Incidental Diagnosis of Parathyroid Lesions by Preoperative Use of Next-Generation Molecular Testing.

BACKGROUND: Parathyroid glands can mimic thyroid follicular lesions on fine-needle aspiration (FNA) cytology and can lead to unnecessary or incorrect surgery. Newer molecular panel tests using next-generation sequencing (NGS) include analysis of cell type-specific gene expression profiles such as parathyroid. The study aim is to determine the frequency and clinical implications of parathyroid tissue identification by molecular testing in cytologically indeterminate "thyroid" lesions. METHODS: Molecular analysis of indeterminate thyroid FNA specimens is obtained routinely and relies on amplification-based NGS inclusive of PTH-specific expression profiles. For this study, we retrospectively examined the clinical data and management of patients with molecular results positive for PTH expression from May 2014 until May 2016. RESULTS: Among 4765 consecutive patients with indeterminate cytology for a presumed thyroid nodule, NGS instead indicated a parathyroid lesion in 20 patients (0.42%). The clinical data of 15 patients were available, and the subsequent clinical management was altered in 93% (14/15 patients), including five (33%) eucalcemic patients who could avoid unnecessary surgery. Primary hyperparathyroidism was not suspected in seven patients until the molecular analysis results, and primary hyperparathyroidism was diagnosed in one (14%). During parathyroid exploration, most patients (6/8, 75%) required concurrent thyroidectomy or lobectomy, but thyroid preservation was still possible in two patients. A parathyroid gland was histologically confirmed in 89%. CONCLUSIONS: In 0.42% of patients with indeterminate cytology results, next-generation molecular results will indicate the presence of a parathyroid lesion. When this occurs, it is accurate and can robustly impact clinical management (93%).

Changes in Resident Graduate Characteristics in a Large Pathology Training Program, 1994 to 2013.

The field of pathology has changed dramatically over the recent decades and has become more complex with emphasis toward subspecialization. These changes potentially influence resident training as programs and trainees search for cutting-edge skills in the evolving field. Over the last 20 years, our institution's residency education was modified profoundly to emphasize subspecialty practice. Furthermore, efforts were made to search for and recruit candidates who desired such training. In this study, we examined a 20-year time period to determine how these changes may have influenced the characteristics of our resident graduates. For each trainee who graduated from our pathology residency program (1994-2013), the following parameters were evaluated: highest academic degree, gender, graduating medical school, type of training, number of publications during residency, enrollment in fellowships, and type of career position. The data collected were divided into 4 time periods. Fisher exact test and 2-tailed t test were used for statistical analyses comparing the first half (1994-2003) to the latter half (2004-2013) of the study. In the second half, there were more graduates who pursued single track pathology training-anatomic pathology or clinical pathology versus combined anatomic/clinical pathology training (P = .035), more first author and total publications per graduate during residency (P < .001), more graduates who enrolled in fellowships (P < .001), and a greater tendency toward an academic career position than all other types combined (P = .034). In parallel to the subspecialization trends in our department, we witnessed changes in the characteristics of our resident graduates whose interests and career choices have become more focused.

Cerebrospinal Fluid Cytology of Lyme Neuroborreliosis: A Report of 3 Cases with Literature Review.

Lyme disease can affect the central nervous system causing a B-cell-predominant lymphocytic pleocytosis. Since most reactions to infection in the cerebrospinal fluid (CSF) are typically T-cell predominant, a B-cell-predominant lymphocytosis raises concern for lymphoma. We present 3 Lyme neuroborreliosis cases in order to illustrate the challenging cytomorphological and immunophenotypic features of their CSF specimens. Three male patients who presented with central nervous system manifestations were diagnosed with Lyme disease. The clinical presentation, laboratory tests, CSF cytological examination and flow-cytometric studies were described for each case. CSF cytology showed lymphocytic pleocytosis with increased plasmacytoid cells and/or plasma cells. Flow cytometry showed the presence of polytypic B lymphocytes with evidence of plasmacytic differentiation in 2 cases. In all cases, Lyme disease was confirmed by the Lyme screening test and Western blotting. In such cases of Lyme neuroborreliosis, flow cytometry of CSF samples employing plasmacytic markers and cytoplasmic light-chain analysis is diagnostically helpful to exclude lymphoma.

Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics.

BACKGROUND: Mutations in the RAS gene in the thyroid gland result in the activation of signaling pathways and are associated with a follicular growth pattern and the probability of a carcinoma outcome ranging from 74% to 87%. In the current study, the authors investigated the cytopathologic and histopathologic features of common RAS mutation subtypes. METHODS: Malignant, indeterminate, and selected benign thyroid cytology cases were tested prospectively for the presence of NRAS61, HRAS61, and KRAS12/13 mutations. For each case, the Bethesda System for thyroid cytopathology diagnosis, additional cytologic descriptors, and surgical pathology outcomes were documented. The Fisher exact test and Wilcoxon 2-sample test were used for statistical comparison between the groups. RESULTS: A total of 204 thyroid fine-needle aspiration cases with RAS mutations (93.6% of which were associated with indeterminate cytopathology diagnoses) and corresponding surgical pathology resection specimens were identified. The KRAS12/13 mutation was associated with a significantly lower carcinoma outcome (41.7%) when compared with HRAS61 (95.5%) and NRAS61 (86.8%) mutations (P<.0001). Furthermore, oncocytic change was observed in a significantly higher percentage of cytology and resection specimens with KRAS12/13 mutations (66.7% and 75.0%, respectively) in comparison with those with HRAS61 (4.5% and 4.5%, respectively) and NRAS61 (15.4% and 14.7%, respectively) mutations (P<.0001). RAS mutations also were identified in cases of poorly differentiated carcinoma (NRAS61), anaplastic carcinoma (HRAS61), and medullary thyroid carcinoma (HRAS61 and KRAS12/13). CONCLUSIONS: Subclassification of RAS mutations in conjunction with cytopathologic evaluation improves presurgical risk stratification, provides better insight into lesional characteristics, and may influence patient management. In particular, KRAS12/13-mutated thyroid nodules were found to be different from HRAS61-mutated and NRAS61-mutated nodules with regard to cytopathologic and surgical outcome characteristics.

Tumor-to-tumor metastasis (TTM) of breast carcinoma within a solitary renal angiomyolipoma: a case report.

Angiomyolipomas of the kidney have been known to harbor malignant neoplasms including renal cell carcinoma. We report a case of a tumor-to-tumor metastasis (TTM) involving metastatic breast carcinoma and angiomyolipoma. The patient was a 67-year-old female with a history of invasive ductal carcinoma of the breast. Follow-up positron emission tomography 9 years later revealed a left renal mass, suspicious for a primary renal neoplasm, as well as a suspicious subpectoral lymph node. An ultrasound-guided needle biopsy of the lymph node demonstrated metastatic breast carcinoma. The patient underwent a left radical nephrectomy. Pathologic examination demonstrated an ill-defined 2cm estrogen receptor (ER)-positive metastatic breast carcinoma within a 6cm angiomyolipoma. To our knowledge, this is the first reported case of metastatic breast carcinoma to a solitary renal angiomyolipoma. This case highlights the importance of a patient's prior history of malignancy, as well as appropriate sampling of renal neoplasms.