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B cell lymphomas of C57L/J mice; the role of natural killer cells and T helper cells in lymphoma development and growth.

The Hodgkin's-like Type B neoplasms which arise spontaneously in aging C57L mice (25% incidence at 21 months of age) were first reported over 40 years ago, but since then relatively little has been published about these lymphomas. Based on previous studies in SJL mice, we investigated the phenotypic and functional properties of C57L-derived lymphomas in relation to Mtv29-encoded vSAg expression by the tumor cells, and their ability to stimulate TCR Vbeta-restricted T cells. The cell surface phenotype of the C57L lymphomas indicates a B cell origin (sIg(+), MHC II(+)). These B lymphoma cells also express co-stimulatory molecules [B7-1 (CD80) and HSA (CD24)], and stimulate marked proliferation of syngeneic CD4(+) T cells. C57L B lymphoma cells exhibit Mtv-encoded mRNA by northern analysis, and also stimulate IL-2 production from Vbeta16(+) T cell hybrids, suggesting a role for Mtv 29 in this syngeneic T cell response. After transfer to syngeneic recipients, primary C57L lymphomas grow slowly, if at all. However, tumor growth is greatly accelerated by pretreatment of C57L recipients with anti-asialo GM1 antibody (but not anti-CD8 mAb), suggesting that NK cells play a major role in inhibiting lymphoma growth. If, in addition to anti-asialo GM1, the mice are also pretreated with anti-CD4 mAb, tumor growth is markedly inhibited, indicating that the lymphoma-responsive syngeneic CD4(+) T cells promote tumor growth. Therefore, although the vSAg-induced response stimulated by vSAg29 expressing lymphoma cells in syngeneic TCR Vbeta-restricted CD4(+) T cells is an important etiologic factor in this type of B cell neoplasm both in C57L and in SJL mice, the final outcome of the spontaneous neoplastic process appears strongly influenced by endogenous NK activity in aging mice.

Animals↗

[Adenocarcinoma of the umbilicus].

INTRODUCTION: Most of the umbilical neoplastic processes are metastatic whereas primary adenocarcinoma is scarce and hard to distinguish from a secondary process. Our observation illustrates this difficulty. OBSERVATION: A fifty year-old woman had developed chronic omphalitis over several years. She consulted for a multinodular, erythemato-violine, oozing and deep infiltrating tumor of the umbilicus which had been developing for two months. The anatomopathological exploration of a biopsy of the lesion suggested a clearly differentiated adenocarcinoma whose digestive origin was the most likely. Investigations for a primary neoplasm were negative. Polychemotherapy was efficient with eight months recline. DISCUSSION: Umbilical metastases are referred to as Sister Marie Joseph nodule. They essentially correspond to a metastatic localization of an intra abdominal adenocarcinoma. The major problem consists in distinguishing a Sister Marie Joseph nodule where the neoplasm remains indefinite from an adenocarcinoma developed from an embryonic remainder. The existence in our patient's case history of a chronic omphalitis developing for Years and the negative tests for a primary neoplasm suggest a primary adenocarcinoma of the umbilicus.

Abdominal Neoplasms↗

Enlargement of the nasolacrimal canal in the absence of neoplasia.

BACKGROUND: Asymmetrical enlargement of the nasolacrimal canal and nasolacrimal duct in the absence of associated neoplasm in uncommon. A dilemma in proper management in encountered because the subject is not well discussed in the medical literature. DESIGN: Case series. PARTICIPANTS: Three patients with abnormal enlargement of the nasolacrimal canal on computed tomography (CT) are analyzed. Two patients had a history of intermittent acquired dacryocystocele, whereas one had no associated lacrimal disorder. INTERVENTION: To relieve their obstructive symptoms, one patient was treated with lacrimal probing and silicone intubation, and the other patient was treated with dacryocystorhinostomy. The third patient, who was asymptomatic, elected observation alone. MAIN OUTCOME MEASURES: Anteroposterior diameters of the nasolacrimal canal were measured from the CT scans of these cases and compared with normative data derived from radiologic and anatomic studies. RESULTS: The maximal anteroposterior diameters of the nasolacrimal canals from these patients were 12.5, 15.4, and 15.1 mm, all well above the upper range of normal (8-10 mm). These enlarged nasolacrimal canals were not associated with any neoplastic process. Follow-up CT scans showed no change in size of the nasolacrimal canal. CONCLUSION: Nasolacrimal canal enlargement may occur without neoplasia of the lacrimal sac or nasolacrimal duct. In the absence of other features suggestive of neoplasia, appropriate management is aimed at treatment of lacrimal obstructive symptoms, if present, and serial CT scans. Open biopsy of the nasolacrimal duct is not necessary in asymptomatic patients with stable CT findings.

Adult↗

Tuberculosis presenting as a laryngeal tumour.

As the prevalence of tuberculosis in the U.K. increases, uncommon clinical presentations of the disease may be encountered by the otolaryngologist. We describe just such a case, where a caucasian patient presented with laryngeal lesion, considered to be highly suspicious of a neoplastic process rather than an infective one. We discuss the pathogenesis of tuberculous laryngitis, and review the differential diagnosis and management of the condition.

Aged↗

Comprehensive genome-wide comparison of DNA and RNA level scan using microarray technology for identification of candidate cancer-related genes in the HL-60 cell line.

Genome-wide scans for DNA and RNA changes in the HL-60 cell line relative to normal leukocytes were conducted. Microarray-based comparative genome hybridization (CGH) studies were performed with the Spectral Genomics Human Bacterial Artificial Chromosome (BAC) 3MB system. Transcriptional measurements of approximately 12,500 human genes were monitored using Affymetrix U95A GeneChips. In HL-60, genomic DNA amplification of the 8q24 locus, trisomy 18, and deletions at loci 5q11.2 approximately q31, 6q12, 9p21.3 approximately p22, 10p12 approximately p15, 14q22 approximately q31, 17p12 approximately p13.3, and monosomy X were detected. After obtaining locus information about the RNA transcripts from the Affymetrix database, 4368 genes were stratified both according to status of RNA expression and the DNA copy number of their designated loci. The expression level of 2326 (53.25%) of 4368 transcripts is concordant with DNA copy number. Examples of specific, highly expressed, cancer-associated genes in amplified loci include SERPINB10, MYC, TYMS, HEC, and EPB41L3, while CD14, GZMK, TCF7, FOS, MLH3, CTNNA1, IRF1, VIM, CRK, MAP3K1, STAM, MAX, SFRG5, ENC1, PURA, MNT, RASA1, GLRX, UBE2B, NR3C1, PTENP1, BS69, COPEB, SKIP, PIM2, and MIC2 represent cancer-associated genes in deleted loci with decreased expression. The complementary usage of genome-wide DNA and RNA scans should enhance the identification of candidate genes in the neoplastic process.

Adult↗

Translocation (3;3)(p14;q29) as the primary chromosome abnormality in a peritoneal mesothelioma.

Mesothelioma is a relatively rare malignant neoplasm arising from the serosal lining of the pleural, peritoneal, and pericardial cavities. Mesotheliomas are known to be associated with asbestos exposure. The karyotypes of these tumors have mostly been so complex as to preclude the identification of primary chromosome abnormalities. We present the cytogenetic analysis of two macroscopically distinct abdominal tumors, both diagnosed as peritoneal mesothelioma, occurring in a woman with a history of heavy asbestos exposure. Both tumors contained the same three karyotypically abnormal but cytogenetically related clones, with a balanced t(3;3)(p14;q29) as the primary chromosomal change. The fact that several chromosome abnormalities were common to both tumors strongly indicates that they arose through intraperitoneal spreading of a single neoplastic process; that is, they were not pathogenetically independent lesions. Our findings, taken together with previously published cytogenetic data on peritoneal mesotheliomas, indicate that a proportion of these tumors may be characterized by simple, balanced chromosomal rearrangements. At least a subset of peritoneal mesotheliomas arises through the same pathogenetic mechanisms that are involved in the pleural forms of this disease.

