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PubMed1997

Nodular erythema elevatum diutinum mimicking cutaneous neoplasms.

AIMS: We describe the cutaneous pseudoneoplastic lesions in two patients with nodular erythema elevatum diutinum, a rare chronic disorder in which polymorph nuclear fragmentation (leukocytoclasis) is present within dermal nodules showing spindle cells and fibrosis. In both cases diagnostic difficulty was encountered clinically and pathologically and various benign and malignant neoplasms were considered in the differential diagnosis. METHODS AND RESULTS: Immunohistochemically the spindle cells were negative for CAM5.2, AE1/3, S100 protein and desmin (D33). They were positive for vimentin and focally positive for CD34 and alpha-smooth muscle actin. Some of the spindle cells were positive for Mac 387 and KP1(CD68). By electron microscopy, the lesions were shown to consist of fibroblasts/myofibroblasts and fusiform macrophages. CONCLUSIONS: Increased awareness of the features described will help to avoid misdiagnosis as a neoplastic process.

Adult↗
PubMed2001

CXCR3 expression in human central nervous system diseases.

The CXCR3 chemokine receptor, expressed on activated T lymphocytes, is seen within the central nervous system (CNS) in inflammatory conditions where a T-cell response is prominent. However, the distribution of CXCR3 in parenchymal CNS cells is unknown. Using a monoclonal antibody against CXCR3 and post-mortem tissue of patients with and without CNS pathology, we have determined its expression pattern. CXCR3 was found in subpopulations of cells morphologically consistent with astrocytes, particularly reactive astrocytes, and in cerebellar Purkinje cells. It was also detected in arterial endothelial and smooth muscle cells, particularly in areas associated with atherosclerotic plaques. CXCR3-positive astrocytes were particularly prominent in the CNS of HIV-positive patients, in patients with Multiple Sclerosis (MS), in ischaemic infarcts and in astrocytic neoplasms. Immunofluorescence studies of mixed adult primary glial cultures and fetal glial cultures also showed expression of CXCR3 in astrocytes. CXCR3 mRNA was detected in Purkinje cells by in situ hybridization with a CXCR3-specific probe. Thus, the predominant expression of CXCR3 in reactive astrocytes may indicate that it plays a role in the development of reactive gliosis in a variety of infectious, inflammatory, vascular and neoplastic processes in the CNS. The relationship between CXCR3 expression in astrocytes to its expression in Purkinje cells, endothelial cells and smooth muscle cells is yet to be determined.

AIDS Dementia Complex↗
PubMed2003

Proliferation kinetics and apoptosis of serrated adenoma of the colorectum.

To elucidate the proliferation kinetics and cell loss by apoptosis of serrated adenoma (SA) of the colorectum, we performed Ki-67 immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated deoxyuridine-triphosphate nick-end labeling (TUNEL) method for 24 SA, and compared the results to those of normal colonic mucosa (n = 15), hyperplastic polyp (HP) (n = 18) and traditional tubular adenoma (TA) (n = 55). The growth fraction (Ki-67 labeling index) of SA was 18.8%, which was significantly lower than those of TA (40.1%) and HP (23.8%), while the apoptotic index of SA (0.14%) was significantly lower than that of TA (1.17%). The proliferative compartment in SA was distributed either basally (47%, 60/117 crypts), or in the intermediate portion (51.3%, 55/117 crypts), and there was no superficial translocation of the proliferative compartment, which was seen in 81.2% (361/445 crypts) of TA crypts. These results indicate that SA is a tumor with low proliferative activity and its growth would be maintained by a low extent of cell loss by apoptosis. The results also indicate the neoplastic process in SA is characterized by the disorder of cell migration, maturation and exfoliation similar to HP, and its epithelial cell maturation and migration occasionally occur bidirectionally, toward the surface and to the bottom of the crypt.

Adenoma↗
PubMed1998

Identification of activating c-kit mutations in adult-, but not in childhood-onset indolent mastocytosis: a possible explanation for divergent clinical behavior.

