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PubMed1995

Osteosarcoma versus malignant fibrous histiocytoma of bone in patients older than 40 years. A clinicopathologic and immunohistochemical analysis with special reference to malignant fibrous histiocytoma-like osteosarcoma.

BACKGROUND: It is often difficult to discriminate between osteosarcoma and malignant fibrous histiocytoma (MFH) of bone, especially in older patients because of the clinical similarities, including the lytic radiologic appearance. A histologic analysis of MFH-like osteosarcoma, which closely resembles MFH of bone both clinically and radiologically, has not yet been conducted thoroughly, and therefore this issue remains controversial. METHODS: Using clinicopathologic and immunohistochemical techniques, the authors studied 24 cases of osteosarcoma arising in patients older than 40 years of age and compared them with 20 cases of MFH of bone from similarly aged patients. RESULTS: Radiography revealed that 68.2% of the osteosarcoma cases were predominantly lytic, whereas all cases of MFH of bone showed either a predominantly or purely lytic pattern. Histologically, osteosarcoma was subclassified as conventional osteoblastic (54.2%), MFH-like (29.2%) containing various amounts of tumor osteoid and/or bone in each of the cases, and conventional fibroblastic (4.2%), whereas all the cases of MFH of bone had a storiform-pleomorphic pattern. Immunohistochemically, no overexpression of p53 protein was found in MFH-like osteosarcoma, whereas it tended to occur more frequently in osteoblastic osteosarcoma (66.7%) and MFH of bone (50.0%). The Ki-67 labeling index was significantly lower in MFH-like osteosarcoma than in MFH of bone. The 5-year survival rate was 18.2% in patients with osteoblastic osteosarcoma, 66.7% in patients with MFH-like osteosarcoma, and 21.5% in patients with MFH of bone. A significant difference in the survival curve was observed between osteoblastic and MFH-like osteosarcoma. CONCLUSIONS: It is proposed that MFH-like osteosarcoma, which shows characteristically different clinical and histologic features from that of conventional osteosarcoma, thus may be considered a variant of osteosarcoma.

Adult↗

PubMed2000

Pre-malignant and malignant lymphoproliferations in an HCV-infected type II mixed cryoglobulinemic patient are sequential phases of an antigen-driven pathological process.

Type II mixed cryoglobulinemia (MC) is a systemic vasculitis characterized by the presence in the serum of a monoclonal cryoprecipitable IgM with rheumatoid factor (RF) activity. Hepatitis C virus (HCV) has been recognized as its major etiologic factor. Because MC frequently evolves into overt B-cell non-Hodgkin's lymphoma (NHL), chronic HCV infection is hypothesized to lead to both benign and malignant lymphoproliferative disease. In this study, we investigated mutations in the V(H) and V(K) genes of the B-cell clone originating the overt B-cell lymphoma in a subject with MC. Mutational patterns were analyzed longitudinally in two bone marrow biopsies obtained at the stage of MC, as well as in multiple involved tissues (bone marrow, liver, and peripheral blood cells) at the stage of overt NHL. Hybridization of variable-diversity-joining (VDJ) PCR products with a probe specific for the neoplastic clone indicated that the lymphoma originated from one of the clones over-stimulated during MC. This clone producing an IgM highly homologous to a protein with RF specificity may explain the MC syndrome in the patient. Moreover, the presence of an IgH ongoing mutation process and the expression of an Ig antigen receptor significantly homologous to an anti-HCV protein support the hypothesis that the MC syndrome and the subsequent evolution to NHL are antigen-driven lymphoproliferative processes possibly sustained by HCV. Furthermore, the marked reduction in intra-clonal diversity in the last bone marrow biopsy obtained at the stage of overt NHL points out a minor dependence of the cells on the antigen-driven mechanism, although an intrinsic propensity of the neoplastic cell to undergo replacement mutations cannot be excluded.

Amino Acid Sequence↗

PubMed2004

Second malignant neoplasms in childhood acute lymphoblastic leukemia: primitive neuroectodermal tumor of the chest wall with germline p53 mutation as a second malignant neoplasm.

