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PubMed1988

Systemic sclerosis in association with multiple primary pulmonary malignancy--a marker of internal malignancy?

Multiple pulmonary malignancy is uncommon and has not been reported in association with systemic sclerosis. We now report such a case in which it is likely that the connective tissue disease occurred as a marker of the internal malignancy. Systemic sclerosis is not generally a reliable indicator of malignant change, but it is possible that in patients who are immunosuppressed, either therapeutically or inherently, the onset of systemic sclerosis should prompt investigation for an underlying cause.

Carcinoma, Squamous Cell↗

PubMed2000

Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma.

BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.

Adult↗

PubMed2001

Malignant glioma as a secondary malignant neoplasm after radiation therapy for craniopharyngioma: report of a case and review of reported cases.

BACKGROUND: The development of a secondary neoplasm in childhood cancer survivors attains growing importance due to the reported excellent survival and therefore the long exposure to potentially carcinogenic effects of treatment. CASE REPORT: We report a 14-year-old girl in whom a large craniopharyngioma (CP) was diagnosed. After surgery, radiation therapy (RT) was given for residual tumour. Discrete progression necessitated further surgery, resulting in permanent tumour control. Soon after the second surgery hypothalamic-pituitary dysfunction developed together with obesity. Supportive hormone therapy was initiated. Growth hormone (GH) therapy was also given for 15 months. Four years after the diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected, with the main lesion being at the dorsal edge of the irradiated area. The girl died 1 month later from this secondary presumably radiation-induced tumour. Only recently a second child with RT for a CP was diagnosed with malignant glioma in our hospital. CASE REPORTS IN THE LITERATURE: 12 other cases of malignant glioma have been reported after RT for CP. Including our present cases, the mean latency period was 10.7 years (median 9.6 years). However, the shortest latency periods were found in patients who had received GH therapy. In numerous cases, the secondary tumour was seen at the edge of the irradiated volume, and not in the region with the highest absorbed dose. CONCLUSIONS: Therapy-induced secondary gliomas after treatment of CP or other intracranial tumours are rare but dramatic late events with a very poor prognosis. Including our own 2 patients, we reviewed 14 cases of CP with occurrence of a secondary, probably radiation-induced malignant glioma. The short latency periods for patients treated with GH is remarkable. We therefore suspect that GH therapy may accelerate the development of a secondary brain tumour. We are reluctant to recommend GH therapy in conventionally irradiated CP patients. In order to seriously answer the questions about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for all patients who are survivors of childhood cancer.

Adolescent↗

PubMed1977

Immunodiagnostics of malignant diseases. II. The electrophoretic mobility test in the diagnosis of gynecological malignancies.

We applied the electrophoretic mobility test (EMT) to 117 patients. 49 patients suffered from gynecological malignant tumors of different types and eleven had a carcinoma in situ. 57 patients served as a control group, 26 of whom were clinically healthy volunteers and 31 had benign gynecological diseases. In the EMT all malignant cases had inhibition values of at least-5% or even more. All other tested persons, the so-called non-malignant or healthy cases, had an inhibition of less than -5% or even an acceleration of the tanned sheep erythrocytes stabilized with sulfosalicylic acid (ETS).

Antigens↗

PubMed1981

Ectopic human placental lactogen and beta-human chorionic gonadotropin in gastric fluid of patients with malignant and non-malignant conditions of the stomach.

Human placental lactogen (hPL) and beta-human chorionic gonadotropin (beta-hCG) in gastric aspirates and sera of 24 patients with malignant (12 patients) and non-malignant (12 patients) conditions of the stomach were studied. In patients with cancer of the stomach, hPL and beta-hCG were found to be present in gastric aspirate at higher frequency than in serum. The concentration of these hormones in gastric aspirate was higher than in serum. In 2 patients with duodenal ulcer beta-hCG was found to be present in gastric aspirate, 1 of them having the hormone in circulation as well, while none of the 12 patients with non-malignant conditions of the stomach showed presence of hPL in their gastric aspirate or serum.

Adult↗

PubMed1997

Collision of primary malignant neoplasms on the skin: the connection between malignant melanoma and basal cell carcinoma.

Several studies have reported the association of cutaneous malignant melanomas (MM) with carcinomas. Collision malignancies cases from our files were retrieved. Among a series of 78,000 primary cutaneous cancers, 11 were collision tumors of MM with basal cell carcinoma and 106 were basosquamous carcinomas while no association was found between MM and squamous cell carcinomas. It is concluded that coexisting and confluent malignancies of the skin might not always be a random event.

Adult↗

PubMed2003

Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: a prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89.

