Secondary Sarcoma Research Articles

NG2/CSPG4-collagen type VI interplays putatively involved in the microenvironmental control of tumour engraftment and local expansion

In soft-tissue sarcoma patients, enhanced expression of NG2/CSPG4 proteoglycan in pre-surgical primary tumours predicts post-surgical metastasis formation and thereby stratifies patients into disease-free survivors and patients destined to succumb to the disease. Both primary and secondary sarcoma lesions also up-regulate collagen type VI, a putative extracellular matrix ligand of NG2, and this matrix alteration potentiates the prognostic impact of NG2. Enhanced constitutive levels of the proteoglycan in isolated sarcoma cells closely correlate with a superior engraftment capability and local growth in xenogenic settings. This apparent NG2-associated malignancy was also corroborated by the diverse tumorigenic behaviour in vitro and in vivo of immunoselected NG2-expressing and NG2-deficient cell subsets, by RNAi-mediated knock down of endogenous NG2, and by ectopic transduction of full-length or deletion constructs of NG2. Cells with modified expression of NG2 diverged in their interaction with purified Col VI, matrices supplemented with Col VI, and cell-free matrices isolated from wild-type and Col VI null fibroblasts. The combined use of dominant-negative NG2 mutant cells and purified domain fragments of the collagen allowed us to pinpoint the reciprocal binding sites within the two molecules and to assert the importance of this molecular interaction in the control of sarcoma cell adhesion and motility. The NG2-mediated binding to Col VI triggered activation of convergent cell survival- and cell adhesion/migration-promoting signal transduction pathways, implicating PI-3K as a common denominator. Thus, the findings point to an NG2-Col VI interplay as putatively involved in the regulation of the cancer cell-host microenvironment interactions sustaining sarcoma progression.

Ewing Sarcoma Arising After Treatment of Diffuse Large B-cell Lymphoma

We report the case of a patient in whom the diagnosis of Ewing sarcoma arising from a soft tissue was made after successful treatment of diffuse large B-cell lymphoma. A 65-year-old woman presented with a rapidly growing mass in her left scapular region 8 years after successful chemotherapy with the cyclophosphamide, hydroxydaunomycin hydrochloride, vincristine, prednisolone regimen for diffuse large B-cell lymphoma. Computed tomographic examination and magnetic resonance imaging of the thorax revealed an intramuscular tumour measuring 40 mm in size in the left scapular region. Histopathological examination of an open biopsy specimen revealed a small round cell tumour that showed positive staining for CD99. Fluorescence in situ hybridization showed a split signal by a break-apart probe for the EWS gene in chromosome 22q12. Reverse transcriptase-polymerase chain reaction confirmed the expression of EWS-FLI1 fusion transcripts. Based on these findings, the patient was diagnosed as having secondary Ewing sarcoma. Despite adjuvant chemotherapy, however, she died of pulmonary metastases 2 years after the diagnosis of Ewing sarcoma. Therapy-related haematological malignancies with balanced translocations have been reported previously. A mechanism similar to that underlying the development of secondary malignancy might explain the occurrence of this solid cancer.

Sarcoma of the Breast: Outcome and Reconstructive Options

IntroductionSurgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances. Materials and MethodsData from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated. ResultsThirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06). ConclusionSecondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.

The epidemiology of sarcoma.

