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Background Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. Main body The term “PREPARE” designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). Short conclusion PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease.

BACKGROUND The prognosis for patients who develop dedifferentiation of central chondrosarcoma traditionally has been poor. Because not much has been reported about this rare lesion, many uncertainties remain about prognostic factors. METHODS In this retrospective study, the clinical, radiographic, and histologic features and the treatments in 123 patients from the Rizzoli Institute were reviewed in an attempt to define which factors may be related to outcome in patients with dedifferentiated central chondrosarcoma. RESULTS Among 123 patients who were included in this study, 109 patients were treated at the Rizzoli Institute, and 14 patients were seen in consultation. There were 66 males and 57 females, and their average age was 59 years. The femur (62 patients), pelvis (28 patients), and humerus (20 patients) were the most common locations. Radiographically, a soft tissue mass was present in 87% of patients, and a bimorphic pattern was appreciated in 53% of patients. Histologically, the cartilaginous component was considered Grade 1 in 63% of patients and Grade 2 in 37% of patients. In most patients, the dedifferentiated component showed the features of an osteosarcoma (92 patients), followed by fibrosarcoma (19 patients), and malignant fibrous histiocytoma (9 patients). For 101 patients, surgery was a component of their definitive management. In 25 patients, surgery was combined with chemotherapy. The 2-year and 5-year survival rates were 34% and 24%, respectively. The median survival was 13 months (95% confidence interval, 9-17 months). CONCLUSIONS Metastatic disease at diagnosis, malignant fibrous histiocytoma dedifferentiation, and a high percentage of dedifferentiated component were related to poorer outcomes. There was no statistical evidence of any beneficial effect from adjuvant chemotherapy. Cancer 2006. © 2006 American Cancer Society.

Objective: To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. Methods: Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. Results: Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weight n = 27, 0.18/1000 LB) and Escherichia coli (n = 19, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (n = 13), had complications (n = 4) or died (n = 7). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curve = 0.939, H-L = 0.944, sensitivity 76.0%, specificity 90.7%). Conclusions: GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

A 55-year-old male presented with a 1-month history of localized pain caused by an osteolytic and destructive lesion in the right distal femur. Histologically, the tumour consisted of spindle cells intermingled with epithelioid eosinophilic cells arranged in small cords embedded in a hyalinized-to-chondromyxoid stroma. Electron microscopy and immunohistochemistry showed features of myoepithelial differentiation. RT-PCR failed to demonstrate chimeric transcripts of extraskeletal myxoid chondrosarcoma. The final diagnosis was primary malignant myoepithelioma of bone. The patient is alive with lung metastases 13 months after surgery. Primary malignant myoepithelioma of bone is an exceptionally rare neoplasm that should be considered in the differential diagnosis with the more aggressive myxoid spindle cell sarcomas.

Angiosarcomas constitute a heterogeneous group of highly malignant vascular tumors. Angiosarcoma of bone is rare and poorly characterized. For angiosarcoma of soft tissue, some pathways seem to be involved in tumor development. Our aim was to evaluate the role of these pathways in angiosarcoma of bone. We collected 37 primary angiosarcomas of bone and used 20 angiosarcomas of soft tissue for comparison. Immunohistochemistry was performed on constructed tissue microarrays to evaluate expression of CDKN2A, TP53, PTEN, BCL2, CDK4, MDM2, cyclin D1, β-catenin, transforming growth factor-β (TGF-β), CD105, phospho-Smad1, phospho-Smad2, hypoxia-inducible factor-1α, plasminogen activator inhibitor type 1 (PAI-1), VEGF, CD117 and glucose transporter--1. PIK3CA was screened for hotspot mutations in 19 angiosarcomas. In nearly 55% of the angiosarcoma of bone, the retinoblastoma (Rb) pathway was affected. Loss of CDKN2A expression was associated with a significantly worse prognosis. No overexpression of TP53 or MDM2 was found, suggesting that the TP53 pathway is not important in angiosarcoma of bone. Angiosarcoma of bone showed highly active TGF-β signaling with immunoreactivity for phospho-Smad2 and PAI-1. Although the phosphatidylinositol 3-kinase (PI3K)/Akt pathway seems to be active in both tumor groups, different mechanisms were involved: 41% of angiosarcoma of bone showed a decrease in expression of PTEN, whereas in angiosarcoma of soft tissue overexpression of KIT was found (90%). PIK3CA hotspot mutations were absent. In conclusion, the Rb pathway is involved in tumorigenesis of angiosarcoma of bone. The PI3K/Akt pathway is activated in both angiosarcoma of bone and soft tissue, however, with a different cause; PTEN expression is decreased in angiosarcoma of bone, whereas angiosarcomas of soft tissue show overexpression of KIT. Our findings support that angiosarcomas are a heterogeneous group of vascular malignancies. Both angiosarcoma of bone and soft tissue may benefit from therapeutic strategies targeting the PI3K/Akt pathway. However, interference with TGF-β signaling may be specifically relevant in angiosarcoma of bone.