About 80% of children treated for acute lymphoblastic leukemia (ALL) will be long-term survivors. Second malignant neoplasm (SMNs) are a devastating sequelae observed on these children, with an estimated cumulative risk of 2-3.3% fifteen years after diagnosis. Primitive neuroectodermal tumor of bone (PNET) is rarely observed as a SMN following treatment of childhood ALL. The authors described the occurrence of a chest wall PNET of the bone at the site of a central line placement associated with both germ-line and tumor cell p53 mutation in a 8-year-old boy 1 year after completing therapy for standard risk ALL. A review of the literature of 25,051 children treated for ALL discovered 230 SMNs (0.99%), and only one case of PNET of the bone was noted among this group. The occurrence of a SMN in children treated for ALL is a rare event. Such an occurrence, in particular the development of an unusual SMN, should be evaluated for a germline p53 mutation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Malignant rhabdoid tumor: a highly malignant childhood tumor with minimal karyotypic changes.

Malignant rhabdoid tumors (MRT) are rare; thus very few cytogenetic studies of this type of tumor have been performed. We report the results of cytogenetic studies of 10 MRTs from various anatomic primary sites. Six cases had normal diploid karyotypes with no detectable rearrangements or aneuploidy except for occasional tetraploid cells. In 4 of these cases the tumor phenotype was verified by electron microscopic studies. In a seventh case only normal cells were identified in short-term culture, but a del(13)(q14) appeared after 4 months in culture. A soft tissue MRT contained a translocation, t(8;15)(q12;p11), and a liver MRT contained a del(3)(q21) or t(3;?)(q21;?). The single case of a primary brain MRT had monosomy 22 with deletion of part of the remaining chromosome 22. Our findings indicate that visible chromosomal rearrangements occur in fewer than half of MRTs. When combined with other reported series, our study indicates that monosomy 22 is a non-random chromosomal abnormality in primary MRT of the brain.

Brain Neoplasms↗

PubMed1981

Adjuvant reactivity predicts survival in patients with "high-risk" primary malignant melanoma treated with systemic BCG. EORTC Malignant Melanoma Cooperative Group Writing Committee.

We report the prognostic importance of strength of reaction to BCG, tumor histology and clinical factors in patients with previously untreated high-risk (Clark, III, IV and V) primary malignant melanoma. One hundred and one such patients receive high-dose BCG (1 x 10(8) viable units) by Heaf gun as an adjuvant to standardized primary surgery according to EORTC Protocol 18741. Univariate analysis of disease-free interval (DFI) indicates that the degree of maximum reaction to BCG (p = 0.0003), Breslow thickness (p = 0.0003) and Clark level (p = 0.002) are highly significant prognostic factors. When a multivariate model using Cox's proportional hazard regression was used for DFI, the degree of maximum reaction to BCG and Breslow thickness were by far the most significant criteria. A prognostic equation wa obtained to predict DFI from maximum BCG reaction and Breslow thickness. From analysis of the "scores" calculated in this way it appears that the two variables act independently. This technique permits the determination of values that are predictive of DFI and discriminate between subgroups of patients with different DFI characteristics (5 groups, p less than 0.0001). This exercise was repeated for survival and similar results were obtained. The degree of a patient's immune reaction to BCG administered therapeutically is of paramount importance in determining the likelihood of survival. This factor and the Breslow thickness can be integrated to produce a mathematical equation which accurately predicts survival for appropriately treated melanoma patients.

Adolescent↗

PubMed1995

Overall and site-specific risk of malignant melanoma associated with nevus counts at different body sites: a multicenter case-control study of the German Central Malignant-Melanoma Registry.

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

Arm↗

PubMed1978

Malignant mouse melanoma cells do not form tumors when mixed with cells of a non-malignant subclone: relationships between plasminogen activator expression by the tumor cells and the host's immune response.

