Cytological features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

INTRODUCTION: The noninvasive encapsulated follicular variant of papillary carcinoma (EFVPC) was recently renamed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) because of its unique genetic alterations and biological behavior. The objective of this report is to help cytopathologists and cytotechnologists improve diagnostic accuracy and determine the need for cytogenetic studies during adequacy evaluation of thyroid fine-needle aspirations. MATERIALS AND METHODS: Fifty-five cases of surgery-proven noninvasive EFVPC with corresponding cytology material were reviewed. These cases were collected over 17 years, from 1999 to 2016. RESULTS: Thirty-four of 55 (61.8%) cases were diagnosed as follicular neoplasm or suspicious for follicular neoplasm on cytology. Eighty to ninety percent of cases showed scant colloid, cellular smears with small clusters of follicular cells with nuclear atypia including enlarged nuclei, oval-shaped nuclei, nuclear grooves, mild chromatin powdering, and rare nuclear pseudo-inclusions. CONCLUSIONS: NIFTP has unique features: cytologically similar to follicular neoplasms, and nuclear atypia falling between atypia of undetermined significance (category III) and suspicious for/and papillary thyroid carcinoma (category V/VI) (The Bethesda System for Reporting Thyroid Cytopathology).

Ultrasound guided FNA of thyroid performed by cytopathologists enhances Bethesda diagnostic value.

BACKGROUND: Ultrasound (US) guided fine needle aspiration (FNA) biopsy of thyroid are examined and reported by cytopathologists based usually on The Bethesda System for Reporting Thyroid Cytopathology (BTC) regardless of the procedure's performers. This study is designed to determine whether there is any performer-dependent difference. METHODS: Six hundred and fifty-one thyroid US-FNAs in correlation with surgical follow-up (SFU) were studied. The statistical analysis was performed using the surgical pathology diagnosis as the gold standard. RESULTS: Among the 283 cases performed by cytopathologists, there were 8 (2.8%) nondiagnostic (BTC I), 197 (69.6%) benign (BTC II), 31 (11%) atypical (BTC III), 14 (5%) suspicious for follicular neoplasm (BTC IV), 12 (4.2%) suspicious for malignancy (BTC V), and 21 (7.4%) positive for malignancy (BTC VI), and there were 55 (19.4%) cases with SFU. The 368 cases performed by others showed 76 (21%) BTC I, 238 (65%) BTC II, 26 (7%) BTC III, 10 (3%) BTC IV, 9 (2.5%) BTC V 5, and 9 (2.5%) BTC VI, and there were 26 (7%) cases with SFU. The cytopathologist group achieved better sensitivity (91.3 vs.78%); slightly better specificity (83.3 vs. 82%); better positive predictive value (87.5 vs. 70%); similar negative predictive value (88.2 vs. 88%); and better overall accuracy (87.8 vs. 81%) compared with the non-cytopathologist group. Overall the difference for all statistical values is significant different (P = 0.041). CONCLUSION: US-FNA performed by cytopathologists showed a lower unsatisfactory rate and significantly better overall statistical values. Cytopathologists may play an important role in thyroid patient care. Diagn. Cytopathol. 2016;44:787-791. © 2016 Wiley Periodicals, Inc.

Fine-needle aspiration of small pulmonary nodules yields material for reliable molecular analysis of adenocarcinomas.

INTRODUCTION: Early molecular characterization with Kirsten rat sarcoma factor, epidermal growth factor, and anaplastic lymphoma kinase are critical to manage pulmonary adenocarcinoma. Fine-needle aspiration (FNA) of lesions <2 cm are routine in our institution and are used in molecular analysis. We report our experience. MATERIALS AND METHODS: We searched our databank for primary pulmonary adenocarcinomas diagnosed by FNA between January 2009 and April 2013. Size of the lesion aspirated, molecular results, and sample source (FNA versus surgical specimen) were recorded. We compared the frequency of mutations identified by FNA versus surgical specimens and the frequency of mutations in lesions by size (<1 cm, 1-2 cm, >2 cm). RESULTS: We identified 397 primary pulmonary adenocarcinomas. Molecular studies were requested by the clinician in 89 (22%) of primary adenocarcinomas. FNAs were used in 55 cases; 51 (93%) yielded sufficient material for molecular studies; surgical tissue were used in 34 cases; 33 (97%) yielded sufficient material for molecular studies. The insufficient specimens came from 2 FNAs of 0.6 cm nodules, an FNA of a 2 cm nodule, and a core biopsy. CONCLUSIONS: FNA was adequate for molecular analysis of small nodules. In nodules greater than 0.6 cm, the adequacy is comparable to surgical tissue. There was no statistically significant change in mutation rate by size (53%-58%). Importantly, FNA of small lesions for cytological diagnosis and molecular analysis is encouraged by our data and experience in order to provide early treatment.