Sarcomas account for over 20% of all pediatric solid malignant cancers and less than 1% of all adult solid malignant cancers. The vast majority of diagnosed sarcomas will be soft tissue sarcomas, while malignant bone tumors make up just over 10% of sarcomas. The risks for sarcoma are not well-understood. We evaluated the existing literature on the epidemiology and etiology of sarcoma. Risks for sarcoma development can be divided into environmental exposures, genetic susceptibility, and an interaction between the two. HIV-positive individuals are at an increased risk for Kaposi’s sarcoma, even though HHV8 is the causative virus. Radiation exposure from radiotherapy has been strongly associated with secondary sarcoma development in certain cancer patients. In fact, the risk of malignant bone tumors increases as the cumulative dose of radiation to the bone increases (p for trend <0.001). A recent meta-analysis reported that children with a history of hernias have a greater risk of developing Ewing’s sarcoma (adjusted OR 3.2, 95% CI 1.9, 5.7). Bone development during pubertal growth spurts has been associated with osteosarcoma development. Occupational factors such as job type, industry, and exposures to chemicals such as herbicides and chlorophenols have been suggested as risk factors for sarcomas. A case-control study found a significant increase in soft tissue sarcoma risk among gardeners (adjusted OR 4.1, 95% CI 1.00, 14.00), but not among those strictly involved in farming. A European-based study reported an increased risk in bone tumors among blacksmiths, toolmakers, or machine-tool operators (adjusted OR 2.14, 95% CI 1.08, 4.26). Maternal and paternal characteristics such as occupation, age, smoking status, and health conditions experienced during pregnancy also have been suggested as sarcoma risk factors and would be important to assess in future studies. The limited studies we identified demonstrate significant relationships with sarcoma risk, but many of these results now require further validation on larger populations. Furthermore, little is known about the biologic mechanisms behind each epidemiologic association assessed in the literature. Future molecular epidemiology studies may increase our understanding of the genetic versus environmental contributions to tumorigenesis in this often deadly cancer in children and adults.

CT-Guided Percutaneous Vertebroplasty of the Upper Cervical Spine Via a Translateral Approach

Background: The clinical management of spinal hemangiomas and osteolytic metastases involving the upper cervical spine (C1-C3) is challenging. Symptoms vary from simple vertebral pain to progressive neurological deficits. Surgery and radiotherapy have been the treatment options for years. Surgery, however, can result in complications, such as hemorrhage, and may be counter-indicated when the treatment goal is primarily palliative due to multiple metastases, an unfavorable prognosis and/or a poor performance state. On the other hand, radiotherapy carries the risk of inducing secondary sarcomas or producing radionecrosis. Percutaneous vertebroplasty (PVP) was recently introduced as an alternative for treating patients in whom surgery and radiotherapy are counter-indicated. As of yet, there are few PVP case reports. Objective: This study aimed to evaluate the safety and efficacy of PVP using a computed tomography (CT)-guided translateral approach via the space between the carotid sheath and vertebral artery for hemangiomas or metastatic lesions at C1-C3 under local anesthesia. Study Design: CT-guided PVP was performed in 15 patients with hemangiomas or metastatic lesions at C1-C3 and clinical outcomes were evaluated. Setting: An interventional therapy group at a medical center in a major Chinese city. Methods: Fifteen consecutive patients had a total of 15 cervical vertebral bodies treated with CT-guided PVP via a translateral approach. The patients were followed up for a mean postoperative period of 8.3 months (range, 1-40 months). Pain status was assessed using a visual analog scale (VAS). The presence of complications was assessed preoperatively (baseline) and at 24 hours, 2 weeks, and one, 3, 6, 12 and 24 months postoperatively, or until the patient died or was lost to follow-up. Results: Fifteen consecutive patients were successfully treated with CT-guided PVP via a translateral approach. Their mean VAS score decreased from 7.7 ± 2.9 preoperatively to 1.4 ± 1.5 by the 24 hour postoperative time point, and was 1.2 ± 1.3 at 2 weeks, 1.2 ± 1.3 at one month, 1.4 ± 1.3 at 3 months, 0.6 ± 0.9 at 6 months, 0.3 ± 0.5 at 12 months, and 0 at 24 months after the procedure. The mean VAS score at all of the postoperative time points differed significantly from the preoperative baseline score (P &lt; 0.05). No severe complications were observed. Mild complications included 2 cases (13.3%) of asymptomatic cement leakage into the epidural space, one case (6.67%) of anterior leakage from the vertebral body, and 2 cases (13.3%) of paravertebral leakage. Limitations: This was an observational study with a relatively small sample size. Conclusions: The safety and efficacy of CT-guided PVP using a translateral approach via the space between the carotid sheath and vertebral artery were demonstrated in patients with hemangioma or metastasis in the upper cervical spine. CT-guided PVP via a translateral approach should become a treatment option for such patients. Key words: CT-guided percutaneous vertebroplasty, upper cervical spine, translateral approach, hemangioma, osteolytic metastasis, pain

