Tenosynovial Giant Cell Tumor (TCGT) is a rare neoplasm affecting the synovium of joints, bursae, and tendon sheaths. The overproduction of CSF1 by a minority of the tumor population, works in an autocrine and paracrine fashion to drive tumor growth. Pathology of the reactive, monocytic component has been well elucidated, while understanding of the true neoplastic cells and the sources of CSF-1 overproduction remain relatively unknown. Podoplanin (PDPN, gp38) is a cell surface glycoprotein that is expressed on fibroblast-like synoviocytes, is upregulated in rheumatoid arthritis and many cancers, governing cell mobility, epithelial-mesenchymal transition and other functions, while being associated with prognosis in many solid tumors. We showed the expression of PDPN increased in TGCT compared to patient-controlled healthy synovium. Flow cytometry partitioned PDPNhigh cells into PDPNhigh/CD90+ or PDPNhigh/CD14+ populations. Quantitative real-time polymerase chain reaction analysis of the PDPNhigh/CD90+ cells revealed a 10-fold increase in CSF1 expression. Therefore, we conclude that the fibroblast-like synoviocytes are characterized by the expression of both PDPN and CD90, drive tumor progression, and play an essential role in the pathophysiology of TGCT.

Tenosynovial Giant Cell Tumor (TCGT) is a rare neoplasm affecting the synovium of joints, bursae, and tendon sheaths. The overproduction of CSF1 by a minority of the tumor population, works in an autocrine and paracrine fashion to drive tumor growth. Pathology of the reactive, monocytic component has been well elucidated, while understanding of the true neoplastic cells and the sources of CSF-1 overproduction remain relatively unknown. Podoplanin (PDPN, gp38) is a cell surface glycoprotein that is expressed on fibroblast-like synoviocytes, is upregulated in rheumatoid arthritis and many cancers, governing cell mobility, epithelial-mesenchymal transition and other functions, while being associated with prognosis in many solid tumors. We showed the expression of PDPN increased in TGCT compared to patient-controlled healthy synovium. Flow cytometry partitioned PDPNhigh cells into PDPNhigh/CD90+ or PDPNhigh/CD14+ populations. Quantitative real-time polymerase chain reaction analysis of the PDPNhigh/CD90+ cells revealed a 10-fold increase in CSF1 expression. Therefore, we conclude that the fibroblast-like synoviocytes are characterized by the expression of both PDPN and CD90, drive tumor progression, and play an essential role in the pathophysiology of TGCT.

The percent of underrepresented minority (URM) students who apply to medical school has minimally changed in the past 40 years. Due to the lack of URM applicants, consequent matriculation of URMs is grossly disproportionate from their percent representation of the United States (U.S.) population. Increasing diversity among medical students and physicians has previously been identified as essential to decreasing healthcare disparities among U.S. minorities. Therefore, it is vital to recognize barriers to applying to medical school among URMs. To identify and assess prevalence of barriers, surveys were distributed to participants of MedAchieve, a mini-medical school program of diverse high school students in New York City. Of students who will be first in their immediate family to attend college, 80% perceived a barrier of pursuing medical school. Specified barriers indicated include cost of medical school (77%), lack of guidance/role models (54%), and predicted inability to do well in medical school classes (54%). At the end of the program, a statistically significant reduction in the barrier of lack of guidance/role models was seen. This study highlights the benefit of mini-medical school programs, especially programs with a mentoring component, to decrease perceived barriers of applying to medical school among URMs and suggests the potential role of similar programs to increase diversity in medicine and to decrease healthcare disparities among minorities in the United States.