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PubMed2005

Clinicopathologic features, treatment, and prognosis of postirradiation osteosarcoma in patients with nasopharyngeal cancer.

OBJECTIVES: Postirradiation osteosarcoma (PIOS) arising after radiation of nasopharyngeal cancer (NPC) is rare and seldom reported. In this article, we report its clinicopathologic features, outcome, and prognostic factors. STUDY DESIGN: Retrospective cohort study. METHODS: Fifteen patients with NPC were determined to have PIOS after reviewing 426 patients with osteogenic sarcomas. Their clinical records, image and pathologic slides, and follow-up data after treatment were collected to perform analysis. RESULTS: The incidence rate of PIOS in NPC was approximately 0.037% (15/40,719), which occupied approximately 3.5% (15/426) among all kinds of osteogenic sarcomas. The latent time of PIOS after irradiation for NPC ranged from 4 to 27 years, with a mean of 13.3 years. The location where PIOS arose included 33.3% (5/15) from maxilla, 46.7% (7/15) from mandible, and 20% (3/15) from a mixture of nasal cavity and paranasal sinuses. Radiologically, soft tissue mass, bone destruction, and tumor new bone formation were the main characteristics. Pathologic subtypes included 53.3% (8/15) of fibroblastic osteosarcoma, 33.3% (5/15) of chondroblastic osteosarcoma, and 13.3% (2/15) of mixed type osteosarcoma. Of 15 patients with PIOS, 12 patients were treated with curative intent, and the remaining 3 patients with palliative intent. For 12 patients who had undertaken ablative surgery, 1 patient had residual tumor, and 6 patients had tumor recurrence. The survival time after treatment for all patients ranged from 7 to 41 months, with a mean of 18 months. Kaplan-Meier estimates of 1 year and 2 year survival rates were 60% and 24%, respectively. Statistical analysis showed that sex and tumor bone formation are significant prognostic factors. CONCLUSIONS: PIOS in NPC is a highly malignant disease with poorer prognosis than in other sites. Surgery combined with pre- and postoperative chemotherapy might be an effective way to improve survival.

Adolescent↗

PubMed2006

High expression of intestinal-type mucin (MUC2) in intraductal papillary mucinous neoplasms coexisting with extrapancreatic gastrointestinal cancers.

OBJECTIVES: It is known that intraductal papillary mucinous neoplasm (IPMN) is associated with a high incidence of extrapancreatic neoplasms. We tried to uncover the characteristics and gene expressions of IPMNs that coexist with other extrapancreatic gastrointestinal cancers. METHODS: We retrieved the surgical specimens from 54 IPMN patients, including 7 cases of IPMNs that coexisted with extrapancreatic gastrointestinal cancers. The immunohistochemical staining (p21, Bcl-2, p53, intestinal-type secretory mucin [MUC2], and MUC5AC) and the pathological subtypes of the tumor papillae (the intestinal type, pancreaticobiliary type, null type, or unclassified type) were analyzed. RESULTS: MUC2 expression was noticed more frequently in the IPMN coexisting with extrapancreatic cancers (6/7) than in the IPMN without extrapancreatic cancers (18/47; P = 0.04). There were no differences in p21 (P = 0.12), p53 (P = 0.25), and MUC5AC (P = 1.0) expressions between the 2 groups. IPMN with extrapancreatic cancers was noticed in all subtypes of papillae. CONCLUSIONS: Regardless of the subtypes of papillae, transcription of the MUC2 might be related with the synchronous extrapancreatic gastrointestinal cancer development that is seen with IPMN. Therefore, careful systemic surveillance is needed to detect coexisting gastrointestinal cancer for all the subtypes of IPMN with MUC2 expression.

Carcinoma, Pancreatic Ductal↗

PubMed2004

Upper extremity limb salvage with microvascular reconstruction in patients with advanced sarcoma.