Context.—Clear cell chondrosarcoma (CCC) is commonly considered to be a low-grade subtype of chondrosarcoma. However, a few cases of CCC behave as high-grade lesions (with early metastases or multiple/synchronous locations). Objective.—To investigate morphologic features that can help predict the aggressiveness of these CCCs. Design.—To investigate possible hallmarks of this aggressiveness, we are presenting the clinicopathologic features of 6 cases of CCC, 4 of which presented aggressive features and 2 low-grade behavior. The patients were 5 men and 1 woman; their ages ranged from 22 to 47 years. Histologic appearance, ultrastructure, and immunohistochemical expression of metalloproteinase 1 and 2 and their inhibitors were evaluated in all 6 cases. Results.—Pain was the most common symptom; the lesions were located in the femur (4), humerus (2), and vertebral body (1), with 1 patient presenting a double/synchronous lesion. Although no major differences were detected using conventional light microscopy, an ultrastructural analysis—at variance with usual cases—showed a lack of superficial microvilli in more than 50% of neoplastic cells in the aggressive cases, therefore suggesting a less differentiated phenotype. In addition, metalloproteinase 2 was more diffusely expressed in the aggressive tumors than in the conventional CCCs, whereas p53 labeling was always negative. Conclusions.—The aggressive behavior of some CCCs may be, at least in part, correlated to a lesser degree of cell differentiation and to the expression of tumor cell proteins, such as metalloproteinase 2, which are able to favor neoplastic spreading.

Summary Five cases of ameloblastic fibrosarcomas (AFS) are reported. The tumour was characterized histologically by a biphasic pattern: the malignant mesenchymal component had the features of an intermediate grade fibrosarcoma in 3 cases, malignant fibrous histiocytoma and osteogenic sarcoma in 2 cases. The epithelial odontogenic component had a benign appearance cytologically. In 1 patient, in the recurrence only the malignant mesenchymal component was present. AFS is a fully malignant tumour, in fact 1 patient died of the tumour after inadequate surgical treatments, and 2 patients had a recurrence after intralesional surgery. The treatment of choice was achieved when surgery with wide surgical margins was performed. As MFH and OGS features are present in the malignant mesenchymal component of this tumour we prefer to use the broad term ameloblastic sarcoma instead of AFS.

In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant upregulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant upregulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered.

Eighty cases of primary fibrosarcoma of bone from the Rizzoli Institute are reviewed. There was a slight male predominance with a wide patient age distribution. Roentgenologically, low grade fibrosarcomas had generally well-defined margins and a "soap-bubble" appearance. High grade tumors appeared permeative and more aggressive. Histologically, the majority of tumors were high grade (3 and 4). Prognosis correlated well with the grade of the tumor. The 10-year survival rate was 83% for low grade sarcomas and 34% for high grade tumors. Local recurrence was a bad prognostic sign.

