properties of carvacrol. MATERIALS AND METHODS: 3,4-benzopyrene-induced carcinogenesis model using Wistar rats was used. Leiomyosarcoma cells from Wistar rats were used to study carvacrol antiproliferative activity in vitro. The carvacrol antiplatelet properties were investigated with platelet aggregation assay and flow cytometry technique. The production of thromboxane B2, final metabolite of platelet aggregation, was evaluated by radioimmunoassay. RESULTS: Our study revealed significant anticarcinogenic properties of carvacrol. We observed 30% decrease of 3,4 benzopyrene carcinogenic activity in vivo. Antiproliferative activity of carvacrol (IC(50)) was 90 microM and 67 microM for 24 h and 48 h of incubation of cells, respectively. Carvacrol possessed also mild antiplatelet effect, inducing the decrease of thromboxane A2 production in platelets and as a result - restrictive expression of the GPIIb/IIIa platelet receptor. CONCLUSION: Our data demonstrated that carvacrol possesses anticarcinogenic, antiproliferative and antiplatelet properties.

Immortalized mouse mammary fibroblasts lacking dioxin receptor have impaired tumorigenicity in a subcutaneous mouse xenograft model.

Although the dioxin receptor, the aryl hydrocarbon receptor (AhR), is considered a major regulator of xenobiotic-induced carcinogenesis, its role in tumor formation in the absence of xenobiotics is still largely unknown. Trying to address this question, we have produced immortalized cell lines from wild-type (T-FGM-AhR+/+) and mutant (T-FGM-AhR-/-) mouse mammary fibroblasts by stable co-transfection with the simian virus 40 (SV-40) large T antigen and proto-oncogenic c-H-Ras. Both cell lines had a myofibroblast phenotype and similar proliferation, doubling time, SV-40 and c-H-Ras expression and activity, and cell cycle distribution. AhR+/+ and AhR-/- cells were also equally able to support growth factor- and anchorage-independent proliferation. However, the ability of T-FGM-AhR-/- to induce subcutaneous tumors (leimyosarcomas) in NOD/SCID-immunodeficient mice was close to 4-fold lower than T-FGM-AhR+/+. In culture, T-FGM-AhR-/- had diminished migration in collagen-I and decreased lamellipodia formation. VEGFR-1/Flt-1, a VEGF receptor that regulates cell migration and blood vessel formation, was also down-regulated in AhR-/- cells. Signaling through the ERK-FAK-PKB/AKT-Rac-1 pathway, which contributes to cell motility and invasion, was also significantly inhibited in T-FGM-AhR-/-. Thus, the lower tumorigenic potential of T-FGM-AhR-/- could result from a compromised adaptability of these cells to the in vivo microenvironment, possibly because of an impaired ability to migrate and to respond to angiogenesis.

Antiproliferative and anticarcinogenic effects of an aqueous preparation of Abies alba and Viscum album se abies, on a L-1210 malignant cell line and tumor-bearing Wistar rats.

Extracts of plants have been widely tested for possible anticarcinogenic properties. In the present study a traditional remedy, consisting of an aqueous extract of mixed parts of the tree Abies alba and its mistletoe Viscum album se abies was tested on benzo(alpha)pyrene(BaP)-induced tumors in Wistar rats and on the L-1210 malignant cell line. Two main groups of male Wistar rats subcutaneously injected by 10 mg of BaP, a dose inducing 100% carcinogenesis, a control group (C-G, 15 rats) and a treatment group(TR-G, 18 rats), were used for the study. Five animals bearing BaP-induced tumors were also tested (TR-1-G). Animals of the TR-G were orally administered with the aqueous extract at doses of 50 ml/kg b.w, from the day of BaP injection and of the TR-1-G, from the 120th day of injection, till death. L-1210 malignant cells in cultivation, were administered with a powder obtained by condensation and lyophilization of the extract, at various concentrations and cytotoxicity was measured by the microculture tetrazolium assay. Autopsy of the rats, revealed metastasis in the lungs of the animals of all groups and the tumors developed were histologically identified as leiomyosarcomas. The results indicated that the extract of the above plants possess anticarcinogenic effects, documented by: a) its antiproliferative effects on L-1210 cells (IC50 = 49.6 +/- 1.4 micrograms/ml), b) the significant prolongation of life and reduction of tumor growth rate of the animals of the TR-G in comparison to the C-G, c) the inhibition by 16.6% of tumor induction in the TR-G and d) the prolongation of life and the necrotic effects of the extract on the tumors of the animals in the TR-1-G. The antiproliferative effects of the Abies alba and Viscum album se abies extract may be due to the lectins and thionins contained in Viscum album, as well as to the monoterpenes contained in Abies alba. Soft tissue tumors sensitive to the extract, are widespread among human organs, even in larynx, and are usually resistant to chemotherapy.