Cytologic features of lipid-rich variant of pancreatic endocrine tumor-report of two cases with literature review.

Pancreatic endocrine tumor (PET) is an uncommon neoplasm of the pancreas with distinct cytomorphologic features. Lipid-rich PET, a rare variant, histologically deviates from that of a conventional PET. There is only one case report of the cytologic features of this rare entity in the literature. We report two cases of lipid-rich PETs diagnosed by endoscopic ultrasound-guided FNA biopsy. Case 1 showed large aggregates, small clusters, and single cells with plasmacytoid appearance, small uniform nuclei, coarse chromatin, and prominent nucleoli. Abundant distinct small cytoplasmic vacuoles were present in almost all tumor cells and the background was clean. Case 2 showed flat cohesive sheets of medium-sized uniform cells with indistinct plasmacytoid appearance, uniform nuclei, fine and evenly distributed chromatin, and inconspicuous nucleoli. Distinct small cytoplasmic vacuoles were seen only focally. Immunohistochemical stains in cell blocks of both cases confirmed the diagnosis of PET. Lipid-rich PET may be misinterpreted on cytology specimens if the pathologist is not aware of this rare entity since it mimics clear cell carcinoma of the kidney, adrenal cortical neoplasm, or adenocarcinoma of the pancreas.

High single-pass diagnostic yield of a new 25-gauge core biopsy needle for EUS-guided FNA biopsy in solid pancreatic lesions.

BACKGROUND: Current limitations of EUS-guided FNA include the need for multiple passes and on-site cytology assessment and lack of core specimen. Recently, a new 25-gauge core biopsy needle (PC25) was developed to overcome these limitations. OBJECTIVE: To determine the diagnostic yield of EUS-guided FNA aspiration biopsy (FNAB) when using the PC25 needle among patients with solid pancreatic lesions. DESIGN: Retrospective analysis. SETTING: Academic tertiary referral center. PATIENTS: Fifty consecutive patients with a solid pancreatic lesion underwent EUS-guided FNAB with PC25. INTERVENTIONS: EUS-guided FNAB with PC25. MAIN OUTCOME MEASUREMENTS: The primary outcome was the diagnostic yield in single and overall passes of EUS-guided FNAB when using the PC25 needle for pancreatic solid lesions. RESULTS: Cytologic analysis showed malignancy in 38 patients on the first pass, with a cumulative sensitivity of 83%, 91%, and 96% on passes 1, 2, and 3, respectively. Although visible core was reported in 46 patients (92%), histologic core was seen in 16 patients (32%). Histologic analysis showed malignancy in 29 patients on the first pass, with a cumulative sensitivity of 63% and 87% on pass 1 and passes 1 to 4, respectively. The sensitivity, specificity, and accuracy in combined cytologic and histologic results were 85%, 100%, and 86% for single pass and 96%, 100%, and 96% on multiple passes, respectively. No complications were seen. LIMITATIONS: A retrospective study design at a single center using a single arm. CONCLUSION: EUS-guided FNAB with the PC25 needle showed excellent single-pass and overall diagnostic yields. This needle appears to maintain a high cytologic yield, similar to standard 25-gauge FNA needles, while also providing some histologic core tissue.

Multimodality imaging of ß-cells in mouse models of type 1 and 2 diabetes.