Limb salvage is a viable alternative to amputation in many cases of advanced sarcoma. The authors examined their experience with microvascular reconstruction of upper extremity defects after sarcoma resection, focusing on oncologic and functional outcomes. A retrospective analysis yielded 17 patients who underwent 18 free flap procedures and met the inclusion criteria. Most patients (71 percent, n = 12) had recurrent sarcoma at presentation to the authors' institution. Malignant fibrous histiocytoma was the most common pathologic subtype (n = 6). High-grade tumors were present in 94 percent of patients (n = 16). The free flap survival rate was 100 percent. The rectus abdominis flap was the most common free flap used (39 percent; n = 7). Local recurrence occurred in nine flaps (50 percent), and five patients ultimately required amputations. Six patients (35 percent) had distant recurrence. The mean Enneking score for limb function was 73 percent of the maximum (21.9 of 30). The 5-year disease-specific survival rate was 61.3 percent. In select patients with advanced upper extremity sarcoma undergoing limb salvage, microvascular flap reconstruction can provide reliable, safe coverage with reasonable preservation of function.

Adult↗

PubMed2005

Primary malignant lymphoma of the brain: frequent abnormalities and inactivation of p14 tumor suppressor gene.

Ten primary central nervous system lymphomas (PCNSL, brain lymphomas) were examined for p14 gene exon 1beta deletion, mutation and methylation by Southern blot analysis, nucleotide analysis of polymerase chain reaction clones and Southern blot-based methylation assay. In Southern blot analysis, from the signal densities of the hybridized bands and their similarities to those of exons 2 and 3 in our previous quantitative study, we found that exon 1beta was homozygously deleted in four cases, hemizygously deleted in five cases and not deleted in one case. Thus, the same deletion patterns covered the entire p14 gene for all cases except for one case, which suggested the hemizygous deletion of exons 1beta and 2 and homozygous deletion of exon 3. In addition, although exon 1beta mutation is rare in various tumors, we detected a missense mutation (L50R) in one case with a hemizygous deletion. Methylation of the 5'CpG island of the p14 gene was not suggested for any case without homozygous deletion. Our observation of frequent p14 gene abnormalities (90%) and inactivation (40-60%) was in striking contrast to the same pathological subtype of systemic lymphoma in which p14 gene abnormalities and inactivation were infrequent, suggesting a difference in carcinogenesis between PCNSL and systemic lymphoma.

Adult↗

PubMed2005

Continuing challenges in childhood non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma in children includes a number of different pathological subtypes and, with improved diagnostic techniques and better understanding of the natural history of each type, treatment strategies have become more tumour-specific. Original staging systems are now less useful in determining treatment stratification and there is a need for careful analysis of large cohorts of patients, treated in the same manner, to determine the clinical and biological features that, with current therapies, are of prognostic value. Novel imaging techniques, such as positron emission tomography, and molecular techniques to detect low-level marrow involvement are likely to be incorporated into new risk grouping. These will be used to determine the extent of initial disease and evaluate more accurately the speed and quality of response to chemotherapy. With high cure rates, it becomes particularly important to minimize late effects of therapy and the introduction of monoclonal antibodies in combination with chemotherapy may provide a method for improving outcome in poor risk groups and reducing sequelae by allowing reduction in chemotherapy in good risk patients.

Adolescent↗

PubMed2006

A case representing coexistence of acute myeloblastic leukemia and dedifferentiated liposarcoma: the possible role of chemotherapy in triggering dedifferentiation.

Acute myelogenous leukemia (AML) is a hematological disorder that is characterized by an abnormal proliferation of immature myeloid cells. Dedifferentiated and well-differentiated liposarcomas are the two pathological subtypes of liposarcoma, based on the WHO classification. Transition from well-differentiated to dedifferentiated liposarcoma is a well-recognized phenomenon. Well-differentiated tumors are known to have low malignancy grade. However, when dedifferentiation occurs, the tumor acquires the aggressive features of a fully malignant lesion. This process largely is believed to progress in a time-dependant manner; however, time is not the only factor of importance. The potential roles of other factors in this transition are still unclear. To date, the coexistence of AML and liposarcoma has not been reported in the literature. In this paper, we report on a case of coexistence of AML and liposarcoma, and on the unusual behavior of a well-differentiated tumor after dedifferentiation occurs.

Abdominal Neoplasms↗

PubMed2004

Role of radiology in the treatment of malignant hilar biliary strictures 1: review of the literature.

