Faculty Bibliography

Objectives: With the removal of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) from the follicular variant of papillary thyroid carcinoma (FVPTC) categorization, the question arises as to how the molecular profile of invasive encapsulated FVPTC (IEFVPTC) compares with NIFTP. Our study aimed to examine the molecular alterations associated with NIFTP, IEFVPTC, and infiltrative FVPTC (iFVPTC) to determine whether these entities are actually distinct at the molecular level.
Method(s): Forty-five NIFTP cases, 12 IEFVPTC cases, and 8 iFVPTC cases from 1/2013 to 8/2016 were assessed for presurgical fine-needle aspiration ThyroSeq V2 nextgeneration sequencing results.
Result(s): The NIFTP cases displayed alterations in BRAF K601E/EIF1AX, BRAF T599-R603, NRAS x15 (two with additional PTEN and one with P53), KRAS x3, HRAS x11 (one with an additional TERT/ EIF1AX), PAX8-PPARgamma x5, PTEN, THADA x3, MET x2, copy number alteration, EF1AX, and DICER1. The IEFVPTC displayed alterations in RAS x5 (1 NRAS/TERT, 2 HRAS, 2 NRAS), BRAF-K601E x2, and BRAF-pG469A with gene expression profile; PAX8-PPARgamma x2; THADA-IGF2BP3; and ETV6/ NTRK3. The iFVPTC cases displayed alterations in RAS x2 (NRAS and HRAS), TERT x2, BRAF-V600E mutation, ALK, MET, and NTRK3.
Conclusion(s): NIFTP and IEFVPTC cases most commonly displayed RAS mutations (64.4% and 41.7%, respectively) and lacked aggressive BRAF-V600E mutations, whereas iFVPTC harbored aggressive mutations such as BRAF-V600E and TERT more commonly, with fewer RAS mutations. The possibility of NIFTP and IEFVPTC being on a premalignant to malignant continuum must be raised and these entities may be more similar to each other than to other entities such as iFVPTC

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.

Our aim was to investigate the outcomes of fibroadenomas recommended for surgical excision due to large size (>2cm) or interval growth. A retrospective review of our institutional radiology database from 2007 to 2015 was performed. We identified 167 biopsy-proven fibroadenomas recommended for surgical consultation. Of these, 75 (45%) cases actually underwent excision, 7 (9%, 95% CI: 4-18%) of which were upgraded to phyllodes tumors upon histopathological examination. Our results support the current recommendation to surgically excise breast lesions diagnosed as fibroadenomas with size >2cm or with interval growth due to the considerable risk of finding phyllodes tumors.

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.

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.

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

Objectives: Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in cytology specimens can be challenging. Recent literature showed p40 had higher specificity than p63 for this purpose. Methods: We identified 190 cytology cases with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry, including specimens from fine-needle aspirations (FNAs) and effusions. Results: ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases, respectively, regardless of specimen site. Among lung FNAs of primary pulmonary ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20 pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n = 14), more cases were positive for p40 than p63. Conclusions: Polyclonal p40 yields a level of false positivity in ACAs similar to p63, which is highest in effusions and is not limited to lung origin.