Summary: We report a case of primary diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma of the CNS, in a 68-year-old woman. The disease mimicked intracranial hypotension syndrome and was diagnosed only at autopsy (CSF cytologic results were negative). CT revealed hydrocephalus with effacement of the cerebral convexity sulci and abnormal contrast enhancement in the right sylvian and frontoparietal fissures, whereas MR imaging showed diffuse marked dural and leptomeningeal contrast enhancement. In retrospect, these nonspecific findings correlated with the extensive leptomeningeal invasion in the cerebral hemispheres, brain stem and spinal cord. The clinical, radiologic, and pathologic features of diffuse meningeal melanomatosis are reviewed.

The cases of forty-six patients who had dedifferentiated chondrosarcoma were reviewed. Two groups were identified: one in which a low-grade malignant chondrosarcoma was the precursor lesion and one in which a moderate to high-grade malignant chondrosarcoma was the precursor lesion. The radiographic features of these lesions ranged from that of a cartilaginous lesion that appeared to be benign to that of a destructive osteolytic tumor in which the cartilaginous component was overshadowed by the dedifferentiated component. Only three of the forty-six patients survived for more than two years. Resection alone, even when it was wide or radical, was not successful in controlling this lethal sarcoma.

This retrospective study examined 10 patients with osteoid osteoma and ? patients with osteoblastoma localized in the sacrococcyx. In the sacrum, the diagnosis was delayed compared to other sites. Curettage through a posterior approach is the treatment of choice. Radiotherapy as well as embolization of feeding arteries may be used for the most aggressive lesions. Prognosis is generally good with a low incidence of local recurrence(

A correlation between chemotherapy-induced necrosis and prognosis has been reported in Ewing sarcoma. To identify factors influencing histologic response data from 122 patients with Ewing sarcoma surgically treated were reviewed. Primary chemotherapy was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, actinomycin-D, and etoposide. Patients with complete necrosis or only scattered foci of viable tumor cells were good responders (GRs), the remaining patients poor responders (PRs). Age, sex, site and size of the tumor, fever at diagnosis, and lactate dehydrogenase level were clinical variables investigated. Mean age was 13.3±6 in GR and 18.1±9 in PR (P18 years (P=0.003). Female were more likely to achieve a GR (F 64% vs. M 42%, P

Background: Dedifferentiated chondrosarcomas that arise in osteochondromas are extremely rare lesions for which very little information on treatment and outcome is available in the literature. The purpose of the present study was to describe the specific clinical, radiographic, and histologic features of this lesion and to evaluate the oncologic outcome after different treatment strategies. Methods: We reviewed the files of the Rizzoli Institute between 1970 and 2002 and identified eighteen patients for whom adequate records and histologic images were available and in whom a high-grade sarcoma had been diagnosed at the same location as a preexisting osteochondroma. Radiographic studies, histologic slides, and clinical records were reviewed, the features of those studies were tabulated, and prognostic features and the results of treatment were identified. Results: The patients included twelve men and six women with an average age of forty-six years (range, twenty-two to seventy-four years). Eight lesions occurred in patients with multiple osteochondromas, and ten occurred in patients with solitary lesions. The most common locations were the pelvis (six lesions) and the femur (five lesions). Symptoms included pain, swelling, and a growing mass; the average duration of symptoms was eighteen months. Radiographically, ten lesions appeared as a conventional secondary chondrosarcoma arising in an exostosis, whereas eight showed typical signs of dedifferentiation. Histologic evaluation of the cartilage component demonstrated thirteen grade-1 and two grade-2 chondrosarcomas. In three cases, no cartilage component was recognized. The dedifferentiated component was considered to be an osteosarcoma in nine cases (including six cases in which it was osteoblastic and three in which it was fibroblastic), a malignant fibrous histiocytoma in eight, and a fibrosarcoma in one. The dedifferentiated component represented an average of 59% (range, 20% to 100%) of the lesion. For the fifteen patients who were managed at the authors' institution, the two and five-year survival rates were 47% and 29%, respectively; the median survival time was fourteen months. Patients who were managed with a combination of surgery and chemotherapy had a better overall survival rate than did those who were managed with surgery alone (p = 0.03). Conclusions: Dedifferentiated chondrosarcoma arising in a preexisting osteochondroma is an extremely rare lesion with a poor prognosis. In the present small series, overall survival was better when wide surgical resection was combined with adjuvant chemotherapy. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. Copyright © 2007 by the Journal of Bone and Joint Surgery, Incorporated.

