Rhabdomyosarcoma of the head and neck in pediatric patients: a systematic review.

BACKGROUND: Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common solid sarcoma in children. The most usual site of occurrence are the head and neck regions. RMS presents a variety of histologic features, and so differential diagnosis with other small round cell tumors is needed. Hence, it has been very useful to the field to undertake additional immunohistochemical studies to determine the diagnosis and, on occasions, to assign subtype tumors. MATERIAL AND METHODS: A systematic review of three databases (Medline, Biological Science Collection and Health & Medical Collection) was carried out with the purpose of analyzing rhabdomyosarcoma cases reported in the literature, specifically with localization in the head and neck regions in children. This strategy allowed us to identify the main anatomical site of appearance, the subtype of RMS, average age, histologic characteristics and immunohistochemistry markers used in a usual and any additional way. RESULTS: According to the selection criteria in this systematic review, twelve articles, and fourteen cases were identified that highlight that the histological diagnosis usually presents cellular heterogeneity. Therefore, immunohistochemistry is needed to confirm the diagnosis. CONCLUSIONS: Histologic characterization is not always sufficient for a conclusive diagnosis of RMS. Therefore, immunohistochemistry is helpful to determine the subtype and consequently, sometimes the behavior, treatment and prognosis. Additional markers may vary according to the institution and the need of particular cases.

Impact of Cadmium Mediated by Tobacco Use in Musculoskeletal Diseases.

Tobacco use has a negative impact on health due to its relationship with the development of high-mortality diseases, such as pulmonary cancer. However, the effect of cadmium (Cd), present in tobacco smoke, on the development of joint diseases has been scarcely studied. The objective of this review is to discuss the evidence regarding the mechanisms by which Cd exposure, through tobacco smoke, may lead to the development of osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA). There's evidence suggesting a string association between moderate to severe OA development and tobacco use, and that a higher blood concentration of Cd can trigger oxidative stress (OS) and inflammation, favoring cartilage loss. At the bone level, the Cd that is inhaled through tobacco smoke affects bone mineral density, resulting in OP mediated by a decrease in the antioxidant enzymes, which favors the bone resorption process. In RA, tobacco use promotes the citrullination process through Cd exposure and increases OS and inflammation. Understanding how tobacco use can increase the damage at the articular level mediated by a toxic metal, i.e., Cd, is important. Finally, we propose prevention, control, and treatment strategies for frequently disabling diseases, such as OA, OP, and RA to reduce its prevalence in the population.

Implementation of semi-automated cloning and prokaryotic expression screening: the impact of SPINE.

The implementation of high-throughput (HTP) cloning and expression screening in Escherichia coli by 14 laboratories in the Structural Proteomics In Europe (SPINE) consortium is described. Cloning efficiencies of greater than 80% have been achieved for the three non-ligation-based cloning techniques used, namely Gateway, ligation-indendent cloning of PCR products (LIC-PCR) and In-Fusion, with LIC-PCR emerging as the most cost-effective. On average, two constructs have been made for each of the approximately 1700 protein targets selected by SPINE for protein production. Overall, HTP expression screening in E. coli has yielded 32% soluble constructs, with at least one for 70% of the targets. In addition to the implementation of HTP cloning and expression screening, the development of two novel technologies is described, namely library-based screening for soluble constructs and parallel small-scale high-density fermentation.

Risk factors for latent tuberculosis infection among children in New York City.

