National Cancer Institute®
Last Modified: May 1, 2002
UI - 11764658
AU - De Neve W; Claus F; Duthoy W; De Meerleer G; De Wagter C
TI - Intensity modulation techniques for improvement of normal tissue tolerance.
SO - Front Radiat Ther Oncol 2002;37():163-73
AD - Division of Radiotherapy, Ghent University Hospital, Ghent, Belgium. email@example.com
UI - 11867783
AU - Koyama T; Fletcher JG; Johnson CD; Kuo MS; Notohara K; Burgart LJ
TI - Primary hepatic angiosarcoma: findings at CT and MR imaging.
SO - Radiology 2002 Mar;222(3):667-73
AD - Department of Diagnostic Imaging and Nuclear Medicine, School of Medicine, Kyoto University, Japan.
PURPOSE: To evaluate and describe cross-sectional imaging findings in patients with pathologically confirmed primary hepatic angiosarcoma. MATERIALS AND METHODS: Findings from imaging examinations in 13 patients with pathologically confirmed primary hepatic angiosarcoma were retrospectively reviewed (computed tomographic [CT] images obtained in 10 patients and magnetic resonance [MR] images obtained in five patients were available for review). Two gastrointestinal radiologists evaluated lesion number, size, attenuation and signal intensity characteristics, and the pattern and degree of contrast material enhancement. Medical records were reviewed for clinical features associated with angiosarcoma. RESULTS: Angiosarcoma appeared as multiple nodules (n = 6), as dominant masses (n = 6), or as a diffusely infiltrating lesion (n = 1). Multiple nodules were hypoattenuating at unenhanced and contrast material--enhanced CT (six of six patients). When dominant masses were encountered at MR imaging, T2-weighted MR imaging demonstrated heterogeneous internal architecture (four of four patients) similar to that of hepatocellular carcinoma. Multiphase contrast-enhanced CT and MR images showed dominant masses to have heterogeneous and progressive enhancement (three of three patients). Clinical features associated with angiosarcoma included splenic metastases (six of 13 patients), thrombocytopenia (seven of 13 patients), disseminated intravascular coagulation (four of 13 patients), and hemolytic anemia (three of 13 patients). CONCLUSION: Primary hepatic angiosarcoma exhibits a spectrum of appearances that reflect its varied pathologic features.
UI - 11867201
AU - Dan'ura T; Kawai A; Morimoto Y; Naito N; Yoshida A; Inoue H
TI - Apoptosis and expression of its regulatory proteins in soft tissue sarcomas.
SO - Cancer Lett 2002 Apr 25;178(2):167-74
AD - Department of Orthopaedic Surgery, Faculty of Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Information for the occurrence and extent of apoptosis in soft tissue sarcoma (STS) and their clinical implication are limited. In 102 cases of STSs, apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method and expression of Bcl-2, Bax, MIB-1 and p53 protein was examined immunohistochemically. The apoptotic index of the STSs ranged from 0 to 15% with an average value of 1.9%. The mean values of positive cell staining for Bcl-2, Bax, MIB-1 and p53 protein were 32.1, 40.8, 17.0 and 20.3%, respectively. The extent of apoptosis and expression of Bcl-2 protein were correlated to the histologic types of the tumor. Synovial sarcoma had a significantly higher expression of Bcl-2 protein, and lower incidence of apoptosis. STS underwent apoptosis at a constitutional level. There were no significant relationships between extent of the apoptosis, expression of its regulatory proteins and prognosis of the patients.
UI - 11920169
AU - Agbalika F; Marolleau JP; Brouet JC
TI - Interleukin-6 stimulates HHV-8 replication in bone marrow cultures and infected cell lines.
SO - Hematol J 2000;1(1):48-52
AD - Laboratory of Virology, Hopital Saint-Louis, Paris, France.
