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PubMed1995

Immunophenotypic characterization of cutaneous lymphoid neoplasia in the dog and cat.

Clinical, histopathological and immunohistochemical findings are presented from a series of cutaneous lymphoid neoplasms including canine epitheliotrophic lymphoma (n = 7), canine non-epitheliotrophic cutaneous lymphoma (n = 10), canine cutaneous plasmacytoma (n = 10) and feline non-epitheliotrophic cutaneous lymphoma (n = 6). Three cases of canine epitheliotrophic lymphoma expressed the CD3 T-lymphocyte marker, but the remainder were negative for this molecule and for a panel of B-cell markers. Non-epitheliotrophic cutaneous lymphoma was shown to be predominantly of T-cell phenotype (CD3+) in the dog (eight of 10 cases) and cat (five of six cases), the remaining cases in both species being of B-cell origin, expressing the gamma heavy chain of immunoglobulin (with or without lambda light chain). One canine non-epitheliotrophic B-cell lymphoma expressed IgG of the IgG2 subclass. Two of the biopsies from dogs with cutaneous plasmacotyoma were shown to express immunoglobulin alpha chain (one with lambda chain) and two neoplasms were positive for immunoglobulin gamma chain (both with lambda chain). One of the latter immunoglobulins was of the IgG4 subclass. In the majority of all cases of cutaneous lymphoid neoplasia examined, there was a local polyclonal immune response, manifested as infiltration by a mixed population of plasma cells expressing IgG (IgG2, IgG4), IgA or IgM. In the feline tumours CD3+ small T lymphocytes were included in these infiltrates.

Animals↗
PubMed1999

Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma.

Conventional chondrosarcoma (CSA) of the skull base is an uncommon neoplasm that can resemble chordoma, and indeed it is misdiagnosed frequently as such. This has important clinical implications, because when treated with similar aggressive treatment strategies, CSA has a much better prognosis than chordoma. In an effort to identify those morphologic and immunohistochemical features that help to identify conventional skull base CSA correctly and to understand its prognosis better, particularly compared with chordoma, when treated with surgery and proton beam irradiation, the authors performed a clinicopathologic analysis of 200 CSAs. The patients ranged in age from 10 to 79 years (mean, 39 years), 87 patients were male and 113 patients were female, and most presented with symptoms related to the central nervous system. Approximately 6% of the tumors arose in the sphenoethmoid complex, 28% originated in the clivus, and 66% developed in the temperooccipital junction. Histologically, 15 tumors (7.5%) were classified as hyaline CSA, 59 (29.5%) as myxoid CSA, and 126 (63%) as mixed hyaline and myxoid CSA. A total of 101 (50.5%) tumors were grade 1, 57 (28.5%) had areas of grades 1 and 2, and 42 (21%) were pure grade 2 neoplasms. The vast majority of patients originated from referring hospitals, and the diagnosis was changed prospectively at our institution to CSA from chordoma in 74 patients (37%). Of the tumors studied immunohistochemically, 96 of 97 (98.9%) stained for S-100 protein, 0 of 97 (0%) stained for keratin, and faint staining for epithelial membrane antigen was seen in 7 of 88 tumors (7.95%). All patients underwent high-dose postoperative fractionated precision conformal radiation therapy with a dose that ranged from 64.2 to 79.6 Cobalt-Gray-equivalents (median, 72.1 Cobalt-Gray-equivalents, given in 38 fractions. The 200 patients had a median follow-up of 63 months (range, 2.1 mos - 18.5 yrs). Tumor control was defined as lack of progression by clinical and radiographic assessment. Based on this definition, there were three local recurrences, and two of these patients died of tumor-related complications. The 5- and 10-year local control rates were 99% and 98% respectively, and the 5- and 10-year disease-specific survival rates were both 99%. In contrast to CSA, the 5- and 10-year survival rates of chordoma have been reported to be approximately 51 % and 35% respectively, and in our institution intensive treatment has resulted in 5- and 10-year progression-free survival rates of 70% and 45% respectively. CSA of the skull base can be distinguished reliably from chordoma, and this distinction is important because skull base CSA has an excellent prognosis when treated with surgery and proton beam irradiation, whereas chordomas have a substantially poorer clinical course despite similar aggressive management.

Adolescent↗
PubMed1997

[Stromal tumors of the stomach. Review of the literature and description of a case of "uncommitted" stromal tumor].

