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Intraductal papillary neoplasms of the pancreas. A clinicopathologic study of six patients.

A clinicopathologic study was conducted on six patients with intraductal papillary neoplasms of the pancreas. The patients were of both sexes and their ages ranged from 64 to 79 years. Three patients had a long history of symptoms mimicking chronic pancreatitis. The tumors involved the main pancreatic duct in the head-body region either diffusely or focally. Histologic examination showed papillary proliferations of well-differentiated, mucus-secreting cells that occasionally stained for carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9). The proliferations filled the main pancreatic duct, and extended into smaller ducts in some cases. In three patients, the lesions contained foci of pronounced to severe cellular atypia and carcinoma in situ. None of our series or any similar cases reported in the literature has shown invasion into peripancreatic tissue, metastasis, or tumor recurrence after pancreatectomy. Because of their favorable prognosis, intraductal papillary neoplasms should be considered low-grade malignancies that must not be confused with the common ductal adenocarcinoma.

Adenocarcinoma, Papillary↗

Risk of advanced proximal adenoma and cancer according to rectosigmoid findings in the Korean population.

Colorectal cancer is one of the leading causes of cancer death in the United States and Europe. Recently, the incidence of colorectal cancer has been increasing remarkably in Korea. To reduce the high incidence, screening of colorectal cancer in asymptomatic individuals has been advocated. Sigmoidoscopy is simpler, faster, and better tolerable than total colonoscopy, but the scope cannot reach the proximal colon segment and, therefore, may miss proximal colon cancer. In the present study, we intended to investigate the prevalence of proximal adenoma and cancer according to the findings in rectosigmoid colon and to find their risk factors. Data were collected retrospectively from 1541 consecutive patients who underwent total colonoscopy at the Department of Gastroenterology, Hanyang University, between October 2003 and December 2004. Neoplasms were classified as diminutive adenoma (< or =5 mm), small adenoma (6-9 mm), advanced adenoma (> or =10 mm, with villous component or high-grade dysplasia), and cancer. The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal (from cecum to descending colon) colon. The prevalence of advanced proximal adenoma was associated with severe rectosigmoid findings. On the other hand, the prevalence of proximal colon cancer did not show such a tendency. Among the 131 patients with proximal advanced adenoma, 66% had no neoplasm in the rectosigmoid colon. Moreover, among the 27 patients with proximal cancer, 52% had no neoplasm in the rectosigmoid colon. Multivariate logistic regression analysis revealed that age, gender, and advanced rectosigmoid adenoma were the risk factors of advanced proximal adenoma, but nothing was associated with the risk for proximal colon cancer. Advanced rectosigmoid adenoma may be the predictor of advanced proximal adenoma, especially in old males. However, nothing is related to the risk for proximal colon cancer. Therefore, colonoscopy may be more adequate for colorectal cancer screening than sigmoidoscopy in the Korean population.

Adenoma↗

Comparative genomic hybridization analysis of astrocytomas: prognostic and diagnostic implications.

Astrocytoma is comprised of a group of common intracranial neoplasms that are classified into four grades based on the World Health Organization histological criteria and patient survival. To date, histological grade, patient age, and clinical performance, as reflected in the Karnofsky score, are the most reliable prognostic predictors. Recently, there has been a significant effort to identify additional prognostic markers using objective molecular genetic techniques. We believe that the identification of such markers will characterize new chromosomal loci important in astrocytoma progression and aid clinical diagnosis and prognosis. To this end, our laboratory used comparative genomic hybridization to identify DNA sequence copy number changes in 102 astrocytomas. Novel losses of 19p loci were detected in low-grade pilocytic astrocytomas and losses of loci on 9p, 10, and 22 along with gains on 7, 19, and 20 were detected in a significant proportion of high-grade astrocytomas. The Cox proportional hazards statistical modeling showed that the presence of +7q and -10q comparative genomic hybridization alterations significantly increased a patient's risk of dying, independent of histological grade. This investigation demonstrates the efficacy of comparative genomic hybridization for identifying tumor suppressor and oncogene loci in different astrocytic grades. The cumulative effect of these loci is an important consideration in their diagnostic and prognostic implications.