INTRODUCTION: The significance of HHV-8 DNA detection in bone marrow stromal cells from patients with multiple myeloma is still controversial. Since IL-6 plays a key role in the pathogenesis of myeloma, we studied the effect of this lymphokine on HHV-8 DNA detection. MATERIALS AND METHODS: Amplification of HHV-8 DNA from long-term bone marrow cultures established from normal individuals in the presence or absence of 1 ng/ml IL-6 and from an HHV-8 infected ISI cell line. RESULTS AND CONCLUSIONS: IL-6 increased HHV-8 replication in seven of ten bone marrow cultures as well as in the ISI cell line. Quantitative PCR showed a 3-100-fold increase in HHV-8 DNA copy number/microg DNA. These data suggest that when IL-6 is present in the micro-environment, HHV-8 replicates and may be amplified in the absence of systemic infection in patients without cellular immune deficiency.
UI - 11884051
AU - Stefanovski PD; Bidoli E; De Paoli A; Buonadonna A; Boz G; Libra M;
TI - Morassut S; Rossi C; Carbone A; Frustaci S Prognostic factors in soft tissue sarcomas: a study of 395 patients.
SO - Eur J Surg Oncol 2002 Mar;28(2):153-64
AD - Division of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy.
AIMS: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas. METHODS: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival. CONCLUSIONS: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival. Copyright Harcourt Publishers Limited.
UI - 11846301
AU - Breitfeld PP; Lyden E; Raney RB; Teot LA; Wharam M; Lobe T; Crist WM;
TI - Maurer HM; Donaldson SS; Ruymann FB Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.
SO - J Pediatr Hematol Oncol 2001 May;23(4):225-33
AD - Intergroup Rhabdomyosarcoma Study Group, Children's Cancer Group, Arcadia, California, USA. firstname.lastname@example.org
PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.
UI - 11925138
AU - Amant F; de la Rey M; Dorfling CM; van der Walt L; Dreyer G; Dreyer L;
TI - Vergote I; Lindeque BG; Van Rensburg EJ PTEN mutations in uterine sarcomas.
SO - Gynecol Oncol 2002 Apr;85(1):165-9
AD - Division of Gynecological Oncology, Department of Obstetrics and Gynecology, UZ Gasthuisberg, Leuven, Belgium. Frederic.Amant@uz.kuleuven.ac.be
OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.
UI - 11925150
AU - Moore RG; Steinhoff MM; Granai CO; DeMars LR
TI - Vulvar epithelioid sarcoma in pregnancy.
SO - Gynecol Oncol 2002 Apr;85(1):218-22
AD - Department of Obstetrics and Gynecology, Program in Women's Oncology, Brown University, Providence, Rhode Island 02905, USA. email@example.com
BACKGROUND: Epithelioid sarcoma is a soft tissue tumor rarely found centrally and even less commonly on the vulva. Vulvar sarcoma in pregnancy is also exceedingly rare with only five cases reported to date, none of which have been an epithelioid sarcoma. CASE: We report a case of a 29-year-old woman presenting with a vulvar epithelioid sarcoma at 36 weeks of gestation. The patient underwent a radical resection 6 weeks postpartum followed by chemotherapy. Despite a radical hemivulvectomy and doxorubicin and ifosfamide chemotherapy, she developed pulmonary metastasis and died of tumor-related pulmonary failure secondary to her disease 612 months after diagnosis. To our knowledge this is the first case of a vulvar epithelioid sarcoma presenting during pregnancy. The English literature is reviewed and a total of 18 previous cases of vulvar epithelioid sarcoma have been reported outside of pregnancy. Insight into the biological behavior and therapeutic management of this disease is discussed. CONCLUSION: The optimal management of vulvar epithelioid sarcoma remains to be determined. However, it would seem that early and aggressive surgical resection provides the best possibility for cure. The role of radiation and/or chemotherapy remains to be determined.
UI - 11859200
AU - Martin SA; Sears DL; Sebo TJ; Lohse CM; Cheville JC
TI - Smooth muscle neoplasms of the urinary bladder: a clinicopathologic comparison of leiomyoma and leiomyosarcoma.
