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PubMed1997

Recent results in color compositing of three-parameter magnetic resonance scans as a preoperative aid to the management of upper limb sarcomas.

We report on improved image quality and some recent clinical results with volume-rendered, color composite, multiparameter, magnetic resonance (MR) datasets and their color histograms. In a previous article we demonstrated the major components of an interactive visualization environment for multiparameter T1-, T2-, PD-weighted MR volume datasets. These are compositing of the three parametric volumes, color volume rendering of the resulting composite, interactive segmentation of the tissues based on color cluster statistics derived from display of the three-dimensional (3D) histogram, and head-tracking stereo display. We herein review the system design and describe improvements to the quality of the color volume rendering, in the display of the 3D color histogram data, and in the specification of the volume renderer's opacity function. Finally, we report on some recent clinical results using our system.

Arm↗

PubMed1998

[Cytogenetic changes in low grade central osteosarcomas].

Low grade central osteosarcomas are a group of rare bone neoplasms morphologically simulating benign bone tumors or tumor-like lesions (fibrous dysplasia, nonossifying fibroma, osteoblastoma, chondromyxoidfibroma or aneurysmal bone cyst). Because of the apparent bland histology they may be misinterpreted as benign lesions despite their primary low malignant behavior and late metastatic potential including the capability to transform into a highly malignant sarcoma. In contrast to high grade osteosarcomas cytogenetic studies of these entities are very rare. Karyotyping including FISH analysis with painting- and centromere-specific probes was done in 2 cases of low grade central osteosarcomas (fibrous dysplasia like type). One case was a primary lesion in the upper femur, the other was a recurrent lesion in the upper humerus. Additionally a static DNA cytometry using Feulgen stained imprints was carried out in both cases. In the first case clonal aberrations with a Robertsonian translocation between chromosomes #14 und #15, balanced translocations including chromosomes #5 and #21, #12 and #20, and a supernumary ring chromosome derived from chromosome #1 were detected in a near diploid karyotype. The second case displayed the development from a DNA-diploid to a DNA-peritetraploid lesion during a follow up of six years. Cytogenetic different marker chromosomes and again ring chromosomes were detected in a near tetraploid karyotype. Low grade central osteosarcomas of fibrous dysplasia like type may be characterized by chromosomal aberrations including ring chromosomes. Regarding the last feature these cytogenetic findings resemble those found in low grade parosteal osteosarcomas and other mesenchymal lesions of borderline behavior or low malignancy grade (for example dermatofibrosarcoma protuberans, low grade liposarcoma).

Adolescent↗

PubMed1990

Expression of HLA-A,B,C, beta 2-microglobulin (beta 2m), HLA-DR, -DP, -DQ and of HLA-D-associated invariant chain (Ii) in soft-tissue tumors.

Non-neoplastic mesenchymal cells, along with 33 benign and 87 malignant soft-tissue tumors (STT) were examined for expression of HLA-A,B,C, beta 2-microglobulin (beta 2m), HLA-DR, -DP, and -DQ molecules and the HLA-D associated invariant chain (Ii). Serial frozen sections were immunostained using monoclonal antibodies (MAbs) to monomorphic framework determinants of HLA sublocus products, beta 2m and Ii, and to CD53, a recently defined broadly distributed pan-leucocyte molecule. Compared with the normal state, an induction/neo-expression of HLA-A,B,C/beta 2m was found in a considerable number of tumors of muscle, peripheral nerve, cartilage-forming, adipose, and vascular tissues. Conversely, some tumors of fibrous origin and of autonomic ganglia showed an abnormal abrogation/loss of HLA-A,B,C/beta 2m with respect to their cells of origin. Small, round tumor cells present in various types of STT exhibited a heterogenous pattern of expression of these molecules with a preponderance of HLA-A, B,C/beta 2m-negativity. HLA-D/Ii determinants were rarely detectable in STT. Besides their expression in some fibrohistiocytic tumors, they were only occasionally found in tumors of smooth-muscle, peripheral-nerve and vascular origin as well as in one clear-cell sarcoma. In all tumors but one, there was no microtopographic association between HLA-D/Ii-positive tumor cells and inflammatory cells. CD53 allowed discrimination between dendritic interstitial cells (DIC) and neoplastic cells and additionally revealed that, in contrast to other solid tumors, STT are generally characterized by an extreme scarcity of lymphohistiocytic infiltrates. Our data indicate that, aside from very rare exceptions, aberrant induction or abrogation of MHC molecules in STT occurs in the absence of lymphohistiocytic stromal infiltrates, suggesting that these alterations might not be a consequence of local cytokine effects.