Adolescent↗

Cytologic differential diagnosis of papillary pattern in breast aspirates: correlation with histology.

Papillary neoplasms, fibroadenoma, fibrocystic change, low-grade ductal carcinoma, and apocrine carcinoma are among "gray zone" lesions in breast cytology. They often have cellular smears with a papillary or pseudopapillary pattern. To better define cytologic criteria useful in distinguishing these entities, we correlated them with histology. Papanicolaou and giemsa stained smears from 33 aspirates and their corresponding histology were reviewed. Of these, 28 had an initial cytologic diagnosis or suspicion of papillary neoplasm, while five cases were not diagnosed cytologically as papillary but the histologic diagnosis was a papillary neoplasm. Cytologic features evaluated included cellularity, architecture, apocrine/single/columnar cells, nuclear atypia, intranuclear inclusions, calcifications, background, myoepithelial cells, and bipolar, naked nuclei. Discriminating cytologic features grouped by final histologic diagnosis were as follows: Papillary neoplasm (14 cases): Hemorrhagic/cystic background, 3-dimensional papillary clusters, columnar cells, and fibrovascular cores. Myoepithelial cells within clusters and background naked, bipolar nuclei were inconspicuous. Fibroadenoma (4 cases): Two-dimensional branching clusters often with folding, moderate myoepithelial cells in clusters, moderate to numerous background bipolar nuclei, often forming doublets in smear background, cellular stroma. Ductal carcinoma (11 cases): Papillary ductal carcinoma in situ in 5 of 11 cases, cribriform/tubular architecture in 6 of 11. Absence or paucity of myoepithelial within clusters and background bipolar nuclei was noted. Fibrocystic change (4 cases): Two-dimensional clusters, moderate myoepithelial cells within clusters, and moderate bipolar nuclei in the background. The presence and quantity of myoepithelial cells, bipolar naked nuclei in the background, and ductal cell architecture were the only consistently useful cytologic features in distinguishing breast lesions with a papillary pattern. Ann Diagn Pathol 5:34-42, 2001.

Adult↗

Cerebrospinal fluid changes after intravenous injection of gadolinium chelate: assessment by FLAIR MR imaging.

Fluid-attenuated inversion recovery (FLAIR) sequence is currently used in clinical practice. Some reports emphasize the possibility that, in pathologic conditions, intravenous injection of gadolinium chelates may lead to an increased signal inside the cerebrospinal fluid (CSF). The aim of this study was to evaluate the presence of CSF signal changes in pathologic conditions causing blood-brain barrier disruption or neovascularization when imaging is performed after intravenous injection of gadolinium. We obtained FLAIR sequences after gadolinium injection from 33 patients affected by different intracranial pathologies and 10 control subjects. Patients were affected by ischemic stroke in the subacute phase, from 2 to 7 days from onset of symptoms (12 patients), meningiomas (8 patients), high-grade gliomas (5 patients), previous surgical procedures for intra-axial neoplasms (5 patients), and multiple sclerosis with active plaques (3 patients). Magnetic resonance imaging was performed in patients and controls using a 1.5-T magnet, using T2- and T1-weighted FLAIR sequences. The FLAIR sequence was acquired before and 1-3 h after injection of a standard dose of gadolinium. In those patients affected by ischemic lesions, FLAIR sequences were repeated the next days and 3-4 days later. The CSF signal was visually evaluated by two readers and scored from 0 to 3 depending by the degree of enhancement. The location of CSF signal changes (close to the lesion, hemispheric, or diffuse) was also considered. The CSF signal was markedly increased after 3 h from intravenous injection of gadolinium in all the patients with stroke, in those with previous surgery, and in those with high-grade gliomas whose neoplasm's surface was in contact with the subarachnoid spaces (SAS) or ventricles; a strong enhancement was also evident inside the necrotic component of the tumor. The CSF changes were more evident close to the pathology and/or in the hemisphere involved by the pathology. Moderate CSF enhancement was observed in the SAS close to meningiomas. No signal changes were evident in all the others. In those patients with stroke imaged in the following days, CSF signal showed to be diffuse to both hemispheres the next day and returned to normal values within 2 days. In patients affected by pathologies with blood-brain barrier breakdown or neovascularization close the SAS or the ventricles, CSF changes, related to gadolinium leakage, are likely when FLAIR sequences are acquired 2-24 h after i.v. injection of the contrast. This pattern should be known in order to differentiate it from that of subarachnoid hemorrhage.