PURPOSE: To evaluate the prognostic value of metastases, extension into bone, and alpha-fetoprotein (AFP) elevation in children with malignant sacrococcygeal germ cell tumors (GCTs) prospectively collected in two cooperative Maligne Keimzelltumoren (MAKEI) protocols (83/86 and 89). PATIENTS AND METHODS: Between October 1983 and October 1995, 76 of 210 registered patients with sacrococcygeal primaries presented either with pure yolk sac tumor, embryonal carcinoma (EC), or yolk sac tumor and EC mixed with immature and mature teratoma elements. Stages T1 and T2 disease were diagnosed in 15 and 61 children, respectively, 41 patients had metastases, and 35 children presented with extension into bone. At diagnosis, 22 children had an AFP elevation of less than 10,000 ng/mL. Thirty-six children showed an AFP level between 10,000 and 100,000 ng/mL, and 12 patients had values of greater than 100,000 ng/mL. Five patients died of complication during treatment and were excluded from further evaluation. Seventy-one patients could be analyzed. RESULTS: The 5-year relapse-free survival rate (RFS, Kaplan-Meier) was 0.76 +/- 0.03 (54 of 71 patients; median observation time, 54 months after diagnosis). The RFS of patients with and without metastases was different, but not significantly so (0.71 v 0.82). The outcome of patients with extension into bone (n = 31) and without this extension (n = 40) was 0.71 versus 0.80 (RFS, 5 years). Above-normal AFP level had no prognostic significance (P =.52). CONCLUSION: In children with malignant sacrococcygeal GCTs treated with an intensive, short-interval, platinum-based regimen, the stage, extent of metastases, extension into bone, and AFP level had no prognostic significance.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Malignant fibrous histiocytoma (giant cell type) associated with a malignant mixed tumor in the salivary gland of a dog.

A 12-year-old male Boxer dog presented with a 5 x 5 x 7-cm partially encapsulated mass in the right mandibular salivary gland. Histologically, the mass was composed of neoplastic epithelial and mesenchymal cells. The mesenchymal component consisted of two cell populations arranged in different patterns: coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled with neoplastic epithelial cells and containing osteoid and well-formed bone trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis of these histological features, two malignant salivary tumors were diagnosed: a malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor. Immunohistochemical studies demonstrated keratin 5 and 8 expression by the neoplastic epithelial cells, indicating a probable salivary ductal origin, and vimentin expression by all mesenchymal elements, suggesting a fibroblastic line of differentiation.

Animals↗

PubMed2005

Differential effects of all-trans-retinoic acid (RA) on Erk1/2 phosphorylation and cAMP accumulation in normal and malignant human prostate epithelial cells: Erk1/2 inhibition restores RA-induced decrease of cell growth in malignant prostate cells.

OBJECTIVE: All-trans-retinoic acid (RA) regulates cellular growth, differentiation and apoptosis in human prostate by binding to RA receptors. Non-genomic retinoid effects on signal transduction kinases in the cytoplasm are also described in several cells but they are still unknown in prostate cells. METHODS: Using an epithelial cell line derived from normal human prostate (EPN), and normal (NPEC) and malignant (CPEC) epithelial primary cultures of human prostate, we have examined effects of RA on both extracellular signal-regulated kinase 1/2 (Erk1/2) and cAMP accumulation. Then we have verified the effect of the inhibition of Erk1/2 on RA-induced growth arrest and apoptosis in malignant cells. RESULTS: In NPEC and in EPN treated with RA for up to 24 h, Western blot analyses of Erk1/2 phosphorylation show that RA causes a rapid activation of Erk1/2 within 5 min, which is maintained for 30 min, followed by a return to basal levels. In CPEC, the activated phosphorylation levels persist up to 24 h. While basal cAMP levels are not affected by 30 min treatment with RA in both EPN and NPEC, levels are increased in CPEC. Forskolin-induced cAMP levels are decreased by RA in all cell types. CPEC were incubated for up to 96 h with RA with and without the inhibitor of Erk1/2, UO126. CPEC incubated with RA and UO126 for 72 h showed a significant arrest of cell growth and after 96 h apoptosis in 11% of cells. CONCLUSIONS: We show rapid effects of RA on cytoplasmic messenger pathways in human prostate, and that responses can differ between normal and malignant cells. The inhibition of these pathways could improve the efficiency of RA in prostate cancer growth control.

Aged↗

PubMed1979

Scanning electron microscopy of exfoliated malignant and non-malignant human urothelial cells.