Adipose Tissue↗

PubMed2001

Malignant melanoma with a myxoid stroma: a diagnostic pitfall on fine-needle aspiration biopsy.

Malignant melanoma (MM), both primary and metastatic, may be associated with a prominent myxoid stromal reaction causing diagnostic confusion on fine-needle aspiration biopsy (FNAB), most often with sarcomas that demonstrate a myxoid stroma, particularly malignant peripheral nerve sheath tumor (MPNST). We present a case of a 32-yr-old man with no past medical history who presented with a unilateral neck mass clinically suspicious for lymphoma. FNAB produced a specimen composed of large sheets of anaplastic cells encased in a myxoid stroma that was S100 and vimentin-positive but HMB-45-negative. A diagnosis of MPNST was made. Excision demonstrated a metastatic MM of unknown primary, with a prominent myxoid stromal reaction. A repeat HMB-45 was again negative. Electron microscopy demonstrated intracytoplasmic melanasomes and cisternae of rough endoplasmic reticulum with intracisternal parallel tubules, confirming the diagnosis. Although HMB-45 is typically negative in both tumors, S100 should be strongly positive in myxoid MM and only focal in MPNST.

Adult↗

PubMed2001

Second malignancies after ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study.

BACKGROUND: Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients. PATIENTS AND METHODS: Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine. doxorubicin, ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide as a randomized question. Second cancer incidences were estimated by competing risk analyses; standardized incidence ratios (SIR) in comparison to registry data were compiled. RESULTS: After a median observation time of 56 months (32 months for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two, ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased 20-30 fold in comparison to the general population. The cumulative second cancer risk five years after diagnosis of the Ewing tumor was 0.0093 for the total group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after five years. CONCLUSIONS: The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.

Adolescent↗

PubMed2006

Reproducibility of MDM2 and CDK4 staining in soft tissue tumors.

MDM2 and CDK4 immunostaining can be useful adjuncts in diagnosing liposarcoma among soft tissue neoplasms. We examined the reproducibility of MDM2 and CDK4 staining between 2 laboratories and between tissue microarrays and whole tissue sections. Sixty-two soft tissue tumors were immunostained at the Bergonié Institute, Bordeaux, France, and the Curie Institute, Paris, France. We also examined 203 soft tissue neoplasms on standard tissue sections and tissue microarrays. There was high concordance of results obtained from the 2 laboratories (with 2 different pathologists) for MDM2 (kappa, 0.93) and CDK4 (kappa, 0.8) staining. There also was excellent concordance between results on tissue microarray and on whole tissue sections for MDM2 (kappa, 0.80) and CDK4 (kappa, 0.93). Immunostaining for MDM2 and CDK4 is a reproducible technique that may be exported to different laboratories for routine use. Tissue microarray is indicated for studying large series.

Biomarkers, Tumor↗

PubMed2006

Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody.

BACKGROUND: Friend leukaemia integration-1 (FLI-1) antibody is a useful marker for Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and vascular tumours. However, it is also expressed in subsets of lymphoblastic lymphoma, Merkel cell carcinoma (MCC) and desmoplastic small round cell tumour (DSRCT). AIM: To determine expression of FLI-1 in various benign and malignant neoplasms, by immunohistochemical analysis on 4323 tumours using multiple tumour microarrays, as well as on whole sections. RESULTS: FLI-1 was expressed in 46/62 EWS/PNETs, 2/3 olfactory neuroblastomas, 7/102 small cell carcinomas of the lung, 10/34 MCCs, 1/14 rhabdomyosarcoma, 19/132 non-Hodgkin's lymphomas, 2/3 DSRCTs, and in 53/74 benign and malignant vascular tumours. In addition, 27/508 squamous cell carcinomas, 19/837 adenocarcinomas, 10/400 urothelial bladder cancers, 1/40 basal cell carcinomas, 3/29 liposarcomas, 1/40 glioblastoma multiforme and 9/29 medullar carcinomas of the breast expressed FLI-1. The sensitivity and specificity of FLI-1 to distinguish EWS/PNET from all types of malignancies were 74.2% and 96.0%, respectively. Finally, the sensitivity and specificity of FLI-1 to distinguish EWS/PNET from other small round cell tumours (SRCTs) were 74.2% and 91.6%, respectively. CONCLUSION: This study was the first to show that FLI-1 can be seen in a variety of solid tumours, some of which had never been explored before. This finding should be kept in mind, especially when using FLI-1 as a marker for finding the primary origin of poorly differentiated metastatic tumour. Finally, despite the expression of FLI-1 in numerous malignancies, it is still considered to be highly sensitive and specific in distinguishing EWS/PNET from other tumour types in general and from other SRCTs in particular.