Beneficial effects of a vanadium complex with cysteine, administered at low doses on benzo(alpha)pyrene-induced leiomyosarcomas in Wistar rats.

BACKGROUND: Vanadium is a potent environmental and body metal, possessing remarkable antitumor and antidiabetic properties. Vanadium salts and complexes have been widely investigated for their anticarcinogenic properties in experimental carcinogenesis. In the present study the antitumor effects of a new vanadium complex with cysteine in relation to identical doses of vanadyl sulfate and cysteine, in tumor bearing rats are investigated. MATERIALS AND METHODS: Male wistar rats were injected with benzo(alpha)pyrene and divided into four groups of 21 rats each. Control group was treated only with BaP. The first group(TR-1) was treated by vanadyl sulfate per os at daily doses of 0.5 mg of V/kg b.w per day. The second (TR-2) by cysteine at doses of 4.5 mg/kg b.w per day and the third group (TR-3), by the complex V(III)-cysteine at daily doses of V 0.5 mg/kg b.w (containing cysteine at concentrations of 4.5 mg/b.w). Treatment was started when tumors were developed (evidenced from a palbable mass at the site of Bap injection) and went on till death. Toxicological tests were performed in 27 rats divided into a control group and two test groups; T-1 administered with vanadyl sulfate at daily doses of 18.5 mg V/kg b.w and T-2 group with V(III)-cysteine complex at daily doses of 18.5 V/kg b.w, for 9 weeks. Mean survival time, death rate, tumor growth rate, the carcinogenic potency of BaP, and the anticarcinogenic potency in relation to histological findings in each treatment group were calculated in each group in order to evaluate the antitumor effects of the substances used. RESULTS: Vanadyl sulfate, cysteine and V(III)-cysteine exerted antitumor effects on leiomyosarcoma bearing Wistar rats. However, V(III)-complex exerted much more potent effects than the other treatments, significantly prolonging mean survival time, retarding tumor growth rate and decreasing the carcinogenic potency of BaP in the TR-3 group, in comparison to the control and the TR-1 and TR-2 groups. Moreover V(III)-cysteine complex resulted in complete remission of 4 (19.7%) of the tumor bearing rats. Blood, urine, biochemical routine tests as well as autopsy did not reveal any toxic effects either of vanadyl sulafate or V(III)-cysteine complex. CONCLUSIONS: Vanadyl sulfate, cysteine and V(III)-cysteine complex exerted antitumor effects in tumor bearing rats. The V(III)-cysteine complex, however, exerts much more potent effects, as evident from the results of the present study. These beneficial effects of the above complex, in combination with its low toxicity provide evidence suggest its possible application in the treatment of human malignant diseases.

Dose-related preventive and therapeutic effects of antioxidants-anticarcinogens on experimentally induced malignant tumors in Wistar rats.

A combination of antioxidants-anticarcinogens, consisting of vitamins C and E, selenium and 2-mercaptopropionyl glycine (2-MPG), was administered orally for the prevention (PRG) and treatment (TRG) of benzo(a)pyrene (BaP)-induced malignant tumors (leiomyosarcomas), in Wistar rats. In order to evaluate dose-related effects, a low dose vitamin (0.15 g/kg b.w. per day of vit.C and 0.05 g/kg b.w. per day of vit.E) and a high dose (1.5 g/kg b.w. per day of vit.C and 0.5 g/kg b.w. per day of vit.E) combination was administered, in prevention and treatment groups. Selenium was administered in doses of 2 microg/kg b.w. per day and 2-MPG in 15 mg/kg b.w. per day, in all groups. Daily estimations of 24 h urine volume levels of thiobarbituric acid reacting substances (MDA) were performed in 20 animals, divided into a control group, a BaP-injected group, a tricapryline-injected group and a BaP-injected and treated by the low dose combination group. Results revealed that the low dose combination failed to exert any beneficial effect on mean survival time of animals treated either preventitively or therapeutically. An increased number of animals bearing a second (lung) tumor was, in addition, found in autopsy and histological examination in the low dose combination (PRG and TRG) and the high dose TRG groups. The high dose combination groups manifested a significant prolongation of the mean survival time of animals; complete remission of tumors developed in 16.8% of the animals in the treatment group and a 5.2% prevention of tumor formation in the preventive group, without any evidence of an increased number of double tumor formation in the PRG group. Urine MDA increased significantly in animals injected by BaP during the first 10 days and since the 90th day (formation of palpable tumors) after injection, in relation to control and tricapryline-injected groups. Complete prevention of urine MDA-increased values was obtained in BaP-injected and treated by the low dose combination animals. Results indicate that high doses (megadoses) of the antioxidant-anticarcinogen vitamins C and E in combination with carefully selected other antioxidants possessing supplementary actions, are probably needed in order to achieve a sufficient prevention and treatment of malignant diseases.