OBJECTIVE: Although identification and appropriate treatment of children with latent tuberculosis (TB) infection (LTBI) is considered critical to the control and elimination of TB in the United States, there are limited data on risk factors for LTBI in pediatric populations. METHODS: To further improve targeted screening for LTBI, we performed a matched case-control study from September 1996 to December 1998. We actively surveyed 24 primary care clinics serving Northern Manhattan and Harlem twice monthly for case participants 1 to 5 years old with LTBI, defined as a child with a Mantoux tuberculin skin test (TST) >/=10 mm and a normal chest radiograph. Two age- and clinic-matched control participants with TSTs equal to 0 mm were enrolled per case. To determine risk factors for LTBI, a bilingual research worker reviewed the medical records of study participants and administered a questionnaire to the parents of participants. RESULTS: We enrolled 96 cases and 192 controls whom did not differ by age, gender, ethnicity, and race; overall, the mean age of participants was 2.9 years, 51% were male, 80% were Hispanic, and 9% black. Logistic regression analysis demonstrated that contact with an adult with active TB, foreign birth, foreign travel, and a relative with a positive TST were predictive of case status. In contrast, a history of a previous negative TST proved protective and BCG immunization was not an independent risk factor for a positive TST, suggesting that boosting was not important in this population. CONCLUSIONS: We identified several risk factors for LTBI in children that can be used to refine targeted surveillance for TB among Hispanic immigrant populations in the United States.

Lymphoepitheliomalike carcinoma: an unusual variant of endometrial cancer. A report of two cases.

Two undifferentiated carcinomas of the endometrium with a prominent inflammatory reaction that were morphologically similar to nasopharyngeal cancers occurred in two patients who had postmenopausal bleeding. Tumor cells in both patients were large with indistinct cytoplasmic borders, vesicular nuclei, and prominent nucleoli, were arranged in sheets, in groups, or singly, and surrounded by an intense inflammatory component of lymphocytes, plasma cells, and karyorrhectic debris. Tumor cells were keratin (AE1/EA3) and epithelial membrane antigen (EMA) positive and leukocyte common antigen (LCA) negative. All three methods used for the detection of Epstein Barr virus (EBV) infection were negative. The first patient (International Federation of Gynecology and Obstetrics [FIGO] stage IVB) received chemotherapy and is alive and free of disease 9 months after diagnosis. The second patient (FIGO stage IIIC) received radiation therapy and chemotherapy 6 months after evidence of extensive retroperitoneal disease and died of disease 1 year after diagnosis. Tumors with these histologic features have been designated as lymphoepitheliomalike carcinomas (LELC) when they occur outside the nasopharynx. LELC can occur in the endometrium and, in this location, may not be associated with EBV infection.

Utilization of molecular genetics in the differentiation between adrenal cortical adenomas and carcinomas.

Distinction between benign adrenal cortical proliferative lesions and adrenal cortical carcinoma has been approached by a combination of histological, immunohistochemical, and macroscopical parameters. Modern imaging studies allow detection of small adrenal cortical lesions that may be incorrectly diagnosed. Differentiation between benign and malignant tumors of the adrenal cortex was attempted by microdissection of nine cases of adrenal cortical hyperplasia, 10 cortical adenomas, and 18 adrenal cortical carcinomas with subsequent polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of five microsatellites of putative tumor suppressor gene loci: p53 gene (17p), the neuroblastoma candidate gene (1p), the p16 gene (9p), the von Hippel Lindau gene (3p), and the retinoblastoma gene (13q). None of the hyperplastic lesions or cortical adenomas showed LOH of any of the gene markers used. Conversely, genetic changes were observed in 61% (11 of 18) of the cases of carcinoma. Forty-four percent of the lesions showed LOH for p53 (7 of 16). LOH of 1p, 3p, and 9p were seen in 22%, 22%, and 26%, respectively. LOH of the retinoblastoma gene was seen in 80% or four of five of the informative cases studied. We conclude that LOH studies may be used to distinguish malignant from nonmalignant adrenal cortical proliferations. Relative infrequency of LOH in 3p may furthermore help to differentiate adrenal lesions from clear cell carcinomas of the kidney.

Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malignant breast lesions.