Mastocytosis represents a mast cell proliferative disease that generally runs a benign clinical course, with spontaneous remissions mostly by puberty in childhood-onset disease, although rare forms, particularly in adult-onset disease, can be associated with (pre)malignant hematologic disorders and very rarely present as mast cell leukemia or malignant mastocytosis. Reasons for this divergent clinical behavior of childhood- versus adult-onset disease are unknown. Recently, two activating mutations in the intracellular domain of the proto-oncogene c-kit, which encodes a tyrosine kinase receptor for the mast cell growth factor stem cell factor, have been detected in the human leukemic mast cell line HMC-1. We have therefore studied lesional skin biopsies from patients with adult- and childhood-onset indolent mastocytosis for the presence of these codon 560 and 816 mutations. C-kit coding DNA sequences were amplified and analyzed by mutation-specific restriction analyses, and mutated polymerase chain reaction products were additionally cloned and sequenced. The codon 816 mutation was found in all six samples from adult patients, but not in any of the 11 specimens from children. In addition, the codon 560 mutation could be demonstrated for the first time in indolent mastocytosis, namely in two of four specimens from adult patients, but not in those from two children. These data thus provide a possible explanation for the divergent clinical behavior of adult- versus childhood-onset indolent mastocytosis, with the first being associated with an activating mutation, possibly as part of a neoplastic process, and the latter representing most likely a reactive process of an as yet unknown pathogenesis.

Adult↗
PubMed2000

Angiogenesis in the uterine cervix.

Our objective was to present current data pertaining to angiogenesis of the uterine cervix. We conducted a computerized search to identify relevant studies published in the English language literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, uterine cervix, intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966 through June 1999. In contrast to the cyclic phases of the menstrual cycle of the ovary and endometrium in which angiogenesis plays a significant physiologic role, angiogenesis in the uterine cervix is involved primarily in neoplastic processes. These include intraepithelial disease, human papilloma-related disease, and microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis appears to be a prognostic indicator for overall survival and disease-free survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy such as TNP-470 have been reported and concurrent antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.

Journal Article↗
PubMed2001

Overview. Cytogenetic analysis in haematology.

Cytogenetic analysis has contributed greatly to our understanding of the nature of leukaemia and lymphoma. Study of these two groups of diseases has revealed general truths about the nature of the neoplastic process. Cytogenetic analysis has demonstrated that haematological neoplasms result from a somatic mutation occurring in a haemopoietic, lymphoid or multipotent stem cell. Complete remission has been related to disappearance of the clone of cells bearing the mutation whereas the occurrence of clonal evolution has often been found to be indicative of increasingly aggressive disease. Cytogenetic analysis of leukaemias and lymphomas has led to the discovery of numerous proto-oncogenes; these generally play a crucial role in proliferation and differentiation of normal cells with a perturbation of their function leading to neoplasia. In addition, cytogenetic evidence has suggested a role for loss of function of cancer-suppressing genes in haematological neoplasms. Cytogenetic analysis has also made major contributions to precise diagnosis and to the assigning of prognosis and, furthermore, by identifying good and poor prognostic groups has improved the management of patients. Good-prognosis patients have been spared unnecessary treatment and, conversely, more intensive treatment for some diseases associated with a cytogenetic abnormality that was previously indicative of a poor prognosis has improved the outcome for these patients.

Chromosome Aberrations↗
PubMed2002

Emerging biological therapies for pancreatic carcinoma.

AIMS: The incidence of pancreatic carcinoma remains approximately equal to its mortality, with the vast majority of patients having advanced disease at presentation. This review is an update of the promising novel approaches involving biological therapy that may be used in conjunction with new chemotherapeutic agents in the near future. METHODS: A literature review was performed using the National Library of Medicine's Pubmed database, combined with recently published data from the AGA and ASCO conferences. RESULTS: Rapid progress is being made in gene and molecular technology potentially enabling us to inhibit pancreatic carcinogenesis and to reduce disease progression. Different targets include signal transduction inhibitors, gene therapy, genetic prodrug activation therapy, antisense therapy, immunotherapy, matrix metalloproteinase and cyclo-oxygenase-2 inhibition and hormonal manipulation. CONCLUSION: A variety of biological agents are currently undergoing clinical trials, targeting different areas of the pancreas'neoplastic process. .

