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: 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 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.

Objectives/UNASSIGNED:Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (NEFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Excluding "carcinoma" from the new terminology shifted NIFTP out of the malignant category and altered Bethesda System for Reporting Thyroid Cytopathology (BSRTC) rates of malignancy (ROMs) on thyroid fine-needle aspiration (FNA). Because of potential effects on management guidelines, we examined our ROM data. Methods/UNASSIGNED:In total, 750 thyroid FNAs with surgical resections from January 2013 to June 2016 were reviewed (including 87 NIFTPs). ROM was recorded for each BSRTC category: classifying NEFVPTC/NIFTP as "malignant" and reclassifying NEFVPTC/NIFTP as "nonmalignant." Results/UNASSIGNED:ROM changes were as follows: nondiagnostic (ND), no change; benign, 5.5% to 2.5%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 42.3% to 22.3%; follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 48.7% to 17.9%; suspicious for malignancy (SFM), 93.6% to 61.7%; and positive for malignancy, 100% to 97%. Conclusions/UNASSIGNED:Decreased ROM was seen in most BSRTC categories, most significantly in AUS/FLUS, FN/SFN, and SFM categories.

Introduction: Because of the indolent nature and potentially conservative treatment of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)- an entity recently removed from the malignant papillary thyroid carcinoma (PTC) category, it is crucial to identify features of this entity pre-operatively. Our group has recently published our findings that several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC and follicular adenoma (FA) on fine-needle aspiration (FNA). Therefore, we set out to determine the reproducibility of these results. Materials and Methods: Pre-surgical FNA slides from NIFTP (n=30), classical PTC (n=30) and FA (n=30) collected from 1/2013-8/2016 were reviewed by 7 cytopathologists blind and independently. Presence of cytomorphologic features was recorded and compared to determine concordance amongst cytopathologists. For each feature, the concordance was compared between NIFTP, PTC and FA by Fisher's Exact Test. Utilizing the majority consensus for presence or absence of each cytomorphologic feature, differences amongst NIFTP, PTC and FA presurgical FNAs were assessed for each feature by Fisher's Exact Test. Results: For all the cytomorphologic features, the concordance rates amongst the pathologists ranged between 78 to 93%. The concordance rates were similar between the NIFTP, PTC and FA groups (Table 1). Comparing each cytomorphologic feature (present/absent determined by majority consensus) amongst the NIFTP, PTC and FA groups displayed statistically significant differences for all features (Table 2). Conclusions: The current study supports our previous findings that there are cytomorphologic differences between the three surgical pathology groups-NIFTP, PTC and FA, and shows that these results are reproducible. The presence or absence of each feature viewed in combination as a profile may assist the cytopathologist in raising the possibility of NIFTP pre-operatively, potentially aiding clinicians in deciding whether a more conservative treatment plan is appropriate. (Table Presented)

Introduction: The success of cell block preparation is crucial for ancillary diagnostic tests in cytology. However, achieving an optimal cell block can be challenging. We observed that cell block cellularity is best in cases with visible blood clots in the fine-needle aspiration (FNA) needle wash solution. Therefore, we hypothesized that the adequacy of cell block preparation will improve if FNA aspirates are allowed to first form a clot in the collection tube. Materials and Methods: We created a modified cell block preparation technique allowing FNA samples to clot in a dry tube prior to addition of any liquid media or further cell block preparation (Figure 1). The clinical data, FNA procedure and the cellularity of cell blocks of the clotting group (37 cases) and the conventional needle wash group (33 cases) were compared. Cellularity was evaluated using a scoring system (0 = acellular, 1Z 10 - 50 cells, 2 = > 50 cells). Results: 28 cases (78%) received a score of 2 in the clotting group compared to 12 (36%) in the conventional needle wash group. 5 (15%) received a score of 1 in the clotting group compared to 3 (9%) in the conventional group; 4 received a score of 0 (11%) in the clotting group versus 18 (55%) in the conventional group. The difference in cell block cellularity between the two methods was statistically significant (p < 0.001) (Figure Presented) (Table 1). Immunohistochemistry (15 cases) and molecular analyses (2 cases) was performed in the clotting group compared to 10 and 1 case, respectively in the conventional group. Conclusions: Our study demonstrates that clotting method is superior to the conventional needle wash method. The clotting method avoids diluting FNA samples in liquid media and maximizes the collection of cellular material by holding the aspirate tightly in a blood clot

Introduction: Minimally invasive tissue sampling for acquisition of diagnostic material and ancillary testing can be accomplished by fineneedle aspiration (FNA) and/or core needle biopsy (CNB). FNAs afford the capability of rapid on-site evaluation (ROSE) with confirmation of proper needle placement during a procedure. Traditionally, our interventional radiology (IR) group has performed FNAs first to ensure proper needle placement in targeted lesions followed by CNBs. With the number of FNAs increasing significantly each year, we sought to change IR practice- from performing dual FNA-CNB procedures to performance of CNBs without a preceding FNA- as a quality improvement initiative. Our aims were twofold: 1. Better allotment of cytotechnologists' resources dedicated instead to FNA-only ROSE endoscopic ultrasound(US)-guided gastrointestinal FNAs, FNA-CNB pulmonary cases, and US-guided thyroid FNAs; and 2. Increasing cost savings by reducing redundancy of duplicate procedures and workups. We sought to compare this practice change to the original practice to ensure maintenance of good sensitivity of IR procedures. Materials and Methods: Dual sampling utilizing FNA-CNB was only applied to pulmonary cases to ensure adequate material for molecular studies. Other lesions underwent CNB-alone. Quality assurance data for FNA-CNB versus CNB-alone from 09/2016-02/2017 was tabulated and sensitivities were calculated. Results: Beginning 09/2016, the number of CNBs alone increased secondary to the quality initiative (Figure 1). Six months after the start of the initiative the overall sensitivity of CNB alone was 96% versus 98% for CNB-FNA (Table 1.) Conclusions: Both FNA and CNB are excellent modalities to collect lesional tissue for analysis. Our preliminary quality improvement analysis has demonstrated comparable sensitivities in diagnosis utilizing CNB-alone versus FNA-CNB. These findings support continued utilization of CNBalone by IR. In this way cytopathology time and resources can be better utilized in other areas and for FNAs of other lesions. (Figure Presented)