Malignant strictures of the biliary tree are an uncommon cause of obstructive jaundice. There are a number of pathological subtypes, but tumours in this region tend to have similar clinical and diagnostic features and therapeutic and prognostic implications. We review the published literature on this topic discussing diagnostic modalities and treatment options with a focus on radiological intervention. Diagnosis currently is best achieved using a range of procedures. Direct cholangiography remains the gold standard in delineating anatomy, but the invasiveness of this procedure limits its use as a purely diagnostic tool. Magnetic resonance technology, in particular magnetic resonance cholangiopancreatography, has an increasing role as accessibility is improved. Treatment of these tumours is difficult. Surgical resection and palliative biliary enteric bypass are the most common methods used with endoscopic and percutaneous therapies reserved for palliating patients not fit for surgery. There is little firm evidence to suggest that any one palliative modality is superior. Interventional radiology is particularly suitable for palliative management of difficult and expansive lesions as the anatomy can preclude easy access by surgical or endoscopic techniques. Good palliative results with minimal mortality and morbidity can be achieved with percutaneous stenting.

Bile Duct Neoplasms↗

PubMed2002

Multiple sclerosis.

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system (CNS). Diagnosis rests upon identifying typical clinical symptoms and interpreting supportive laboratory and radiological investigations. The etiology is unknown; however, strong evidence suggests that MS is an autoimmune disease directed against CNS myelin or oligodendrocytes. Genetic factors are important in the development of MS. Contributing environmental determinants (possibly including infectious agents) appear important but remain unidentified. Both cell-mediated and humorally mediated immune mechanisms contribute to pathological injury. Axonal damage occurs in addition to demyelination and may be the cause of later permanent disability. Distinct pathological subtypes may differentiate among patients with MS. Treatment is directed at acute attacks (with corticosteroids) and reduction of attack frequency (primarily with type-1 beta interferons and glatiramer acetate). Research into the causes and treatments of MS has expanded our knowledge of this disease and promises improved care for MS patients in the future.

Atrophy↗

PubMedDate not supplied

Hemangioma from head to toe: MR imaging with pathologic correlation.

Hemangioma is a common benign vascular neoplasm that closely resembles normal vessels and can be found in all organs of the human body. Vascular lesions can be classified as infantile hemangiomas or vascular malformations on the basis of their natural history, location, cellular turnover, and histologic characteristics. The magnetic resonance (MR) imaging features of vascular malformations of the central nervous system depend on the pathologic subtype. Soft-tissue vascular malformations can be categorized with combined MR imaging and MR angiography as either high- or low-flow. Osseous vascular malformations commonly demonstrate a high-signal-intensity trabecular pattern at both T1- and T2-weighted MR imaging. A group of more aggressive vascular neoplasms, including hemangioendothelioma, hemangiopericytoma, and glomus tumor, have a nonspecific appearance at MR imaging. In the liver and spleen, hemangiomas are typically hyperintense at T2-weighted MR imaging, with a centripetal filling pattern after administration of gadopentetate dimeglumine. Vascular lesions can involve several organs or systems in angiomatous syndromes. MR imaging allows characterization of a hemangioma with typical features, which vary depending on anatomic location. Familiarity with these features facilitates diagnosis and management of these anomalies.

Angiomatosis↗

PubMed2004

EphA2 expression is associated with aggressive features in ovarian carcinoma.