Aged↗

Adenocarcinoma of the prostate in perspective.

Adenocarcinoma of the prostate is responsible for one of every nine deaths from cancer in Canada. In this review epidemiologic factors are considered and current staging systems are outlined. The American Urological System is recommended for staging because of its ability to reflect changes in the understanding of the biologic behaviour of this neoplasm. The adoption of a quantitative grading scheme is suggested to complement the information obtained from the staging assessment. The routes of spread of this disease, along with the procedures used to assess metastatic involvement, are described. Immunologic methods for the analysis of prostatic acid phosphatase have been shown to be superior to the enzymatic methods previously used, and the role of the new techniques is discussed. Emphasis is placed on radiotherapy and endocrine therapy for the treatment of this neoplasm, and the concept of withholding endocrine therapy until symptoms appear is discussed. Potential future developments in this field are considered.

Acid Phosphatase↗

Asymptomatic intracardiac metastasis from a low-grade endometrial stromal sarcoma with successful surgical resection.

BACKGROUND: The endometrial stromal sarcoma (ESS) is a rare neoplasm of the uterine origin. Intracardiac metastasis from the low-grade ESS is an extremely rare event. A case of a patient who successfully underwent surgical extraction of metastatic tumors of the low-grade ESS in the right ventricle is described in the present report. CASE: A 48-year-old woman was considered recurrence of the low-grade ESS 4 years after the initial operation for this disease. The CT scanning and magnetic resonance imaging demonstrated solid masses in the pelvis, the lungs, the inferior vena cava, and the right ventricle. The chemotherapy was effective against the recurrent tumors except for intracardiac site. Although she had no symptoms of right-sided heart failure, surgical resection of the intracardiac masses was successfully performed. Pathological examination confirmed intracardiac recurrent low-grade ESS. CONCLUSION: Surgical approach to intracardiac metastasis of the low-grade ESS is considered viable because of an excellent long-term prognosis in this disease and the likelihood of fatal heart failure or sudden death in untreated cases.

Endometrial Neoplasms↗

Results of intersphincteric resection of the rectum with direct coloanal anastomosis for rectal carcinoma.

Between 1977 and 1987, 519 patients underwent operation for rectal carcinoma. Sixty-three patients underwent intersphincteric resection with direct coloanal anastomosis (CAA), and 77 had an abdominoperineal resection (APR). Curative surgery was achieved in 57 and 65 patients, respectively. Both groups were comparable regarding age, stage of tumors, and localization of tumors. During the mean period of 6.7 years (range: 3 to 13.6 years), all patients were examined according to a predefined follow-up plan. From those patients with curative surgery, 11% presented with pelvic recurrence and 33% with distant metastases after coloanal anastomosis; the rates of recurrence and distant metastases after APR were 17% and 35%, respectively. The corrected 5-year survival rates were 62% following CAA and 53% following APR. Eighty-five percent of the patients with CAA reported good functional results regarding anal continence. Our study demonstrates that the intersphincteric resection with CAA is a valuable surgical technique for rectal carcinoma with the benefit of preservation of continence. It is suitable for neoplasms with high- and medium-grade differentiation (G1 to G2) and a localization that allows a minimum distal clearence of 3 cm.

Abdominal Muscles↗

Epidermal growth factor binding in intracranial neoplasms: preliminary biochemical and clinicopathological findings.

