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[Second primary malignant neoplasms in patients treated in the Otolaryngology Clinic AM of Lodz in the years 1981-1989].

The incidence of multiple primary malignant tumours in 913 patients treated during 9 years for malignant neoplasms was investigated. In 24 (2.63%) cases second primary malignant neoplasm was diagnosed, mostly (in 19 cases-2.1%) it was correlated to cancer of larynx. In 18 cases (75% of all multiple tumours) neoplasms were metachronous, in 5-synchronous, and in one case--it was multifocal neoplasm (in both tonsils). In 3 patients three separate primary neoplasms were observed.

Adult↗

Influence of dietary components on occurrence of and mortality due to neoplasms in male F344 rats.

The influence of dietary components on the occurrence of, and mortality from spontaneous neoplasms in male F344 rats was investigated. The dietary regimens studied included restriction of specific dietary components (energy, fat, protein and mineral), as well as different sources of dietary protein (casein, soy protein and lactalbumin). A statistical approach based on contributing causes of death was used to obtain the mortality due to all neoplasms, and the relative onset rate of frequently observed neoplasms, e.g., leukemia, pituitary adenoma, testicular interstitial cell tumor, etc. Only the regimen involving energy restriction reduced the mortality due to all neoplasms. Neither reduction of individual components without energy restriction, nor replacement of casein with soy protein or lactalbumin as the protein source affected mortality. Analyses of the relative onset rate of selected neoplasms also indicated that only a reduction of energy intake suppressed the occurrence of most of these neoplasms. Other dietary regimens, at most, suppressed a few types of neoplasm. It is concluded that a reduction in energy intake is a key dietary factor for the prevention of neoplastic diseases in rats.

Age Factors↗

DNA Methylation-Based Classification of Kidney Neoplasms.

Renal neoplasms are morphologically and molecularly heterogeneous, with their diagnosis often hindered by interobserver variability and overlapping microscopic features. A subset of cases is unclassifiable despite immunohistochemical, mutation, and cytogenetic-based diagnostic workup. Through examination of the genome-wide DNA methylation signatures of over 2000 renal neoplasms, we identified 23 coherent groups that correlate with known neoplasm types and identified novel clinically relevant subtypes of existing neoplasm types. We used machine learning models to develop and validate a classifier trained on DNA methylation profiles of 1284 samples. The classifier was tested on an external data set of 287 renal neoplasms with >90% concordance between expected neoplasm type and high-score DNA methylation-based classification. Discordance between the original histologic label and methylation class led to potential reclassification of some cases. This work demonstrates proof of principle for the feasibility of a DNA methylation classifier as a clinically useful tool to assist in the diagnosis of renal neoplasms.

Humans↗

Interobserver discrepancy using the 1998 World Health Organization/International Society of Urologic Pathology classification of urothelial neoplasms: practical choices for patient care.

PURPOSE: Morphological classifications designed by experts to stratify neoplasms according to biological potential must define categories that are reproducible among practitioners or the schemes actually create the heterogeneous populations that they seek to avoid. The application of the 1998 World Health Organization/International Society of Urologic Pathology scheme for urothelial neoplasms was studied in a community practice setting. We documented interpretive discrepancies for each category of neoplasm and determined whether a period of pathologist education may have a positive effect on the frequency of discrepant interpretations. The results suggest that patients may benefit from modifying the classification system. MATERIALS AND METHODS: A consecutive series of specimens was divided into learning and study sets that were each independently examined by 3 pathologists. Specimens in the learning set were interpreted without previous structured education, while those in the study set were interpreted immediately after intensive education. Interpretations for each specimen were compared and interpretive discrepancies were analyzed. RESULTS: Case distribution after education was similar among the pathologists but interpretations for any particular specimen often differed. The level of interpretive discrepancies varied according to the morphological similarity among categories in the classification scheme and was not necessarily decreased by education. When pathologists were required to discriminate between papillary urothelial neoplasm of low malignant potential and low grade carcinoma, the discrepancies were 50% after education compared with 39% before education. In contrast, there were no discrepancies when the discrimination was between papillary urothelial neoplasm of low malignant potential and high grade carcinoma or carcinoma in situ. Eliminating categories with poor reproducibility markedly improved the likelihood of unanimous agreement among practitioners but a probably irreducible level of 10% discrepancies remained. CONCLUSIONS: The 1998 World Health Organization/International Society of Urologic Pathology classification of urothelial neoplasms requires certain discriminations that cannot be reliably made by practitioners. Modifying the scheme to create categories of low grade neoplasm and high grade carcinoma would markedly increase its practical value to patients without significantly altering patient care.