Non-epithelial non-lymphomatous neoplasms of the gastrointestinal tract are known as stromal tumors (GISTs) because of the tissues in which they originate (4), (16). These neoplasms are rare and account for about 4% of all the tumors of the stomach. Their malignancy and biological and anatomopathological behaviour are related to clinical problems, since their histopathological picture is both complex and controversial. Modern immunohistochemical and ultrastructural (12), (26) studies have identified forms of myogenic or neural origin, which are more differentiated, as well as mixed types with both components, and types, though surely stromal, of uncertain origin, therefore called "uncommitted" (22), (25). The latter are extremely rare and, since it is not yet possible to classify them, some Authors use the term GIST only for these groups. A report of a clinical case of "uncommitted" GIST offers the opportunity to review the literature, highlighting the increased incidence of these tumors (which is probably related partially to the improved diagnostic techniques (3)), their potential malignancy and the difficulty of a correct classification and, therefore, a clear prognosis.

Humans↗
PubMed1982

Immunology of human gastric cancer: a preliminary report.

The immunological spectrum in fifteen patients with gastric cancer is presented. Patients were divided in three groups. Those with nonadvanced cancer, those with advanced but resectable lesions and those with advanced but nonresectable tumors. Preoperatively, elevated levels of circulating immune complexes (CIC) associated with hyporesponsiveness to phytohemagglutinin (PHA) and in mixed lymphocyte culture (MLC) as well as a positive leukocyte inhibitory serum factor (LIF-S) were found in nearly half of the patients. Inhibitory or enhancing autologous serum factors were detected. Postoperatively, immunologic parameters return to normal in patients with nonadvanced cancer, while in advanced cancer, antibody and cell-mediated immune response remained altered, with some changes associated with chemotherapy. These findings are probably related with the presence or absence of tumor and offer a distinct approach in evaluating the immunologic response of a tumor-bearing patient.

Adult↗
PubMed1984

The sensitivity of rainbow trout and other fish to carcinogens.

Systematic design of replacement chemicals with reduced toxicities will require knowledge of mechanisms of action of parent compounds, especially in species which occupy the environment of most likely exposure. For aquatic systems, the rainbow trout has proven a valuable model for studying mechanisms of carcinogenicity. By comparison, small aquarium species show great potential as in situ field monitors of aquatic contamination by toxic chemicals but are less developed for mechanism studies. Fish species, especially rainbow trout, have also proven useful alternatives to traditional rodent models for comparative studies on mechanisms of action of nonaquatic carcinogens. These kinds of comparative studies form an essential basis for extrapolation of animal studies to man. Carcinogenicity testing of individual compounds and their replacements can provide only limited information on the expected impact of such chemicals on natural populations, since these populations are unavoidably exposed to potent modulators of the carcinogenic response. Hence any program which aims at redesign of commercial chemicals with reduced toxicities must have as a prior aim the full understanding of the mechanisms of joint carcinogen-inhibitor-promotor interactions. Because of their high sensitivity, low cost per individual, and low background tumor incidences, fish models such as the rainbow trout may be the only vertebrate models in which it is economically practical to initiate such complex studies.

Aflatoxin B1↗
PubMed2006

Mapping of somatostatin receptor types in GH or/and PRL producing pituitary adenomas.

BACKGROUND: Somatostatin is a tetradecapeptide exerting inhibitory action on endocrine and exocrine cell secretion and proliferation. Somatostatin receptors (SST) are widely expressed in various neoplasms including endocrine tumours. Using immunohistochemistry, the expression of SST(1), SST(2A), SST(2B), SST(3), SST(4), and SST(5) was studied in tissue microarrays (TMAs), using a series of 90 human pituitary adenomas producing growth hormone and/or prolactin, including 30 of each somatotroph, lactotroph, and mixed somatotroph/lactotroph adenoma type. METHODS: For immunohistochemistry, the standard avidin biotin complex method enhanced by tyramide was used, using polyclonal antisera for all SST types. A four point scoring system was used to assess the membranous immunopositivity. RESULTS: All SST types were positive in all tumour types, showing varying immunoreactivity scores. SST(5) and SST(2A) were the predominant receptors, showing strong expression in high frequency in all three adenoma types. Strong expression of SST(1) was higher in lactotroph adenomas than in other tumour types. CONCLUSIONS: The immunohistochemical results of SST expression are in agreement with most findings of previous molecular studies. The fact that SST(2A) expression is predominant suggests that pharmaceutical octapeptide somatostatin analogues may act through this receptor, while the role of SST(2B) may be merely synergistic.

Adenoma↗
PubMed1990

A radioimmunoassay for measuring alpha-amidating enzyme activity.

A sensitive alpha-amidating enzyme (alpha AE) assay using C-terminal glycine-extended substance P (SP-Gly) as a substrate was developed. The product, substance P (SP), was measured by a radioimmunoassay with specific polyclonal antibodies which recognize SP with an affinity 10,000-fold higher than that of SP-Gly. The sensitivity of the radioimmunoassay was 5 fmol. Enzyme activity could be readily detected with 25 ng alpha AE partially purified from the conditioned medium of rat medullary thyroid carcinoma CA-77 cells. The Km and Vmax values were 2.0 +/- 0.2 microM and 1.7 +/- 0.1 nmol/mg/min (mean +/- SE, n = 3), respectively. The assay enabled the kinetic characterization of alpha AE from a single rat pituitary homogenate. Optimal Cu2+ required was 30 microM and greater than 3 mM of ascorbate was needed for maximal enzyme activity. The sensitivity of this assay will aid efforts to examine the regulation of in vivo alpha AE activity.

Animals↗
PubMed1997

Suppression of substance P biosynthesis in sensory neurons of dorsal root ganglion by prodrug esters of potent peptidylglycine alpha-amidating monooxygenase inhibitors.

Substance P as well as many other neuropeptides are synthesized as glycine-extended precursors and converted to the biologically active C-terminal amides by posttranslational modification. The final step of posttranslational processing is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM). In a previous study, N-substituted homocysteine analogs were found to be potent inhibitors of PAM partially purified from conditioned medium of cultured rat medullary thyroid carcinoma CA-77 cells. These compounds, however, were only modest inhibitors of substance P production in cultured dorsal root ganglion cells, possibly because of poor cell penetration. Several ester derivatives of hydrocinnamoyl-phenylalanyl-homocysteine, one of the most potent PAM inhibitors, were prepared to increase the intracellular accessibility of these compounds. Hydrocinnamoyl-phenylalanyl-(S-benzoyl-homocysteine) benzyl ester was identified as the most potent compound, inhibiting substance P biosynthesis in dorsal root ganglion cells with an IC50 of 2 microM. Inhibition of PAM resulted in a concomitant increase in the glycine-extended substance p (substance P-Gly) precursor peptide. In the presence of 3 microM benzyl ester derivative, the intracellular substance P-Gly level was 2.4-fold higher while the substance P level was 2.1-fold lower than the corresponding peptides in control cells. These results suggest that PAM inhibition represents an effective method for suppression of substance P biosynthesis and, therefore, may have therapeutic utility in conditions associated with elevated substance P levels. Furthermore, PAM inhibition may also prove useful in decreasing other amidated peptides.

Animals↗
PubMed1988

Rearrangement of T-cell receptor and immunoglobulin heavy chain genes in childhood acute mixed lineage leukaemia.

Rearrangement of the beta and gamma chain genes of the TCR gene complex and of the Ig heavy chain genes were examined in three cases of childhood acute mixed lineage leukaemia. Blast cells, classified morphologically as acute lymphoblastic leukaemia (ALL) in one child and acute non-lymphocytic leukaemia (ANLL) in the other two, all co-expressed markers associated with both T (CD7, TdT) and myeloid (CD33) cells. Cytogenetic analysis detected abnormalities associated with myeloid leukaemia. Immunoglobulin heavy chain genes were not rearranged in two patients but a novel rearrangement was seen in the third. No rearrangement of the beta or gamma chains of the T-cell receptor complex were seen. Acute mixed lineage leukaemia may thus arise from a pluripotent precursor cell capable of both lymphoid and myeloid differentiation.

Antigens, Differentiation↗
PubMed1996

Macromolecule adducts as biomarkers of exposure to environmental mutagens in human populations.

A cancer epidemiologist recently said that "adduct measurement has so far been of little use to epidemiological research." This remark gives us a starting point for the discussion of the purposes of measuring macromolecule adducts that originate from electrophilic compounds or metabolites in humans and animals. Historically, methods for adduct monitoring were developed as a means of determining target doses that, combined with measurements of genotoxic potencies, could be used for risk assessment. With mass spectrometric methods, adducts can be quantified at levels that are thousands of times lower than those in which the cancer incidence associated with this exposure is detectable in disease-epidemiological studies. Furthermore, mass spectrometric techniques permit identification of the chemical structure of the adduct, particularly in the case of hemoglobin adducts. Adduct measurement therefore constitutes not only a means of risk estimation but it may be used as a complement of disease epidemiology in situations in which, for statistical reasons, the risk is too low to be detectable--which does not signify that the risk is acceptably low. It also gives a possibility of identification of the dangerous components in mixed exposures and of the relevant reactive intermediates in cases of complex metabolism.

Biomarkers↗
PubMed2007

Epithelioid osteosarcoma presenting as a rapidly expanding maxillary mass.