SO - Am J Surg Pathol 2002 Mar;26(3):292-300
AD - Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
We report the clinicopathologic, immunohistochemical, and DNA ploidy findings of 18 leiomyosarcomas of the urinary bladder. In addition, we compare these malignant smooth muscle tumors with 10 cases of urinary bladder leiomyoma. The 14 male and four female patients with leiomyosarcoma ranged in age from 25 to 88 years (mean 64 years). The tumors ranged from 3.0 to 15.0 cm (mean 7.1 cm) in greatest dimension and were moderately to highly cellular, consisting of interlacing fascicles of spindled cells with mild to marked nuclear atypia. Coagulative tumor necrosis was identified in 14 cases (78%), and mitotic activity ranged from 1 to 42 mitotic figures (MF) per 10 high power fields (HPF) (mean 12 MF/10 HPF). Tumors were classified as either high-grade (12 cases) or low-grade (six cases) based on nuclear atypia, mitotic activity, and tumor necrosis. Actin positivity was present in 15 tumors (83%), and desmin immunoreactivity was present in seven tumors (39%). All cases were negative for epithelial markers and S-100. Proliferative activity, as assessed by MIB-1 staining, ranged from 0.1% to 51.4% (median 9.1%). Seven (39%) of the leiomyosarcomas were DNA aneuploid, eight (44%) were tetraploid, and three (17%) were diploid. Five patients underwent radical cystoprostatectomy, one radical cystectomy, seven had partial cystectomy, two underwent pelvic exenteration, and three patients had transurethral resection only. Follow-up information was available on all 18 cases and ranged from 2 to 68 months (mean 22 months). Of the 12 patients with high-grade tumors, six (50%) died of disease from 2 to 20 months (mean 7 months) after diagnosis and three patients (25%) are alive with metastatic tumor. Two of the six patients with low-grade leiomyosarcoma died of tumor, 61 and 68 months after diagnosis. There were five male and five female patients with leiomyoma ranging in age from 22 to 78 years (mean 61 years). The tumors ranged from 0.5 to 4.5 cm (mean 1.6 cm) in greatest dimension, were well circumscribed, and had low cellularity. Mitotic activity, necrosis, and cellular atypia were absent, and the tumors were strongly positive for both actin and desmin. MIB-1 staining ranged from 0% to 3.8% (median 0.8%). Seven (87.5%) of the leiomyomas were DNA diploid or near-diploid and one (12.5%) was DNA aneuploid. Six patients were treated with transurethral resection and four with partial cystectomy. All 10 patients were alive at the last follow-up (mean follow-up 75 months), and no tumor recurred or metastasized. Our study shows that low-grade leiomyosarcomas are capable of malignant behavior, and high-grade leiomyosarcomas appear to behave more aggressively than low-grade tumors. In addition, the diagnosis of urinary bladder leiomyoma should be reserved for noninfiltrative smooth muscle tumors lacking mitotic activity, cytologic atypia, and necrosis.
UI - 11981942
AU - Watanabe K
TI - Leiomyosarcoma versus myofibrosarcoma.
SO - Am J Surg Pathol 2002 Mar;26(3):393-4; discussion 394-6
UI - 11900566
AU - Laskin WB; Miettinen M
TI - Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues.
SO - Arch Pathol Lab Med 2002 Apr;126(4):425-31
AD - Department of Pathology, Northwestern University Medical School, Chicago, IL 60611-3053, USA. firstname.lastname@example.org
CONTEXT: Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. OBJECTIVE: To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. DESIGN: Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. RESULTS: Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). CONCLUSIONS: Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).
UI - 11914621
AU - Aubry MC; Myers JL; Colby TV; Leslie KO; Tazelaar HD
TI - Endometrial stromal sarcoma metastatic to the lung: a detailed analysis of 16 patients.