BACKGROUND In primary central high-grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy. METHODS The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases. RESULTS The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5-year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5-year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS The authors concluded that the histologic subtype of primary central high-grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor. Cancer 2003;97:3068–75. © 2003 American Cancer Society. DOI 10.1002/cncr.11456

Aneurysmal bone cysts (ABCs) are benign bone lesions that may arise de novo in bone or rarely in soft tissue. Typically, there is no definite pre-existing lesion (primary ABC).

BACKGROUND. The clinical and pathologic features of 46 patients 40 to 60 years old with Ewing sarcoma family tumor (ESFT) diagnosed at the authors' institute between 1972 and 2000 were reviewed. METHODS. Ten patients with metastatic tumors at presentation went elsewhere for treatment; 35 of 36 remaining cases with localized disease were treated at the authors' institution according to different chemotherapy protocols activated in successive years. In patients with nonmetastatic tumors local treatment was surgery in 9 patients, radiotherapy in 16, and surgery followed by radiotherapy in 10. RESULTS. At follow-up times ranging from 6 and 34 years (mean, 17.8 years), 15 patients (42.9%) remained continuously disease-free, 19 experienced recurrence, and 1 died of chemotherapy-related toxicity. The 5- and 10-year event-free survivals were 42.9% and 35.2%, respectively, and the 5- and 10-year overall survivals were 46.1% and 42.8%, respectively. Comparing this group of patients with 586 cases of younger patients seen in the same period at Rizzoli, the only difference between the 2 groups was a significantly higher rate of tumors located in the soft tissues with a larger volume in the older group. The results achieved were comparable in the 2 groups, although the older group had a lower chemotherapy dose-intensity and a higher rate of WHO grade 4 hematologic toxicity. CONCLUSIONS. For patients with localized disease treated with adjuvant and neoadjuvant chemotherapy the results were essentially comparable in the 2 groups. It is concluded that patients 40 years or older with ESFT should be treated in the same way as younger patients and included in treatment trials for these tumors. Cancer 2007. © 2007 American Cancer Society.

We evaluated the rate of second malignancies in 1205 patients with osteosarcoma of the extremity treated at our Institution with different protocols of adjuvant and neoadjuvant chemotherapy. Twenty-six patients (2.15%) developed a second malignant neoplasm at a median of 7.6 years (1 to 25 y) after primary osteosarcoma treatment. Of these, 2 developed a third cancer which were not considered in the series. Second neoplasms were leukemia (10), breast (7), lung (2), kidney (2), central nervous system cancer (2), soft tissue (1), parotid (1), and colon (1). The rate of second neoplasms was significantly higher in female patients, and the latent period shorter in hematologic tumors compared with solid tumors. Ten of these 26 patients are disease free at a median of 7.7 years (range 1 to 15 y) after the last treatment. The rate of second malignancies observed in the osteosarcoma group was significantly higher than that observed in the control group of 1160 patients with benign tumors treated in the same period at our Institute (2.2% vs. 0.8%, P