Clinical features and outcomes in patients with secondary Ewing sarcoma

Ewing sarcoma (EWS) is rarely diagnosed as a second malignancy. We sought to describe a cohort of patients with secondary EWS and investigate if patient characteristics and survival differ between patients with secondary and primary EWS. Patients with EWS or peripheral primitive neuroectodermal tumor (PNET) reported to the Surveillance, Epidemiology, and End Results Program (SEER) database from 1973 to 2008 were evaluated based on primary or secondary tumor sequence. Overall survival was estimated by Kaplan-Meier methods and evaluated using the log-rank test. Competing risk analysis was used to describe risk of death due to malignancy rather than other causes. Fifty-eight cases of secondary EWS were reported, accounting for 2.1% of all EWS cases. The median latency from primary malignancy to secondary EWS was 64 months (range 1-282 months). 12.1% of patients with secondary EWS received radiation to the site of secondary tumor during therapy for their primary malignancy. Patients with secondary EWS were more likely to have axial tumors (77.4% vs. 62.5%; P = 0.03) and smaller tumors (75.0% vs. 48.2% <8 cm; P = 0.001). Five-year overall survival from diagnosis was inferior for patients with secondary compared to primary EWS (34.3% vs. 52.2%; P = 0.002). However, patients with secondary tumors were less likely than those with primary EWS to die from their malignancy [hazard ratio 0.44; 95% confidence interval (CI) 0.23-0.85]. Secondary EWS accounts for a minority of cases of EWS. Tumor size and site and patient survival differ among patients with primary and secondary EWS.

Risk Factors Associated With Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study

Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified. We conducted a nested case-control study of secondary sarcomas (105cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors. Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR= 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma. Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk.

Development of secondary skull sarcoma after treatment for childhood acute myeloid leukemia

Secondary cancer is a serious late complication in childhood leukemia survivors. Here, we report a case of secondary skull sarcoma developing after treatment for childhood acute myeloid leukemia, including bone marrow transplantation (BMT). This patient had breast cancer 1 year before treatment for the skull sarcoma. The patient underwent macroscopic total removal of the skull tumor with bone margin with postoperative radiation therapy and did not develop tumor recurrence for 25 months. Our patient's experience suggests that survivors of childhood leukemia are at risk of developing skull sarcoma and that multi-agent chemotherapy, including anthracycline, TBI used as conditioning for BMT, and development of GVHD, are possible risk factors. Considering the possibility of multiple secondary malignancies in such patients, careful long-term follow up is mandatory.

Timeline errors undermine hypothesis; ‘famous patient’ did have secondary osteogenic sarcoma and tuberculosis

Internal Medicine JournalVolume 42, Issue 4 p. 472-474 Timeline errors undermine hypothesis; ‘famous patient’ did have secondary osteogenic sarcoma and tuberculosis I. Gawler, I. Gawler The Gawler Foundation, Yarra Junction, Victoria, AustraliaSearch for more papers by this author I. Gawler, I. Gawler The Gawler Foundation, Yarra Junction, Victoria, AustraliaSearch for more papers by this author First published: 13 April 2012 https://doi.org/10.1111/j.1445-5994.2012.02737.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume42, Issue4April 2012Pages 472-474 RelatedInformation

Bone Infarct-Associated Sarcoma Detected on FDG PET/CT

Secondary sarcomas arising on the background of a bone infarct are extremely uncommon. Based on the knowledge of classic imaging patterns, however, lesions like bone infarcts can be recognized during positron emission tomography/computed tomography studies, which are now being performed increasingly in cancer patients. We demonstrate the detection of this rare entity on positron emission tomography/computed tomography and its correlation on magnetic resonance imaging in a 56-year-old man with asymptomatic multifocal osteonecrosis secondary to steroid treatment for polymyositis.

Abstract P6-08-03: MYC Amplification and Overexpression Discriminate Secondary from Primary Angiosarcoma of the Breast