SO - Am J Surg Pathol 2002 Apr;26(4):440-9
AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. email@example.com
Pulmonary metastases of endometrial stromal sarcoma (ESS) are uncommon and can pose diagnostic problems. We reviewed lung specimens from 16 patients with metastatic ESS. Patients were 31-77 years of age at the time of lung biopsy. Uterine ESSs were diagnosed an average of 9.8 years before lung biopsy in 11 patients. Uterine ESSs were originally called smooth muscle tumors in three additional patients. Thirteen patients were evaluated for new pulmonary nodules, seven of whom were asymptomatic. Nodules were multiple in 14 and solitary in four, ranging from 1.0 to 8.0 cm in greatest dimension. One patient died of metastatic disease; 14 were alive and seven of these were without disease (mean follow-up 4.1 years). Diagnostic considerations in 12 consultation cases included ESS, sclerosing hemangioma, carcinoid tumor, lymphangioleiomyomatosis, endometriosis, hemangiopericytoma, and lymphoma. Tumors were well circumscribed and usually solid, composed of plump spindle cells arranged in short fascicles. Two tumors were predominantly cystic. Sex cord-like stromal differentiation was identified in three. Neoplastic cells stained for vimentin (93%), estrogen and progesterone receptor (100%), smooth muscle actin (57%), desmin (50%), and keratin (46%). Metastatic ESS should be included in the differential diagnosis of nonepithelial neoplasms in women.
UI - 11914631
AU - Dacic S; Finkelstein SD; Sasatomi E; Swalsky PA; Yousem SA
TI - Molecular pathogenesis of pulmonary carcinosarcoma as determined by microdissection-based allelotyping.
SO - Am J Surg Pathol 2002 Apr;26(4):510-6
AD - Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, Pennsylvania, USA. firstname.lastname@example.org
Pulmonary carcinosarcoma is a rare, biphasic tumor composed of malignant epithelial and mesenchymal elements. Its histogenesis is controversial in light of the presence of divergent cell lineages and the clonal nature of malignancy. To address these issues, we performed an extensive comparative genotypic analysis using microdissection to secure representative mesenchymal and epithelial components from each of six cases of pulmonary carcinosarcoma. Loss of heterozygosity was analyzed with a panel of 12 polymorphic microsatellite markers designed to indicate allelic loss and situated in proximity to known tumor suppressor genes located on 1p, 3p, 5q, 9p, 10q, and 17p. In accordance with the relatively greater biologic aggressiveness of this tumor type, both the epithelial and mesenchymal components showed extensive allelic loss, most notably for 3p, 5q, and 17p. More importantly, we found overall equivalent patterns of acquired allelic loss between the two components on an individual case basis, strongly supporting the monoclonal origin of these neoplasms. Minor differences in the allelic fingerprint between the two cell lineages could be explained by progressive accumulation of allelic loss alterations that appear to occur more frequently in the mesenchymal component of the tumor. The data support the efficacy of microdissection-based allelic fingerprinting to delineate the relationship between different morphologic components of a single neoplasm.
UI - 11821409
AU - Bao KK; Skalka AM; Wong I
TI - Presteady-state analysis of avian sarcoma virus integrase. I. A splicing activity and structure-function implications for cognate site recognition.
SO - J Biol Chem 2002 Apr 5;277(14):12089-98
AD - Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
Integrase catalyzes insertion of a retroviral genome into the host chromosome. After reverse transcription, integrase binds specifically to the ends of the duplex retroviral DNA, endonucleolytically cleaves two nucleotides from each 3'-end (the processing activity), and inserts these ends into the host DNA (the joining activity) in a concerted manner. In first-turnover experiments with synapsed DNA substrates, we observed a novel splicing activity that resembles an integrase joining reaction but uses unprocessed ends. This splicing reaction showed an initial exponential phase (k(splicing) = 0.02 s(-1)) of product formation and generated products macroscopically indistinguishable from those created by the processing and joining activities, thus bringing into question methods previously used to quantitate these reactions in a time regime where multiple turnovers of the enzyme have occurred. With a presteady-state assay, however, we were able to distinguish between different pathways that led to formation of identical products. Furthermore, the splicing reaction allowed characterization of substrate binding and specificity. Although integrase requires only a 3' hydroxyl with respect to nucleophiles derived from DNA, it specifically favors the cognate sequence CATT as the electrophile. These experimental results support a two-site "switching" model for binding and catalysis of all three integrase activities.
