High Prevalence of Distinct Human Herpesvirus 8 Contributes to the High Incidence of Non-acquired Immune Deficiency Syndrome-Associated Kaposi's Sarcoma in Isolated Japanese Islands.

Background: Non-acquired immune deficiency syndrome (AIDS) Kaposi's sarcoma (KS) is extremely rare in Japan but highly endemic in Okinawa, especially in Miyako Islands. We aimed to elucidate the exact incidence and cause of this high prevalence. Methods: Non-AIDS KS cases in Okinawa Prefecture over the past 31 years were reviewed, and human herpesvirus 8 (HHV8) seroprevalence in Miyako Islands was determined. We examined whole-genome sequences of 3 HHV8 strains and performed whole-exome sequencing of 4 male patients from Miyako Islands. Results: Approximately half of the non-AIDS KS cases in Okinawa Prefecture were from Miyako Islands. The age-adjusted incidence rate was 0.87/105 per year for Miyako Islands and 0.056/105 per year for the rest of Okinawa. Human herpesvirus 8 seroprevalence was 15.4% in Miyako Islands. The 3 HHV8 genomes isolated from Miyako islanders formed a phylogenetically branch distinct from those of previously sequenced HHV8 strains and shared specific mutations in 9 proteins. These mutations were verified in Okinawan patients other than those from Miyako Islands. Whole-exome sequencing of the 4 male Miyako Islanders did not reveal shared pathogenic mutations. Conclusions: Miyako Islands are an endemic area of non-AIDS KS. The high rate of a distinct HHV8 may contribute to the high incidence of KS in the region.

Pulmonary metastases from angiosarcoma: a spectrum of CT findings.

BACKGROUND: Though a few reports have summarized the computed tomography (CT) findings of pulmonary metastases from angiosarcoma, the detailed CT findings of cysts are not well known, except for their characteristic thin walls. PURPOSE: To retrospectively summarize the CT findings of pulmonary metastases from angiosarcoma, focusing mainly on the CT findings of cysts. MATERIAL AND METHODS: Thirty-three patients with pulmonary metastases from angiosarcoma were selected retrospectively. Two radiologists reviewed and assessed patients' chest CT images on a consensus basis for nodules, cysts, the CT halo sign, pneumothorax, pleural effusion, and enlarged lymph nodes. Cysts were also evaluated by wall thickness and smoothness, air-fluid levels, and vessels or bronchi penetrating the cysts. The relationship between cysts and pneumothorax was assessed using the Chi-square test. RESULTS: Nodules were found in 28 (85%) patients. Cysts were found in 19 (58%) patients; 17 had thin and smooth walls, 10 had thin and irregular walls, and four had thick and irregular walls. In addition, 12 patients showed vessels or bronchi penetrating the cysts, and six showed air-fluid levels. The CT halo sign, pneumothorax, pleural effusion, and mediastinal lymphadenopathy were seen in 19 (58%), 16 (48%), 26 (78.8%), and five (15.2%) patients, respectively. Pneumothorax occurred significantly more frequently in patients with cysts (P = 0.002). CONCLUSION: Cysts showed variability in their walls, and air-fluid levels and vessels or bronchi penetrating the cysts appeared to be characteristic findings, which may be useful for detection and accurate diagnosis in patients with pulmonary metastases from angiosarcoma.

A Novel Chromosomal Translocation Associated With COL1A2-PDGFB Gene Fusion in Dermatofibrosarcoma Protuberans: PDGF Expression as a New Diagnostic Tool.

IMPORTANCE: Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer that develops in the deep dermis to subcutaneous adipose tissues. A COL1A1-PDGFB gene fusion, leading to the constitutive expression of PDGFB, is the tumorigenic mechanism in most DFSP cases. OBJECTIVES: To evaluate the specificity of PDGFB expression as a diagnostic marker of DFSP and to determine whether other pathomechanisms (ie, gene fusions) exist in patients with DFSP without the COL1A1-PDGFB fusion gene. DESIGN, SETTING, AND PARTICIPANTS: All patients with DFSP registered in the pathologic database of the University of the Ryukyus from January 1, 1997, through December 31, 2013, and Gunma University from January 1, 1996, through December 31, 2011, were included in this analysis. Samples were obtained from 30 patients presenting with DFSP tumors. We examined the clinicopathologic characteristics and the expression of PDGFB, PDGFRß, PDGFRα, CD34, nestin, factor XIIIa, fibronectin, α-smooth muscle actin, S-100 protein, and Ki-67 in 30 DFSP cases and 48 non-DFSP mesenchymal tumor cases by immunohistochemical analysis. We then analyzed tumor tissues for the presence of the COL1A1-PDGFB fusion gene. We also tested whether other genes enriched in fibroblasts formed fusion products with PDGFB by reverse transcription-polymerase chain reaction analysis, using gene-specific primers. MAIN OUTCOMES AND MEASURES: We aimed to analyze tumor tissues for the presence of the COL1A1-PDGFB fusion gene to investigate expression of PDGFB in DFSP tumors. RESULTS: PDGFB expression was detected in 28 (93%) of 30 patients with DFSP. PDGFB was not homogenously expressed in DFSP tumor cells, whereas CD34 and nestin were often expressed throughout the tumor mass. In 1 DFSP tumor, the COL1A1-PDGFB fusion gene was not detected even though PDGFB was expressed. We identified a novel COL1A2-PDGFB fusion gene in this tumor. CONCLUSIONS AND RELEVANCE: Our findings indicate that PDGFB protein is expressed in most DFSP tumors and may be a useful diagnostic tool when used in conjunction with CD34 and nestin expression analysis. These PDGFB expression data, in addition to our discovery of a novel PDGF fusion gene, strongly support the concept that DFSP is a PDGFB-dependent tumor type.