Aged↗

Cytogenetic and interphase FISH analyses of 73 basal cell and three squamous cell carcinomas: different findings in direct preparations and short-term cell cultures.

Cytogenetic analysis performed on 73 sporadic basal cell carcinomas (BCCs) and three squamous cell carcinomas (SCCs) showed different findings in direct preparations (24 hours) and in short-term cell cultures. Except for loss of the Y chromosome, not one of the other clonal (+6, +16, add(2)(q37), del(3)(q13), add(1)(p31), and near triploidy) or sporadic changes found in direct preparations was found in cell cultures and vice versa. Clonal trisomy 6 found in two BCC direct preparations and demonstrated by interphase fluorescence in situ hybridization in 8 other cases seems to be a nonrandom change in basal cell carcinoma. Immunohistochemistry showed that the cell type investigated was different in the two methods of analysis used: epithelial in direct preparations and fibroblastic in cell cultures. Thus, the results obtained in direct preparations indicate the BCC or SCC epithelial karyotype, whereas the aberrations found in cell cultures indicate the presence of chromosome instability in the fibroblastic stroma. The apparent lack of correspondence between direct and indirect preparations and the presence of clonal chromosome changes in both epithelial and stromal cells suggest tumor cell heterogeneity of BCC. The fibroblastic stroma seems to be implicated in the neoplastic process. This is not evident in SCC, in which clonal changes are present only in direct preparations. The chromosomal distribution of the breakpoints involved in structural changes in direct and cell culture preparations is random; together with those reported in the literature, the breakpoints found in BCC cultures show, however, a cluster to 1p36, 3q13, 9q22, 14p11, 15p11, and Xp11 bands. We did not find any significant correlations between BCC cytogenetic results and the clinical data (site, age, sex, recurrence). The incidence of cases of BCC (38%) and of SCC (100%) showing clonal chromosome changes agree with their benign and malignant nature, respectively. Finally, a significantly high incidence of constitutional inv(9) and dup(9)(q11q21) was found in the group of patients with BCC.

Abdominal Neoplasms↗

Calvarial sarcoid mimicking metastatic disease.

A 61-year-old white woman presented with localized cutaneous Boeck's sarcoid and multiple lytic skull lesions mimicking metastatic carcinoma. Complete workup revealed no neoplastic process; biopsy of the skull lesions showed noncaseating granulomas consistent with sarcoid. Although rare, calvarial sarcoid can occur.

Biopsy↗

Controversies in mycosis fungoides.

Most clinicians agree that mycosis fungoides is the prototypic cutaneous T cell lymphoma. However, certain clinical characteristics indicate that this disorder may begin as a reactive rather than a neoplastic process. The concept of a nonneoplastic etiopathogenesis of mycosis fungoides is further supported by recent data on the function of Langerhans cells, a population of epidermal cells known to play a critical role in immune surveillance and the development of contact sensitivity. It has been suggested that chronic occupational exposure to environmental allergens results in persistent antigenic stimulation, leading to a breakdown in immune surveillance and eventually, malignancy. Modern laboratory technics have enhanced the clinician's ability to diagnose and stage mycosis fungoides. Data obtained from such studies have indicated that systemic spread may occur much earlier in the course of disease than has previously been appreciated. The therapeutic implications of such knowledge are as yet uncertain.

Allergens↗

What's new in dermatopathology?

This review emphasizes the important work in dermatopathology reported in the past 3 years. In reviewing the recent contributions in the field, four areas appear to have received particular attention: (1) new information concerning the histogenesis of cutaneous tumors based on the dual functional capacities of cells; (2) the Langerhans cell and its role in inflammatory and neoplastic processes; (3) prognostic factors in stage I malignant melanoma; and (4) the use of new immunofluorescent and immunohistochemical technics as diagnostic tools in cutaneous pathology.

Carcinoma↗

A practical approach to hemoperitoneum in the dog and cat.