UI - 11821408
AU - Bao KK; Skalka AM; Wong I
TI - Presteady-state analysis of avian sarcoma virus integrase. II. Reverse-polarity substrates identify preferential processing of the U3-U5 pair.
SO - J Biol Chem 2002 Apr 5;277(14):12099-108
AD - Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
The integrase-catalyzed insertion of the retroviral genome into the host chromosome involves two reactions in vivo: 1) the binding and endonucleolytic removal of the terminal dinucleotides of the viral DNA termini and 2) the recombination of the ends with the host DNA. Kukolj and Skalka (Kukolj, G., and Skalka, A. M. (1995) Genes Dev. 9, 2556-2567) have previously shown that tethering of the termini enhances the endonucleolytic activities of integrase. We have used 5'-5' phosphoramidites to design reverse-polarity tethers that allowed us to examine the reactivity of two viral long terminal repeat-derived sequences when concurrently bound to integrase and, additionally, developed presteady-state assays to analyze the initial exponential phase of the reaction, which is a measure of the amount of productive nucleoprotein complexes formed during preincubation of integrase and DNA. Furthermore, the reverse-polarity tether circumvents the integrase-catalyzed splicing reaction (Bao, K., Skalka, A. M., and Wong, I. (2002) J. Biol. Chem. 277, 12089-12098) that obscures accurate analysis of the reactivities of synapsed DNA substrates. Consequently, we were able to establish a lower limit of 0.2 s(-1) for the rate constant of the processing reaction. The analysis showed the physiologically relevant U3/U5 pair of viral ends to be the preferred substrate for integrase with the U3/U3 combination favored over the U5/U5 pair.
UI - 11955733
AU - Yap J; Chuba PJ; Thomas R; Aref A; Lucas D; Severson RK; Hamre M
TI - Sarcoma as a second malignancy after treatment for breast cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1231-7
AD - Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
BACKGROUND: Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer. METHODS: Cases with primary invasive breast cancer (n = 274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973-1997). The database was then queried to determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method. RESULTS: The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis, respectively (p = 0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast cancer (27-35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer. CONCLUSIONS: Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is small. Angiosarcoma is significantly more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. The small difference in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy does not supersede the benefit of radiotherapy.
UI - 11955745
AU - Rovirosa A; Ascaso C; Ordi J; Abellana R; Arenas M; Lejarcegui JA;
TI - Pahisa J; Puig-Tintore LM; Mellado B; Armenteros B; Iglesias X; Biete A Is vascular and lymphatic space invasion a main prognostic factor in uterine neoplasms with a sarcomatous component? A retrospective study of prognostic factors of 60 patients stratified by stages.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1320-9
AD - Department of Radiation Oncology, Hospital Clinic i Universitari, Barcelona, Spain. email@example.com
BACKGROUND: Sarcomatous neoplasms of the uterine corpus are still a challenge in terms of obtaining prognostic factors and the most optimum complementary treatment to surgery. The most important prognostic factor is stage; relapses usually appear during the first 2 years, and most patients die within the first 3 years. We have performed a multivariate study of prognostic factors, stratifying patients by stage, to determine their impact on overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival. Special emphasis has been given to vascular and lymphatic space invasion (VLSI). METHODS: Sixty patients diagnosed with uterine neoplasms with a main sarcomatous component were treated at Hospital Clinic i Universitari of carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. Treatment: 58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space invasion, myometrial invasion, mitotic index, tumor size, unicentricity/multicentricity, necrosis, and radiotherapy. Statistics: the S and Cox proportional risk models. The partial effect of each risk factor was calculated by hazard ratio (HR) with a confidence interval of 95%. RESULTS: Early stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI was present in 23% of the cases. Myometrial invasion greater than 50% had an impact on disease-free survival and local relapse-free survival (HR was 9.75 and 3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma type made the overall survival worse (HR = 10.54). CONCLUSIONS: Vascular and lymphatic space invasion was a relevant prognostic factor in our series, with an impact on overall survival and distant metastasis-free survival in early stages. In advanced stages, VLSI had no impact on survival, but was present in 89% of cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages had a more aggressive behavior, and there was a higher incidence of poor prognostic factors in these stages. Nevertheless, prospective studies are still needed on prognostic factors and on the best treatment option.