Abstract Background: Secondary angiosarcoma of the breast is defined as a sarcoma developed in the irradiated field in patients previously treated for breast carcinoma. These tumors represent 25% to 50% of sarcomas developed after irradiation for breast cancer and are of poor outcome. Up to now, there are no criteria to distinguish primary from secondary angiosarcomas. The aim of this work was to identify molecular features able to discriminate these two types of tumors. Material and Methods: Our study was mainly based on the use of whole genome (SNP array) and whole transcriptome (mRNA and miRNA microarray) approaches. Others methods included quantitative PCR, reverse transcription quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. All patients’ records were reviewed and the clinical information about the primary and secondary sarcomas was recorded. For all radiation-induced sarcomas, the patients’ radiotherapy plans were reviewed and it was confirmed that the tumors respected the classic Cahan's criteria to confirm their secondary nature. Results: Amplification (5 to 50 fold) of the MYC oncogene was found in all breast secondary angiosarcomas (19 cases) but in none of primary angiosarcomas (6 cases) (p-value = 2.353e-05). MYC amplification was associated with mRNA and protein overexpression of this gene. In tumors with a MYC amplification, numerous genes corresponding to MYC targets and coding for mRNA or miRNAs were found to be deregulated as compared with expression levels observed in tumors without amplifications. These data point to the pathways preferentially involved in the pathogenesis of secondary angiosarcomas of the breast. The relationships between clinical, pathological and biological features are studied. Conclusions: MYC is amplified and overexpressed in secondary angiosarcomas of the breast. We suggest to exploit these characteristic features as a diagnostic criteria to distinguish primary from secondary angiosarcomas of the breast. Furthermore, those newly identified characteristics of secondary angiosarcomas could serve as a basis for tailored therapeutic approaches. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-03.

Familiäre Tumorerkrankungen im Knochen

Familial diseases leading to bone tumor formation are rare. They are mainly caused by genetic alterations of cell cycle constituent genes, such as retinoblastoma syndrome (RB1) and Li-Fraumeni syndrome (p53), of genes involved in growth-regulating transcriptional cascades, such as enchondromatosis (PTHR1) and multiple hereditary exostoses (EXT1, EXT2) or of genes maintaining chromosomal stability, such as Rothmund-Thomson (RECQL4), Werner (WRN) and Bloom syndromes (BLM). This leads to multiple benign bone tumors, which may undergo secondary malignant transformation (enchondromatosis: enchondromas, multiple hereditary exostoses: osteochondromas) or bone sarcomas, mainly osteosarcomas, such as primary (Li-Fraumeni, Rothmund-Thomson, Werner and Bloom syndromes) or secondary manifestations (retinoblastoma syndrome) of the underlying disease. Some of these lesions also carry an increased risk for developing additional malignant diseases. In contrast to sporadically occurring similar tumors, differences in manifestation in time, topography or histology may be present which can aid in the correct recognition of the underlying syndrome.

Late sarcoma development after curettage and bone grafting of benign bone tumors

Background and aim Rarely sarcomas develop in previous benign lesions, after a long term disease free interval. We report the experience on these rare cases observed at a single Institution. Patients and methods 12 cases curetted and grafted, without radiotherapy developed sarcomas, between 1970 and 2005, 6.5–28 years from curettage (median 18, average 19). Age ranged from 13 to 55 years (median 30, average 32) at first diagnosis; tumors were located in the extremities (9 GCT, benign fibrous histiocytoma, ABC, and solitary bone cyst). Radiographic and clinic documentation, for the benign and malignant lesions, were available. Histology was available for 7 benign and all malignant lesions. Results To fill cavities, autogenous bone was used in 4 cases, allograft in 2, allograft and tricalcium-phosphate/hydroxyapatite in 1, autogenous/allograft in 1, heterogenous in 1. For 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 osteosarcoma, 3 malignant fibrous histiocytoma, and 1 fibrosarcoma. Conclusions Recurrences with progression from benign tumors are possible, but the very long intervals here reported suggest a different cancerogenesis for these sarcomas. This condition is extremely rare accounting for only 0.26% of all malignant bone sarcomas treated in the years 1970–2005 and represents only 8.76% of all secondary bone sarcomas treated in the same years. This incidence is the same as that of sarcomas arising on fibrous dysplasia, and is lower than those arising on bone infarcts or on Paget's disease. This possible event must be considered during follow-up of benign lesions.

Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood

To compare patterns of long-term deaths due to secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer in a cohort of patients followed over a median of 28 years. The study included 4,230 patients treated at eight institutions, who were at least 5-year survivors of a first cancer, representing 105,670 person-years of observation. Complete clinical, chemotherapeutic, and radiotherapeutic data were recorded, and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. The integral dose was estimated for the volume inside the beam edges. The causes of death obtained from death certificates were validated. In total, 134 events were due to second malignant neoplasm(s) (SMN). We found that the standardized mortality ratio decreased with increasing follow-up for second carcinomas and sarcomas, whereas the absolute excess risk (AER) increased for a second carcinoma but decreased for second sarcomas. There was no clear variation in SMN and AER for hematological malignancies. We found a significant dose-response relationship between the radiation dose received and the mortality rate due to a second sarcoma and carcinoma. The risk of death due to carcinoma and sarcoma as SMN was 5.2-fold and 12.5-fold higher, respectively, in patients who had received a radiation dose exceeding 150 joules. Among patients who had received radiotherapy, only those having received the highest integral radiation dose actually had a higher risk of dying of a second carcinoma or sarcoma.

Sarcoma of the sella after radiotherapy for pituitary adenoma

Secondary malignancies are infrequent sequelae of pituitary radiotherapy. The goal of the present case study is to analyze clinical features of a selected group of cases to define the special characteristics of these tumors. We report the illustrative case of a 38-year-old man with acromegaly who had transsphenoidal surgery and radiotherapy 7 years before presenting with a sellar high-grade sarcoma. Transsphenoidal and transcranial resection, as well as repeated gamma knife radiosurgery, could not prevent tumor progression and development of meningiosis sarcomatosa. We performed a thorough search of the literature and reviewed numerous publications and reports on primary and secondary sarcomas of the sella. Our search revealed 51 cases of mesenchymal malignancies after sellar radiotherapy. For further analysis, we identified and selected a group of patients based on the criteria for studying radiation-induced tumors as described by Cahan.Compared to the surgically treated group, secondary sarcomas of the sella are more frequent in patients who have had radiotherapy. These tumors occur at normal dose schedules with long latencies. Their growth is very aggressive and they may develop meningiosis sarcomatosa. Until now, no treatment modalities have been able to stop the progression of these neoplasms. Radiation-induced sarcoma is a rare sequela of pituitary radiotherapy. It is important for the treating physician to keep in mind the possibility of post-radiation sarcoma development. Additionally, one must include these tumors into the differential diagnosis in pituitary patients presenting with tumor recurrence more than 5 years after radiotherapy in combination with a secondary lack of hormonal activity.

Secondary fibrosarcoma of the brain stem treated with cyclophosphamide and Imatinib

Radiation-induced midbrain fibrosarcoma is a rare, highly aggressive tumor, which is associated with poor prognosis. We present the case of a 48-year old man with brainstem fibrosarcoma 20 years following radiation therapy received for a pituitary tumor. We discuss this case in the context of the diagnostic criteria for these tumors, and previous reports of secondary and primary sarcomas of the central nervous system.

Treatment and outcome of giant cell tumors of the pelvis

Background and purpose Giant cell tumors (GCTs) of bone rarely affect the pelvis. We report on 20 cases that have been treated at our institution during the last 20 years.Methods 20 patients with histologically benign GCT of the pelvis were included in this study. 9 tumors were primarily located in the iliosacral area, 6 in the acetabular area, and 5 in the ischiopubic area. 8 patients were treated by intralesional curettage and 6 by intralesional resection with additional curettage of the margins. 3 patients with iliacal tumors were treated by wide resection. 2 patients were treated by a combination of external beam irradiation and surgery, and 1 patient solely by irradiation. In addition, 9 patients received selective arterial embolization one day before surgery. Of the 6 patients with acetabular tumors, 1 secondarily received an endoprosthesis and 1 was primarily treated by hip transposition. The patients were followed for a median time of 3 (1–11) years.Results 1 patient with a pubic tumor developed a local recurrence 1 year after intralesional resection and additional curettage of the margins. The recurrence presented as a small soft tissue mass within the scar tissue of the gluteal muscles and was treated by resection. No secondary sarcoma was detected and none of the patients developed pulmonary metastases or multicentricity. No major complication occurred during surgery.Interpretation We conclude that most GCTs of the pelvis can be treated by intralesional procedures. For tumors of the iliac wing, wide resection can be an alternative. Surgical treatment of tumors affecting the acetabular region often results in functional impairment. Pre-surgical selective arterial embolization appears to be a safe procedure that may reduce the risk of local recurrence.