Carcinoma, Transitional Cell↗

Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.

12E7 Antigen↗

S-100beta protein--serum levels in children with brain neoplasms and its potential as a tumor marker.

OBJECTIVE: To determine if serum S-100beta levels are elevated in children with brain neoplasms and if it can be used as a tumor marker for children with brain neoplasms. DESIGN: Prospective cohort study. SETTING: Urban, tertiary care, children's teaching hospital. PATIENTS: 136 healthy children and 27 children with brain neoplasms. METHODS: Serum levels of S-100beta were measured in 136 healthy children to serve as controls and 27 children with brain neoplasms, who underwent biopsy or resection of the mass. Patients were then classified into astrocytoma or non-astrocytoma groups. MEASUREMENTS AND MAIN RESULTS: The median serum S-100beta level for the control group was 0.27 mcg/l (range, 0.06-2.6 mcg/l), and for the brain neoplasm group was 0.2 mcg/l (range, 0.01-2.1 mcg/l), (p = 0.09). There were 13 children with astrocytomas and 14 with non-astrocytomas. The S-100beta levels for the astrocytoma group was 0.25 mcg/l (range, 0.05-1.1 mcg/l) and for the non-astrocytoma group 0.17 mcg/l (range, 0.01-2.1 mcg/l), (p = 0.47). CONCLUSIONS: Serum S-100beta levels are not elevated in children with brain neoplasms compared to healthy children, nor are they elevated in children with astrocytomas compared to non-astrocytomas. The S-100beta protein does not appear to be useful as a serum tumor marker in children with brain neoplasms.

Adolescent↗

Positive immunohistochemical staining of KIT in solid-pseudopapillary neoplasms of the pancreas is not associated with KIT/PDGFRA mutations.

Solid-pseudopapillary neoplasms of the pancreas are uncommon neoplasms of low malignant potential and of uncertain histogenesis. A small percentage of patients develop metastatic disease and some succumb to disease. The management of patients with metastatic disease or unresectable tumor, and patients who are just not good surgical candidates is problematic. Novel therapy targets are needed. Successful treatment of metastatic and unresectable gastrointestinal stromal tumors with KIT kinase inhibitor, imatinib mesylate (Gleevec), makes it intriguing to look at the status of KIT in solid-pseudopapillary neoplasms of the pancreas. In this study, we investigated KIT expression in 50 solid-pseudopapillary neoplasms by immunohistochemical staining. Of the 50 (50%) solid-pseudopapillary neoplasms, 25 showed diffuse expression (in >50% neoplastic cells) of KIT and additional five (10%) cases showed focal staining (in 10-50% neoplastic cells). Expression of KIT was not associated with tumor behavior and prognosis. A subset of 11 cases showing diffuse KIT expression detected by immunohistochemical staining were further evaluated for the presence of activating mutations in KIT exons 9, 11, 13 and 17, and PDGFRA exons 12 and 18 using PCR amplification followed by direct sequencing. However, no KIT or PDGFRA mutations were identified in any of these 11 cases tested, suggesting that the overexpression of KIT is probably not due to activating mutations in KIT or PDGFRA. The exact mechanism of KIT overexpression in solid-pseudopapillary neoplasms remains to be elucidated. One possible mechanism is gene dose effect (increased copies of KIT gene). Experience in gastrointestinal stromal tumors and other tumors have shown that mutation-mediated activation of KIT or PDGFRA is a prerequisite for clinical response with imatinib mesylate. Thus, lack of mutations in KIT or PDGFRA in solid-pseudopapillary neoplasms suggests that imatinib mesylate is less likely to be effective in the treatment for patients with metastatic disease or unresectable tumor, and patients who are just not good surgical candidates.

Adolescent↗

Prevalence, distribution and factors associated with the presence and the potential for malignancy of cutaneous neoplasms in 174 dogs admitted to a clinic in northern Greece.