UI - 11955749
AU - Schwartz DL; Einck J; Hunt K; Bruckner J; Conrad E; Koh WJ; Laramore GE
TI - The effect of delayed postoperative irradiation on local control of soft tissue sarcomas of the extremity and torso.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1352-9
AD - Department of Radiation Oncology, Seattle VA Medical Center/Puget Sound Health Care System, Seattle, WA 98108, USA. firstname.lastname@example.org
PURPOSE: The impact of delayed adjuvant radiotherapy in patients treated by surgical resection for peripheral or torso soft tissue sarcoma has not been well characterized. We retrospectively examined this issue in an institutional patient cohort. METHODS AND MATERIALS: One hundred two adult patients were treated at the University of Washington Medical Center between 1981 and 1998 with postoperative radiotherapy for cure of a newly diagnosed soft tissue sarcoma. Of this group, 58 patients had primary intermediate- or high-grade disease of the extremity or torso (50 extremity/8 torso). Tumor histology was predominantly malignant fibrohistiocytoma, synovial cell sarcoma, and leiomyosarcoma. The group was dichotomized according to time interval from definitive resection to the start of adjuvant radiation. Twenty-six patients had a short delay, defined as <4 months, and 32 patients had a long delay of >or=4 months. Both groups were balanced with regard to site, size, margin status, and tumor depth; however, the long-delay group had a larger proportion of high histologic grade lesions and was treated more frequently with chemotherapy (31/32 [97%] for long-delay patients vs. 14/26 [54%] for short-delay patients). Median follow-up was 49.5 months (range: 7-113 months). Median follow-up for patients still alive was 54 months (range: 9-113 months). Survival outcomes were estimated by the Kaplan-Meier method. RESULTS: Overall local relapse-free survival at 5 years from the time of definitive resection was 74%. On univariate analysis, estimated 5-year local relapse-free survival was significantly improved in the short-delay group (88% vs. 62% for the long-delay group, p = 0.048 by log rank). Overall distant relapse-free survival, disease-free survival, and overall survival at 5 years were 77%, 68%, and 86%, respectively. These survival outcomes were statistically equivalent in both radiation delay groups. There was no evidence to suggest that delaying adjuvant systemic therapy for postoperative radiation negatively impacted distant relapse-free survival, disease-free survival, or overall survival. Patterns of failure analysis revealed that 11/12 disease failures in the long-delay group had a local component, with five patients presenting with solitary local recurrences. Severe chronic radiation-related soft tissue or peripheral nerve morbidity was infrequent (5/58 or 8.6%) and similar in both groups. CONCLUSIONS: Postoperative radiation delays of 4 months or greater were associated with inferior local disease control for intermediate- and high-grade soft tissue sarcomas of the extremity and torso. Our results suggest that timing postoperative radiation before postoperative chemotherapy may optimize local therapy for such patients without adversely affecting distant disease control, long-term morbidity, or overall survival. Prospective testing of this hypothesis is warranted.
UI - 11957149
AU - Antonescu CR; Busam KJ; Iversen K; Kolb D; Coplan K; Spagnoli GC;
TI - Ladanyi M; Old LJ; Jungbluth AA MAGE antigen expression in monophasic and biphasic synovial sarcoma.
