title: Absence of human herpesvirus-8 in pulmonary inflammatory myofibroblastic tumor: immunohistochemical and molecular analysis of 20 cases.
abstract: Inflammatory myofibroblastic tumors are uncommon lesions composed of spindled myofibroblasts within a variable background of collagen and inflammatory cells. Although the true nature of these lesions is not fully elucidated, identification of consistent cytogenetic alterations in the anaplastic lymphoma kinase (ALK) gene suggests that they may be neoplastic. A small number of inflammatory myofibroblastic tumors have been reported to harbor human herpesvirus-8 (HHV-8), implicating the virus in its pathogenesis. In this study, 20 cases of pulmonary inflammatory myofibroblastic tumor were analyzed for the presence of HHV-8 with immunohistochemical and molecular methods. In all cases, antibodies to the latent nuclear antigen of the virus were applied. Four open reading frames (ORFs), including ORFs K2, 16, 26, and 72, were targeted utilizing real-time polymerase chain reaction (PCR). The cohort included 9 men and 11 women with a mean age of 37 years (range, 1-81). Microscopically, the tumors were composed of cytologically bland spindle cells with myofibroblastic differentiation. On immunohistochemical studies, 20% of cases (4/20) demonstrated diffuse cytoplasmic positivity with ALK. Immunohistochemical staining for the latent nuclear protein of the virus was negative in all cases (0/20). All tumors (100%, 20/20) tested with real-time PCR were negative for all four ORFs, whereas 100% (10/10) of positive control Kaposi sarcoma cases were positive. Her2 gene expression was present in all (20/20) inflammatory myofibroblastic tumors confirming the presence of amplifiable deoxyribonucleic acid in the tissue lysate. This study documents the absence of HHV-8 in pulmonary inflammatory myofibroblastic tumors, suggesting that further investigation is required to clarify the pathogenesis of this lesion.
authors.affiliation: Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Tavora
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shilo
authors.forename: Irem H
authors.initials: IH
authors.lastname: Ozbudak
authors.forename: Jean M
authors.initials: JM
authors.lastname: Przybocki
authors.forename: Guanghua
authors.initials: G
authors.lastname: Wang
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Teri J
authors.initials: TJ
authors.lastname: Franks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009379:Neoplasms, Muscle Tissue / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D009687:Nuclear Proteins / Q000032:analysis; D016366:Open Reading Frames; D010750:Phosphoproteins / Q000032:analysis; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D015203:Reproducibility of Results
chemical_list: D004279:DNA, Viral; D009687:Nuclear Proteins; D010750:Phosphoproteins; C118485:latent nuclear antigen (LNA); C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases