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PubMed2001

Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis.

BACKGROUND: It has yet to be established whether proliferative activity in the macroscopically normal colonic mucosa is causally correlated with neoplastic risk. Measurement of proliferative activity in human subjects is of necessity usually undertaken using indirect methods with inherent limitations, and relatively little has been published on the effect of normal biological variables on such indices. AIMS: To establish the validity of mitosis counts following whole crypt microdissection as an index of the crypt cell proliferative state (CCPS) and to examine the effect of normal biological variables (age, sex, and colonic site) and colonic neoplasia on the mitotic index in macroscopically normal human colon. SUBJECTS: Mucosal samples were obtained at colectomy or colonoscopy from 107 individuals (24 controls, 23 sporadic adenoma patients, 31 sporadic carcinoma patients, and 29 patients with familial adenomatous polyposis (FAP)). METHODS: Mucosal specimens were hydrated, hydrolysed, and small groups of crypts separated from the main specimen under a dissecting microscope. The total number of mitoses/crypt were counted by one observer for each of 10 complete crypts. RESULTS: Validation work established that whole crypt mitoses counts were reliable and reproducible. There was no relation between age and mean mitoses/crypt (Pearson correlation coefficient -0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80-4.66)) among controls but there was no gender difference in the three disease groups. For all disease groups and controls, the crypt mitotic count showed a significant linear increase (p=0.004) from the rectum to the caecum. Biopsies from within 5 cm of the macroscopic margin of a carcinoma (near) gave a mean mitosis count of 12.6 while those from more than 10 cm (far) were lower but not significantly so (p=0.12) with a count of 9.0. The mean mitoses/crypt were similar for the controls and adenomas (5.6 and 4.7, respectively) but greater for the cancers and especially for FAP (8.3 and 14.2, respectively). Statistical analysis confirmed that there were significant differences (p<0.05) between controls and all disease groups together, between sporadic disease and FAP, and between adenoma and carcinoma subjects at each of the four colonic sites. Post hoc comparison by t test showed significantly greater CCPS for FAP compared with controls (p<0.001) and for sporadic cancer versus controls (p=0.04). CONCLUSIONS: Whole crypt microdissection and mitosis counting is a reliable, reproducible, and robust technique for assessing CCPS in the human colon. CCPS is unaffected by age but increases from the distal to the proximal colon. CCPS is increased if a sporadic cancer is present and markedly increased in FAP. However, the precise relation of an increased CCPS to the neoplastic process remains uncertain.

Adenoma↗
PubMed1967

Incidence and significance of argentaffin and paneth cells in some tumours of the large intestine.

The incidence of argentaffin and Paneth cells in epithelial tumours of the large intestine was investigated. Argentaffin cells were found in adenomatous polyps, villus adenomas, polyposis coli, Peutz-Jehgers' polyps, juvenile polyposis, and adenocarcinomas. Paneth cells were not found in metaplastic or juvenile polyps. The crypt unit was destroyed in neoplasia and argentaffin and Paneth cells occurred either as a result of sequestration or were taking part in the neoplastic process. The crypt unit was retained in the disorders of epithelial growth. The identification of argentaffin and Paneth cells enabled the crypt to be defined and thus provided a useful, practical aid in the differentiation between neoplasms and disorders of epithelial growth.

Adenocarcinoma↗
PubMed2005

Cyclooxygenase 2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications.

BACKGROUND: Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials. AIMS: To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications. METHODS: Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry. RESULTS: Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p = 0.423). CONCLUSION: COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.

Adult↗
PubMed1975

Systemic endotheliomatosis: a case report.

A 48-year-old Caucasian man was found to have a rare neoplastic process of vascular endothelial origin. The clinical presentation was that of plum-colored cutaneous plaques of the lower extremities. The histopathology, natural history, and treatment of this case are discussed and compared with previously reported cases. It is suggested that this disease entity represents a malignant state with systemic involvement and a poor prognosis.

Biopsy↗
PubMed1986

Expression of blood group antigens in urinary tract tumours: prospective fluorescence study using cryostat sections of fresh frozen tissues.

Cryostat sections of fresh frozen tissues were used in a prospective study of blood group H and A antigen fluorescence in 73 transitional cell carcinomas of the bladder. The aim was to evaluate antigen expression without subjecting the tumour tissues to organic solvents that extract blood group active glycolipids. Deletion of the genetically predicted antigen was twice as common in tumours of pT1 or greater stage than those of pTa stage and also twice as common in poorly differentiated than in moderately well differentiated tumours. The considerable heterogeneity and overlap, however, in patterns of reactivity in tumours of various histopathological stages and grades and the effect of secretor status on antigenicity meant that there was no obvious antigenic feature that correlated precisely with invasive stage or differentiation grade. It remains to be determined whether the antigen positive and antigen negative tumours represent different disease entities with differing clinical courses. Our results indicate, however, that studies of the blood group antigens in urinary tract tumours are more likely to be of value in research into biochemical disorders in the neoplastic process than in routine clinical assessment as a guide to treatment.