Midstream urine samples were taken from 35 patients with histologically diagnosed urinary bladder carcinoma, from 27 patients without history or sign of malignancy or infection in the urinary tract, and from eight patiens with cystitis. The urine was filtered through Millipore filters, or Nuclepore filters, pore size 5.0 microns, on which the cells were caught. From the same patients biopsies were obtained from different anatomic regions of the urinary bladders as well as from the carcinomas that were present. The filters and the biopsies were examined with scanning electron microscopy (SEM). The exfoliated cells trapped on the filters were in good morphological condition. Idential characteristics of the cell surface morphology were recognized in the biopsies and the exfoliated cells from each patient. In non-malignant cases the cells displayed the regional morphological charcteristics of the urinary bladder. Bacteria and an increased number of red and white blood cells were attached to the cell surface of numerous exfoliated cells in patients with cystitis, but no pleomorphic microvilli were detected in these patients. In cases of malignancy exfoliated cells with pleomorphic microvilli on their surface were detected. A large majority of the exfoliated cells shed in the urine with pleomorphic microvilli on their surfaces still retained enough regional surface characteristics to determine their origin. Some of the cells were completely covered with pleomorphic microvilli and it was impossible to determine their origin.

Biopsy↗

PubMed1993

Bone marrow findings in malignant histiocytosis and/or malignant lymphoma with concurrent hemophagocytic syndrome.

We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg. nu lambda and gamma kappa were manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients. Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears to be an important factor of profound cytopenia in patients of MH and/or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkin's disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.

Adolescent↗

PubMed1994

RHAMM, a receptor for hyaluronan-mediated motility, on normal human lymphocytes, thymocytes and malignant B cells: a mediator in B cell malignancy?

RHAMM (Receptor for HA Mediated Motility) is a novel HA receptor that has been linked to regulating cell locomotion and density dependent contact inhibition of fibroblasts, smooth muscle cells, macrophages, lymphocytes, astrocytes and sperm. The ubiquitous expression of RHAMM suggests the existence of multiple isoforms, and indeed, RHAMM is found in various cellular compartments, namely nuclear, cytosolic, membrane-bound and extracellular. In this review, we emphasize the evolving role of RHAMM in B cell malignancies, and examine the function of RHAMM in T cell development in the thymic microenvironment. Both the motile behaviour of progenitor thymocytes (CD3-CD4-CD8-) and malignant B cells from multiple myeloma (MM), plasma cell leukemia, and hairy cell leukemia was blocked by monoclonal antibodies to RHAMM, suggesting that motility may correlate with increased expression of RHAMM at the cell surface. Interestingly, the soluble form of RHAMM is able to inhibit fibroblast locomotion, and it is likely that a balance between expression of both forms determines, in part the motility of cells. RHAMM appears to play a fundamental role in the immune system and the ability of RHAMM to function as a motility receptor is likely to be due to complex variables including the extent to which soluble RHAMM is secreted. RHAMM expression characterizes circulating monoclonal B cells as abnormal. potentially invasive and/or metastatic components of myeloma and may underlie the malignant behavior of these cells.

B-Lymphocytes↗

PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗

PubMed1994

Malignant fibrous histiocytoma in chordoma--immunohistochemical evidence of transformation from chordoma to malignant fibrous histiocytoma.

Sarcomatous transformation in chordoma (dedifferentiated chordoma) is a very rare condition and has been emphasized as a distinct entity because of its more aggressive clinical course. Here we describe a case of dedifferentiated chordoma (chordoma associated with malignant fibrous histiocytoma) arising from the sacrococcygeal region of a 55-year-old woman. The results of immunohistochemical stain in the chordoma area were strong positive for cytokeratin, epithelial membrane antigen and S-100 protein. The spindle and giant cells in the transitional areas of chordoma and malignant fibrous histiocytoma were positive for cytokeratin and epithelial membrane antigen in addition to vimentin and alpha-1-antichymotrypsin. The spindle and giant cells in the central area of malignant fibrous histiocytoma were negative for cytokeratin and epithelial membrane antigen, but positive for vimentin and alpha-1-antichymotrypsin. This supports the pathogenesis of sarcomatous transformation from chordoma.

Chordoma↗

PubMed1998

Expression of c-MET/HGF receptor mRNA and protein in human non-malignant and malignant prostate tissues.