Chromosomal analysis of primary and metastatic Rous sarcomas in the rat

The chromosomes of 13 primary and 4 secondary Rous sarcomas (RSV–SR) in the rat have been studied in fixations directly from the tumour. The general character of the chromosomal spectrum in the primary sarcomas was similar to that of the Rous sarcomas in the mouse and the Chinese hamster. However, normal diploid stemlines were considerably more frequent in the rat sarcomas; among the heteroploid stemlines it was noticeable that polyploids were absent and that pseudodiploidy seemed to be a more important evolutionary pathway than in the mouse and the Chinese hamster. Trends towards a non-random chromosomal engagement were noticed, both in the primary sarcomas and in the metastases derived from them.

Secondary sarcomas after radiotherapy for breast cancer

Radiotherapy (RT) has been a risk factor for development of soft tissue sarcomas (STS). The objective of the current study was to quantify the risk of STS after RT and surgery for breast cancer (BCa), assess time trends, and compare long-term survival of patients with RT-associated and non-RT-associated angiosarcoma (AS) using the Surveillance, Epidemiology, and End Results (SEER) database. Women with BCa reported to SEER in 1973 to 2003 were included. Kaplan-Meier curves and proportional hazards models, reported as hazards ratios (HR) with 95% confidence intervals (95% CI), were used. Survival of patients who developed RT-associated AS was compared with that of patients with primary AS of the thorax and upper extremities. The cohort of 563,155 BCa patients was divided into 2 groups: those who received RT (37%) and those who received no RT. RT use increased with time (P<.0001). A total of 948 patients developed STS 1 to 29 years after BCa diagnosis. RT patients had a higher incidence of all STS (31 vs 22 per 100,000 person-years; HR, 1.5 [95% CI, 1.3-1.8]), AS (HR, 7.6; 95% CI, 4.9-11.9), and malignant fibrous histiocytomas (MFH) (HR, 2.5; 95% CI, 1.6-3.9). RT remained a significant predictor after adjustment for covariates (HR, 1.4; 95% CI, 1.2-1.7). Partial mastectomies (HR, 7.1; 95% CI, 3.2-16), RT (HR, 2.2; 95% CI, 1.1-4.3), and lymph node dissections (HR, 2.6; 95% CI, 1.3-5) were found to be independent risk factors for AS. The hazard of STS after RT peaked at 10 years, reaching the non-RT hazard at approximately 23 years. The 5-year survival for STS was 38%. There was no difference in survival noted between RT-induced and non-RT-induced AS. RT was found to increase the risk for STS, in particular AS and MFH. Patients who received RT for BCa should be followed closely for >20 years.

Pleomorphic giant cell carcinoma of the urinary bladder

In this report, we present the clinicopathologic features of 8 cases of the pleomorphic giant cell variant of urothelial carcinoma. This is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The pleomorphic giant cell component varied from 20% to 100% of the tumor specimen; in 2 cases, the pleomorphic giant cell component composed greater than 50% of the tumor with 1 case showing pure pleomorphic giant cell carcinoma. The architectural pattern of the tumor varied from infiltrating pleomorphic tumor with bizarre giant cells to solid expansile nests with discohesive growth pattern; a hypocellular desmoplastic stromal response was present in 2 cases (25%) with single cells in sclerotic stroma. At histology, giant, bizarre, anaplastic cells with frequent typical or atypical mitotic figures were present in all cases. Seven mixed cases had concurrent conventional high-grade urothelial carcinoma; 2 cases presented features of micropapillary or lymphoepithelioma-like urothelial carcinoma. Variable size intracytoplasmic vacuoles were present in 2 cases. All patients had advanced-stage cancer (>/=pT3), and 6 (75%) had lymph node metastases. Immunohistochemical staining demonstrated that both pleomorphic giant cell and associated conventional urothelial carcinoma were positive for cytokeratins 7, CAM 5.2 and AE1/AE3, and epithelial membrane antigen; P63, thrombomodulin, and uroplakin III were positive in 6, 3, and 2 cases, respectively. Follow-up information was available in all cases (range, 6-74 months; mean, 20 months). Five of the patients died of disease from 6 to 17 months, and 2 patients were alive with metastases at 11 and 19 months. One patient had no evidence of disease at 74 months. In summary, pleomorphic giant cell is an aggressive variant of urothelial carcinoma associated with poor prognosis that presents at an advanced clinical stage. In limited samples, it may be misdiagnosed as secondary carcinoma or sarcoma, a pitfall of paramount importance for its clinical management.