Antineoplastic Agents, Hormonal↗
PubMed2000

The expression of Ep-CAM (17-1A) in squamous cell cancers of the lung.

Immunotherapy trials using monoclonal antibodies 323/A3 and 17-1A that recognize Ep-CAM, including trials focused on cancer of the lung, currently are underway. Nevertheless, there have been few comprehensive evaluations of the expression of Ep-CAM in specific types of neoplastic processes, including cancer of the lung. The current study of 60 human subjects with squamous cell cancer (SCC) of the lung, selected at random, was undertaken (1) to examine the expression of Ep-CAM in SCC and associated uninvolved bronchial mucosa, bronchial epithelial hyperplasia, and dysplasia, and (2) to correlate the results with established prognostic indicators and survival of patients. In both the uninvolved bronchial mucosa and epithelial hyperplasia, the expression of Ep-CAM in luminal cells was significantly higher compared with its expression in the matched basal cells (P = .003, P < .0001, respectively). When Ep-CAM scores of basal and luminal cells present in uninvolved bronchial mucosa and epithelial hyperplasia were combined, we observed a statistically significant stepwise increase in Ep-CAM expression from uninvolved bronchial mucosa to epithelial hyperplasia to SCC, suggesting its involvement in malignant transformation of SCC. The expression of Ep-CAM was significantly higher in poorly to moderately differentiated SCC compared with well-differentiated SCC (P = .04). An increase in the expression of Ep-CAM with increasing size or local extent of the primary tumor approached statistical significance (P = .09). The expression of Ep-CAM increased significantly with increasing involvement of regional lymph nodes (P = .02). Similarly, the expression of Ep-CAM increased with the increasing TNM stages (P = .04). Kaplan-Meier Survival analysis using the same categorizations showed that increasing tumor size, nodal status, and stage were significantly associated with poor patient survival (P = .04, .01, .01, respectively). There was, however, no statistically significant association between patient survival and staining intensity of carcinomas for Ep-CAM. We conclude that expression of Ep-CAM increased during the progression of SCC of the lung and, therefore, may play a role in the carcinogenesis of this disease.

Antigens, Neoplasm↗
PubMed2001

Inflammatory pseudotumor of lymph node and spleen: an entity biologically distinct from inflammatory myofibroblastic tumor.

Inflammatory pseudotumors (IPTs) of the lymph node and spleen are an uncommon, benign cause of lymphadenopathy and/or splenomegaly that often bear striking clinicopathologic similarities to the inflammatory myofibroblastic tumors (IMTs) found in soft tissues. These tumors have classically been grouped together under the umbrella category of "inflammatory pseudotumor." Recent evidence shows that IMTs are in fact neoplastic processes that often harbor balanced chromosomal translocations involving the ALK kinase gene. These translocations result in expression of ALK kinase in IMTs as assessed by immunohistochemical studies. However, the relationship between IMT and IPT of the lymph node and spleen is uncertain. To determine if ALK tyrosine kinase expression is also present in IPT, 13 cases of IPT (9 involving lymph nodes, 4 splenic lesions) were examined for the presence of ALK tyrosine kinase by immunohistochemical staining on paraffin-embedded tissue. In addition, in situ hybridization studies for Epstein-Barr virus--encoded RNAs (EBER) and immunoperoxidase studies for human herpesvirus-8 (HHV8)--specific proteins were performed. All cases had clinical, morphologic, and immunophenotypic findings typical of IPT and had varying proportions of fibroblastic and inflammatory components. Age ranged from 11 to 75 (median, 40) years; 8 subjects were male, and 5 were female. None of the cases (0 of 13) had positive staining for ALK kinase or HHV8, and in 1 a lymph node (1 of 13) was focally positive for EBV (EBER) by in situ hybridization. The absence of ALK kinase as detected by immunohistochemical studies in IPT of the lymph node and spleen suggests that this entity is biologically distinct from the histologically similar IMT.

