mTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma.

Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates, and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (N=274), most (90%) associated with human immunodeficiency virus. Tissue microarray slides were stained with human herpes virus-8, Friend leukemia integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF receptor-ß, VEGF, and phospho-mTOR. Both intensity and extent of staining were scored. Multiplying these scores for each core yielded total staining H-scores. Human herpes virus-8 was positive in 87% and Friend leukemia integration 1 transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+ (95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were phospho-mTOR+. There was no significant difference in staining among patients with low (<500 cells/mm3) or preserved CD4 T-cell counts. Immunohistochemistry confirms upregulation of the mTOR, PDGF, VEGF, and c-kit pathways in a large cohort of KS samples. Of proteins tested, pS6, downstream of mTOR, demonstrated the highest proportion of strong positivity (67.1%). These results support the possibility of using targeted inhibitors in KS. Overexpression was independent of CD4 count, suggesting that even patients with low counts may be targeted therapy candidates.

Bone marrow aspiration in resource poor environment: our experience in Kenya.

Bone marrow aspiration examination is performed mainly to evaluate haematological disorders. Several bone marrow aspiration needles are available that include the Salah, Klima, Jamshidi and Islam. However, cost is an issue in our local environment as most of our patients are not medically insured. We describe our experience of bone marrow aspiration using an 18-gauge lumbar puncture needle at the posterior superior iliac spine. The technique is safe and cost effective and the site is easily accessible, even in obese patients. The crush preparations provide good morphology, therefore avoiding repeats. Additional training is not required for the procedural technique. We recommend this technique for use in resource challenged settings.

Telecytology in East Africa: a feasibility study of forty cases using a static imaging system.

We conducted a pilot study to assess the feasibility of telecytology as a diagnostic tool in difficult cases originating from a hospital in East Africa. Forty cytology cases considered difficult by a referring pathologist were posted on a telepathology website. Six pathologists independently assessed the static images. Telecytology diagnoses were compared with the consensus diagnoses made on glass slides and also with the histogical diagnoses when available. The diagnostic agreement of the six pathologists was 71-93% and tended to be higher for pathologists with more experience. Reasons for discordance included poor image quality, presence of diagnostic cells in thick areas of smears, sampling bias and screening errors. The consensus diagnoses agreed with histological diagnoses in all 17 cases in which a biopsy was performed. Diagnostic accuracy rates (i.e. telecytology diagnosis vs. histological diagnosis) for individual pathologists were 65-88%. To ensure diagnostic accuracy both referring and consulting pathologists must have adequate training in cytology, image acquisition and image-based diagnosis and the diagnostic questions of importance must be clearly communicated by the referring pathologist when posting a case.