The binding capacity for epidermal growth factor (EGF) was determined in 34 intracranial neoplasms (14 glioblastoma, seven low-grade gliomas, six meningiomas, and seven others) and four specimens of normal brain by using [I125]EGF. EGF binding and binding affinity of the sites in the tumour and brain samples were compared to placenta and rat liver. All specimens of normal brain were negative. Ten of 14 glioblastoma specimens contained EGF binding (level range 10-39,660 fmol/mg protein), however, ligand binding affinity was high in only three tumours. Only one of nine low-grade gliomas contained EGF binding activity. Five of six meningiomas contained EGF binding sites (level range 49-776 fmol/mg protein) and binding affinity was high in two. When present EGF binding activity was found in all cellular fractions except the cytosol. There were no clinical or histopathological features within major tumour groups that were predictive of either high or specific EGF binding activity. These preliminary studies have confirmed that EGF receptor-like activity is present in the particulate fractions of intracranial neoplasms of both mesenchymal and neuroctodermal origin. In a large proportion of these tumours the EGF binding affinity is low, suggesting either a less specific or truncated EGF binding site.

Brain Neoplasms↗

Angiosarcoma replacing bone marrow--a case report.

BACKGROUND: Clinical syndromes caused by marrow replacement by neoplastic cells are usually proven to arise from cells of hematopoetic or carcinomatous lineage. Diffuse marrow replacement by mesodermal origin sarcoma is rare in adults, and angiosarcoma replacing bone marrow is a very rare neoplasm. METHODS: A case of bone marrow replacement by angiosarcoma in a 54-year-old African American man is described with a review of pertinent literature. The unique histopathologic features of this phenomenon are also described. RESULTS: Histopathologic exam of trephine bone marrow biopsy revealed replacement of marrow spaces by a proliferating highly vascular malignant neoplasm with features of high-grade angiosarcoma. CONCLUSION: Few reports in the literature describe angiosarcomatosis of the bone marrow. It is important to recognize this unusual presentation to avoid confusion with other more common bone marrow replacing entities and to promote recognition that more efficacious treatment is needed.

Bone Marrow Neoplasms↗

Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy.

PURPOSE: We studied 363 patients with stage Ta bladder tumors during long-term followup who were classified according to the 1998 WHO and International Society of Urological Pathology consensus classifications. We determine whether various immunohistochemical and molecular markers could predict tumor progression. MATERIALS AND METHODS: A total of 680 patients in western Sweden with a first diagnosis of bladder carcinoma in 1987 and 1988 were registered and followed for at least 5 years. There were 363 (53%) tumors that were papillary stage pTa. The tumors were classified as papillary urothelial neoplasm of low malignant potential in 95 patients, low grade papillary urothelial carcinoma in 160 and high grade carcinoma in 108. Of the patients in the latter group 95 were subdivided into WHO grade 2 and 13 into WHO grade 3. Tissue from the primary tumors that progressed in stage during followup was further analyzed with immunohistochemical methods (p21, p53, Ki67 and pRb), DNA ploidy and mitotic frequency. The results were compared with those in matched controls (nonprogressors). RESULTS: Recurrence developed in 35% of patients with papillary urothelial neoplasm of low malignant potential compared to 71% with low grade urothelial carcinoma and 73% with high grade carcinoma (p <0.0001). No papillary urothelial neoplasm of low malignant potential progressed in stage. Disease progressed in 4% of patients with low grade compared to 23% with high grade carcinoma (p <0.0001). Of the patients with WHO grade 3 disease progressed in 45% compared to grade 2 in 20% (p <0.0011). At first diagnosis p53 score was significantly higher (p <0.0022) among patients with WHO grade 2 carcinoma which later progressed compared to that in matched controls but there was no significant difference regarding the other markers. In contrast to grade 2 most grade 3 carcinoma was aneuploid, had high mitosis frequency, high p53 and Ki67 scores as well as loss of retinoblastoma gene expression. CONCLUSIONS: The 1988 WHO and International Society of Urological Pathology consensus classifications divide noninvasive papillary bladder tumors into 3 subgroups with different clinical behavior, which seems to be an advantage compared with the 1973 WHO classification. A disadvantage is that the high grade carcinoma group contains 2 subgroups with different progression rates and immunohistochemical marker profiles, corresponding to the 1999 WHO grades 2 and 3. Grade 2 tumors in patients that progressed in stage years later seem to have different immunohistochemical and molecular marker profiles compared to those in matched controls.

Aged↗

Thallium-201-SPECT and 99Tc-HM-PAO SPECT imaging to study functionally cerebral supratentorial neoplasms: the biological basis of the functional imaging interpretation.