BACKGROUND Dedifferentiated parosteal osteosarcoma (DPOS) is a variant of osteosarcoma in which a high-grade sarcoma coexists with a conventional parosteal osteosarcoma (c-POS), either at presentation (synchronous type) or at the time of recurrence (metachronous type). Only approximately 60 patients have been reported in the literature. The objective of this study was to analyze the clinicopathologic and radiographic features of a relatively large number of patients with DPOS in an attempt to define further the histologic and biologic behavior of this rare entity. METHODS In a series of 120 patients with parosteal osteosarcoma who were seen at the Rizzoli Institute from 1958 to 2000, the authors identified 29 patients who were diagnosed with DPOS. The authors reviewed the clinical and radiologic features, histologic sections, treatments, and outcomes in this group of patients with DPOS. RESULTS Twelve patients were male, and 17 patients were female. The patients ranged in age from 15 years to 65 yrs (average, 36 years; median, 32 years). One tumor involved the scapula, one involved the ilium, and another involved the skull. All 26 of the other tumors were located in the long bones (14 in the femur, 5 in the humerus, 3 in the tibia, 3 in the fibula, and 1 in the ulna). In 18 patients, radiographic areas of lucency were seen within an otherwise sclerotic lesion. Histologically, the dedifferentiated component was high-grade osteoblastic osteosarcoma in 14 patients, fibroblastic osteosarcoma in 10 patients, giant cell-rich osteosarcoma in 3 patients, and chondroblastic osteosarcoma in 2 patients. All tumors were Stage IIB, and invasion of the medullary canal was detected in 19 patients (65%). Twenty-eight patients underwent surgery, and 18 of those patients received chemotherapy (5 patients received neoadjuvant chemotherapy, and 13 patients received adjuvant). Nine patients were dead and 20 patients were alive (average follow-up, 107 months; range, from 3 months to 36 years) at the last follow-up. Of the nine patients who died, one patient received no treatment, five patients underwent surgery (with three patients achieving adequate margins) in combination with chemotherapy, and three patients underwent surgery only (with adequate margins achieved). Of the 20 patients who remained alive, 13 patients underwent surgery (with 10 patients achieving adequate margins) in combination with chemotherapy, whereas 7 patients underwent surgery only (all with adequate margins). Seven of the nine patients who died had widespread metastases. One patient died of causes unrelated to the tumor, and another patient died shortly after undergoing resection of a lesion in the skull. CONCLUSIONS Dedifferentiation occurred in approximately 24% of patients with c-POS. The prognosis for patients with DPOS was better than the prognosis for patients with dedifferentiated central and dedifferentiated peripheral chondrosarcoma. Cancer 2005. © 2005 American Cancer Society.

The medical records of patients with high-grade osteosarcoma observed at the authors' institution between 1972 and 1999 were reviewed to study whether osteosarcoma in preadolescent patients has a different biology and a worse prognosis than in older patients. To assess epidemiologic differences, the first analysis evaluated 1,603 patients regardless of tumor stage and site and treatment received. In the second analysis, only 1,136 patients (317 preadolescent and 819 older patients) with nonmetastatic extremity osteosarcoma, treated with the same protocols of chemotherapy, were evaluated to assess differences in prognosis and in the pattern of relapse. Most preadolescents were female (56% vs. 44%, P < 0.0001), and most tumors were located in the extremity (95% vs. 5%, P < 0.001). The 5-year event-free survival (60% [95% CI 53-67%] vs. 58% [95% CI 46-63%]), the overall survival (67% vs. 65%), the rate of amputation (24% vs. 25%), time (21 vs. 22 months) and type of first relapse (systemic 98% vs. 95%, local 2.3% vs. 4.7%) the site of first metastases (pulmonary, 87% vs. 89%), and good histologic response to preoperative treatment (65% vs. 63%) were essentially the same. The authors concluded that there is no need to employ different therapies for the two groups.

Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.