BACKGROUND: Osteosarcomas of the jaws account for less than 10% of reported neoplasms of this type. Patients with osteosarcoma in this region tend to be in the late-third to mid-fourth decades of life. The osteoblastic, chondroblastic, and fibroblastic variants constitute the majority of lesions. METHODS: A mass was observed in the maxilla of a 50-year-old male who presented for a complete odontectomy. Over the ensuing weeks, the mass substantially increased in size, despite multimodality treatment efforts. RESULTS: Radiographic findings revealed a mixed density mass of the left maxilla. Histologic, immunohistochemical, and electron microscopy examination of the tumor showed a malignant mesenchymal neoplasm consisting of sheets of epithelioid and spindle cells exhibiting focal osteoid formation. CONCLUSIONS: We report a rare and aggressive case of epithelioid osteosarcoma arising in the maxillofacial complex.

Epithelioid Cells↗
PubMed1984

Low-grade papillary adenocarcinoma of palatal salivary gland origin.

The clinicopathologic features of five low-grade papillary adenocarcinomas of palatal salivary gland origin are presented and seven well-documented cases from the literature are reviewed. Patients in our series ranged in age from 30 to 77 years (median 48). Symptoms were nonspecific and related to a mass present for a long duration. Histologically, these were complex cystic, papillary, focally solid tumors that were partially encapsulated. Cytologically, they were composed of bland, predominantly cuboidal cells with eosinophilic or clear cytoplasm. Four tumors were initially considered to be benign mixed tumors, but long-term follow-up indicates that these are slowly growing, malignant neoplasms. Three patients developed solitary cervical lymph node metastases from 2 to 21 years after initial presentation. One tumor underwent an anaplastic transformation to solid adenocarcinoma, and this was from the only patient in our series who died with tumor. Low-grade papillary adenocarcinoma is a clinicopathologically distinctive salivary gland neoplasm, with histologic features unlike those of other papillary salivary gland tumors.

Adenocarcinoma↗
PubMed1987

Metastatic granulosa cell tumor with pattern of sex cord tumor with annular tubules.

A case of malignant, complex sex cord tumor with multiple differentiations in a 38-year-old woman is presented. The neoplasm presented originally as a pure granulosa cell tumor, and in the second look operation as a sex cord tumor with annular tubules (SCTAT). Six years later abdominal metastases revealed a mixed pattern of granulosa and Sertoli cell tumor admixed with SCTAT. The patient died despite chemotherapy. Analysis of the 10 previously reported cases of malignant SCTAT shows that tumor size is the main prognostic indicator. Mitoses, atypia, and stromal invasion seem also to bear prognostic implications when present. The association of both granulosa and Sertoli cells with SCTAT seems to provide a clue for SCTAT being a peculiar intermediate phenotypical expression of pluripotential stem sex cord cells of the gonads.

Adult↗
PubMed1998

Monoclonality in fibroadenomas with complex histology and phyllodal features.

Fibroadenoma is a common cause of benign breast masses in young women. These women have a slightly increased risk of subsequent breast cancer, particularly if their tumors have complex histologic patterns. We assessed monoclonality in fibroadenomas and correlated the results with histologic analysis. We performed a clonal analysis of 52 fibroadenomas from 43 patients using X-chromosome inactivation studies. The cases included fibroadenomas with complex and simple histology. Areas examined were predominantly stroma but epithelium was also present. DNA was isolated from paraffin-embedded tissue and was subjected to polymerase chain reaction amplification of the human androgen receptor gene with and without predigestion of the DNA with Hha 1. If a monoclonal process was identified, the epithelial and stromal components were subsequently microdissected and reanalyzed. 36/43 (83.7%) women were heterozygous. We studied 45 tumors in these 36 informative women. 1/20 (5% complex fibroadenomas and 1/25 (4%) simple fibroadenomas were monoclonal. The epithelial component of both monoclonal fibroadenomas was polyclonal. The one monoclonal simple fibroadenoma was also the only one with mixed features to contain a phyllodes component. In this case, monoclonality was found in the stroma of both the fibroadenoma and phyllodes regions. Monoclonality has been previously associated with phyllodes phenotype, but not with fibroadenomas, except for 3 fibroadenomas that recurred as phyllodes tumor. We report that monoclonality may also be seen occasionally in complex fibroadenomas, and was found in a tumors with mixed fibroadenoma/phyllodes features without clinical recurrence for 4 years.

Breast Neoplasms↗
PubMed1986

Cryoproteins.