Nineteen patients with histologically diagnosed supratentorial cerebral neoplasms carried out CT and/or MRI, 201T1 SPECT and 99mTc-HM-PAO studies preoperatively. 99mTc-HM-PAO SPECT images revealed information about both tumoral perfusion and intracellular concentration of mediators converting 99mTc-HM-PAO to hydrophilic derivates (glutathione and other yet unknown factors) within viable tumoral cells while 201T1 SPECT images about permeability, extension of tumoral capillary network and viable tumoral cells presence. Basing on the different mechanisms of the tracer uptake, cerebral supratentorial tumors could be distinguished in three groups: 1) cerebral tumors presenting 201T1 very high uptake (201T1 index > 1.5) and homogeneous and high retention of 99mTc-HM-PAO (CBI > or = 1.05) (meningiomas, PRL adenoma); histologically these neoplasms presented very rich neoformed capillary network; 2) cerebral neoplasms with 201T1 high uptake (201T1 index > 1.5) and with inhomogeneous retention of 99Tc-HM-PAO (high grade gliomas amd metastasis); microscopically these tumors presented vascular proliferation, necrosis and high cellularity; 3) cerebral neoplasms characterized by 201T1 low uptake (201T1 index < 1.5) and lower retention of 99Tc-HM-PAO than cerebellum (low grade gliomas); at microscopic examination these neoplasms were characterized by absence of vascular proliferation and necrosis. These results suggest coupled 201T1/99Tc-HM-PAO SPECT is necessary to discriminate intra-axial from extra-axial tumor localization (lacking CT or MRI) and to detect the grade of malignancy of gliomas and tumor cell presence within necrotic areas.

Adult↗

Urinary tract morphometry. An overview.

An overview is presented of the application of morphometry to conditions in the urinary tract, with the work of a number of researchers briefly summarized. The data discussed show that morphometric techniques are already being successfully applied in the differential diagnosis and grading of some diseases of the prostate, urinary bladder and kidney. In the prostate, nonneoplastic changes can be differentiated from neoplasms and prostatic carcinomas can be more precisely graded. Both cytologic and histologic preparations of bladder carcinomas can be graded by morphometric techniques. Morphometry has found another application in assisting in the distinction between normal kidneys and those with "minimal-change" disease. The specific criteria pertaining to the use of morphometric methods in each of these situations are also discussed.

Humans↗

[Meningioma. Classification and grading].

Meningiomas account for the most frequent primary intracranial neoplasms in adults. In 1993, the so-called atypical meningioma has additionally been introduced in the revised edition of the WHO Classification of Tumors of the Central Nervous System and should characterize meningiomas with an increased propensity to recur. Since the given qualitative histological criteria apply both to the "atypical" and anaplastic meningioma, mere histological grading appears somewhat critical. Therefore, additional parameters were tested for their contribution to meningioma grading: First of all, we succeeded in defining 3 meningioma "grades" by calculating corresponding 95% confidence intervals for the morphometrically assessed Ki-67 indices of 160 meningiomas in total, the validity of which was proved by comparison with the "recurrence"-free intervals. Histologically, atypical meningiomas were distinguished by a "syncytial", poorly structured growth pattern and macronucleoli. Only occasionally, nuclear pleomorphism, necroses and mitotic figures were found. Cytogenetics revealed, in 50% of the "atypical" and anaplastic meningiomas, partial loss of the short arm of one chromosome 1 (1p-). Histochemically, we could demonstrate, that the tissue non-specific type of alkaline phosphatase (ALPL), which is coded on chromosome 1p, is a convenient recurrence- and progression-associated marker enzyme for meningiomas with 1p-loss (loss of enzyme activity in 30/39 of intermediate and 8/8 anaplastic meningiomas). We favor to address the WHO "atypical" meningioma as meningioma of the intermediate type, since the attribute "atypical" in the context of histological diagnoses is highly susceptible to misinterpretations.

Adult↗

Neurofibrosarcoma.