Adult↗
PubMed2004

Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice.

BACKGROUND & AIMS: The emergence of oxyntic atrophy and metaplastic cell lineages in response to chronic Helicobacter pylori infection predisposes to gastric neoplasia. We have described a trefoil factor family 2 (TFF2; spasmolytic polypeptide) expressing metaplasia (SPEM) associated with gastric neoplasia in both rodent and human fundus. To examine the relationship of SPEM to the neoplastic process in the H. felis -infected C57BL/6 mouse, we have now studied the association of SPEM-related transcripts with preneoplasia. METHODS: SPEM-related transcripts were identified by microarray analysis of amplified cRNA from SPEM, and surface mucous cells were isolated by laser capture microdissection from the same gastric sections from male C57BL/6 mice infected with H. felis for 6 months. Expression of SPEM-related transcripts was assessed by in situ hybridization and quantitative RT-PCR, as well as immunohistochemistry for prothymosin alpha. RESULTS: Eleven SPEM-related transcripts were identified as detectable only in SPEM. The expression of the SPEM-related transcripts was validated by in situ hybridization and quantitative PCR. One transcript, the noncoding RNA Xist, was only identified in SPEM cells from the infected male mice. Ten of the 11 transcripts as well as TFF2 were also expressed in regions of gastritis cystica profunda. Immunocytochemistry for one of the identified proteins, prothymosin alpha, demonstrated prominent nuclear staining in SPEM and gastritis cystica profunda. CONCLUSIONS: The expression of SPEM-related transcripts in regions of gastritis cystica profunda suggests that SPEM represents a precursor lineage for the development of dysplasia in this animal model of gastric carcinogenesis.

Animals↗
PubMed2004

Implications of PET based molecular imaging on the current and future practice of medicine.

The last quarter century has witnessed the introduction of a variety of powerful techniques that have allowed visualization of organ structure and function with exquisite detail. This in turn has brought about a true revolution in the day-to-day practice of medicine. Structural imaging with x-ray computerized tomography and magnetic resonance imaging has added tremendously to many areas of medicine, including preoperative evaluation of patients. Many surgical procedures have been replaced by minimally invasive techniques, which have become a reality only because of the availability of modern imaging modalities. However, despite such accomplishments, structural imaging is quite insensitive for detecting early disease in which there often are no gross structural alterations in organ anatomy. Therefore, these modalities should be complemented by methodologies that can detect abnormalities at the molecular and cellular levels. The introduction of [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in 1976 as a molecular imaging technique clearly has shown the power of this approach for treating a multitude of serious disorders. The impact of FDG-PET has been particularly impressive in patients with cancer diagnosis, for whom it has become important in staging, monitoring response to treatment, and detecting recurrence. In this review, we emphasize the role of FDG-PET in the assessment of central nervous system maladies, malignant neoplastic processes, infectious and inflammatory diseases, and cardiovascular disorders. New radiotracers are being developed and promise to expand further the list of indications for PET. These include novel tracers for cancer diagnosis and treatment capable of detecting hypoxia and angiogenesis. Prospects for developing new tracers for imaging other organ diseases also appear very promising.

Animals↗
PubMed2002

Disarticulation resections of the mandible: a prospective review of 16 cases.