UNLABELLED: This study was undertaken to assess the relationship between the degree of 99mTc-MIBI uptake in breast lesions and the following histologic factors: neovascularity, desmoplastic reaction, cellular proliferation and mitochondrial density. METHODS: Forty-two patients who previously underwent MIBI breast imaging (4 false-negative, 12 false-positive, 15 true-negative, 11 true-positive) were studied. Immunohistochemical staining was performed for neovascularity (Factor VIII antigen), desmoplasia (alpha-actin antigen), mitochondrial density (mitochondrial antigen) and cellular proliferation (MIB-1 antigen). The degree of microscopic staining was correlated with region of interest measurements of MIBI uptake on scintigraphy. RESULTS: There was a poor correlation between MIBI uptake and the degrees of neovascularity (r = 0.08, p > 0.05) and intracellular mitochondrial density (r = 0.04, p > 0.05) while there was a moderate correlation with cellular proliferation (r = 0.4, p < 0.05) and desmoplasia (r = 0.55, p < 0.001). CONCLUSION: The degree of MIBI uptake in breast lesions is multifactorial, but it appears to be related more to the degree of desmoplastic activity and cellular proliferation than neovascularity and mitochondrial density.

Phase I trial of photodynamic therapy in the treatment of recurrent superficial transitional cell carcinoma of the bladder.

OBJECTIVES: A Phase I trial of photodynamic therapy (PDT) in the treatment of superficial transitional cell carcinoma (TCC) of the bladder was performed. METHODS: Twenty patients with recurrent superficial TCC of the bladder after receiving a mean of 2.6 (range 1 to 6) courses of intravesical therapy were treated with PDT. The photosensitizer Photofrin II dose was 1.5 or 2.0 mg/kg. A 630-nm intravesical red laser was used to activate the photosensitizer 2 days after administration of Photofrin II. A 0.01% intralipid solution was used as a bladder-filling medium to scatter light and achieve more homogeneous light distribution. Light doses from 5.1 to 25.6 J/cm2 (total dosage 1500 to 5032 J) were used to illuminate the bladder. RESULTS: Twenty patients underwent 21 treatments with PDT. Complications included asymptomatic reflux in 4 patients. One other patient, treated at the highest total light dose, experienced bladder contraction and fibrosis. Nine patients (45%) had no tumor evident at cystoscopy, on random biopsies, or in urinary cytology at the 3-month evaluation after treatment. Four patients remained without recurrent disease for 23 to 56 months. Sixteen of 20 (80%) patients experienced recurrence, and 8 of the 16 underwent cystectomy. CONCLUSIONS: An intravenous photosensitizer dose of 1.5 mg/kg Photofrin II followed by light energy in the range of 13 J/cm2 (total light dose 2500 to 3250 J) was defined as a safe treatment parameter and resulted in tumor responses. With present technologies, administration of PDT requires careful dosimetry.

Adrenocortical neoplasms: role of prognostic markers MIB-1, P53, and RB.

Differentiation between benign and malignant adrenocortical neoplasms is made using a combination of clinical and pathologic parameters. Despite these parameters, it is still difficult to predict the biologic potential of some tumors. Forty adrenocortical lesions, including 10 hyperplasias, 10 adenomas, 12 carcinomas and eight metastatic/recurrent adrenocortical carcinomas were studied for the expression of MiB-1, p53, and the retinoblastoma gene product (RB) utilizing immunohistochemical techniques. The mean tumor proliferating fraction (TPF), expressed as the number of MiB-1-positive nuclei per 1,000 tumor cells, was 14.9 in adenomas, 31.5 in hyperplasias, 208.1 in carcinomas and 166.1 in recurrent or metastatic disease. None of the 20 benign lesions had a TPF of > 80, and only one of the 20 malignancies had a TPF of < 80. Nine of the 20 carcinomas were positive for p53. None of the benign lesions were p53 positive. Thirty-nine cases, including benign and malignant ones, were RB positive, and one was uninterpretable. We conclude that prognostic markers can be of great assistance in recognizing adrenocortical carcinomas. High TPF (> 80), as measured by staining with MiB-1, and positive p53 strongly correlate with malignant behavior and therefore may be useful in distinguishing benign from malignant adrenal lesions. Staining for RB does not appear to be a helpful technique.

Loss of heterozygosity on the short arm of chromosomes 1 and 3 in sporadic pheochromocytoma and extra-adrenal paraganglioma.