Hemoperitoneum can occur in animals of any age and can result from many different disease processes. Neoplastic and traumatic conditions are the most common causes. Many of these patients present with hemodynamic instability but stabilize with rational intravenous fluid therapy and abdominal counterpressure. Surgical exploration of the abdomen is indicated in many situations. Surgical therapy is aimed at resection or control of the bleeding focus, removal of any devitalized tissue, and biopsy of additional sites of suspicion. Optimal treatment for all patients with hemoperitoneum frequently requires advanced critical care, anesthesia, and surgical techniques. Finally, the treatment outcome is variable and dependent on the underlying cause and its severity.

Animals↗

[Survival in patients treated with radical cystectomy for bladder carcinoma].

AIM: To analyze survival among cystectomized bladder cancer patients. MATERIAL AND METHODS: A retrospective cohort study comprising data from 166 bladder cancer patients subjected to cystectomy between 1976 and 1998. Patient survival was considered the dependent variable, while sociodemographic data, renal function parameters, the existence of hydronephrosis, anaesthetic risk according to ASA status, the type of urinary diversion involved, the histopathological characteristics and postoperative complications were regarded as the independent variables. Survival was analyzed by the Kaplan-Meier method, comparing survival curves with the Mantel-Haennszel test, and developing a Cox proportional risk model. RESULTS: The mean survival was 81 months (median = 20 months); 82% of the patients died of causes related to the neoplastic process or surgical complications. The probability of survival 60 months after surgery was 35.2%--the figure being higher among patients aged < or = 65 years (p = 0.026), without prior hydronephrosis (p = 0.023), or with normal creatinine levels (p = 0.048). The principal influencing factor was tumor histological stage: for lesions in stage < or = pT2 survival at 60 months was 67.8%, versus 29.1% in stage pT3 and only 6% in pT4. In the presence of lymph node involvement, only 6.1% of the patients were still alive after 5 years. CONCLUSIONS: The local infiltration stage and pelvic node involvement are the two most decisive factors for patients prognosis. Hydronephrosis and increased creatinine levels before cystectomy are the two non-hystopatological parameters associated to a poorer prognosis.

Adult↗

[Myositis ossificans circumscripta: a case report].

Myositis ossificans circumscripta is a benign lesion characterized by focal heterotopic soft tissue ossification, occurring in young people generally after localized trauma. Clinical and radiological appearances may mimic a sarcomatous neoplastic process. We report a case of myositis ossificans occurring after trauma, so as to illustrate the different imaging features of this benign pathology on conventional radiographs and computed tomography.

Adolescent↗

[Muscular metastases disclosing adenocarcinoma].

The authors report the case of a 67-year old man, with no particular medical history, presenting a large swelling of the left thigh. Investigations conclude to metastases located in muscles of the left thigh and of the pelvis, secondary to an adenocarcinoma of presumed pancreatic origin. With reference to this case, features of muscular metastases are reviewed. Muscular metastases seldom occur during the course of a cancer and are exceptionally the first manifestation of a neoplastic process. They are usually described as a painful mass, but symptoms can be misleading and delay diagnosis. Images obtained by ultrasonography, tomodensitometry and magnetic resonance imaging are not specific and histological examination is necessary to confirm the diagnosis.

Adenocarcinoma↗

Virtual bronchoscopy.

Three-dimensional endoluminal tracheobronchial simulations can be derived successfully from thoracic helical CT scans, and can reproduce the appearances of major endobronchial abnormalities confirmed during FB. The prospects of ever-faster CT scanners (capable of submillimeter resolution) merged with greater computer power make it likely that current versions of virtual bronchoscopy images will seem primitive in the future. Initial descriptive reports suggest great potential, but the startling visual appeal of these 3-D portrayals of a patient's airway and mediastinal anatomy and the prospects of exploring this information in real time do not establish its clinical role. Such virtual bronchoscopy findings are generally predictable on the basis of currently available axial CT images alone. The extent to which these 3-D endobronchial renderings improve the already high predictive values of CT requires critical study. In their patients with lung cancer Cicero et al observed that neither the staging nor diagnosis was modified substantially, but virtual bronchoscopy contributed to enhanced understanding of the pathology of the neoplastic process. Whether this added perspective translates to tangible benefits for patients is an intriguing possibility that has yet to be proved. The unique 3-D endobronchial view may offer particular advantages in some individuals and contribute to the patient's noninvasive evaluation. Because of the already high yield of conventional CT, diagnostic yield alone is not likely to be the sole best measure of this evolving technology. Accordingly, future multidisciplinary research investigations will also need to prospectively address nuances of decision-making and measure appropriate patient outcomes. In these efforts the active dialogue between chest clinician and radiologist will remain essential to defining and realizing the true potential of virtual bronchoscopy.