One hundred and seventy-four dogs diagnosed with cutaneous neoplasms in the Animal Medical and Surgical Clinic, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, were studied. Thirty-one types of neoplasm were diagnosed, among which mast cell tumours (13.8%), hepatoid gland adenomas (9.8%), lipomas (5.7%) and histiocytomas (5.7%) were the most common. The prevalence of epithelial, mesenchymal, lymphohistiocytic and melanocytic tumours was 47.7, 40.8, 8.6 and 2.9%, respectively. Potentially malignant neoplasms were less frequently recorded than benign neoplasms. The tumours were single (80.5%) or multiple (19.5%) and located on the head and neck (18.4%), the body trunk (49.4%), the limbs (25.9%) or at multiple sites (6.3%). The factors evaluated in multivariable logistic regression models for possible association with the odds of a tumour's potential for malignancy included the age, the sex and the breed of the dog, as well as the histological type of the neoplasm. Dogs with mesenchymal tumours had two times higher odds of potential for malignancy than those with epithelial tumours. In contrast, dogs with either lymphohistiocytic or melanocytic tumours did not have increased risk of malignancy compared with dogs with epithelial tumours. The odds of tumour malignancy linearly increased with increasing age of the dog by a factor of 1.1 per year. Finally, the effect of the sex and the breed of the dog on the risk of developing cutaneous neoplasms was investigated in an age-matched case-control sample of 348 dogs by conditional logistic regression analysis. The odds of neoplasm presence were two times higher in pure bred dogs than in mongrels but did not differ between cross-breeds and mongrels.

Adenoma↗

Benzene and the dose-related incidence of hematologic neoplasms in China. Chinese Academy of Preventive Medicine--National Cancer Institute Benzene Study Group.

BACKGROUND: Benzene is a widely distributed environmental contaminant known to cause leukemia, particularly acute nonlymphocytic leukemia, and perhaps other hematologic neoplasms and disorders. Few epidemiologic studies, however, have been able to address relationships between the extent of benzene exposure and the level of risk. PURPOSE: A large cohort study was carried out in China to evaluate the risks of developing specific hematologic neoplasms and selected related disorders in relationship to quantitative estimates of occupational benzene exposure. METHODS: A cohort of 74828 benzene-exposed and 35805 unexposed workers employed from 1972 through 1987 in 12 cities in China was identified and followed to determine the incidence of hematologic neoplasms and related disorders. Estimates of benzene exposure were derived from work histories and available historic benzene measurements. Existing pathologic material and supporting medical records were reviewed to establish diagnoses of disease. Relative risks (RRs) (i.e., ratios of incidence rates for specific hematologic neoplasms and related disorders in the benzene-exposed group to incidence rates in the unexposed group) were determined by use of Poisson regression analysis, with stratification by age and sex. RESULTS: For workers historically exposed to benzene at average levels of less than 10 parts per million (ppm), the RR for all hematologic neoplasm combined was 2.2 (95% confidence interval [CI] = 1.1-4.2), and, for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes, the RR was 3.2 (95% CI = 1.0-10.1). For individuals who were occupationally exposed to benzene at constant levels of 25 ppm or more, the RR for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was 7.1 (95% CI = 2.1-23.7). Workers with 10 or more years of benzene exposure had an RR of developing non-Hodgkin's lymphoma of 4.2 (95% CI = 1.1-15.9), and the development of this neoplasm was linked most strongly to exposure that had occurred at least 10 years before diagnosis (i.e., distant exposure) (P for trend = .005, two-sided). In contrast, the risk for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was significantly increased among those with more recent benzene exposure (P for trend = .003, two-sided), but it was not linked to distant exposure (P for trend = .51, two-sided). CONCLUSIONS: The results of this study suggest that benzene exposure is associated with a spectrum of hematologic neoplasms and related disorders in humans. Risks for these conditions are elevated at average benzene-exposure levels of less than 10 ppm and show a tendency, although not a strong one, to rise with increasing levels of exposure. The temporal pattern of benzene exposure appears to be important in determining the risk of developing specific diseases.

Age Distribution↗

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature.

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.

Aged↗

Comparison of epigenetic and genetic alterations in mucinous cystic neoplasm and serous microcystic adenoma of pancreas.