Biomarkers, Tumor↗

PubMed2004

[Comparison of intensity-modulated postoperative radiotherapy with conventional postoperative conformal radiotherapy for retroperitoneal sarcoma].

External postoperative radiation therapy for retroperitoneal sarcoma is an example of treatment using large fields for complex shaped volumes of irradiation. Prescribed dose is limited by tolerance of adjacent organs at risk (OAR). From a recent case treated by conventional conformal radiotherapy (3D-CRT), we evaluate the benefit of five theoretical IMRT plans. Criteria used are calculated from DVH related to delineated PTV and OAR. IMRT should permit to enhance the prescribed dose without increasing dose in the OAR (especially residual kidney, spinal cord and small bowel). This theoretical study show the feasibility of a dose escalation from a treatment dose of 45 Gy delivered by 3D-CRT up to a planning dose of 54 Gy calculated by IMRT with: for the PTV: an improvement of the dose homogeneity about 5% (range 2-6%) and moreover the coverage factor (CF) about 13% (range 9-16%); for the OAR: an improvement of the protection factor (PF) about 20% (range 11-24%); and thus an improved conformity index (CI = CF x PF) about 25% (range 15-32%).

Feasibility Studies↗

PubMed1990

Soft-tissue sarcomas: MR imaging and MR spectroscopy for prognosis and therapy monitoring. Work in progress.

The authors studied the usefulness of hydrogen-1 T2 measurements and phosphorus-31 magnetic resonance (MR) spectroscopy as indicators of prognosis and monitors of response to therapy in a group of patients with soft-tissue sarcomas. All eight patients were treated with combined local hyperthermia and fractionated radiation therapy, followed by surgical resection of the tumor. Each patient underwent T2 measurements and five patients underwent MR spectroscopy (phase encoded in one dimension) before treatment, after the first hyperthermia treatment, at the end of the therapy course, and just before surgery. Catheter thermometry was performed at each hyperthermia treatment. The T2 and MR spectroscopic variables were compared with thermometric data and the histologic findings from the complete surgical specimen. Changes in T2 correlated with histologic grade of tumor and thermometric data. The pretherapy tumor pH correlated positively, and changes during therapy in pH, ratio of phosphocreatine to inorganic phosphate (Pi), ratio of nucleoside triphosphate to Pi, and the phosphomonoester signal-to-noise ratio correlated negatively, with the percentage of tumor necrosis on the surgical specimen. These preliminary data suggest MR imaging and MR spectroscopy may be useful in the evaluation of such patients before and during therapy.

Adult↗

PubMed2005

Extraskeletal myxoid chondrosarcoma metastatic to the pancreas: a case report.

Extraskeletal myxoid chondrosarcoma (EMC) is a low-grade sarcoma characterized by developing metastases and local recurrence in high rate. It is mainly deep seated in the proximal extremities. The most common metastatic sites are the lungs, soft tissues, lymph nodes, bones and the brain. To our knowledge, no case of clearly defined EMC has been reported to date developing a metastasis in the pancreas. We describe a case of a man suffering from EMC who developed a single pancreatic metastasis 20 years after the initial diagnosis. A 49-year-old man was submitted to surgical excision of an EMC, in left thigh, 20 years ago. Fourteen years after the initial diagnosis a local recurrence in left thigh occurred. Multiple lesions of metastatic origin, in both lungs, were excised via thoracotomies until the time being. In 2003, as a part of a periodically performed imaging control, an abdominal CT scan was performed revealing a solid lesion in the pancreas. Distal pancreatectomy was performed. The histopathology of the excised specimen proved to be the one of metastatic lesion of EMC. The above-mentioned case of EMC is, as far as we know, the first one described developing a certain pancreatic metastasis.

Chondrosarcoma↗

PubMed1979

Immunotherapeutic trials of murine and guinea-pig solid tumors by oral administration of BCG.