Proteins producing phenomena after exposure to the cold are reviewed but concentrating mainly on those that can produce aggregates within the laboratory. From three large series the frequencies were I. Mixed Cryoglobulins (polyclonal 50 p. 100, monoclonal 18 p. 100); II. Monoclonal Cryoglobulin (25 p. 100); III. Cryofibrinogen (3 p. 100) and IV. Cold Agglutinins (polyclonal 2 p. 100, monoclonal 2 p. 100). Mixed cryoglobulins present with any of the features of immune complex disease, but with the onset of renal involvement, over 50 p. 100 of the patients are dead within 5 years. Monoclonal cryoglobulins present with flat lesions in dependent areas, most reflecting an underlying or impending malignant B-cell neoplasm. Cryofibrinogen, missed in heparinised samples, is associated with thrombophlebitis migrans and sometimes underlying cancer, especially of the pancreas. Cold agglutinins cause Raynaud's phenomenon and haemolytic anaemia and the blood must be centrifuged at 37 degrees C. Treatments are discussed and are certainly encouraging in about one-third of the patients.

Anemia, Hemolytic, Autoimmune↗
PubMed1999

Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles.

As part of a study of the effects of low-level radiation, 1,343 Beagles, including 671 males and 672 females, were evaluated over their full lifetime for the occurrence of mammary neoplasia; there were 139 control males and 138 control females and 532 irradiated males and 534 irradiated females. All nodules found in surgical specimens or at necropsy were evaluated histologically. The overall incidence, metastasis and recurrence rates, and contribution to mortality of mammary neoplasms were determined. Based on this unique opportunity to correlate morphologic characteristics with ultimate biological behavior of all mammary tumors in a defined canine population, we propose a histogenetically based reclassification of epithelial mammary tumors. Of the 672 female dogs, 70.8% (476) had at least one mammary neoplasm; 60.7% (408) had more than one. Two male dogs had mammary neoplasms. Of 1,639 mammary carcinomas in the 672 females, 18.7% (307) were classified as ductular carcinomas (arising from the small interlobular or intralobular ductules), whereas 80.7% (1,322) were classified as adenocarcinomas of other histogenetic origin. Of 73 fatal carcinomas, ductular carcinomas accounted for 48 fatalities (65.8%), whereas other adenocarcinomas accounted for only 20 fatalities (27.4%). Radiation had no effect on this ratio. Ductular carcinomas also had a higher rate of metastasis than did adenocarcinomas. Existing classifications of mammary carcinomas do not recognize the characteristic morphologic features, the degree of malignancy, and the prognostic importance of these ductular carcinomas. Metastasis rates did not differ between simple and complex carcinomas or between those lesions and adenocarcinomas in mixed tumors. True carcinosarcomas metastasized more frequently (100%, or 5/5) than did adenocarcinomas in mixed tumors (34.4%, or 22/64), emphasizing the importance of not lumping these tumors under the classification of malignant mixed tumors.

Adenocarcinoma↗
PubMed1986

Phenotypic profile of clones from early cultures of human metastatic melanomas and its modulation by recombinant interferon gamma.

Fifty-six tumor clones isolated by cloning in soft agar from early cultures (before the 10th in vitro passage) of two different human metastatic melanomas (Me9229 and Me28) were characterized by FACS analysis for surface expression of class-I and class-II HLA antigens and of melanoma-associated antigens (MAA) with a panel of 15 monoclonal antibodies (MAbs). A marked phenotypic heterogeneity involving MAA and/or HLA markers was observed among the clones derived from both tumors. The differences among the tumor clones and between them and the uncloned melanoma were qualitative and quantitative for each antigen considered. Clones derived from Me9229 expressed the same HLA profile as the parental culture (class I+, class II-) while strong heterogeneity was observed for MAA expression. Clones from Me28 presented a marked heterogeneity for class-I and class-II HLA antigens but were more homogeneous for MAA. The phenotype of the clones was repeatedly checked over the first month in culture and found to remain generally unchanged and not linked to the cell cycle. However, major changes in antigenic expression of the clones could be observed upon treatment with recombinant interferon-gamma (rIFN-gamma): class-I and -II HLA antigens could be induced or augmented while a moderate inhibition was seen on MAA expression. Furthermore, an apparent hierarchy in expression and/or induction of class-II antigens by rIFN-gamma was observed among the tumor clones. DR antigens were more frequently expressed (Me28 clones) and upon treatment with rIFN-gamma reached higher levels than DP and DQ products. Taken together these results indicate that antigenic heterogeneity for MAA and HLA antigens can be detected in cells isolated from early cultures of human metastatic melanomas and suggest that the original uncloned tumor might be considered as a complex mixed population made up of a number of neoplastic cells each expressing a distinct phenotype which can be modulated by lymphokines such as IFN-gamma.

Antibodies, Monoclonal↗