PURPOSE: This article provides a review of the disarticulation resection of the mandible for various benign and malignant tumors and non-neoplastic processes. In so doing, the author proposes a classification to describe extension of pathology into the condylar region, thereby requiring its sacrifice. Recommendations are also proposed for preservation versus sacrifice of the meniscus when performing a disarticulation resection of the mandible. Finally, complications are evaluated in this type of mandibular resection. PATIENTS AND METHODS: This review is based on the author's accumulated clinical data obtained from performing disarticulation resections on 16 patients who presented with 10 different pathologic diagnoses. Disarticulation resections are performed for 3 different patterns of extension of pathologic processes into the condylar region, designated as type I, type II, and type III by the author. These designations reflect the radiographic involvement of the condyle or subcondylar region of the mandible by the pathologic entity. The designations of type II and type III extensions are diagnosis dependent, whereas type I extension is independent of diagnosis. RESULTS: Five patients in this series presented with type I condylar extension, 2 patients presented with type II condylar extension, and 9 patients presented with type III condylar extension. The meniscus required sacrifice in 3 of the 16 patients. Complications occurred in 3 of 16 patients and included 1 dislocation of the plate into the middle cranial fossa, 1 dislocation of the plate inferiorly and posteriorly to the mastoid process, and 1 cutaneous exposure of the plate. CONCLUSIONS: Disarticulation resections are rarely required variants of segmental resection of the mandible, and they are required by a variety of pathologic processes of the jaws and contiguous structures. The placement of a reconstruction bone plate with an affixed condylar prosthesis is well tolerated by patients and is associated with few complications. These reconstruction bone plates favorably support facial form, symmetry, and occlusion such that many patients delay their definitive bony reconstruction. Because these condyles are temporary prostheses, the surgeon should consider their removal with bony reconstruction of the disarticulation defect as soon as possible after the ablative surgery.

Bone Plates↗
PubMed2002

Matrix metalloproteinases and matrix metalloproteinase inhibitors in lung cancer.

Preclinical studies have provided evidence that matrix metalloproteinases (MMPs), a family of zinc-containing proteolytic enzymes, facilitate tumor invasion, the establishment of metastases, and the promotion of tumor-related angiogenesis. Matrix metalloproteinase inhibitors (MMPIs) have been shown to inhibit tumor growth and dissemination in preclinical models. Not all lung cancers express the MMPs believed to be most important in promoting the neoplastic process, and there are conflicting reports regarding the prognostic significance of MMPs in lung cancer. However, it is possible that these observations are because of limitations in the procedures for measuring MMPs. Many investigators believe that MMPs are universally involved in tumor progression; this hypothesis was the basis for initiating seven phase III MMPI trials in lung cancer. Four studies were closed at completion of the predefined accrual goal, and three were closed early. There were no significant differences in survival in a non-small cell lung cancer prinomastat study, and in a small cell lung cancer marimastat trial. The results of the remaining five studies have not been reported. At this point it appears that MMPIs will probably not play a major role in the treatment of advanced lung cancer patients.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Common paraneoplastic syndromes.

Cancer has many effects on the veterinary patient. One group of syndromes that must be paid particular attention to is the paraneoplastic diseases. These are a group of changes that occur in the body at sites distant from the actual tumor. Paraneoplastic syndromes can affect many different body systems. Paraneoplastic diseases are important to recognize for many reasons. Often the paraneoplastic change is the earliest indication of cancer and, thus, neoplasia must be included on any differential list when typical paraneoplastic changes are found in the routine medical work-up. Paraneoplastic syndromes can also be used as markers of remission. Many of the paraneoplastic changes will disappear when remission is achieved, and will reappear once the period of remission had come to an end. Identification of paraneoplastic changes is also important in that often they must be treated before treatment of the primary disease can occur. Treating the remote effects of cancer will increase quality of life. Although many different paraneoplastic syndromes exist, hypercalcemia, hypoglycemia, cachexia and anemia are the most clinically significant in the veterinary patient. Chronic treatment most commonly involves removal or treatment of the primary or inciting neoplastic process. The acute treatment of these syndromes can occur quickly. Rapid identification and treatment will allow the patient to have a better prognosis and will help to improve quality of life.

Anemia↗
PubMed2001

Tcf-3 expression and beta-catenin mediated transcriptional activation in aggressive fibromatosis (desmoid tumour).

Aggressive fibromatosis harbours mutations resulting in beta-catenin protein stabilization. Primary cell cultures demonstrate constitutive tcf activation in aggressive fibromatosis. Expression and co-immunoprecipitation studies suggest that beta-catenin binds and activates tcf-3 in this tumour. This is the first demonstration of tcf-3 activation by beta-catenin stabilization in a human neoplastic process.

Cytoskeletal Proteins↗
PubMedDate not supplied

Prostate cancer vs hyperplasia: relationships with prostatic and adipose tissue fatty acid composition.