Mouse melanoma clones B559 and B78 are highly tumorigenic when injected into C57BL/6J mice. Tmor formation by these cells is suppressed when they are mixed with nonmalignant bromodeoxyuridine-grown clone C3471 before injection. C3471 cells suppress tumor formation only in immunocompetent hosts; mixtures of B559 and C3471 cells or C3471 cells alone form tumors in antithymocyte serum (ATS)-treated mice. Explants of C3471 tumors grown in ATS-treated mice form tumors in immunocompetent mice, most of which regress. Inability of C3471 or mixtures of C3471 with malignant cells to grow in normal mice, as contrasted with ability to grow in immunosuppressed mice, indicates that host response is involved. Both tumorigenic clones have high plasminogen activator activity, whereas nontumorigenic clone C3471 has none. Mixture of either tumorigenic clone with C3471 cells decreases plasminogen activator in vitro. C3471 tumor explants from ATS-treated mice initially express plasminogen activator, but lose the capacity to express this activity upon prolonged cultivation in vitro. Explants from B559 tumors retain plasminogen activator in long term culture. Close physical contact between C3471 and B559 cells appears essential both for inhibiton of plasminogen activator expression by B559 cells in vitro, and for tumor suppression in vivo. These findings suggest that production of plasminogen activators by tumor cells may play an important role in suppressing the host's immune response locally to an inoculum of syngeneic tumor cells.

Animals↗

PubMed1981

Morphological studies in malignant tumors of the peripheral nervous system (neurofibrosarcoma, malignant schwannoma, schwann cell sarcoma).

9 cases of malignant tumors of the peripheral nerve sheaths have been observed and their morphology including ultrastructures have been studied. 5 cases could be classified as neurofibrosarcomas, I as a Schwann cell sarcoma. Another cases may be grouped with the melaninproducing Schwann cell sarcomas and 2 cases with the "epitheloid Schwann cell sarcomas". The latter group, their separation or their connection to soft tissue sarcomas and to the "medullo-epitheliomas" of peripheral nerves are discussed.

Adult↗

PubMed1995

Risk of nodal metastases from malignant salivary gland tumors related to tumor size and grade of malignancy.

Indications for elective treatment of the neck are not well defined in salivary gland tumors. We retrospectively reviewed 153 cases of malignant salivary gland tumors treated from 1965 to 1985 at the Hospital de Oncología, Mexico City. There were 106 parotid cancers, 26 in the submandibular gland and 21 in minor salivary glands. Median follow-up was 48 months. In T1-2 tumors there was a 12% incidence of nodal metastases as compared with 27% in T3-4 cancers (P = 0.01). Thirty-six elective neck dissections were performed. Patients with high-grade tumors had an increased risk (50%) of occult node metastases, while no cases were found in low-grade carcinomas (P < 0.05). The risk of neck recurrence was higher in N+ (23.5%) than in N0 patients (3.2%). The 5-year actuarial survival was significantly better in low-grade tumors (78%), T1-2 tumors (85%) and negative nodes (63%) than in high-grade neoplasms (49%), T3-4 tumors (35%) and positive nodes (P = 0.001, P = 0.001 and P = 0.04, respectively).

Adolescent↗

PubMed1996

Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome.

Hardcastle syndrome is a rare, autosomally dominant inherited skeletal dysplasia, characterized by diaphyseal sclerosis, medullary stenosis, pathological fractures, bony infarction, and malignant transformation. A 19-year-old proband is presented and discussed, adding a fourth family to the world literature. Radiographic screening of family members is suggested from puberty onward. Thallium scanning is proposed as a more tumor-sensitive screening agent in affected individuals.

Adult↗

PubMed1990

Comparative studies on the expression of gastrointestinal-cancer-associated antigen, PA8-15, CA19-9 and the blood-group antigens in non-malignant and malignant human pancreatic tissues.

The expression of PA8-15 antigen and the blood-group-related antigens A, B, O, Le(a), Le(b), Le(x), and Le(y), as well as CA19-9, were examined in the normal pancreas and in specimens from benign and malignant pancreatic tissue by the avidin-biotin-immunoperoxidase technique. A correlation was found between the expression of PA8-15, Le(a), and CA19-9 in some cases. However, in the cancer tissues in which neither Le(a) nor CA19-9 could be demonstrated, strong expression of PA8-15 was observed. The reactivity of monoclonal antibody (mAb) PA8-15 with pancreatic cancer tissue was not inhibited by the preincubation of the sections with the mAb anti-Le(a) (CO514) and mAb CA19-9 (CO19-9) indicating that the epitope recognized by PA8-15 is different from that detected by the other two antibodies. Moreover, unlike Le(a) and CA19-9, PA8-15 was also expressed in cancer cells of patients of the Le(a-b-) type. The results suggest that mAb PA8-15 recognizes a sialylated molecule related to Le(a) but different from CA19-9, and seems to be an additional useful marker for pancreatic cancer.

