Educational Case: Developmental Neck Masses and Other Neck Tumors.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Frequency and extent of cytokeratin expression in paraganglioma: an immunohistochemical study of 60 cases from 5 anatomic sites and review of the literature.

The absence of cytokeratin expression in paraganglioma helps to differentiate it from other neuroendocrine neoplasms such as carcinoid tumor. Although rare cytokeratin positive paragangliomas have been reported, there are no large systematic studies of this phenomenon. The aim of this study was to determine the frequency and extent of cytokeratin expression in paragangliomas using a large cohort of cases from multiple anatomic sites. Immunohistochemical staining for keratin AE1/AE3 (mouse monoclonal, MAB3412; Millipore) and CAM 5.2 (mouse monoclonal, 349 205; Becton-Dickinson) was performed on whole-tissue sections from 60 resected paragangliomas from the head and neck (36), thorax (10), abdomen (8), intradural/epidural spine (5) and bone, left iliac (1). Cytokeratin expression was identified in only 2/60 (3.3%) cases. One was a mediastinal paraganglioma with moderate to strong expression of keratin AE1/AE3 and CAM 5.2 in <5% tumor cells. The other was a lumbar intradural paraganglioma positive for CAM 5.2 (moderate to strong, 80% of tumor cells) but negative for keratin AE1/AE3. All other paragangliomas (58/60, 96.7%) were negative for keratin AE1/AE3 and CAM 5.2. This study - the largest series of cytokeratin-stained whole-tissue sections of paragangliomas to date - supports the dictum that most paragangliomas are cytokeratin negative. Rare exceptions may be site-related.

Role of ThinPrep liquid-based cytology in evaluation of the endocervical canal in patients with abnormal cervical screening.

INTRODUCTION: Endocervical sampling is frequently used as an adjunct to colposcopy. Few studies address the role of endocervical brushing (ECB) with liquid-based cytology (LBC) for evaluation of the endocervical canal. We assessed the roles of ThinPrep (TP) LBC of ECB specimens and cell blocks (CBs). MATERIALS AND METHODS: Pathology archives were searched for ECB specimens from 2010-2015. Preceding Papanicolaou test interpretation, human papillomavirus status, concurrent and follow-up surgical specimens, and ECB diagnoses were recorded. CB cellularity, when available, was scored on a scale of 0 to 4. The cellularity of the TP and CBs was compared. RESULTS: Of 365 ECB cases, 6 (1.6%) were insufficient for diagnosis, compared with a 5% rate for endocervical curettings. Eleven ECB cases (3%) showed low cellularity. Of the 241 (66%) cases with concurrent biopsies, the ECB diagnosis agreed with the biopsy diagnosis (within 1 grade) in 198 (82%) cases. In 9 (2.5%) cases, ECB was the only means of diagnosis of a high-grade squamous intraepithelial lesion / adenocarcinoma in situ confirmed on follow-up. Compared with TP LBC, the CBs (performed in 84 [23%] of cases) were of greater cellularity in 30 (42%) and of equal cellularity in 17 (24%). None of the CBs showed an additional epithelial abnormality missed in TP LBC. CONCLUSIONS: TP LBC is capable of detecting endocervical epithelial abnormalities and may be used as a substitute for endocervical curettings. Performing a CB did not lead to detection of additional abnormalities, although it complemented TP findings and facilitates the performance of ancillary studies.

Cytologic findings of an adult rhabdomyoma in the parapharyngeal space: A report of a case and review of the literature.

Adult extracardiac rhabdomyomas are rare benign mesenchymal tumor arising from skeletal muscle. While they are often located in the larynx and pharynx, the incidence in the parapharyngeal area is extremely rare with only 1 documented cytology case report to date. We report a case of an adult extracardiac rhabdomyoma in the parapharyngeal space diagnosed cytologically with subsequent histologic confirmation. The patient is a 57-year-old man with history of weight loss, hematuria, dysphagia, and airway encroachment. Computerized tomography of his abdomen showed a large left renal mass. While the patient was in the operating room for the resection of his renal mass, a fine-needle aspiration from left the parapharyngeal mass was performed. The smears showed uniform bland polygonal cells with abundant eosinophilic cytoplasm and peripherally located nuclei. Immunohistochemical stains performed on the cell block showed the tumor cells were desmin positive and negative for S-100 and PAX-8, supporting the diagnosis of an adult rhabdomyoma. Subsequent resection of the mass confirmed the diagnosis of an adult extracardiac rhabdomyoma.

Highly synergistic effect of sequential treatment with epigenetic and anticancer drugs to overcome drug resistance in breast cancer cells is mediated via activation of p21 gene expression leading to G2/M cycle arrest.

Epigenetic alterations such as aberrant DNA methylation and histone modifications contribute substantially to both the cause and maintenance of drug resistance. These epigenetic changes lead to silencing of tumor suppressor genes involved in key DNA damage-response pathways, making drug-resistant cancer cells nonresponsive to conventional anticancer drug therapies. Our hypothesis is that treating drug-resistant cells with epigenetic drugs could restore the sensitivity to anticancer drugs by reactivating previously silenced genes. To test our hypothesis, we used drug-resistant breast cancer cells (MCF-7/ADR) and two epigenetic drugs that act via different mechanisms--5-aza-2'-deoxycytidine (decitabine, DAC), a demethylating agent, and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor--in combination with doxorubicin. We show that the sequential treatment of resistant cells, first with an epigenetic drug (DAC), and then with doxorubicin, induces a highly synergistic effect, thus reducing the IC(50) of doxorubicin by several thousand fold. The sequential treatment caused over 90% resistant cells to undergo G2/M cell cycle arrest, determined to be due to upregulation of p21(WAF1/CIP1) expression, which is responsible for cell-cycle regulation. The induction of p21(WAF1/CIP1) correlated well with the depletion of DNA methyltransferase1 (DNMT1), an enzyme that promotes methylation of DNA, suggesting that the p21(WAF1/CIP1) gene may have been methylated and hence is inactive in MCF-7/ADR cells. Microarray analysis shows expression of several tumor suppressor genes and downregulation of tumor promoter genes, particularly in sequentially treated resistant cells. Sequential treatment was found to be significantly more effective than simultaneous treatment, and DAC was more effective than SAHA in overcoming doxorubicin resistance. Synergistic effect with sequential treatment was also seen in drug-sensitive breast cancer cells, but the effect was significantly more pronounced in resistant cells. In conclusion, the sequential treatment of an epigenetic drug in combination with doxorubicin induces a highly synergistic effect that overcomes doxorubicin resistance in breast cancer cells.