Mucinous cystic neoplasms and serous microcystic adenomas account for the majority of cystic tumors of pancreas. Mucinous cystic neoplasms and serous microcystic adenomas have different frequencies of progression to malignancy. The genetic and epigenetic alterations of these tumors have not been studied in detail. In this study, we compared methylation status of p16, p14, VHL, and ppENK genes by methylation-specific PCR (MSP), and genetic alterations including K-ras and beta-catenin gene mutations, chromosome 3p loss, and microsatellite instability in 15 mucinous cystic neoplasms (10 benign and 5 borderline) and 16 serous microcystic adenomas. There were no significant differences between mucinous cystic neoplasms and serous microcystic adenomas in methylation of p16 (14%, 2/14 and 12%, 2/16), p14 (15%, 2/13 and 37%, 6/16), VHL (0/14 and 7%, 1/14), and ppENK (0/14 and 0/13), respectively. K-ras mutation was present only in mucinous cystic neoplasms but not in serous microcystic adenomas (33%, 5/15 versus 0/16; P =.004). In addition, LOH at 3p25, the chromosomal location of VHL gene, was present in 57% (8/14) of serous microcystic adenomas compared with in 17% (2/12) of mucinous cystic neoplasms (P =.03). No beta-catenin mutation, microsatellite instability, or mutation of transforming growth factor beta type II receptor was present in either type of tumors. In conclusion, K-ras mutations and allelic loss of VHL locus at 3p25, but not methylation, distinguished mucinous cystic neoplasms and serous microcystic adenomas. The differences in genetic alterations but not epigenetic alterations may explain the pathogenesis and progression to malignancy of these cystic tumors of pancreas.

Adenoma↗

CD5-positive B-cell neoplasms of indeterminate immunophenotype: a clinicopathologic analysis of 26 cases.

The flow cytometric classification of CD5-positive small B-cell neoplasms is dependent largely on the differential expression of CD23 and FMC-7. Occasional CD5-positive neoplasms with prominent co-expression of these antigens are encountered, precluding definitive immunophenotypic classification. The authors studied the clinicopathologic features of 26 neoplasms with this indeterminate immunophenotype. Available morphologic material was reviewed and analysis of CYCLIN D1 derangement was performed in selected cases by a combination of immunohistochemical, molecular, and cytogenetic techniques. Individual neoplasms were classified based on correlation of morphologic features and results of CYCLIN D1 studies. The neoplasms were classified into five categories: chronic lymphocytic leukemia (14 cases), "favor chronic lymphocytic leukemia" (3 cases), mantle cell lymphoma (3 cases), lymphoplasmacytic lymphoma (1 case), and unclassifiable (5 cases). Three of the unclassifiable neoplasms had morphologic features of mantle cell lymphoma, but CYCLIN D1 derangement could not be demonstrated. Neither relative expression of CD23 and FMC-7 nor intensity of CD20 or surface immunoglobulin expression was helpful in final classification. The authors conclude that CD5-positive small B-cell neoplasms with an indeterminate immunophenotype are a heterogeneous group, requiring additional studies for final classification. The majority (65%) appear to be chronic lymphocytic leukemia, with most of the remaining cases either definitively mantle cell lymphoma or unclassifiable.

Adult↗

Use of cross-sectional imaging in predicting surgical location of parotid neoplasms.

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of using the retromandibular vein as seen on cross-sectional imaging to help differentiate superficial lobe from deep lobe tumors. METHODS: Of the patients who had parotid neoplasms between January 1997 and July 2002, we were able to identify 44 patients with preoperative imaging studies that were available for evaluation. The films were reviewed by a single head and neck radiologist to determine whether the neoplasms involved the superficial, deep, or both lobes of the parotid gland (total). The lateral margin of the retromandibular vein was used as a marker for the facial nerve, since the nerve is not always visible on CT and MRI scans. The radiologist's findings were then compared with the findings during surgery. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of predicting the location of neoplasms were then calculated. RESULTS: For lesions in the superficial lobe, cross-sectional imaging was able to predict the location of the neoplasm with a sensitivity of 0.91 (95% CI, 0.70-0.98), specificity of 0.86 (95% CI, 0.63-0.96), PPV of 0.88 (95% CI, 0.67-0.97), and NPV of 0.90 (95% CI, 0.67-0.98). For lesions in both lobes (total), cross-sectional imaging was able to predict the location of the neoplasm with a sensitivity of 0.94 (95% CI, 0.68-0.99), specificity of 0.89 (95% CI, 0.71-0.97), PPV of 0.83 (95% CI, 0.58-0.96), and NPV of 0.96 (95% CI, 0.78-0.99). CONCLUSION: Use of the retromandibular vein as a marker for the facial nerve is a sensitive method for identifying the location of parotid gland neoplasms on cross-sectional imaging. This supports the accuracy of using preoperative imaging to detect the position of parotid neoplasms with respect to the facial nerve.

Adult↗

Total serum alkaline phosphatase activity in dogs with mammary neoplasms: a prospective study on 79 natural cases.