Adenocarcinoma↗

PubMed1990

Reticulin fibre content of bone marrow infiltrates of malignant non-Hodgkin's lymphomas (B-cell type, low malignancy)--a morphometric evaluation before and after therapy.

A morphometric study was performed on bone marrow infiltrates of non-Hodgkin's lymphomas (B-cell type, low malignancy) to evaluate the content of argyrophilic (reticulin) fibres in the various subtypes before and after therapy. In congruence with the corresponding lymph node lesions, subtypes consisted of lymphocytic lymphoma--chronic lymphocytic leukaemia (CLL, n = 39), centroblastic-centrocytic lymphoma (CB-CC, n = 35), lymphoplasmacytoid immunocytoma (LPI, n = 22) and finally hairy cell leukaemia (HCL, n = 21). In comparison with control specimens, morphometric measurements on trephine biopsies (initial staging procedure) disclosed a borderline or minimal increase in reticulin in CLL and moderate fibrosis in CB-CC and LPI, whereas HCL had the greatest increase in fibres. The marrow surrounding focal or patchy lymphoma infiltrates of CLL and CB-CC displayed no relevant changes in fibre density with respect to the control samples. Following chemotherapy, repeated trephine biopsies (restaging procedure) were obtainable from 38 patients. There was no significant decrease in the fibre content of CLL, CB-CC and LPI infiltrates. In HCL an incomplete reduction was recorded after interferon treatment. So-called benign lymphoid lesions may be distinguished from focal-patchy infiltrates of CB-CC and LPI not only by showing a central localization, but also by the absence of significant amounts of reticulin. However, considering the density of the reticulin fibres, a clear-cut discrimination of these lymphoid aggregates from an early nodal-central growth pattern of CLL is not feasible in many cases.

B-Lymphocytes↗

PubMed1994

[Position and recommendations of the Malignant Melanoma Committee of the German Society of Dermatology on diagnosis, treatment and after-care of malignant melanoma of the skin. Status 1993/94].

The Melanoma Committee of the German Dermatological Society has prepared this position paper on prognostic factors, classification and clinical staging of cutaneous malignant melanoma and has recommended guidelines for diagnosis, treatment and follow-up. The aim is to achieve a consensus procedure for dealing with this tumour.

Aftercare↗

PubMed1996

[Levodopa and malignant melanoma--case report and review of the literature. A contribution to causal relationship between levodopa and the development of malignant melanoma].

A 72-years old man with Parkinson's disease was treated with levodopa for 14 years. A superficial spreading melanoma (Breslow depth 1,8 mm Clark level IV) was diagnosed, developing on the back from a pigment lesion which had present for more than 10 years. Other case reports suggest a relationship between the administration of levodopa and the growth of malignant melanoma. On the other hand, epidemiological studies found no correlation. Furthermore, in vitro and in vivo studies have shown a possible anti-tumor effect of levodopa. Critical analysis of the literature leads to the conclusion, that there is no increased melanoma risk from levodopa.

Aged↗

PubMed1999

Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy.

We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype.

Aneuploidy↗

PubMed1998

Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration.