A case of leiomyosarcoma arising in the spermatic cord is described. A 83-year-old man required medical care for an irreducible inguinal hernia. The patient underwent herniorraphy and transinguinal radical orchiectomy. Macroscopically, the spermatic cord was enlarged by a gray-tan and ill-defined neoplasm measuring 4 x 4 x 3 cm. Histologically, this proliferation was composed of atypical spindle cells with blunted end nuclei and eosinophilic cytoplasm. Immunohistochemistry and ultrastructure confirmed the smooth muscle nature of the neoplastic cells. The diagnosis of leiomyosarcoma of the spermatic cord was made. To improve the assignment of this rare lesion to its specific anatomic location, we analyzed the immunohistochemical and ultrastructural characteristics of the smooth muscle tumoral cells and in particular those of the intracellular filament aggregates.

Although more and more patients with Ewing's sarcoma of bone (ESB) are being treated by surgery, the relative role of surgery and radiotherapy in the local treatment of this tumor has yet to be determined. Because the outcome of ESB may differ according to the anatomical site of the tumor, results reported in the literature, which generally refer to series with tumors located in all sites, may be selection biased. Therefore, we have retrospectively evaluated patients with ESB exclusively in the extremity and locally treated by surgery or radiotherapy. Two hundred and sixty-eight patients treated at Rizzoli 1979-1996 for non-metastatic ES of the extremities were assessed. Chemotherapy was administered according to four sequentially activated protocols. One hundred and thirty-six patients were treated by surgery, 70 by surgery and radiotherapy, and 60 patients by radiotherapy. Two patients underwent only chemotherapy. The follow-up range was 5-23 years (mean 13 years). One hundred and fifty-two patients remained continuously free of disease, 108 relapsed, 2 died of chemotherapy toxicity and 6 developed a second malignancy. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 62 and 69%. Although patients of all groups were matched for possible risk factors, the rates of 5-year EFS and local control were significantly lower in patients treated with radiotherapy compared to patients treated by surgery or surgery and radiotherapy (48% vs 66%, p=0.002; 80% vs 94%, p=0.0001). Furthermore, in group 3 there were 6 secondary malignancies. Our results indicate that surgery should always be considered in the local treatment of ES of the extremities. Postoperative radiation therapy must be added in case of inadequate surgical margins.

BACKGROUND Investigation of the relation between primary tumor and metastatic disease is necessary for the identification of predictive factors for postrecurrence survival (PRS) in patients with recurrent osteosarcoma. METHODS Cellular levels of P-glycoprotein, ErbB-2, p53, and Bcl-2 expression were evaluated in primary tumor biopsy and metachronous pulmonary metastasis specimens from 19 patients with high-grade osteosarcoma. Results were analyzed for differences between primary tumor and pulmonary metastases and for correlations between expression patterns and survival. RESULTS Positive staining in lung metastases was noted in 68%, 53%, 32%, and 84% of patients for P-glycoprotein, ErbB-2, p53, and Bcl-2, respectively. These percentages were higher than those observed in primary tumor specimens for all genetic markers evaluated, with a significant difference in the percentage of patients with positive staining for P-glycoprotein (68% vs. 32%; P = 0.05) and a near-significant difference in the percentage of patients with positive staining for Bcl-2 (84% vs. 53%; P = 0.08). Patients with ErbB-2 expression in the primary tumor were more likely to have multiple metastases and shorter recurrence-free intervals compared with patients in whom ErbB-2 expression was not observed, whereas differences in P-glycoprotein, p53, and Bcl-2 expression were not related to differences in metastatic pattern. PRS was influenced by p53 expression levels in pulmonary metastases, with patients who had negative staining for p53 having a significantly better PRS rate relative to patients with positive staining for p53 (3-year PRS rate: p53-negative, 64%; p53-positive, 17%; P = 0.008). CONCLUSIONS In the current study of patients with high-grade osteosarcoma, most patients exhibited increased cellular expression of P-glycoprotein, ErbB-2, and Bcl-2 in recurrent pulmonary metastases compared with primary tumor. Further studies aimed at investigating the relation between altered p53 expression in lung metastases and postrecurrence survival are recommended. Cancer 2004. © 2004 American Cancer Society.

