The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA.

The Hematopathology Molecular Genetics subcommittee presents recommendations for molecular diagnostic testing in acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndrome, and lymphomas and for the development of an interfacility consultation service.

FIGO Stage III Metastatic Gestational Choriocarcinoma Developed From an Antecedent Partial Hydatidiform Molar Pregnancy Bearing a Numerical Chromosomal Aberration 68, XX: A Case Report and Literature Review.

A 36-yr-old, gravida 5 para 4 woman presented with uterine bleeding and was discovered to have a 3.7-cm uterine mass with multiple, bilateral, lung metastases. Six months earlier, the patient was diagnosed with a partial hydatidiform mole that demonstrated a rare chromosomal karyotype 68, XX[12]. The patient's serum ß-human chorionic gonadotropin was elevated from baseline to 12,039 mIU/mL before the treatment. A total hysterectomy was performed and revealed a markedly hemorrhagic, extensively necrotic choriocarcinoma. The tumor mass invaded to a depth of 1/3 of the uterine wall thickness. Cytogenetic analysis of the choriocarcinoma revealed the same 68, XX karyotype, as observed in the antecedent partial hydatidiform mole. A clinical diagnosis of advanced stage invasive choriocarcinoma was rendered, with a risk factor score of 5. Following the development of chemoresistance to a single-agent (methotrexate) regimen, the patient subsequently received 5 cycles of chemotherapy (EMA-CO), without any major complication. She is currently >5 yr posttreatment and is asymptomatic. Her most recent imaging studies, including scans of chest and brain, show no evidence of disease, and her serum ß-human chorionic gonadotropin level has remained consistently below detectable levels.

Collagenous fibroma (desmoplastic fibroblastoma) with a new translocation involving 11q12: a case report.

Collagenous fibroma (or desmoplastic fibroblastoma) is a rare, benign tumor usually centered in the subcutaneous tissue composed of spindle-shaped to stellate fibroblasts and myofibroblasts in a densely collagenous background. Three previous case reports have described a t(2;11)(q31;q12) in this entity. Herein, we report a case of collagenous fibroma of deep soft tissue with t(11;17)(q12;p11.2). The breakpoint at chromosome 11q12 appears to be pathogenetic in this rare neoplasm.

On the intraoperative molecular status of renal allografts after vascular reperfusion and clinical outcomes.

Many hypothesize that subtle inflammation and immune activity detected in the intraoperative period are linked to adverse postkidney transplant clinical outcomes. To this end, renal allografts were analyzed for expression of pro-inflammatory, inflammation-induced adhesion molecules, immune activation as well as anti-apoptotic genes expressed 15 min after vascular reperfusion (zero-hour) to determine whether this analysis can aid in predicting the occurrence of delayed graft function (DGF), acute rejection (AR), and the quality of graft function at 6 mo. Intraoperative biopsies were obtained from 75 consecutively performed renal allografts in which consent was obtained 15 min after vascular reperfusion. These biopsies were analyzed by quantitative real-time PCR for transcription of 15 select genes and by standard histopathology. Posttransplant clinical outcomes were also analyzed in respect to intraoperative transcriptional profiles and clinical parameters available at the time of transplantation. This study demonstrates that a limited and hypothesis-driven PCR-based transcriptional profile of the zero-hour kidney biopsy predicts posttransplant clinical outcomes including DGF, early AR, and the quality of renal function 6 mo posttransplantation. For some clinical endpoints, the combined use of molecular analysis and established clinical indicators available at the time of transplantation further enhances the quality of prognosis. The transcriptional profiling data provide absolutely essential data to the predictive models, particularly with respect to AR and renal function 6 mo posttransplantation.

Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection.

BACKGROUND: Long-term survival of a graft requires inhibition of host immune effectors, but protective responses emanating from the graft might be equally important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), and Bcl-xL in rodent allo and xenografts correlates with long-term survival. Little is known of the pattern of expression of such protective genes and the implication thereof in clinical transplantation. METHODS: We analyzed, by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, expression of A20, HO-1, and Bcl-xL in 31 renal allograft biopsies from patients with suspected rejection. RESULTS: A20 is not expressed in nonrejecting (NR) grafts. Its expression is increased in grafts undergoing acute and chronic rejection (AR and CR) but is weaker in CR. HO-1 is not expressed in NR grafts; it is up-regulated in AR but not CR. Bcl-xL is detected in all biopsies with decreased levels in CR. Expression of A20, HO-1, and Bcl-xL localizes mainly to endothelial, smooth muscle, and infiltrating mononuclear cells. CONCLUSIONS: This data demonstrate that A20 and HO-1 are up-regulated in response to immune injury inferred by AR. Given the antiapoptotic and antiinflammatory functions of these genes, we hypothesize that their expression survives to limit graft injury by maintaining cell viability and controlling inflammation. Their reduced expression in CR as compared with AR represents either inadequate response to injury or a sequelae of prior injury that jeopardizes further tissue response to immune attack.

Immunobiology and privilege of neuronal retina and pigment epithelium transplants.

Despite the existence of ocular immune privilege, immune rejection may be a barrier to successful retinal transplantation. We have examined in mice the extent to which the subretinal space (SRS) is an immune privileged site, and whether retinal pigment epithelium and neuronal retinal tissue have properties of immune privileged tissues. We report that (1) The SRS is an immune privileged site; (2) Neonatal RPE is an immune privileged tissue; (3) Neuronal retina is a partially immune privileged tissue; and (4) Microglia within neonatal neural retina grafts promote photoreceptor differentiation, become activated, and induce sensitization of the recipient and serve as targets of immune rejection.