Anna P. Matynia

Impact of rapid on-site evaluation on the adequacy of endoscopic-ultrasound guided fine-needle aspiration of solid pancreatic lesions: A systematic review and meta-analysis

Rapid on‐site evaluation (ROSE) has the potential to improve adequacy rates for endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) of solid pancreatic lesions, but its impact is context‐dependent. No studies exist that summarize the relationship between ROSE, number of needle passes, and resulting adequacy rates.

Molecular genetic biomarkers in myeloid malignancies.

CONTEXT Recent studies using massively parallel sequencing technologies, so-called next-generation sequencing, have uncovered numerous recurrent, single-gene variants or mutations across the spectrum of myeloid malignancies. OBJECTIVES To review the recent advances in the understanding of the molecular basis of myeloid neoplasms, including their significance for diagnostic and prognostic purposes and the possible implications for the development of novel therapeutic strategies. DATA SOURCES Literature review. CONCLUSIONS The recurrent mutations found in myeloid malignancies fall into distinct functional categories. These include (1) cell signaling factors, (2) transcription factors, (3) regulators of the cell cycle, (4) regulators of DNA methylation, (5) regulators of histone modification, (6) RNA-splicing factors, and (7) components of the cohesin complex. As the clinical significance of these mutations and mutation combinations is established, testing for their presence is likely to become a routine part of the diagnostic workup. This review will attempt to establish a framework for understanding these mutations in the context of myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia.

A novel approach to quantitating leukemia fusion transcripts by qRT-PCR without the need for standard curves.

Acute myeloid leukemia patients with recurrent cytogenetic abnormalities including inv(16);CBFB-MYH11 and t(15;17);PML-RARA may be assessed by monitoring the levels of the corresponding abnormal fusion transcripts by quantitative reverse transcription-PCR (qRT-PCR). Such testing is important for evaluating the response to therapy and for the detection of early relapse. Existing qRT-PCR methods are well established and in widespread use in clinical laboratories but they are laborious and require the generation of standard curves. Here, we describe a new method to quantitate fusion transcripts in acute myeloid leukemia by qRT-PCR without the need for standard curves. Our approach uses a plasmid calibrator containing both a fusion transcript sequence and a reference gene sequence, representing a perfect normalized copy number (fusion transcript copy number/reference gene transcript copy number; NCN) of 1.0. The NCN of patient specimens can be calculated relative to that of the single plasmid calibrator using experimentally derived PCR efficiency values. We compared the data obtained using the plasmid calibrator method to commercially available assays using standard curves and found that the results obtained by both methods are comparable over a broad range of values with similar sensitivities. Our method has the advantage of simplicity and is therefore lower in cost and may be less subject to errors that may be introduced during the generation of standard curves.

Lymphomatoid Granulomatosis in a 14-Year-Old Boy with Trisomy 21 and History of B-Lymphoblastic Leukemia/Lymphoma

ABSTRACT Background: Lymphomatoid granulomatosis is a EBV-driven lymphoproliferative disorder that has been reported in association with immunodeficiency, but only exceptionally in patients with hematopoietic malignancy. Case report: A 14-year-old boy with trisomy-21 and a history of B-lymphoblastic leukemia/lymphoma (B-ALL) diagnosed 1.5 years prior, on maintenance chemotherapy, presented with fever and respiratory symptoms. Chest X-ray revealed right-lower-lobe consolidation. He was treated for pneumonia but continued to be febrile with worsening respiratory status, with development of additional pulmonary and liver nodules. No infectious etiology was identified. Following nondiagnostic lung and liver biopsies, the largest pulmonary mass was resected. The histopathologic findings were diagnostic of lymphomatoid granulomatosis. There was no residual B-ALL. The patients status continued to deteriorate and he died shortly thereafter. Conclusion: Relative immunosuppression due to maintenance therapy for B-ALL can lead to lymphomatoid granulomatosis.