Aims . To describe the outcomes of a large number of patients with pelvic osteosarcoma, and to define the guidelines for appropriate treatment. Methods . We reviewed 60 consecutive patients with primary pelvic high-grade osteosarcoma. The tumour involved the whole hemipelvis in 15 cases, while the most common location was the iliac wing in 29 cases (48.3%): 25 of these adjacent to or passing the sacroiliac joint. Results . Thirty patients underwent surgery; there were 16 hindquarter amputations and 14 internal hemipelvectomies. All the patients who presented with metastasis died of their disease. In 18 cases wide margins were achieved, however, eight patients experienced local recurrence. Of the series, only eight patients are still alive. Conclusion . The use of intense chemotherapy and surgical wide margin, hardly seems to achieve local control, however, tumour necrosis was correlated with positive prognosis. When internal hemipelvectomy it is not safe enough, amputation must be considered, particularly for cases with sacrifice of the sciatic nerve roots or for older patients where a shorter surgical procedure can be less risky.

Background: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. Patients and methods: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. Results: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). Conclusions: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.

Relatively little is known about occupational and other risk factors for renal-cell carcinoma (RCC). Associations between RCC and occupations, exposures and other factors were investigated in a hospital-based case-control study in Bologna (central-northern Italy). Between 1986 and 1994, 324 histologically confirmed RCC cases were diagnosed at Policlinico S. Orsola-Malpighi in patients from the Province of Bologna. Corresponding control subjects admitted to the same hospital with any diagnosis except RCC were matched for sex, age, and residency. We studied the 249 cases and 238 controls for whom detailed information on occupational history, diet, smoking habits, alcohol and drug intake was obtained. At conditional logistic regression, among males (167 matched pairs), significant matched odds ratios (OR) were found, after adjusting for cigarette smoking and alcohol intake, for high body-mass index BMI (third quartile: OR, 4.91; confidence interval [95% CI], 1.56-15.5; last quartile: OR, 4.42; 95% CI, 1.48-13.18), railway workers (OR, 10.14; 95% CI, 1.46-70.17) and asbestos exposure (OR, 7.11; 95% CI, 1.46-34.51); nearly significant OR were found for managers (OR, 3.59; 95% CI, 0.82-15.59) and metal workers (OR, 2.21; 95% CI, 0.99-5.37). Among females (52 pairs), significant OR were found for BMI > 25.4 (OR, 8.46; 95% CI, 1.02-68.0). Railway workers (on or near to trains) may have increased risk of developing RCC, possibly due to asbestos exposure. Studies are required on possible risks encountered by railway (and metal) workers and by managers.

BackgroundWe analyzed clinical and treatment-related factors influencing the outcome of patients with mesenchymal chondrosarcoma (MC). Twenty-six patients (median age, 31 years) were identified using the Tumor Center and Chemotherapy Department database of the study institute.MethodsPatients received surgery (24 patients) and/or radiotherapy (5 patients), and chemotherapy (12 patients).ResultsAfter a median follow-up of 48 months (7-237 months) 10 patients were alive. The 10-year overall survival (OS) was 27% in those who achieved complete surgical remission and 0% in those who did not (P = 0.0007). A worse 10-year probability of OS was observed in patients who were metastatic at presentation (metastatic 0%, localized 31%, P = 0.02), in patients with soft tissue MC (soft tissue MC 0%, bone MC 29%, P = 0.06) and in hemangiopericytoma-like MC (hemangiopericytoma-like MC 0%, Ewing's-like MC 33.5%, P = 0.9). In those patients who achieved complete surgical remission, the 10-year DFS was 76% for those who received chemotherapy and 17% for those who did not (P = 0.008).ConclusionsOur experience confirmed the importance of complete surgical remission in MC treatment and suggests that the addition of chemotherapy should offer a benefit in terms of DFS. Due to the rarity of MC, multicentrer studies are needed to identify the most active chemotherapy regimen.