Case histories of 10 patients with neurofibrosarcoma, including 14 (70%) with neurofibromatosis, evaluated over 10 years were reviewed to determine the incidence of local and systemic recurrence and the most effective means of therapy for this rare neoplasm. Initial therapy resulted in complete local disease control in only 11 (55%) patients. Local excision, or local excision plus radiation or chemotherapy resulted in local recurrence in 8 of 12 patients. Radical surgery alone, or radical surgery combined with radiation and chemotherapy resulted in local recurrence in 1 of 6. Even with complete local disease control, 7 of 16 (44%) patients died of metastases. Both A.J.C. Clinical Stage II and III patients had a similar poor prognosis. Associated neurofibromatosis did not worsen prognosis. These data suggest that both moderate and high-grade primary neurofibrosarcoma are highly malignant neoplasms and should be treated by radical resection. Preoperative intraarterial Adriamycin and radiation--found to be successful for other highly malignant sarcomas--may be of benefit. Since distant disease occurs despite local control, postoperative adjuvant chemotherapy trials are warranted.

Adolescent↗

Cutaneous mast cell neoplasia in cats: 14 cases (1975-1985).

Cutaneous mast cell neoplasia was diagnosed in 14 cats from January 1975 to September 1985. Review of the available medical records and client communication provided information on tumor description, location, and recurrence, and each cat's current status. Twenty-three cutaneous mast cell neoplasms were surgically excised, examined, and graded histologically. In this study, feline cutaneous mast cell tumors did not metastasize to lymph nodes or viscera, did not recur at a previous excision site, and did not cause or contribute to the death of any cat. A histologic grading system described for canine mast cell tumors apparently provided no prognostic information for the cats in this study. There was a predilection for older male cats to develop cutaneous mast cell tumors, especially on the head and neck.

Animals↗

Relationship of the queuine content of transfer ribonucleic acids to histopathological grading and survival in human lung cancer.

To elucidate the significance of tRNA hypomodified with queuine to the grade of malignancies in human solid tumors, the amount of tRNA having guanosine in place of queuosine was determined in human lung cancer and normal lung tissue, by exchanging the unmodified guanosine residue for [3H]guanine. The reaction is catalyzed by guanine:queuine tRNA transglycosylase. Total tRNA was extracted from 23 different lung cancer specimens and the precursor of isoacceptor tRNA that contains guanine instead of queuine in the first or wobble position of the anticodon [(Q-)tRNA] content was determined. In 12 cases the (Q-)-tRNA was determined in normal lung tissues as well. In each individual, the (Q-)tRNA content in lung cancer tissue was higher than that of the normal lung tissue. The (Q-)tRNA content was not correlated to the surgicopathological staging of the patients but was highly correlated to the histopathological classification of the tumors. The amounts of (Q-)-tRNA were 1.75 +/- 0.67 (SD), 2.36 +/- 0.89, 3.77 +/- 1.39, 5.18 +/- 2.32, and 7.65 +/- 1.34 pmol/A260 in normal, well, moderately, moderately to poorly, and poorly differentiated tumors. The difference from normal to moderately differentiated or less differentiated groups was significant (P less than 0.05). In 10 patients with (Q-)tRNA higher than 3.5 pmol/A260, their cancers relapsed and only 2 were alive after 4 years. In 11 patients with (Q-)tRNA less than 3.5 pmol/A260 in their lung cancer tissues, 7 patients were still alive without any evidence of disease, 3 were dead, and 1 had recurrence of disease. These results, taken together with other previous studies, suggest that a decreased queuosine content of tRNA may be a general feature of neoplasms and may be useful for grading malignancy and perhaps also for the prediction of survival in human lung cancer.

Carcinoma↗

Biology and treatment of malignant glioma.

Malignant gliomas are a heterogeneous group of tumors that are associated with significant morbidity and mortality. The development of the malignant phenotype is the result of a complex series of events that influence gene expression, angiogenesis, and invasion and favor the growth of tumor cells. Currently, the management of malignant glioma consists of symptom control and cytoreduction with a combination of surgery, radiation therapy, and chemotherapy. However, there is no satisfactory regimen available for adjuvant or salvage chemotherapy for these neoplasms. An overview of the biologic mechanisms, grading systems, and treatment options for anaplastic astrocytoma and glioblastoma multiforme is presented.

Astrocytoma↗