Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms.

In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.

An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: a case report.

BACKGROUND: Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported. CASE PRESENTATION: We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock. CONCLUSION: Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality.

Cytodiagnosis of primary lymphoma of bone on fine-needle aspiration cytology specimens: review of 25 cases.

Diagnosis of nodal lymphomas on fine-needle aspiration (FNA) cytologic specimens has been well established. However, cytodiagnosis of primary lymphoma of bone has not been well documented because of its rarity. We undertook a retrospective study of 25 cases of FNA cytologic specimens of primary lymphoma of bone. The slides were available for review in 20 cases; each case was evaluated with 15 cytologic features in conjunction with immunophenotyping and available surgical materials. Three diagnostic categories were assigned, including nondiagnostic (4/16%), suspicious (3/12%), and malignant (18/72%). Among the 18 malignant lymphoma, all were diagnosed on the basis of cytologic materials together with immunocytochemistry, except that two cases also relied on the cell blocks. The nondiagnostic and suspicious cases were subsequently confirmed to be malignant lymphoma on the surgical core biopsies. Of the 25 cases, 23 cases were large B-cell lymphoma, one follicular lymphoma large cell type, and one small lymphocytic lymphoma. False-positive or false-negative cases were not present in this study series. In conclusion, the vast majority of primary lymphoma of bone can be accurately diagnosed and classified on FNA cytologic specimens in conjunction with immunocytochemistry. The nondiagnostic and suspicious categories can be further reduced or eliminated by improving FNA techniques or by recommendation of surgical core biopsies together with other techniques such as flow cytometry and molecular analysis.