OBJECTIVE: ß-Cells that express an imaging reporter have provided powerful tools for studying ß-cell development, islet transplantation, and ß-cell autoimmunity. To further expedite diabetes research, we generated transgenic C57BL/6 "MIP-TF" mice that have a mouse insulin promoter (MIP) driving the expression of a trifusion (TF) protein of three imaging reporters (luciferase/enhanced green fluorescent protein/HSV1-sr39 thymidine kinase) in their ß-cells. This should enable the noninvasive imaging of ß-cells by charge-coupled device (CCD) and micro-positron emission tomography (PET), as well as the identification of ß-cells at the cellular level by fluorescent microscopy. RESEARCH DESIGN AND METHODS: MIP-TF mouse ß-cells were multimodality imaged in models of type 1 and type 2 diabetes. RESULTS: MIP-TF mouse ß-cells were readily identified in pancreatic tissue sections using fluorescent microscopy. We show that MIP-TF ß-cells can be noninvasively imaged using microPET. There was a correlation between CCD and microPET signals from the pancreas region of individual mice. After low-dose streptozotocin administration to induce type 1 diabetes, we observed a progressive reduction in bioluminescence from the pancreas region before the appearance of hyperglycemia. Although there have been reports of hyperglycemia inducing proinsulin expression in extrapancreatic tissues, we did not observe bioluminescent signals from extrapancreatic tissues of diabetic MIP-TF mice. Because MIP-TF mouse ß-cells express a viral thymidine kinase, ganciclovir treatment induced hyperglycemia, providing a new experimental model of type 1 diabetes. Mice fed a high-fat diet to model early type 2 diabetes displayed a progressive increase in their pancreatic bioluminescent signals, which were positively correlated with area under the curve-intraperitoneal glucose tolerance test (AUC-IPGTT). CONCLUSIONS: MIP-TF mice provide a new tool for monitoring ß-cells from the single cell level to noninvasive assessments of ß-cells in models of type 1 diabetes and type 2 diabetes.

Noninvasive imaging of islet grafts using positron-emission tomography.

Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the latter stages of islet graft rejection. A noninvasive method of monitoring islet grafts would aid in the assessment of islet graft survival and the evaluation of interventions designed to prolong graft survival. Here, we show that recombinant adenovirus can engineer isolated islets to express a positron-emission tomography (PET) reporter gene and that these islets can be repeatedly imaged by using microPET after transplantation into mice. The magnitude of signal from engineered islets implanted into the axillary cavity was directly related to the implanted islet mass. PET signals attenuated over the following weeks because of the transient nature of adenovirus-mediated gene expression. Because the liver is the preferred site for islet implantation in humans, we also tested whether islets could be imaged after transfusion into the mouse liver. Control studies revealed that both intrahepatic islet transplantation and hyperglycemia altered the biodistribution kinetics of the PET probe systemically. Although transplanted islets were dispersed throughout the liver, clear signals from the liver region of mice receiving PET reporter-expressing islets were detectable for several weeks. Viral transduction, PET reporter expression, and repeated microPET imaging had no apparent deleterious effects on islet function after implantation. These studies lay a foundation for noninvasive quantitative assessments of islet graft survival using PET.

Bioluminescent monitoring of islet graft survival after transplantation.

Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. A method to image transplanted islets noninvasively and repeatedly would greatly assist studies of islet transplantation. Using recombinant adenovirus, we show that isolated rodent and human islets can be genetically engineered to express luciferase and then imaged after implantation into NOD-scid mice using a cooled charge-coupled device. The magnitude of the signal was dependent on the islet dose. Adenovirus-directed luciferase expression, however, rapidly attenuated. We next tested lentivirus vectors that should direct the long-term expression of reporter genes in transduced islets. Transplanted lentivirus-transduced islets restored euglycemia long term in streptozotocin-treated NOD-scid mice. The signal from implanted lentivirus-transduced islets was related directly to the implanted islet mass, and the signal did not attenuate over the observation period. Viral transduction, luciferase expression, and repeated imaging had no apparent long-term deleterious effects on islet function after implantation. These data demonstrate that the introduction of reporter genes into an isolated tissue allows the long-term monitoring of its survival following implantation. Such imaging technologies may allow earlier detection of graft rejection and the adjustment of therapies to prolong graft survival posttransplantation.