PURPOSE: Depletion of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) has been shown to increase tumor sensitivity to chloroethylnitrosoureas. Temozolomide (TMZ), an analogue of dacarbazine, can deplete AT, suggesting that it may be used to sensitize tumors to chloroethylnitrosoureas. However, the influence of nitrosoureas on the pharmacokinetics of TMZ is unknown, and a pilot study was performed to assess the pharmacokinetics of TMZ given via, various routes to 29 patients (27 malignant melanomas, 2 gliomas) with or without sequential administration of i.v. fotemustine. METHODS: On day 1, TMZ was given intravenously (i.v.), orally (p.o.), or by intra-hepatic arterial infusion (h.i.a.) at four ascending dose levels (150 to 350 mg/m2 per day). On day 2 the same dose of TMZ was given by the same route (or by another route in six patients for determination of its bioavailability), followed 4 h later by fotemustine infusion at 100 mg/m2. Plasma and urinary levels of TMZ were determined on days 1 and 2 by high-performance liquid chromatography after solid-phase extraction. RESULTS: The pharmacokinetics of i.v. TMZ appeared linear, with the area under the curve (AUC) increasing in proportion to the dose expressed in milligrams per square meter (r = 0.86 and 0.91 for days 1 and 2, respectively). The clearance after i.v. administration was 220 +/- 48 and 241 +/- 39 ml/min on days 1 and 2, respectively. The apparent clearance after p.o. and h.i.a. administration was 290 +/- 86 and 344 +/- 77 ml/min, respectively. The volume of distribution of TMZ after i.v., p.o., and h.i.a. administration was 0.4, 0.6, and 0.6 l/kg on day 1 and 0.5, 0.5, and 0.6 l/kg on day 2, respectively. The absolute bioavailability of TMZ was 0.96 +/- 0.1, regardless of the sequence of the i.v.-p.o. or p.o.-i.v. administration, confirming that TMZ is not subject to a marked first-pass effect. A comparison of TMZ pharmacokinetics after i.v. and h.i.a. treatment at the same infusion rate revealed little evidence of hepatic extraction of TMZ. However, the systemic exposure to TMZ (AUC) appeared to decrease at a lower infusion rate. TMZ excreted unchanged in the urine accounted for 5.9 +/- 3.4% of the dose, with low within-patient and high interpatient variability. TMZ crosses the blood-brain barrier and the concentration detected in CSF amounted to 9%, 28%, and 29% of the corresponding plasma levels (three patients). The equilibrium between plasma and ascitic fluid was reached after 2 h (assessed in one patient). CONCLUSION: The sequential administration of fotemustine at 4 h after TMZ treatment had no clinically relevant influence on the pharmacokinetics of TMZ. The potential clinical effect of TMZ given by h.i.a. or by locoregional administration has yet to be established, as has the impact of the infusion duration on patients' tolerance and response rate.

Administration, Oral↗

PubMed1996

[Low malignancy myxofibrosarcoma versus low malignancy fibromyxoid sarcoma. Distinct entities with similar names but different clinical course].

Low-grade myxofibrosarcoma (MFS) and low-grade fibromyxoid sarcoma (FMS) are two distinct entities in the spectrum of myxoid mesenchymal sarcomas with fibroblastic differentiation. Low-grade MFS is seen often in the extremities of elderly patients, subcutaneously more frequent than in deep soft tissues, whereas the majority of cases of low-grade FMS occur in young to middle-aged adults, commonly in deep soft tissues of the shoulder region, the extremities and the trunk. Histologically, low-grade MFS shows a multinodular growth pattern and is composed of round or polygonal tumour cells mixed with elongated, curvilinear, thin-walled blood vessels in a myxoid matrix. The tumour cell nuclei in low-grade MFS display at least moderate nuclear pleomorphism and hyperchromasia. Low-grade FMS, however, is composed of bland fusiform tumour cells arranged in a whorled or swirling pattern, or occasionally more linear, and set characteristically in an alternating fibrous and myxoid stroma. Low-grade MFS recurs frequently but has a very low metastatic potential, whereas low-grade FMS is characterised by an indolent but ultimately malignant clinical course with metastases in more than half of the cases, which underlines the importance of distinguishing between the two entities.

Adult↗

PubMed1986

Characterization of a novel Burkitt's lymphoma-associated antigen: GP70. Reactivity of anti-GP70 antibodies with various malignant and non-malignant cell lines.

A glycoprotein of 70 kDa (GP70) was isolated from sera of Burkitt's lymphoma (BL) patients and used to immunize rabbits. Anti-GP70 antibodies at a high titer were obtained and used for screening of cancer cells of various origin by the indirect immunofluorescence test. Thus, 66% of BL-cell lines tested were positive to GP70. On the other hand, all lymphoblastoid cell lines tested were negative. Moreover, all peripheral blood cells and mononuclear cells from tonsils were negative, indicating specificity of antibodies to malignant transformation. Comparison between positively stained BL-cell lines indicated no correlation between the presence of GP70 and EBNA. Positive stain (1-5%) obtained with bone marrow cells might indicate that anti-GP70 antibodies are directed against a surface membrane differentiation glycoprotein.

Antibodies, Neoplasm↗