ABO Blood-Group System↗
PubMed1989

Angiolymphoid hyperplasia with eosinophilia: possible aetiological role for immunisation.

Five young children (mean age 26.4 months) with angiolymphoid hyperplasia with eosinophilia (Kimura's disease) from either the upper arm or buttock were identified over 18 months. The unusual distribution of the lesions and the young age of the patients suggested a possible association with immunisation. The clinical and histopathological features in these cases were accordingly reviewed. The biopsy specimens showed the usual histological appearances of a prominent inflammatory component, fibrosis, and vascular proliferation associated with aggregates of eosinophils. The features were those of a reactive rather than neoplastic process. Immunohistochemical preparations showed positive staining of variable numbers of plasma cells with antibodies to IgG, IgM, IgA and IgE and a reticular staining of germinal centres with IgM and IgE antibodies. Immunisation histories obtained from the patients' general practitioners showed a remarkable correlation between the distribution of the lesions and the sites of injections and an aetiological role for immunisation in these cases seems likely.

Angiolymphoid Hyperplasia with Eosinophilia↗
PubMed1995

CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance.

AIMS: To determine whether a particular phenotype or antigen is preferentially related to monoclonal gammopathies of undetermined significance (MGUS). METHODS: Bone marrow specimens from 56 patients with MGUS were stained immunocytochemically (ABC peroxidase) for CD38, CD56, CD9, CD10, CD19, CD20, CD22, and MB2. Specimens from patients recently diagnosed with multiple myeloma and reactive bone marrow samples were studied in parallel. RESULTS: CD38 was expressed on all plasma cells from all MGUS samples tested, while 36% were positive for CD56, CD9 and MB2 were both expressed strongly; CD20 was moderately expressed, and staining for CD10 and CD22 was uncommon. For these five B cell antigens there was no clear difference between their expression in MGUS and in multiple myeloma. A great difference was found for CD19: in MGUS this antigen was expressed on 2-91% of plasma cells (mean 35%) and 77% patients had > 10% positive plasma cells; in multiple myeloma its expression was low and only 12% patients had > 10% positive plasma cells. When these results were converted to numbers of CD19 positive plasma cells per 100 nucleated bone marrow cells, reactive bone marrow and MGUS specimens had a similar number of positive plasma cells. There was no correlation between expression of any of the antigens tested. CONCLUSIONS: Many of the so-called pre-B, B or activation antigens are present on plasma cells from MGUS specimens, and expression of CD9, CD10, CD20, CD22, MB2, and CD38 in MGUS was very similar to that in multiple myeloma. CD56 was frequently expressed in MGUS. In this series CD19 was highly expressed in MGUS but not in multiple myeloma. Plasma cells bearing this antigen could represent the non-neoplastic process and determination of its expression could be useful for the diagnosis of MGUS.

Antigens, CD↗
PubMed1997

Telomerase activity in human gynaecological malignancies.

AIM: To evaluate whether increased telomerase activity can be clinically useful for detecting malignant cells in a variety of gynaecological specimens. METHODS: Telomerase activity was examined in frozen tissue samples of histologically confirmed lesions of the endometrium, ovary, and cervix. It was also assessed in exfoliated cells in cervical smears from patients with premalignant and malignant lesions and in ascitic fluid obtained from cases with malignant or non-malignant ovarian tumours. RESULTS: Solid tissues from carcinomas were telomerase positive in all specimens of endometrial (6/6) and cervical (6/6) origin, and in almost all from the ovary (12/13). Normal tissues from the cervix (0/5) and the ovary (0/5) were telomerase negative, but samples from normal endometrium were found to show telomerase activity, possibly due to the cyclical regenerative nature of this tissue. Conversely, dissociated cells in cervical smears from preneoplastic and frankly neoplastic lesions rarely showed detectable telomerase activity. Thus smears from patients with malignant tumours were only positive in one of two patients, whereas those from CIN-2 (0/5) and CIN-3 (1/17) lesions and from normal (0/10) samples were almost all negative. Telomerase activity was also scarcely detectable in cells obtained from ascitic fluid from patients with ovarian tumours. CONCLUSIONS: As in many other organs, telomerase activity is increased in solid tissue specimens from malignant tumours of the female reproductive tract, but it is not yet a reliable indicator of the presence of exfoliated cancerous or precancerous cells in clinical specimens from such lesions. Interpretation should be guarded until more extensive studies have been conducted. The data on solid tissues presented here confirm that activation of this enzyme is a major hallmark of the neoplastic process.