Pheochromocytomas and extra-adrenal paragangliomas are tumors of the paraganglia with similar histological characteristics. We examined 12 sporadic pheochromocytomas and 5 extra-adrenal paragangliomas for loss of heterozygosity (LOH) in chromosomes 1p and 3p using a microdissection technique. Chromosomes 1p34-36, 3p21 and the von Hippel-Lindau (VHL) gene locus (3p25) were analyzed. LOH of a selected region on chromosome 1p was detected in 5 of 11 (45%) informative pheochromocytoma cases and in 0 of 5 (0%) informative extra-adrenal paraganglioma cases. LOH of the chromosome 3p25 VHL gene locus was detected in 5 of 9 (45%) informative pheochromocytoma cases and in 0 of 3 (0%) informative extra-adrenal paraganglioma cases. LOH of 3p21 was detected in 2 of 4 (50%) informative extra-adrenal paraganglioma cases. The allelic deletions in chromosomes 1p and 3p appear to be separate events. In conclusion, significant deletions were found at 1p34-36 and 3p25 in sporadic pheochromocytomas but not in extra-adrenal paragangliomas. These findings suggest (1) that multiple genetic factors may be involved in pheochromocytoma tumorigenesis, and (2) extra-adrenal paragangliomas may have a different genetic mechanism of tumorigenesis compared with pheochromocytomas.

The role of prognostic markers (MiB-1, RB, and bcl-2) in the diagnosis of parathyroid tumors.

Assessment of the malignant potential of parathyroid tumors in the absence of metastasis can be difficult using morphologic criteria alone. The role of prognostic markers that may assist in evaluating aggressive behavior in these tumors has not been fully studied. We performed a retrospective study of 31 parathyroid lesions, including 10 adenomas, 10 atypical lesions, and 11 carcinomas, to evaluate the diagnostic and prognostic role of the MiB-1, p53, RB, and bcl-2 markers by immunohistochemical techniques. The mean tumor proliferative fraction (TPF), expressed as the number of MiB-1-positive nuclei per 1000 cells, was 20.3 in adenomas (range, 5-51), 20.0 in atypical lesions (range, 8-36), and 79.8 in carcinomas (range, 4-133). Only 1 of 20 benign lesions had a TPF more than 40, and only 2 of 11 carcinomas had a TPF less than 40. One atypical lesion and two carcinomas showed scattered cells positive for p53. Patients with the adenoma with increased TPF and the atypical lesion with positive p53 have been free of disease for 16 months. bcl-2 was expressed in 7 (70%) of 10 adenomas, 2 (20%) of 10 atypical lesions, and 4 (36%) of 11 carcinomas. Two of the 11 carcinomas were RB negative, whereas all of the 20 benign lesions were RB positive. We conclude that high TPF (greater than 40 as measured by staining with MiB-1) strongly correlates with malignancy and, therefore, may be useful in the diagnosis of carcinomas. Negative RB stain, although not a common event, may be helpful to exclude benign lesions. Other tumor markers (p53 and bcl-2) were not useful in distinguishing malignant from benign lesions.

Infarcted myxoid fibroadenoma following fine-needle aspiration.

Infarction of breast fibroadenomas is very rare and is frequently associated with physiologic changes, such as pregnancy and lactation. We report a case of an infarcted fibroadenoma following fine-needle aspiration. The patient presented with an asymptomatic breast mass, which was clinically difficult to evaluate. Excisional biopsy was performed 7 days after a nondiagnostic fine-needle aspiration of the mass. Microscopically, the nodule showed features of a classic fibroadenoma of the intracanalicular type with myxoid or mucinous stromal changes, as well as extensive areas of acute infarction. This report provides another example of the changes that may be observed in biopsy specimens obtained after fine-needle aspiration of the breast.

Detection of heterozygosity loss in microdissected fine needle aspiration specimens of breast carcinoma.