Increased total alkaline phosphatase (TALP) activity in the serum, long noticed in canine mammary tumours among other neoplasms, has not been yet associated with malignancy, osseous transformation of neoplastic tissue or histopathological typing. Therefore, the purpose of this study was to correlate this biochemical abnormality with the above-mentioned parameters, in 79 adult to elderly female dogs with mammary neoplasms, without evidence of metastatic or any other disease. Histopathology disclosed that 64 (81%) of these neoplasms were malignant and 15 (19%) benign, belonging to various histological types. Radiology and histopathology revealed the presence of osseous tissue in 18 (22.8%) cases. The malignant neoplasms were subsequently allocated into group A including 46 (74.2%) of epithelial origin and group B with 16 (25.8%) neoplasms of both epithelial and mesenchymal origin ('malignant mixed' tumours). In addition, their benign counterparts were divided into group C (adenomas, fibroadenomas) and group D (benign mixed tumours) that included seven (46.7%) and eight (53.3%) tumours, respectively. Almost 55% of the dogs with malignant and 47% with benign tumours had increased serum-TALP activity. However, no significant difference in serum-TALP activity was found between the dogs with malignant (mean +/- SE: 243.7 +/- 37.4 U/l) and benign (167.9 +/- 38.4 U/l) neoplasms, with (238.9 +/- 45.3 U/l) and without (226.5 +/- 38.3 U/l) osseous transformation, with (298.5 +/- 85.6 U/l) or without (201.2 +/- 30.5 U/l) myoepithelial cell proliferation and with different tumour size (T1/T2: 175.1 +/- 34.9 and T3: 254.5 +/- 42.5 U/l). In histopathological typing, the only difference noticed involved the malignant neoplasms of group A (190.5 +/- 25.5 U/l) compared with group B (378 +/- 124.6 U/l) dogs. The higher increase of serum-TALP activity in 'malignant mixed' tumours could not be attributed to osseous transformation or new ALP isoenzyme production by myoepithelial cells. Increased serum-TALP activity is of no apparent diagnostic (as to tumour type) or prognostic value.

Alkaline Phosphatase↗

[Neonatal neoplasms: a single-centre experience].

INTRODUCTION: Malignant tumors are uncommon in the neonatal period and benign tumors may have malignant potential. OBJECTIVES: To describe the neoplasms diagnosed and treated in newborns (</= 28 days of life) in the Hospital Universitario de Canarias and their association with congenital abnormalities and to evaluate prenatal diagnosis of these tumors. PATIENTS AND METHODS: The medical records of patients with neoplasms diagnosed during the neonatal period in the previous 25 years in our hospital were retrospectively reviewed. The variables analyzed were the percentage of neonatal neoplasms among the total number of cancer cases in children aged less than 14 years, their incidence among all the newborns in our hospital, sex, year of diagnosis, age at clinical diagnosis, the presence or absence of prenatal diagnosis, type of tumor (histologic diagnosis), association with syndromes or other congenital anomalies, treatment, and long-term outcome. RESULTS: Of 260 neoplasms diagnosed in our unit from 1980, 16 (6.1 %) were diagnosed in the neonatal period. The incidence of neonatal neoplasms was estimated to be 276.5 per million live births. Males accounted for 43.8 % and females for 56.2 %, with a mean age at diagnosis of 5.5 days (range 1-28 days). Five neonates (31.2 %) had a prenatal diagnosis, 60 % of which were made in the last 7 years of the study period. A further five newborns were diagnosed at the initial neonatal examination. Histologic diagnoses were neuroblastoma (n = 5; 31.2 %), teratoma/ germ cell tumor (n = 4; 25 %), soft tissue sarcoma (one fibrosarcoma of the thigh and two hemangiopericytoma of the back and heart; 18.8 %), and one case each of mesoblastic nephroma, cerebral tumor (ependymoblastoma), melanoma (associated with giant congenital melanocytic nevi), and acute leukemia (associated with Down syndrome). Treatment consisted of surgery alone (n = 10; 62.5 %) and surgery plus chemotherapy (n = 5; 31.2 %); one patient received no treatment. The overall actuarial survival rate was 87.5 %. Sequelae were observed in 33.3 % of survivors. CONCLUSIONS: The neoplasms most frequently diagnosed in the neonatal period were solid tumors, mainly neuroblastoma and teratomas/germ cell tumors; 12.5 % were associated with syndromes or congenital anomalies. In the last 7 years, the prenatal diagnosis of these entities has improved. Most of the neoplasms responded to therapy, mainly surgery, and long-term outcome was favorable.