Ascites↗
PubMed2002

Pancreatic cancer after remote peptic ulcer surgery.

BACKGROUND: Peptic ulcer surgery may carry an increased risk for pancreatic cancer development. Molecular analysis of K-ras codon 12, frequently mutated in conventional pancreatic cancers, might provide insight into the aetiological mechanisms. METHODS: The relative risk of pancreatic cancer was computed by multivariate and person-year analysis in a cohort of 2633 patients who had undergone gastrectomy. Lung cancer risk was analysed as an indirect means of assessing smoking behaviour. K-ras codon 12 mutational analysis was performed on 15 postgastrectomy pancreatic cancers. RESULTS: There was an overall increased risk of pancreatic carcinoma of 1.8 (95% confidence interval, 1.3 to 2.6) five to 59 years postoperatively, which gradually increased to 3.6 at 35 years or more after surgery (chi(2) test for trend, p < 0.05). Multivariate analysis indicated that parameters other than postoperative interval did not influence the risk. Lung cancer risk was significantly increased after surgery, but no time trend was observed. The spectrum and prevalence of K-ras codon 12 mutations were comparable to conventional pancreatic cancer. CONCLUSIONS: Remote partial gastrectomy is associated with an increased risk of pancreatic cancer. Postgastrectomy and non-postgastrectomy pancreatic cancers may share similar aetiological factors, such as smoking. However, the neoplastic process in patients who have undergone gastrectomy appears to be accelerated by factors related to the surgery itself.

Adolescent↗
PubMed1971

Incidence and distribution of neomembranes of dura mater.

Membranous or membranous-haemorrhagic lesions of the dura mater were found in 46 out of 1,044 consecutive necropsies after excluding those cases where their presence could be interpreted in terms of blood dyscrasia, local neoplastic processes, previous surgery, or marked craniocerebral trauma. The extent of old and recent manifestations of haemorrhage in the membranes increased in a statistically significant relation with their size and thickness. Lesions of different types, or degrees, respectively, were often combined in the same case; a remarkably high incidence of membranous lesions in the falx cerebri was noted. The observations indicate the presence of a progressive, repetitive process in neomembrane formation.

Autopsy↗
PubMed1996

Accumulation of p53 protein in inverted transitional cell papilloma of the urinary bladder.

Aims-To study the possible accumulation of p53 protein in inverted papilloma of the urinary bladder.Methods-Formalin fixed, paraffin wax embedded sections from 14 cases of inverted papilloma of the urinary bladder were studied retrospectively. Accumulation of p53 was detected by immunohistochemistry using a mouse monoclonal antibody directed against p53. p53 protein reactivity was scored as follows: 0 = 10%; 1 = 10% to <30%; 2 = 30% to <50%; and 3 = >50% of cells p53 positive.Results-The 14 sections were scored as follows: 3 in four cases; 2 in four cases; 1 in one case; and 0 in five cases. Overall, nine (64%) of the 14 cases were positive for p53 protein.Conclusions-The accumulation of p53 protein in inverted papilloma of the urinary bladder suggests that p53 may have has an important role in the neoplastic process of this tumour. However, the benign nature of inverted papillomas suggests that p53 protein accumulation is not related to tumour invasiveness and metastasis. p53 reactivity cannot be used as a marker of malignancy for urothelial neoplasia. Further studies are required to determine the role of p53 protein in the oncogenesis of urothelial neoplasms.

Journal Article↗
PubMed1975

Multiple nodular pulmonary amyloidosis. A case report and comparison with diffuse alveolar-septal pulmonary amyloidosis.

A case of multiple nodular pulmonary amyloidosis in a 54-year-old Caucasian man is presented. Discrete symptomless radiodensities had developed in this patient's lungs within a period of three years, leading to a suspicion of a neoplastic process. The amyloid nature of these nodules was demonstrated by biopsy. In this case, as in others previously reported, there was no evidence of systemic disease, and immunoglobulins were normal. Local factors probably play an important part in the pathogenesis of this disease. This entity is to be distinguished from the diffuse type of pulmonary amyloidosis, which has a far graver prognosis. Diffuse alveolar septal amyloidosis is usually associated with primary systemic amyloidosis or multiple myeloma and leads rapidly to respiratory distress.

Amyloidosis↗
PubMed1998

The role of the FHIT/FRA3B locus in cancer.