Efficacy of oral administration of BCG on the growth of various tumors in mice and guinea pigs was studied. The growth-inhibitory effect varied depending on the tumor systems and the experimental conditions. Weekly oral administrations with 5-mg doses of BCG to mice or 80-mg doses of BCG to guinea pigs were ineffective on syngeneic mouse melanoma B16 or syngeneic guinea pig hepatocarcinoma line-10 but effective on syngeneic mouse carcinoma IMC and syngeneic guinea-pig fibrosarcoma H9A. Oral BCG seemed effective also on allogeneic mouse carcinoma Ehrlich, developed with a relatively small size of tumor cell inoculum, and on guinea-pig syngeneic liposarcoma H10. On Ehrlich tumors, oral BCG given once a week seemed to have better effects than did oral BCG given twice a week or subcutaneously once or repeatedly; heat-killed BCG given orally showed no effect. However, it seems premature to draw a definite conclusion on the efficacy of oral BCG on Ehrlich and H10 tumors, because some of these tumors regressed spontaneously even in nontreated control animals. The host responses to oral BCG were studied with the following results. Weekly oral administration with 80-mg doses of BCG to guinea pigs elicited positive skin reactions to 25 TU PPD in about 65 days after the first BCG, while a single sc injection of 8 mg of BCG did so within 10 days. Orally administered BCG organisms were recovered largely from Peyer's patches, a little from the mesenteric lymph nodes, and very little from the liver and the spleen. The BCG distributive pattern was in reverse order when BCG was given subcutaneously. Histologic examinations of Peyer's patches indicated enlargement of germinal centers, in which primitive reticular cells proliferated prominently and the macrophages with tingible bodies scattered frequently.

Administration, Oral↗

PubMed2003

Cavernous sinus exenteration for invasive cranial base tumors.

OBJECTIVE: Invasive tumors involving the cavernous sinus, such as recurrent benign meningiomas or sarcomas, raise therapeutic problems that may be resolved by cavernous sinus exenteration (CSE). METHODS: Our series comprises 18 patients (9 women and 9 men ranging in age from 14 to 64 yr) who underwent CSE during the past 8 years. The tumors in these patients included 12 meningiomas, 3 chondrosarcomas, 1 rhabdomyosarcoma, 1 lipomyosarcoma, and 1 epidermoid carcinoma. Preoperative occlusion of the internal carotid artery was confirmed in 15 cases by a balloon occlusion test. Three patients had a negative balloon occlusion test, and their internal carotid arteries were preserved (n = 1) or revascularized (n = 2) through an external carotid artery-to-middle cerebral artery bypass. RESULTS: CSE was performed as a primary treatment in 5 patients and after one to five recurrences in 13 patients. In all patients, CSE included the internal carotid artery and Cranial Nerves III, IV, and VI and one to three branches of Cranial Nerve V. Orbital exenteration was performed in eight patients, and partial hypophysectomy was performed in five patients. Ten patients had received radiotherapy before CSE, and five patients underwent irradiation after CSE. The operative mortality includes two patients. Cerebrospinal fluid leakage was the main complication in four patients, with three patients having meningitis. Follow-up ranged from 6 months to 5 years, with three deaths from new recurrences at 2, 3, and 4 years after CSE. As compared with their clinical courses before CSE, all patients except the two who died postoperatively benefited from CSE. CONCLUSION: CSE has useful indications in invasive and rapidly growing tumors, including apparently benign meningiomas. A better understanding of the biological behavior of these tumors is necessary for appropriate selection of patients for CSE.

Adolescent↗

PubMed2001

Correlation of intraoperatively irradiated volume and fibrosis in patients with soft-tissue sarcoma of the extremities.

PURPOSE: To investigate the influence of intraoperatively irradiated volume on soft-tissue fibrosis. METHODS AND MATERIALS: Fifty-three patients with soft-tissue sarcoma of the extremities were treated with intraoperative radiotherapy (IORT) (median dose 15 Gy) and postoperative fractionated therapy (median dose 46 Gy). The median follow-up was 41.5 months (range 18-94). Late toxicity was classified according to the LENT-SOMA criteria. A Cox regression model was calculated to identify the parameters that could influence soft-tissue fibrosis Grade 3 or 4. Five parameters were observed: extent of surgical procedure, IORT in case of recurrence, extent of IORT volume, extent of IORT dose, and extent of postoperative volume. In addition, a logistic regression model was calculated to demonstrate the relationship between the IORT volume and fibrosis development. RESULTS: The overall survival rate after 5 years was 84%. The actuarial tumor control rate was 90% after 5 years. Eleven patients developed soft-tissue fibrosis. Five patients developed Grade 3 fibrosis and 1 patient developed Grade 4 fibrosis. Only the IORT volume had a significant influence on Grade 3 or 4 fibrosis development. An IORT volume of 210 cm(3) conveyed a 5% risk (confidence interval 1-20%) of the development of severe fibrosis. The risk of severe Grade 3 or 4 fibrosis increased to 50% (confidence interval 15-80%) if a volume of 420 cm(3) was irradiated. CONCLUSION: The effect of volume in patients treated with IORT was remarkable. The ratio of side effects was relatively low. The risk of soft-tissue Grade 3 or 4 fibrosis increased with the extent of the IORT volume. Compared with the literature, IORT provides excellent local control in these patients.

Adolescent↗