We previously reported the expression of hepatocyte growth factor (HGF), a ligand for c-MET, at the level of mRNA and protein in human prostate tissues. The present study was carried out to evaluate the relationship between c-MET expression and cancer cell proliferation or effect of cancer therapy. The expression both in mRNA and protein levels of c-MET proto-oncogene was determined semi-quantitatively by reverse transcription-competitive polymerase chain reaction (RT-competitive PCR) and Western blot analysis for prostate tissues from 32 Japanese male subjects. In addition, tissue localization of c-MET translation product was examined by immunohistochemistry for corresponding specimens. Although there was significantly higher c-MET protein expression in malignant (prostate cancer treated with/without neoadjuvant endocrine therapy) than in non-malignant prostate tissues (normal prostate and benign prostate hyperplasia; BPH), unexpectedly, c-MET mRNA showed high expression in the non-malignant group. Thus, there was no parallelism between mRNA and protein expressions of c-MET. Endocrine therapy did not alter c-MET mRNA and protein expressions in human prostate cancer. Immunohistochemical localization and expression of c-MET protein was found to be intense in cancer cells and weak in epithelia of normal and hyperplastic prostates. Unconcerted expression of mRNA and protein of c-MET, the reason of which is uninterpretable, is supposed to be one of characteristics of human prostate cancer.

Aged↗

PubMed2002

Expression of lymphocyte-specific chemokines in human malignant glioma: Essential role of LARC in cellular immunity of malignant glioma.

Lymphocytes are frequently observed in human malignant glioma, the mechanism(s) underlying their appearance is not fully understood. To clarify tumor immunity in malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern blot, immunoblot and immunohistochemistry, and examined the correlation with the infiltration of various subsets of lymphocytes. For the 8 chemokines examined (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1alpha), expression of LARC was clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally, expression of TARC and SCM-1alpha was detectable in the majority of glioma cell lines. However, the expression level of most chemokines was low, so that Northern blot analysis could not demonstrate their expression with the exception of LARC in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by phorbol myristate ester in U87 MG cells. The production of LARC protein was demonstrated in 4 of 8 glioblastoma tissues by immunoblotting, and 9 of 33 samples (27.3%) by immunohistochemistry. Interestingly, the positivity of LARC staining was significantly correlated with the infiltration of CD8-, CD4-, and CD45R0-positive cells (p<0.001). Although the constitutive expression level of LARC is low, certain stimulations could strongly induce its expression, and play a crucial role in the tumor immunity of human malignant glioma.

Blotting, Northern↗

PubMed2000

Malignant giant cell tumor of synovium (malignant pigmented villonodular synovitis).

CONTEXT: Pigmented villonodular synovitis (PVNS) is a well-recognized entity that has the potential for extensive local destruction, even though it rarely metastasizes. Rare reports of malignant forms are recorded in the literature. We observed 2 patients in whom examples of PVNS followed an aggressive course with multiple recurrences, metastasis, or degeneration to an appearance resembling malignant fibrous histiocytoma. OBJECTIVE: We studied the occurrence and persistence of aneuploidy for chromosomes 5 and 7 in 2 patients with clinically aggressive PVNS. DESIGN: Fluorescence in situ hybridization was performed for the detection of chromosomes 5 and 7 in the primary lesions, recurrences, and metastases in 2 examples of PVNS. RESULTS: Fluorescence in situ hybridization demonstrated small but significant numbers of cells with trisomies for chromosomes 7 and/or 5 in both the primary and recurrent lesions of both patients. CONCLUSIONS: The presence of consistent chromosomal trisomies (5 and 7) in both patients' examples of PVNS suggests a neoplastic nature for this lesion. The persistence of these trisomies in the primary lesions, recurrences, and metastases supports a molecular link between the primaries, recurrences, and metastases despite changes in morphologic features. The presence of persistent trisomies in the recurrent and metastatic lesions supports the concept of malignant PVNS.

Adult↗

PubMed1989

[Natural killer (NK) activity of peripheral blood and regional lymph nodes in patients with genitourinary malignant tumors. 1. NK activity of peripheral blood in patients with genitourinary malignant tumors].

51Cr-release assay is a popular method to measure the cytotoxicity of natural killer cells, so-called NK activity, but this assay includes trouble-some steps and management because of using radioisotope (RI) reagent. ATP-chemiluminescence assay (ATP assay), a new method, does not require RI. This assay measures intracellular adenosintriphosphate (ATP) volume by Luciferin-Luciferase reaction. In the research for this paper, the NK activity in 40 healthy donors, 40 patients with urological benign diseases and 39 patients with malignant tumors was measured by both 51Cr-release and ATP assay. The values obtained by these two methods showed a high correlation (r = 0.78). And the NK activity in patients with malignant tumors was lower in high stage patients than it was in low stage patients. These results proposed that ATP assay would be more suitable than 51Cr-release assay for measuring not only NK activity but also the other cytotoxic tests, because ATP is present only in living cells and that, in patients with genitourinary malignant tumors, NK activity of peripheral blood would be a useful tumor marker.

Adolescent↗