Bronchoscopy↗

Hypokalemia, metabolic alkalosis, and hypertension: Cushing's syndrome in a patient with metastatic prostate adenocarcinoma.

Ectopic adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing hormone (CRH) are associated with a growing list of tumors. We report a 69-year-old white man with a history of high-grade prostate carcinoma and widely metastatic adenocarcinoma who presented with metabolic alkalosis, hypokalemia, and hypertension secondary to ectopic ACTH and CRH secretion. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Markedly elevated serum cortisol (135 microg/dL), ACTH (1,387 pg/dL), CRH (69 pg/dL), and urine free cortisol (16,276 microg/24 h) levels were found. Chest computed tomographic (CT) scan showed small noncalcified parenchymal densities; however, bronchoscopy and bronchoalveolar lavage washings were unremarkable for a neoplastic process. Abdominal CT scan and magnetic resonance imaging showed multiple small liver lesions and multiple thoracic and lumbar intensities consistent with diffuse metastatic disease. Histological analysis of a biopsy specimen from the thoracic spine showed an undifferentiated adenocarcinoma consistent with a prostate primary tumor. The severe metabolic alkalosis secondary to glucocorticoid-induced excessive mineralocorticoid activity was treated with potassium supplements, spironolactone, and ketoconazole. In this case report, we describe an unusual tumor associated with ectopic ACTH and CRH production and the pharmacodynamic relationship of plasma cortisol levels and urinary cortisol excretion with ketoconazole treatment.

ACTH Syndrome, Ectopic↗

[Pulmonary capillary hemangiomatosis: a rare cause of pulmonary hypertension].

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension characterized by capillary proliferation infiltrating the structures of the pulmonary parenchyma. Although veins are particularly involved, proliferation also affects bronchiolar, interstitial and other structures. We report a case of PCH in a 70-year-old man. Pulmonary artery hypertension was demonstrated by echocardiogram and angiography. Severe emphysema could be seen in a computed tomographic scan of the thorax, even though spirometric values indicated that airflow obstruction was mild. Dyspnea and respiratory insufficiency progressed with marked shunting until death. Tissue inspection at the autopsy revealed capillary proliferation in the alveolar walls with occasional oviform protrusions into air spaces or around small vessels and bronchioles. Endothelial cells in newly formed vessels were not atypical and mitosis was scarce; p53 expression was negative and Ki67 proliferation slight, indicating that PCH is not a neoplastic process as has sometimes been suggested.

Aged↗

Inflammatory pseudotumor of the fossa pterygopalatina: diagnosis and treatment.

Pseudotumor is a term used to describe a space-occupying inflammatory lesion of unknown etiology that clinically simulates a neoplastic process. Pseudotumors of the fossa pterygopalatina and fossa infratemporalis are very rare. In this paper, we describe a patient who developed a pseudotumor in the left fossa pterygopalatina, secondary to an unclassified autoimmune disease, which caused progressive left-sided facialdynia and swelling. The tumor was detected with somatostatin receptor scintigraphy. The lesion was refractory to steroids, also in combination with azathioprine, as well as to surgical intervention. An excellent clinical response was observed after cyclosporine was added. This case is presented here in order to draw attention to the use of somatostatin receptor scintigraphy as a diagnostic tool in visualizing pseudotumors and to document a case that responded excellently to treatment with a combination of low-dose cyclosporine and steroids.

Bone Diseases↗