PURPOSE: EphA2 (epithelial cell kinase) is a transmembrane receptor tyrosine kinase that has been implicated in oncogenesis. There are no published data regarding the role of EphA2 in ovarian carcinoma, which is the focus of the present study. EXPERIMENTAL DESIGN: Nontransformed (HIO-180) and ovarian cancer (EG, 222, SKOV3, and A2780-PAR) cell lines were evaluated for EphA2 by Western blot analysis. Five benign ovarian masses, 10 ovarian tumors of low malignant potential, and 79 invasive ovarian carcinomas were also evaluated for EphA2 expression by immunohistochemistry. All samples were scored in a blinded fashion. Univariate and multivariate analyses were used to determine significant associations between EphA2 expression and clinicopathological variables. RESULTS: By Western blot analysis, EG, 222, and SKOV3 cell lines overexpressed EphA2, whereas A2780-PAR and HIO-180 had low to absent EphA2 expression. All of the benign tumors had low or absent EphA2 expression. Among the invasive ovarian carcinomas examined (mean age of patients was 59.2 years), 60 (75.9%) tumors overexpressed EphA2 and the other 19 tumors had negative or minimal EphA2 expression. There was no association of EphA2 overexpression with ascites, likelihood of nodal positivity, pathological subtype, and optimum surgical cytoreduction (residual tumor <1 cm). However, EphA2 overexpression was significantly associated with higher tumor grade (P = 0.02) and advanced stage of disease (P = 0.001). The median survival for patients with tumor EphA2 overexpression was significantly shorter (median, 3.1 years; P = 0.004); the median survival for patients with low or absent EphA2 tumor expression was at least 12 years and has not yet been reached. In multivariate analysis using the Cox proportional hazards model, only volume of residual disease (P < 0.04) and EphA2 overexpression (P < 0.01) were significant and independent predictors of survival. CONCLUSIONS: EphA2 overexpression is predictive of aggressive ovarian cancer behavior and may be an important therapeutic target.

Adult↗

PubMed2006

Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib.

PURPOSE: In patients with non-small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib. EXPERIMENTAL DESIGN: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival). RESULTS: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01). CONCLUSIONS: EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.

Adult↗

PubMedDate not supplied

Cten mRNA expression is correlated with tumor progression in thymoma.

Cten is a recently isolated gene which has homology with tensin, suggesting that it is a focal adhesion molecule. Tensin family proteins play an important role in cell motility. We attempted to determine the influence of cten expression on clinicopathological features in patients with thymoma who had undergone surgery. Expression of cten messenger RNA was evaluated by reverse-transcription polymerase chain reaction in 45 thymoma samples using a LightCycler. There was no relationship between cten/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression and age, gender or pathological subtypes. However, cten/GAPDH expression was significantly higher in stage IV thymoma (5.463 +/- 7.730) when compared to stage I thymoma (0.905 +/- 0.811; p = 0.0187). Cten/GAPDH mRNA expression was correlated with evidence of tumor progression in thymoma. Consequently, cell motility or migration might play a role in progression of thymoma.

Base Sequence↗

PubMed1994

Baseline measures and outcome predictions.

This paper reviews the methodological issues in the epidemiological study of the outcome from stroke. Data are presented from an unselected series of patients in whom the underlying stroke pathology is clearly defined. Although the natural history varies among the different pathological subtypes of stroke, simple clinical baseline measures of the severity of the neurological deficit (incontinence, loss of consciousness and severity of paresis) and premorbid level of disability and social functioning independently predict disability-free survival by 1 year, and may help direct management and research.

Aged↗

PubMedDate not supplied

Fine needle aspiration of borderline ovarian lesions. Is It useful?

Borderline ovarian tumors are a low grade form of epithelial ovarian carcinoma with a low rate of growth and a low potential to invade or metastasize. According to the new World Health Organization classification, these tumors are placed between clearly benign and obviously malignant tumors because they exhibit some, but not all, of the morphologic features of malignancy. For a distinction between borderline lesions and cystadenomas or carcinomas, 2 criteria are of the utmost importance: presence of nuclear atypia and absence of stromal invasion. The pathologic subtype ofperitoneal implants is probably one of the main prognosticfactors in patients with serous tumors of low malignant potential, while the prognostic value of micropapillary serous carcinoma in patients with noninvasive implants remains debatable. Although fine needle aspiration (FNA) is the most accurate diagnostic method in cytopathology, its value in the diagnosis of borderline lesions is limited, mainly because of its inability to establish the absence of stromal invasion. The diagnostic accuracy of RNA can be improved by supplementing cytologic examination with such diagnostic techniques as immunocytochemistry and cytometry.

Biopsy, Fine-Needle↗

PubMedDate not supplied

Fine needle aspiration cytology of the breast. Experience at an outpatient breast clinic.

OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) of the breast at our institution and to perform quality assurance. STUDY DESIGN: Two hundred forty-six cases with pathologic confirmation were selected and reviewed. A pathologist performed most of the aspirations at an outpatient breast clinic. We correlated cytologic and histologic findings and evaluated the influence of the size, location, grade, and pathologic subtypes and fibrosis in breast lesions on diagnostic results. RESULTS: The likelihood ratios for malignant, suspicious, atypical, benign and unsatisfactory cytologic diagnoses were 98.71, 5.48, 1.09, 0.07 and 0.55, respectively. The absolute and complete sensitivities for malignant lesions were 64.5% and 90.3%, respectively. The specificity was 71.9%. False negative and positive rates were 4.3% and 0.7%, respectively. The predictive value for a malignant cytologic diagnosis was 98.4%. The rate of unsatisfactory samples was 9.3%. The rate of concordance between cytologic and histologic diagnosis was lower for large and diffusely growing lesions (benign and malignant), for malignancies with abundant fibrosis and of unusual types and for carcinomas of low grade. All axillary and recurrent chest wall lesions were diagnosed cytologically. Cell block sections were useful in a small number of cases. CONCLUSION: Understanding the performance and limitations of FNAC can enhance its value as a diagnostic technique in the management of breast disease.

Biopsy, Needle↗

PubMed1998

Long-term risk of first recurrent stroke in the Perth Community Stroke Study.

BACKGROUND AND PURPOSE: Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia. METHODS: Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. RESULTS: Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived >2 days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4). CONCLUSIONS: Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.

Age Factors↗

PubMed2000

Variations in stroke incidence and survival in 3 areas of Europe. European Registries of Stroke (EROS) Collaboration.

BACKGROUND AND PURPOSE: Comparison of incidence and case-fatality rates for stroke in different countries may increase our understanding of the etiology of the disease, its natural history, and management. Within the context of an aging population and the trend for governments to set targets to reduce stroke risk and death from stroke, prospective comparison of such data across countries may identify what drives the variation in risk and outcome. METHODS: Population-based stroke registers, using multiple sources of notification, ascertained cases of first in a lifetime stroke between 1995 and 1997 for all age groups. The study populations were in Erlangen, Germany; Dijon, France; and London, UK. Crude incidence rates were age-standardized to the European population for comparative purposes. Case-fatality rates up to 1 year after the stroke were obtained, and logistic regression adjusting for age group, sex, and pathological subtype of stroke was used to compare survival in the 3 communities. RESULTS: A total of 2074 strokes were registered over the 3 years. The age-standardized rate to the European population was 100.4 (95% CI 91.7 to 109.1) per 100 000 in Dijon, 123.9 (95% CI 115.6 to 132.2) in London, and 136.4 (95% CI 124.9 to 147.9) in Erlangen. Both crude and adjusted rates were lowest in Dijon, France. The incidence rate ratio, with Dijon as the baseline comparison (1), was 1.21 (95% CI 1.09 to 1.34) in London and 1.37 (95% CI 1.22 to 1.54) in Erlangen (P:<0.0001). There were significant differences in the proportion of the subtypes of stroke between populations, with London having lower rates of cerebral infarction and higher rates of subarachnoid hemorrhage and unclassified stroke (P:<0.001). Case-fatality rates varied significantly between centers at 1 year, after adjustment for age, sex, and subtype of stroke (35% overall, 34% Erlangen, 41% London, and 27% Dijon; P:<0.001). CONCLUSIONS: The impact of stroke is considerable, and the risk of stroke varies significantly between populations in Europe as does the risk of death. The striking differences in survival require clarification but lend weight to the evidence that stroke management may differ between northern and central Europe and influence outcome.

Age Factors↗

PubMedDate not supplied

Inverted papilloma.

Two hundred twenty-three cases of inverted papilloma seen at this institution over a 35-year period were reviewed. The number of cases steadily increased over each 5-year period. Common presenting signs and symptoms, association with carcinoma, and results of surgical and radiographic treatment are presented. The pathologic controversy surrounding this disease is discussed, and an argument is made for including all pathologic subtypes and septal, lateral wall, or sinus cases in a common clinical grouping of inverted papilloma. Lateral rhinotomy was found to be associated with fewer recurrences and a better probability of cure than lesser procedures and is recommended as the standard surgical therapy. Radiotherapy was found to be a useful and effective adjunct in cases associated with malignancy or for multiply recurrent and inoperable benign inverted papillomas. Lifelong follow-up is urged.

Adolescent↗