Female↗

Histomorphologic features of spontaneous and chemically-induced pulmonary neoplasms in B6C3F1 mice and Fischer 344 rats.

The histomorphologic features of spontaneous and chemically-induced lung neoplasms in male and female B6C3F1 mice and Fischer 344 rats are described. Primary pulmonary neoplasms in mice and rats were classified as alveolar/bronchiolar (A/B) adenoma or carcinoma (including variants with squamous and mucinous cell differentiation), bronchial adenoma or carcinoma, squamous cell carcinoma or mesenchymal tumors. A/B adenomas and carcinomas were the most common spontaneous pulmonary neoplasms observed in both mice and rats, but were observed less frequently in rats. In the National Toxicology Program (NTP) historical control database the incidence of spontaneous A/B adenomas in male (n = 2,084) and female (n = 2,079) mice is 13.8% and 4.9%, respectively; for A/B carcinomas, it is 5.3% and 2.4%, respectively. In male (n = 3,877) and female (n = 3,919) rats, spontaneous pulmonary neoplasms are rare with historical control rates less than 3% for A/B adenomas or carcinomas in either sex. The spontaneous A/B adenomas and carcinomas observed in mice and rats typically had papillary, solid or mixed (papillary and solid) histologic growth patterns. Pulmonary neoplasms from mice and rats treated with chemical carcinogens reviewed from 2-year studies consisted primarily of A/B adenomas and carcinomas. These tumors had papillary, glandular/tubular, solid or mixed (combination of 2 or more) histologic growth patterns. A few of the A/B neoplasms had areas of squamous or mucinous cell differentiation. Other less frequently occurring spontaneous and chemically-induced neoplasms included squamous cell carcinomas, bronchial adenomas and carcinomas, and sarcomas.

Adenoma↗

Spontaneous vascular neoplasms in aged Sprague-Dawley rats.

Primary benign and malignant vascular neoplasms occurred spontaneously in 8 of 710 male (1.1%) and 4 of 710 female (0.6%) Crl:CD Br strain Sprague-Dawley rats employed in two 2-yr oncogenicity studies (1,400) and as controls in a 1-yr toxicity study (20). Four of 13 neoplasms were found in the spleen; skin and kidney each had 2 neoplasms. Single vascular neoplasms were in the liver, testicle, uterus, mesenteric lymph node, and vagina. Hemangioma was more common (5 males, 2 females) than hemangiosarcoma (3 males, 2 females). Vascular neoplasms were considered the cause of death in 2 females, both with hemangiosarcomas involving the spleen or kidney. One male had 2 primary hemangiomas in separate organs. Vascular neoplasms are infrequently reported [1/82 females (1.2%), 1961; 9/880 both sexes (1.0%), 1985] in this rat strain. The incidence of vascular neoplasms of this report was higher in males (9) than in females (4), in contrast to incidences reported in the literature.

Aging↗

Frequency of ras mutations in liver neoplasms from B6C3F1 mice exposed to tetrafluoroethylene for two years.

Tetrafluoroethylene (TFE) was evaluated for carcinogenicity in inhalation studies because of its high use in the production of Teflon. There was clear evidence of hepatocarcinogenic activity in B6C3F1 mice after 2 yr of TFE exposure. The present study was designed to characterize the mutation profiles of H- and K-ras oncogenes in liver neoplasms in mice after exposure to 0, 312, 625, or 1,250 ppm TFE. ras mutations were identified by restriction fragment length polymorphism, single-stranded conformation polymorphism analysis, and direct sequencing of polymerase chain reaction amplified-DNA isolated from frozen or paraffin-embedded liver neoplasms. A low frequency (15%, 9/59) of H-ras codon 61 mutations was detected in hepatocellular neoplasms when compared with the higher frequency (59% of this study and 56% of historical data) in spontaneously occurring liver neoplasms. There was no difference in the mutation frequency or spectrum among exposure groups or between benign and malignant hepatocellular neoplasms. K-ras mutations at codons 12, 13, and 61 and H-ras mutations at codon 117 were not detected in hepatocellular neoplasms. These data suggest that TFE-induced hepatocellular neoplasms are developed by pathways that are mostly independent of ras mutations. The ras mutation frequency and spectrum were similar to those of the structurally related chemical tetrachloroethylene.

Animals↗