Common fragile sites form gaps at characteristic chromosome bands in metaphases from normal cells after aphidicolin induction. The distribution of common fragile sites parallels the positions of neoplasia-associated chromosomal rearrangements, prompting the proposal that fragility disposes to chromosomal rearrangements. Implicit in this hypothesis is that genes at fragile sites are altered by chromosome rearrangement and thus contribute to neoplastic growth. Chromosome band 3p14.2, encompassing the most inducible common fragile region, FRA3B, has been cloned and the FHIT gene, straddling FRA3B, characterized. The gene is inactivated by deletions in cancer-derived cell lines and primary tumors and Fhit protein is absent or reduced in lung, stomach, kidney, and cervical carcinomas, consistent with function as a tumor suppressor. FRA3B thus fulfills the prophecy that fragile site alterations contribute to the neoplastic process through inactivation of a tumor suppressor gene.

Acid Anhydride Hydrolases↗
PubMed2005

T-box genes in vertebrate development.

The myriad developmental roles served by the T-box family of transcription factor genes defy easy categorization. Present in all metazoans, the T-box genes are involved in early embryonic cell fate decisions, regulation of the development of extraembryonic structures, embryonic patterning, and many aspects of organogenesis. They are unusual in displaying dosage sensitivity in most instances. In humans, mutations in T-box genes are responsible for developmental dysmorphic syndromes, and several T-box genes have been implicated in neoplastic processes. T-box transcription factors function in many different signaling pathways, notably bone morphogenetic protein and fibroblast growth factor pathways. The few downstream target genes that have been identified indicate a wide range of downstream effectors.

Animals↗
PubMed1979

Computed tomography in white-matter disease.

CT scans of 11 patients with proved white-matter disease were reviewed and divided into three categories. The demyelinating (secondary) and diffuse sclerosis groups frequently exhibited abnormal intravenous enhancement and mass shift. This made differentiation from inflammatory and neoplastic processes difficult. In the dysmyelinating disorders, pathologically noted diffuse loss of white matter and absence of inflammatory response appeared on the scans as areas of diffuse and decreased density in the centrum semiovale. There was no evidence of abnormal contrast enhancement.

Adult↗
PubMed1993

Renal manifestations of AIDS.

The kidneys in patients with acquired immunodeficiency syndrome (AIDS) are subject to a variety of insults. Renal manifestations can be seen with imaging studies of AIDS patients. Computed tomographic (CT) and ultrasound (US) scans of 64 patients with AIDS and renal dysfunction were retrospectively reviewed and compared with clinical, laboratory, and, when available, biopsy results. Imaging abnormalities included increased cortical echogenicity, nephromegaly, pyelonephritis, lobar nephronia, focal masses caused by abscess and lymphoma, parenchymal calcification, hydronephrosis, and infarct. Generally, patients with AIDS as a result of intravenous drug abuse and those with multiple risk factors were more likely to have abnormalities demonstrated at imaging as well as poorer prognosis than were patients in the homosexual transmission group in this series. Although US should be the screening study used in patients with AIDS and suspected renal dysfunction, CT and magnetic resonance imaging may be necessary to identify focal infectious, ischemic, and neoplastic processes.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

MR imaging of the adrenal gland: radiologic-pathologic correlation.

Complex physiologic and neoplastic processes affect the adrenal glands. An appreciation of the gross pathologic and histologic correlates of disease aids in understanding the mechanisms by which diagnostic imaging helps characterize adrenal masses. Computed tomographic (CT) densitometry and chemical shift magnetic resonance (MR) imaging would seem to be the most reliable tools in determining whether a given adrenal mass is specifically an adenoma. Such a determination is made on the basis of the presence of substantial amounts of intracytoplasmic lipid. Thus, although a homogeneous mass with a CT attenuation of less than 10 HU or a decrease in signal intensity at opposed-phase MR imaging is diagnostic for adenoma, lesions that do not have these features are indeterminate and may necessitate biopsy. Adrenal myelolipoma also has a distinctive imaging appearance that reflects the presence of macroscopic fat deposits. Diagnosis of adenoma or adrenal myelolipoma is very helpful in the assessment and treatment of asymptomatic patients with adrenal masses and may make biopsy unnecessary. In patients with clinical or biochemical evidence of adrenal disease, MR imaging helps confirm the presence of a mass and allows localization and further characterization of the lesion.

Adrenal Gland Diseases↗
PubMed1980

The ultrasonic appearance of extranodal abdominal lymphoma.

The sonographic manifestations of malignant lymphoma involving 70 extranodal sites in 51 patients are presented. Areas of involvement by nonHodgkin and Hodgkin lymphoma included the liver, spleen, kidneys, stomach, pancreas, and muscles. The sonographic appearance of lymphomatous lesions does not necessarily correlate with histologic subclassification. Similarly, atypical manifestations of lymphoma may resemble a variety of neoplastic and non-neoplastic processes. Extranodal lymphomatous abdominal disease was detected in six patients whose lymphangiograms demonstrated no evidence of disease.

Abdominal Neoplasms↗