SO - Hum Pathol 2002 Feb;33(2):225-9
AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Synovial sarcomas are high-grade malignant mesenchymal tumors carrying a pathognomonic cytogenetic alteration t(X;18) involving the SYT gene on chromosome 18 and either SSX1 or SSX2 on chromosome X. Morphologically, biphasic (BSS) and monophasic (MSS) variants can be distinguished. Cancer/testis (CT) antigens are expressed in a variety of malignant tumors, but not in normal tissues except in germ cells, primarily of the testis. Anti-MAGE monoclonal antibody (mAb) 57B previously showed a high incidence and homogenous reactivity pattern in a preliminary analysis of synovial sarcomas. This study was performed to analyze the expression of MAGE by immunohistochemistry with mAb 57B in 25 synovial sarcomas (12 monophasic, 13 biphasic), which were typed for the t(X;18)-derived fusion transcript by reverse transcriptase polymerase chain reaction (19 SYT-SSX1, 6 SYT-SSX2). 57B immunoreactivity was present in 22 of 25 (88%) cases, and antigen expression was homogeneous in 14 of 22 57B-positive cases. Both morphological variants and both translocation types were immunoreactive; three SYT-SSX1 tumors (one MSS, two BSS) were 57B negative. Our study demonstrates that MAGE is frequently and homogeneously expressed in synovial sarcomas of both morphological variants and both translocation types, making these tumors an attractive target for MAGE antigen-based immunotherapy. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11819129
AU - Imaizumi S; Morita T; Ogose A; Hotta T; Kobayashi H; Ito T; Hirata Y
TI - Soft tissue sarcoma mimicking chronic hematoma: value of magnetic resonance imaging in differential diagnosis.
SO - J Orthop Sci 2002;7(1):33-7
AD - Department of Orthopedic Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishicho, Niigata 951-8133, Japan.
We report six patients with soft tissue sarcoma mimicking traumatic hematoma. The lesions in these patients, showed huge hematomas and were characterized by rapid growth. Cytology of percutaneous; aspiration biopsy samples was performed in all six patients; however, in five patients, findings for malignant cells were negative. Consequently, they were misdiagnosed, resulting in a poor prognosis. We conducted a retrospective study in which we evaluated the clinical findings, the magnetic resonance (MR) images, and computed tomography (CT) scans of the soft tissue sarcomas forming huge hematomas in the lesion. MR imaging revealed the fine tumor mass with enhancement and characterized the hematoma in the lesion in a more precise fashion than did CT. We conclude that MR imaging is a suitable method for differentiating these soft tissue sarcomas from chronic traumatic hematoma.
UI - 11845259
AU - Hernando JJ; Park TW; Kubler K; Offergeld R; Schlebusch H; Bauknecht T
TI - Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial.
SO - Cancer Immunol Immunother 2002 Mar;51(1):45-52
AD - Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. email@example.com
Dendritic cell (DC)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I clinical trial, we have shown that patients with advanced gynaecological malignancies can be effectively vaccinated with DC pulsed with keyhole limpet haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine sarcoma and six subjects with ovarian carcinoma received three to 23 intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed stable disease lasting 25 to 45 weeks, and five experienced tumour progression within the first 14 weeks. KLH- and tumour lysate-specific delayed-type hypersensitivity (DTH) reactions were observed in six and one patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate stimulation were recorded in six patients and in two patients respectively. Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1 cytokine bias. The treatment was safe, well tolerated, immunologically active and except for local cutaneous hypersensitivity devoid of significant adverse effects.
UI - 7749711
AU - Zornig C; Peiper M; Schroder S
TI - Re-excision of soft tissue sarcoma after inadequate initial operation.
SO - Br J Surg 1995 Feb;82(2):278-9
AD - Department of General Surgery, University Hospital Hamburg Eppendorf, Germany. sarcoma of the extremities and trunk underwent surgery and since 1988, patients in whom the initial operation did not achieve safe margins underwent reoperation (67 of the 189). At re-excision an en block resection of the area with wide margins was achieved in 59 patients. Residual tumour was found in 30 specimens (45 per cent). Thirty-six patients received postoperative radiotherapy and/or chemotherapy. After a mean follow-up of 32 (range 1-69) months five patients (7 per cent) had local recurrence. In view of the high rate of local recurrence after local excision of soft tissue sarcoma (70-90 per cent), primary re-excision is indicated after an inadequate initial operation.
