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Carcinogenic activity in Sprague-Dawley rats of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-gluco-pyranose (chlorozotocin).

Sprague--Dawley rats of both sexes received 2 mg/kg body wt (group 1) or 0.4 mg/kg body wt (group 2) of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) intraperitoneally in weekly injections for life. A dose-dependent carcinogenic effect of chlorozotocin was found (animals with malignant tumors in group 1: males 88%, females 89%, in group 2: males 83%, females 63%, in controls: males 10%, females 24%). Chlorozotocin reduced the life expectancy of treated animals significantly, compared to solvent controls. Histologically, the chlorozotocin-induced tumors were shown to be mesotheliomas or sarcomas of the peritoneal cavity (undifferentiated type, fibrosarcomas, myosarcomas).

Animals↗

Expression of beta 2-microglobulin by human benign and malignant mesenchymal and neurogenic tumours.

Human myosarcomas, liposarcomas, meningosarcomas, glioblastomas and malignant schwannomas, their benign counterparts and normal cells from which these tumours derive, were examined for the expression of beta 2-microglobulin (beta 2m). Formalin fixed specimens from these tumours were studied by light microscopy employing the immunoperoxidase method with the use of antibodies directed towards beta 2m. The malignant tumours showed a broad spectrum from unstained to strongly stained tumours, most pronounced among myosarcomas. In addition, most stained tumours displayed a mosaic staining pattern in that unstained areas alternated with stained. There was a tendency towards increased staining for beta 2m in malignant compared to normal cells; this was also observed in the benign tumours although to a lesser degree. The results differ from most earlier studies, mainly of carcinomas which have shown a tendency towards down-regulation of MHC I molecules on the tumour cells. The results are discussed in relation to concepts of immune surveillance of tumours.

Astrocytoma↗

Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes and MorPhology.

With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups.

Adult↗

Unusual sarcomatoid neoplasm of the lung suggesting a myofibrosarcoma.

Myofibrosarcoma is a rare neoplasm that occurs mainly in the head and neck region and extremities of middle-aged patients. It often appears as a low-grade sarcoma and rarely metastasizes. We report the case of a 47-year-old male patient with a malignant mesenchymal pulmonary tumor affecting almost the entire lower left lobe. Clinically suggestive for a lung carcinoma, the tumor showed typical features of a myofibrosarcoma. A major spindle cell component was observed being positive for smooth-muscle actin, calponin, and vimentin, while stainings for desmin, h-caldesmon, alkaline phosphatase (ALK), and extensively studied cytokeratins were negative. Striking was a strong infiltrate with neutrophilic and eosinophilic granulocytes. DNA cytometry revealed aneuploidy with a peak in the near triploid range. Comparative genomic hybridization demonstrated multiple DNA gains and losses correlating with an aggressive clinical course. Shortly after resection of the primary tumor, the patient showed multiple distant metastases in the contralateral lung, the mediastinal lymph nodes, the left adrenal gland, and the pectoral and deltoid muscle, which responded well to chemotherapy. The case report will discuss the evidence for the final diagnosis of a primary pulmonary myofibrosarcoma and the differential diagnosis of sarcomatoid tumors of the lung.

Diagnosis, Differential↗

[Hyperbaric oxygen therapy in radionecrotic lesions].

The Anaesthesia and Recovery Service at the Galeazzi Orthopaedic Centre in Milan has an HOT unit where various cases of necrosis following radiotherapy for neoplasias have been and are still being treated. Some cases of radiodermitis and osteoradionecrosis only cured after HOT treatment are presented. The recovery of the scarring and granulation processes in these cases is attributable to the increased perfusion and above all diffusion of oxygen which activates the heating processes in the hypoxic tissues. An additional advantage of HOT is that patients can be treated in outpatients department (for periods ranging from 25 to 70 days according to the seriousness of the case), thus avoiding long-term hospitalisation and withdrawal from normal working life.

Adult↗

Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review.

BACKGROUND: Sarcomas are a rare complication of radiotherapy for breast carcinoma and patients have a poor prognosis. The incidence, histology, and management of patients with sarcomas were reviewed in the current study. METHODS: The authors reviewed the records of 16,705 patients with breast carcinoma. Of these, 13,472 (81%) were treated with megavoltage radiotherapy and 3233 were treated without at the Institute Curie (Paris, France) between 1981 and 1997. Median doses of 50-55 grays (Gy) in 25-27 fractions were delivered to the whole breast over a period of 5-5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when indicated, by a 16-26-Gy boost to the tumor or tumor bed. Treatment of radiation-induced sarcomas (RIS) consisted mostly of radical surgery and chemotherapy. RESULTS: Overall, 35 patients developed sarcomas. Of these, 27 fulfilled the Cahan criteria. The median follow-up was 9.3 years (range, 1-22.4 years). The latency period ranged from 3 years to 20.3 years. Thirteen sarcomas were located in the breast, 5- in the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula, and 3 in the axilla. Histologic evaluation identified 13 angiosarcomas, 3 osteosarcomas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2 leiomyosarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The cumulative RIS incidence was 0.07% (+/- 0.02) at 5 years, 0.27% (+/- 0.05) at 10 years, and 0.48% (+/- 0.11) at 15 years. Standardized incidence ratios were 10.2 (95% confidence interval, 9.03-11.59) for irradiated patients and 1.3 (0.3-3.6) for nonirradiated patients. Of the 27 patients, 15 died of sarcoma within 1 month to 14.5 years (mean, 34.2 +/- 0.7 months). The 5-year actuarial survival rate after diagnosis of RIS was 36% (+/- 0.11). CONCLUSIONS: The current study confirmed the rarity of RIS. However, it showed that the risk increased with time. Therefore, careful, long-term follow-up of patients treated with radiotherapy is needed for early detection and efficacious treatment of these malignancies.

Adult↗

Abnormalities of cobalt-activated acylase from human sarcoma, carcinoma and the adjacent tissue.

Cobalt-activated acylase form-2 from human uterine myosarcoma, lung adenocarcinoma and the adjacent tissue was isolated, purified and characterized. It was found, that the enzyme from the malignant neoplasms differed both from the normal tissue and benign tumor acylase-2 in its Km value, temperature optimum and effect of some ions. Some abnormal properties (pH dependence, activation by cobalt and thermostability) were common for benign and malignant tumors. In lung tissue adjacent to adenocarcinoma, some deviations of acylase properties were observed, similar to that found in tumor, indicating that biochemical changes may be present also in tissues unaffected by the neoplastic growth by the histopathological criteria.

Adenocarcinoma↗

The role of electron microscopy in the determination of tumour histogenesis.

In the majority of cases the histogenesis and classification of tumours can be unequivocally established by light microscopy, but in some instances the diagnosis remains ambiguous even after special staining techniques have been employed. So wide and varied are the situations in which the electron microscope can help establish a diagnosis that it is impossible to even mention them all in the brief time available. I will therefore present only a brief description of the manner in which one can resolve with the electron microscopy some well known diagnostic problems. This includes distinguishing: (1) an anaplastic carcinoma from a sarcoma; (2) an amelanotic melanoma from other tumours; (3) APUDomas from other tumors; (4) myosarcomas from other tumours; and (5) Ewing's tumour, neuroblastoma and lymphoma from each other.

Adenocarcinoma↗