OBJECTIVE: To use the polymerase chain reaction (PCR) to detect loss of heterozygosity (LOH) in microdissected cells form cytologic smears obtained by fine needle aspiration (FNA) from 20 cases of invasive breast carcinoma. STUDY DESIGN: In each case, histologic sections of the primary tumor were also available. Tumor and nontumor cells were dissected from both the cytologic smear and tissue section in all cases except in three smears that showed only tumor cells. RESULTS: LOH was identified in 10 of 19 informative cases using two polymorphic DNA markers at chromosome 11q13 (INT-2, PYGM). The same results were obtained in both the cytologic and histologic specimens, including three cases that had hypocellular cytologic smears. CONCLUSION: FNA of breast lesions provides adequate samples for direct microdissection of the cytologic smear to detect LOH using PCR amplification.

High CD44 expression on human mesotheliomas mediates association with hyaluronan.

PURPOSE: Malignant pleural mesothelioma is a rare malignancy with major environmental implications regarding passive asbestos exposure. We have conducted an immunohistochemical and functional study to address three questions: (1) What is the representation of CD44 on tumor cells as detected by immunohistochemistry? (2) Do cultured cell lines derived from malignant pleural mesothelioma tissue express the same CD44 phenotypes as the original tumors, and can they serve as a model for the study of CD44 in mesotheliomas? (3) What is the functional status of the CD44 expressed on mesotheliomas, with regard to hyaluronan anchorage? MATERIALS AND METHODS: Thirty-seven samples of pleural mesothelioma were obtained from patients entered on phase I/II protocols conducted in the Surgery Branch of the National Cancer Institute since 1991. The diagnosis was confirmed in all 37 patients by means of a battery of immunohistochemical tests for markers differentiating malignant pleural mesothelioma from adenocarcinoma. Tumor-positive lymph nodes and distant metastases were also examined in six of the patients. Cell lines, established from tumor tissue of six of the patients described above, were used in these experiments. Four (H2596, H2461, H2373, H2452) were derived from primary solid tumors and two (HP-1 and HP-3) were derived from effusions. RESULTS: Immunohistochemical staining with a monoclonal antibody (H4C4) that recognizes a constant region of human CD44 demonstrated that 34 (92%) of the malignant pleural mesotheliomas examined expressed CD44 on 50% to 100% of their cells. The extent of CD44 expression was apparently related to histologic subtype with the highest expression seen in epithelioid mesotheliomas and the least in sarcomatoid tumors. Tumor cell lines established from the primary tumors or effusions of six of the malignant pleural mesothelioma patients showed high expression of the hematopoietic form of CD44. Four of these cell lines exhibited strong attachment to hyaluronan in an in vitro attachment assay, indicating that their CD44 was functional with respect to hyaluronan anchorage. Hyaluronan attachment was specific in that it could be abolished by preincubation with epitope-specific anti-CD44 antibodies or soluble substrate or by hyaluronidase treatment of attachment surfaces. CONCLUSIONS: We conclude that CD44 is highly expressed on human mesotheliomas, that cell lines adequately represent tumor expression, and that CD44 mediates association with hyaluronan, a major component of pleural fluid.

Angiogenesis in uterine cervical squamous cell carcinoma.

This study tested the hypothesis that increased angiogenesis in squamous cell carcinoma of the cervix is an indicator of poor prognosis. We retrospectively studied 70 cases and related the microvessel count to stage and follow-up. We performed immunohistochemical staining for Factor VIII and counted the number of microvessels in a 400x field in the area of greatest density of vessels. The mean vessel count in stage I was 18.3 +/- 5.4 (26 cases), in stage II 18.0 +/- 6.8 (21 cases), in stage III 17.9 +/- 3.9 (18 cases), and in stage IV 22.2 +/- 13.6 (five cases). We found no correlation between the mean vessel count and stage (p < 0.85) or between mean vessel count and disease status on an average follow-up of 21 months (p < 0.65). With a power of approximately 70%, this study excludes the hypothesis that an increased density of microvessels is associated with a worsened prognosis in cervical squamous cell carcinoma.