UI - 11710636
AU - Helpap B
TI - Nonepithelial neoplasms of the urinary bladder.
SO - Virchows Arch 2001 Oct;439(4):497-503
AD - Department of Pathology, Hegau-Klinikum Singen, University of Freiburg, Germany. firstname.lastname@example.org
Nonepithelial tumors are rare in the urinary bladder, but their exact classification is very important in the differential diagnosis between these tumors and epithelial lesions. In the new WHO classification and in the third series of the Armed Forces Institute of Pathology (AFIP) "Atlas of Tumor Pathology" on urinary bladder tumors, various mesenchymal tumors, mixed epithelial and mesenchymal tumors and myofibroblastic proliferations are summarized. In the following we will describe the histology, immunohistology, and cytogenetics of nonepithelial tumors and lesions.
UI - 11903594
AU - Shimazaki K; Ohshima K; Haraoka S; Suzumiya J; Nakamura N; Kikuchi M
TI - Accessory cell tumour: a clinicopathological study of 16 aggressive tumours containing EBV-positive Hodgkin and Reed-Sternberg-like giant cells.
SO - Histopathology 2002 Jan;40(1):12-21
AD - Department of Pathology, School of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonanku, Fukuoka 814-0180, Japan.
AIMS: Lymph nodes contain non-lymphoid accessory cells including follicular dendritic cells and interdigitating dendritic cells. Functionally, these cells belong to the category of immune accessory cells involved in antigen presentation to B or T-lymphocytes. Neoplastic proliferation of these cells is very uncommon. We present here the clinicopathological features of 16 cases of accessory cell tumour. METHODS AND RESULTS: We performed electron microscopic and immunohistochemical examinations, and used in-situ hybridization for EBV-encoded RNA (ISH-EBV) to detect the EBV genome in 11 cases, and Southern blot analysis to assess EBV clonality in two cases. Tumour cells were composed of oval-to-spindle cells arranged in diffuse, vague storiform, fascicular and sometimes whorled patterns in a background of small lymphocytes. In all cases, binucleated or multinucleated Hodgkin and Reed-Sternberg-like giant cells were encountered. Staining for CD68 was positive in all cases. CD21, CD35, Ki-M4p, Ki-FDC1p, and S100 exhibited variable reactivity. ISH-EBV yielded positive labelling in seven of 11 cases, of which five exhibited EBV only in Hodgkin and Reed-Sternberg-like giant cells. Southern blot analysis showed clonality of EBV terminal repeats (EBV-TR) in the two cases examined. Electron microscopic examination showed that many of the tumour cells had numerous interwoven long villous cell processes connected by occasional desmosomes. Many tumours were very refractory to chemotherapy and radiation, with a few exceptions, and half of the cases classified initially as stage IV. A short survival time, of 10 months or less, was observed in seven of 16 patients. CONCLUSIONS: Our study identified more aggressive behaviour of accessory cell tumours. Our results suggest that EBV may potentially induce activation of accessory cells to form Hodgkin and Reed-Sternberg-like giant cells, which correspond with poor prognosis.
UI - 11903598
AU - Kurian KM; Al-Nafussi A
TI - Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases.
SO - Histopathology 2002 Jan;40(1):58-64
AD - Pathology Department, University of Edinburgh, 37 Liberton Brae, Edinburgh EH16 6AG, UK. email@example.com
AIMS: To analyse the clinical and pathological features with long-term follow-up of a series of 12 cases of sarcomatoid carcinoma of the breast. methods and results: The cases were selected from the surgical files of the Department of Pathology, University of Edinburgh, between 1977 and 1988. The following clinical parameters were recorded: the age of the patients, size of tumour, presence or absence of lymph node or distant metastases, and patient survival. Pathological assessment included: the type of epithelial and mesenchymal components, the proportion of monophasic to biphasic tumours and the presence of adjacen