Role of Human Papillomavirus in Penile Carcinomas Worldwide.

BACKGROUND: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. OBJECTIVE: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. DESIGN, SETTING, AND PARTICIPANTS: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HPV DNA prevalence and type distributions were estimated. RESULTS AND LIMITATIONS: HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. CONCLUSIONS: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. PATIENT SUMMARY: About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.

Isolation and Characterization of Multipotential Mesenchymal Stromal Cells from Congenital Pseudoarthrosis of the Tibia: Case Report.

Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease whose etiology and pathogenesis is unknown. Several evidences suggest that decreased osteogenic capacities, impaired local vascularization, and microenvironment alterations may play a role in the pathogenesis of CPT. Additionally, it is not clear if the pathogenesis of this disease is related to the absence of cells with osteogenic capacity of differentiation. In this work, a two-year-old patient diagnosed with CPT underwent an orthopedic surgery to promote bone union in a pseudoarthrosis lesion. Tissue from CPT lesion was excised, and histological evaluation and tissue culture were performed. Histologic analysis of the soft CPT lesion showed the presence of highly cellular fibrous tissue, vascularization, and abundant extracellular matrix. Fusiform cells of mesenchymal appearance were observed but osteoblasts, osteoclasts, chondrocytes, and adipose cells were not found. There was no evidence of osteogenesis. CPT tissue cultured as explants showed, after one month of culture, evidence of osteogenesis, chondrogenesis, and adipogenesis. Cells isolated from explants of CPT tissue showed a fibroblast-like morphology and expressed the mesenchymal stromal cell (MSC) markers: CD105, CD73, and CD90 (CPT-MSC). Functional analysis showed that CPT-MSC differentiate, in vitro, into osteogenic, chondrogenic, and adipocytic cells. CPT-MSC expressed osteocalcin and agrecan. CPT-MSC produced collagen in the presence of ascorbic acid. MSC from BM of normal individuals were used as control. In summary, our results indicate that CPT tissue contains MSC with osteogenic capacity of differentiation. It is possible that CPT microenvironment may contribute to impair the osteogenic capacity of differentiation of CPT-MSC.

Tumores óseos orbitarios / Orbital bone tumors

Reportar la frecuencia de los tumores óseos orbitarios. En un período de ocho años (1998-2005) se realizaron 117 899 biopsias en el Instituto Anatomopatológico "Dr. J. A. O’Daly" de la Universidad Central de Venezuela, de las cuales se identificaron 1 826 biopsias óseas, de las cuales 17 (0,93 por ciento) correspondieron a tumores óseos orbitarios. Se investigaron las variables edad, sexo, localización y tipo de neoplasia. En la revisión se identificaron 10 tumores óseos primarios (8 benignos y 2 malignos), 6 casos de pseudotumores (35 por ciento) y un tumor metastásico (6 por ciento). El osteoma y la displasia fibrosa fueron las condiciones más frecuentes. Los tumores óseos primarios de la órbita son un grupo heterogéneo de condiciones que constituyen el 0,6 por ciento - 2 por ciento de todos los tumores orbitarios.

To evaluate the rate of orbital bone tumours. Our experience over a 8-year period in Instituto Anatomopatologico "Dr. J. A. O’Daly" at the Universidad Central de Venezuela, yielded 17 (0.93 percent) cases of orbital bone tumours from a total of 117 899 biopsies. Data were collected on patient age, sex, tumour localization and type of neoplastic disorders. Results: Ten cases (59 percent) were primary tumours of orbital bone (8 benign and 2 malignant), six patients with tumour-like lesions (35 percent) and one bone metastases. The two most commonly encountered entities were osteoma and fibrous dysplasia. Primary tumours of orbital bone constitute 0,6 percent - 2 percent of all orbital tumours.