Faculty Bibliography

Objectives/UNASSIGNED:Recognizing preoperative characteristics of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is important for clinical management. Therefore, we assessed presurgical NIFTP molecular profiles using fine-needle aspiration (FNA) material. Methods/UNASSIGNED:Presurgical FNA reports of 39 surgically confirmed NIFTP cases from January 2013 through May 2017 were assessed for Afirma and ThyroSeq results. Results/UNASSIGNED:Twenty-one of 39 NIFTP nodules were preoperatively tested with Afirma with two benign and 19 suspicious results. Twenty-seven of 39 nodules were tested with ThyroSeq (nine of 39 had both Afirma and Thyroseq): 18 (67%) had RAS mutations (13 NRAS, four HRAS, one KRAS), and three of 18 had multiple alterations (NRAS + TP53, n = 1; NRAS + PTEN, n = 2). BRAF T599_R603 + EIF1AX mutation (n = 1), PTEN mutation (n = 1), MET overexpression (n = 1), PAX8/PPARG fusion (n = 3), and THADA/IGF2BP3 fusion (n = 3) comprised the remainder. Conclusions/UNASSIGNED:NIFTP cases most commonly displayed suspicious Afirma results and RAS mutations on ThyroSeq, lacking aggressive/BRAF-V600E-like mutations. While NIFTP remains a surgical entity, the lack of aggressive/BRAF-V600E-like mutations can aid in determining the extent of surgery.

OBJECTIVE:Cytomegalovirus (CMV) is a ubiquitous infection typically affecting over 50% of the US population by age 40. We report 8 cases of CMV infections detected in cervical cancer screening tests, the largest series of cases thus far reported in gynecologic cytology specimens. METHODS:A retrospective review of our pathology archival computer database was performed from January 1, 1994 through December 31, 2016 for CMV infections reported in cervical cytology specimens. The slides were retrieved for review if available. RESULTS:The eight patients ranged in age from 21-46 years, with a median age of 27 years and average age of 29.5 years. Two patients were significantly immunocompromised with one patient having AIDS and one patient diagnosed with autoimmune disease. The remaining six patients are considered immunocompetent. Cases were identified most often in the fall and winter months (6 of 8 cases). Seven cases were found using Surepath Pap (SP) liquid-based processing and one case was reported in a classic Papanicolaou smear (CPS). CONCLUSION/CONCLUSIONS:There was no correlation of cytologic presentation of CMV with a distinct cytohormonal pattern or inflammatory constituents. Rare diagnostic cells with changes of CMV infection were seen in 75% of the cases. The presence of CMV did not usually result in adverse patient outcome, except where CMV was one of the multiple opportunistic infections detected in the patient with AIDS.

BACKGROUND: The success of cell block preparation is crucial for ancillary diagnostic tests in cytology. However, achieving an optimal cell block can be challenging. The current study describes a self-clotting-based technique for fine-needle aspiration (FNA) cell block preparations and evaluates its usefulness in comparison with the conventional needle wash technique. METHODS: The clinical data, FNA procedure, and cellularity of cell blocks of the self-clotting group (37 cases) and the conventional needle wash group (33 cases) were compared. The cellularity was evaluated using a scoring system (0 indicated acellular, 1 indicated 1-50 cells, and 2 indicated >50 cells). RESULTS: Approximately 76% of cases in the self-clotting group received a score of 2 versus 36% in the conventional needle wash group. Approximately 14% received a score of 1 in the self-clotting group compared with 9% in the conventional needle wash group, whereas 11% in the self-clotting group received a score of 0 versus 55% in the conventional needle wash group. The differences between the 2 methods were statistically significant. CONCLUSIONS: The results of the current study demonstrate that the self-clotting method is superior to the conventional needle wash method for FNA samples. Cancer Cytopathol 2017. (c) 2017 American Cancer Society.

Background: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), formerly a malignant diagnosis and variant of PTC, has recently been reclassified to NIFTP on surgical pathology. Because of the indolent nature and potentially conservative treatment of NIFTP, it is crucial to identify features early on during patient evaluation which may suggest the possibility of this entity. One such feature is the molecular profile of thyroid nodules determined preoperatively utilizing fine-needle aspiration (FNA) cellular material. Design: Pre-surgical FNA Cytopathology reports of 41 confirmed cases of NIFTP from 1/2013-8/2016 were assessed for molecular testing (Afirma and/or ThyroSeq) results. Results: Bethesda System cytology diagnoses were: Benign (n=1), Atypia of Undetermined Significance (n=24), Follicular Neoplasm (n=14), and Suspicious for Malignancy (n=2). Of the 41 NIFTP cases, 22 nodules were pre-operatively tested with Afirma: 2 were benign; 20 were suspicious. 12 cases were Afirma MTC negative; 4 were BRAF negative. 27 nodules were pre-operatively tested with ThyroSeq: 2 had insufficient material; 15 cases (55.6%) had RAS mutations (11 NRAS, 4 HRAS); 3 of the 15 had two mutations [NRAS and TP53 (n=1); NRAS and PTEN (n=2)]. One additional case with 2 mutations showed BRAF T599-R603 and EIF1AX mutations (n=1). Other isolated molecular changes included PTEN mutation (n=1), MET overexpression (n=1), PAX8/PPARG fusion (n=4), and THADA/IGF2BP3 fusion (n=3). Conclusions: While NIFTP remains a surgical entity, the molecular profile of thyroid nodules can be analyzed pre-operatively in order to determine appropriate treatment. Our findings demonstrate that NIFTP cases most commonly displayed Suspicious Afirma results and RAS mutations on ThyroSeq, and several molecular alterations not characteristic of classical PTC or poorly differentiated/anaplastic thyroid carcinomas. The molecular profile of thyroid nodules must be considered together with the patients' clinical, sonographic and cytologic results in order to raise the possibility of NIFTP early on in determining proper management

BACKGROUND: The noninvasive encapsulated follicular variant of papillary carcinoma (nEFVPTC) has recently been reclassified to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," removing this entity from the malignant category. This re-categorization has had major implications for clinical management. NIFTP has overlapping cytohistologic features with papillary thyroid carcinoma (PTC) and with follicular adenomas (FA), but sonographic data comparing NIFTP to PTC and FA is lacking. Our study examines the sonographic features of NIFTP as compared with PTC and FA. METHODS: Ultrasound scans and Doppler blood flow from subjects who had pre-surgical sonograms and fine needle aspiration biopsies with final surgical pathology diagnoses of NIFTP/nEFVPTC, classical PTC, and FA between 01/2013-08/2016 were assessed. Sonographic and Doppler features as well as Bethesda System (TBS) diagnoses were recorded and analyzed. RESULTS: 40 NIFTP, 58 classical PTC, and 23 FA cases were included. The most common NIFTP pre-surgical TBS cytology diagnosis was Atypia of Undetermined Significance (AUS/FLUS) (40%). NIFTP cases predominantly displayed wider-than-tall shape (100%), smooth borders (75%), occurrence in multinodular glands (82.5%), heterogeneous echogenicity (50%), both perinodular and intranodular Doppler flow patterns (70%), minimal Doppler flow grade (62.5%), and no calcifications (90%). CONCLUSIONS: Our study demonstrates that NIFTP, PTC, and FA display several distinguishing and overlapping sonographic and Doppler features. Sonographic features appear to complement cytology findings and may help raise pre-operative concern for NIFTP in the proper clinical setting, potentially leading to a more conservative management approach.

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.