BCR-ABL PCR testing in chronic myelogenous leukemia: molecular diagnosis for targeted cancer therapy and monitoring.

The use of tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) represents the paradigm for modern targeted cancer therapy. Importantly, molecular monitoring using BCR-ABL real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) for assessing treatment efficacy and quantitating minimal residual disease is a major determinate of practical therapeutic decision-making in the long-term management of this now chronic disease. Herein, we present an overview of CML and the use of TKIs for targeted CML therapy, with an emphasis on the role, application and future aspects of PCR-based molecular monitoring.

Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations.

BACKGROUND: Although thyroid fine-needle aspiration (TFNA) is an excellent test in evaluating thyroid nodules, there are occasionally false negatives (FN). The clinical impact and pathologic features of FN TFNA is understudied in the peer-reviewed literature. METHODS: A cohort of patients with thyroid cancer was separated into those with referring FN TFNA and those with referring true positive (TP) TFNA. Preoperative characteristics, pathologic finding, and clinical outcomes were compared within the 2 groups. RESULTS: A total of 192 patients with TP TFNA (n = 162) and FN TFNA (n = 30) were included in the study. There were no significant differences in the demographics or length of follow-up of the 2 groups. The FN TFNA group was more likely to have a larger clinical nodule size and experienced a significant delay from initial TFNA to surgery. The FN TFNA group was more likely to be diagnosed with the follicular variant of papillary thyroid cancer (73.3% vs 25.9%, P < .001), less likely to have positive lymph nodes at surgery (6.7% vs 35.8%, P = .001), and more likely to undergo 2-step surgery (30% vs 9.9%, P = .007). Despite the delay in diagnosis, persistent/recurrent or metastatic disease, incidence of aggressive histologic variants, and pT4 disease was not different in the 2 groups. CONCLUSIONS: The clinical impact of FN TFNA at our high-volume center is minimal. Cancers in this setting are low grade, and outcomes are not adversely affected despite the delay in diagnosis.

Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis.

OBJECTIVE: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection. STUDY DESIGN: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant. RESULTS: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01). CONCLUSIONS: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis.

Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone.

BACKGROUND: ThinPrep (TP) liquid-based preparations are increasingly being used in nongynecologic specimens. Few studies have evaluated TP as a sole diagnostic modality in the setting of thyroid fine-needle aspiration (T-FNA). Herein, the authors evaluate the usefulness of TP as a sole diagnostic modality in a nonsplit sample. METHODS: Consecutive T-FNAs were identified at 2 tertiary care institutions; 1 institution processed thyroid FNA entirely with TP, and the other used a combination of TP and conventional preparations (CP). Cytodiagnoses, surgical pathology, and/or clinical follow-up were recorded. Performance parameters for the 2 settings were compared. RESULTS: A cytologic diagnosis of positive for malignancy was correct in 98.8% of TP + CP cases and in 100% of TP cases. Papillary thyroid carcinoma cases were definitively diagnosed in 53.1% of T-FNAs prepared by TP + CP compared with 34.4% of T-FNAs prepared with TP alone (P = .0015 by Fisher 2-tailed exact test). Of patients ultimately diagnosed with papillary thyroid carcinoma, 89% were initially treated by total thyroidectomy in the TP + CP group compared with 79.5% in the TP-only group (P = .027 by Fisher exact test). CONCLUSIONS: TP as a sole preparatory technique does not improve the usefulness of T-FNA as a screening test. However, combining CP and TP increases the rate of definitive cytologic diagnosis of malignancy in papillary thyroid carcinoma. Thus, combining TP and CP enhances the diagnostic component of T-FNA.