The objective of the present study was to study whether adipose tissue and prostatic tissue fatty acid composition differentiates between prostate cancer and benign hyperplasia patients. In addition, the present investigation aimed at exploring the extent to which prostatic tissue fatty acid composition differentiates between prostate-confined cancer and extraprostatic disease including possible metastasis. The subjects were 71 male patients from the island of Crete. Half the patients (n=35) had been diagnosed with benign hyperplasia of the prostate, half with prostatic malignancy (n=36). Patients were examined at the outpatient clinic of the urology unit, University Hospital, Medical School, University of Crete. Relative to benign hyperplasia patients, cancer patients had elevated adipose tissue saturated and reduced monounsaturated fatty acid levels. Cancer patients had reduced prostate tissue stearic to oleic acid ratios and stearic acid levels as opposed to hyperplasia patients. The most pronounced difference between cancer patients and hyperplasia patients was a 3-fold elevated prostatic palmitoleic acid in the former group. Relative to benign hyperplasia patients, cancer patients had reduced prostate tissue arachidonic and docosahexaenoic acid levels. Finally, there was a significantly reduced omega-3/omega-6 polyunsaturated fatty acid ratio in the prostate cancer patient as opposed to the benign hyperplasia group. The pronounced elevations in prostatic tissue palmitoleic acid in cancer patients highlight a possible role of this fatty acid in neoplastic processes. The decreased arachidonic acid levels in cancer patients possibly stem from enhanced metabolism of arachidonic acid via lipoxygenase and cyclooxygenase pathways, and the formation of derivatives such as 5-HETE, 15-HETE, 12(S)-HETE and PGE(2).

Adipose Tissue↗
PubMed2000

Tumors of the infratemporal fossa.

Neoplastic processes involving the infratemporal fossa may originate from the tissues in the region, but more often are the result of extension from neighboring structures. Metastatic lesions located in the region are rarely encountered. Because of its concealed localization, tumors may remain unnoticed for some time. Clinical signs and symptoms often arise late, are insidious, and may be mistakenly attributed to other structures. The close proximity of the area to the intracranial structures, the orbit, the paranasal sinuses, the nasopharynx, and the facial area demands careful planning of surgical excision and combined procedures may be called for. Modern imaging techniques have made three-dimensional visualization of the extent of the pathology possible. Treatment depends on the histopathology and staging of the tumor. Several surgical approaches have been developed over the years. Radical tumor excision with preservation of the quality of life remain the ultimate goal for those tumors where surgery is indicated. Experience over a decade with various pathologies is presented.

Journal Article↗
PubMed2000

[Excessive weight loss caused by dysphagia in superior laryngeal nerve neuralgia--a case report].

BACKGROUND: Superior laryngeal nerve neuralgia is a very rare disease typically associated with paroxysmal and lancinating pain mostly localised on one side of the laryngeal region and sometimes radiating into the homolateral jaw or ear. The condition is usually idiopathic and treated successfully with carbamazepine. Even if the symptoms are unusual or not typical for superior laryngeal nerve neuralgia, the condition should be considered as a possible diagnosis if there are no other pathological findings. CASE REPORT: In October 1999, a 44-year old man presented a progressive dysphagia. Complaining about increasing problems in swallowing, he started refusing solid food and lost about 50 kg in two and a half years. In addition, he complained about persistent pain in the right laryngeal region, intensified by chewing or swallowing. Extensive investigations produced no pathological findings, especially no neoplastic process or other consuming diseases. After an injection of local anaesthetic near to the right hypothyroid membrane, the symptoms improved dramatically for a few hours and the diagnosis of superior laryngeal neuralgia was made. To confirm the diagnosis we injected sodium chloride as a placebo without any effect. The condition was successfully treated with 200 mg of carbamazepine three times daily without any major side effects. CONCLUSIONS: Even if the symptoms are not typical and dysphagia and weight loss are the outstanding symptoms, superior laryngeal nerve neuralgia should be considered as the possible diagnosis, especially if no other pathological findings are revealed. Injection of local anesthetic is a valuable tool for diagnosing the disease.

Adult↗