Faculty Bibliography

PURPOSE/OBJECTIVE:The present study aimed to examine the molecular profiles of cytologically indeterminate thyroid nodules stratified by American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) categories and to determine whether certain ultrasonographic features display particular molecular alterations. METHODS:A retrospective review was conducted of cases from January 1, 2016 to April 1, 2018. Cases with in-house ultrasonography, fine-needle aspiration Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnoses, molecular testing, and surgery were included. All cases were diagnosed as TBSRTC indeterminate categories. The ultrasound studies were retrospectively reviewed and assigned TI-RADS scores (TR1-TR5) by board-certified radiologists. The final diagnoses were determined based on the surgical resection pathology. Binary logistic regression analysis was used to study whether demographic characteristics, TI-RADS levels, and TBSRTC diagnoses were associated with ThyroSeq molecular results. RESULTS:Eighty-one cases met the inclusion criteria. RAS mutations were the most common alteration across all TI-RADS categories (TR2 2/2; TR3 10/19, TR4 13/44, and TR5 8/16), and did not stratify with any particular TI-RADS category. Only TR4 and TR5 categories displayed more aggressive mutations such as BRAFV600E and TERT. ThyroSeq results were positively correlated with thyroid malignancy when non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was categorized in the malignant category (odds ratio [OR], 6.859; P<0.01), but not when NIFTP was removed from the malignancy category. Echogenicity scores were found to be negatively correlated with ThyroSeq results in thyroid nodules (OR, 0.162; P<0.01). CONCLUSION/CONCLUSIONS:Higher-risk molecular alterations tended to stratify with the higher TI-RADS categories.

Background. Valganciclovir is the standard of care used for the prevention of Cytomegalovirus (CMV) infections among solid organ transplant (SOT) recipients. Currently there is minimal guidance for prophylaxis in SOT recipients undergoing intermittent hemodialysis (IHD). At Mount Sinai Hospital (MSH), the current practice for CMV prophylaxis in SOT recipients on IHD is valganciclovir 450 mg every other day (Q48H) or three-times weekly (TIW). This study aims to evaluate the safety and effectiveness of these dosing regimens in SOT recipients on IHD. Methods. A single-center, retrospective chart review study was conducted among all MSH SOT recipients on valganciclovir 450 mg Q48H or TIW for CMV prophylaxis and undergoing IHD for at least 30 days. The primary study outcome was the safety of using these valganciclovir doses determined by the incidence of leukopenia, thrombocytopenia, and the administration of growth colony stimulating factor (GCSF). The secondary outcome were the incidences of CMV viremia and CMV disease while on prophylaxis. Results. Eighteen transplant encounters satisfied the inclusion and exclusion criteria. The majority were liver (7, 38.9%) and kidney (5, 27.8%) transplants. Thirteen (72.2%) recipients were on valganciclovir 450 mg Q48H dosing, while 5 (27.8%) were on valganciclovir 450 mg TIW dosing. Both the mean platelet count nadir (131 +/- 93 vs 161 +/- 115) and mean white blood cell count nadir (3.4 +/- 2.5 vs 5.1 +/- 3.8) were lower in the Q48H regimen. Four patients (22.2%) in the Q48H regimen group required GCSF vs none (0.0%) in the TIW regimen. No patient had a detectable CMV viral load while on either prophylactic dose. Two (11.1%) CMV high risk patients on the every other day dosing regimen and one (5.6%) CMV moderate risk patient on the three times weekly regimen developed CMV viremia about 2-3 months after their prophylaxis was stopped.
Conclusion(s): Valganciclovir 450 mg TIW may be safer than and as efficacious as Q48H dosing for prophylaxis in SOT recipients on chronic IHD. This data supports the use of three times weekly dosing as standardized practice at MSH, however more data is necessary to determine a conclusive result (Table Presented)

Background: The American College of Radiology (ACR) 2017 Thyroid Imaging Reporting and Data System (TI-RADS) added a new risk stratification system for classifying thyroid nodules based on sonographic appearance (T1-T5). FNA is generally not recommended for benign or low suspicion nodules. However, other factors such as nodule size and family history may trigger an order for an FNA. Our study aimed to examine the cytologic diagnosis, molecular profiles and surgical follow up in a select group of patients with sonographically benign appearing thyroid nodules.
Design(s): We performed a retrospective review in our pathology database of cases from 1/1/2016-4/1/2018, prior to our institution's adoption of the TI-RADS classification system. Thyroid nodules with in-house ultrasound exam (US), FNA cytology, The Bethesda System (TBS) cytology diagnosis, molecular testing, and surgery were included. The USs from these cases were retrospectively reviewed and assigned TI-RADS scores (TR1-TR5) by a board certified radiologist. There were no TR1 nodules. TR2 (not suspicious) and TR3 (mildly suspicious) nodules were selected for evaluation.
Result(s): From 1/1/2016-4/1/2018, there were a total of 34 patients that fit the selection criteria. Of these, there were 5 TR2 thyroid nodules and 29 TR3 thyroid nodules with corresponding FNA TBS, molecular and surgical diagnoses (table1). (Table presented)
Conclusion(s): Our study shows that sonographically benign appearing/low suspicion thyroid nodules may display molecular alterations; 50% of those proved to be RAS mutations in our study. Approximately 60% of aspirated TR2 nodules and 66% of TR3 nodules were malignant or NIFTP on excision. Despite their lower suspicion index on US, with lower TI-RADS scores, benign appearing nodules on US need to be evaluated in the context of clinical, cytologic and molecular information in order to determine clinical course

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.

BACKGROUND:Recent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients' clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians. METHODS:), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual's stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool's efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options. DISCUSSION/CONCLUSIONS:This study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

Introduction: Ultrasound guided FNA is important in guiding management of thyroid nodules. Complications are usually limited to localized discomfort, bruising, or minor hematomas. At our institution, cytopathologists perform 600 - 900 ultrasound guided thyroid FNAs yearly. Acute transient thyroid swelling is a rare complication. A diffuse swelling of the entire thyroid occurs after a biopsy with a characteristic "cracked appearance" on ultrasound imaging. Cytopathologists and radiologists need to recognize this phenomenon and terminate the procedure. Materials and Methods: We conducted a retrospective review of our pathology and radiology database from 2004 -2015 for documented transient thyroid swelling. We reviewed patient demographic information, thyroid antibody and function studies, allergies/ medical history, and pathology diagnosis (Table 1). Results: We identified 7 cases of transient diffuse swelling of the thyroid from 6,175 thyroid FNAs. In all cases, the thyroid architecture becomes obscured by diffuse enlargement of the thyroid with an internal "cracked appearance" without skin swelling or hematoma (Figure 1). Imaging shows two to three times increase in overall thyroid volume. Patients usually reported acute pain that resolved shortly after the procedure was ceased and ice pack was applied. Post-procedural observation showed resolution of swelling. Patients had no known latex allergy or prior adverse reactions to needles. In most cases, the patients tolerated initial FNA without complications. One patient had a repeat FNA with Benadryl premedication without adverse complications but it is unclear whether there was a preventative effect. Conclusion: This benign, transient reaction should be distinguished from severe complications such as anaphylaxis and hemorrhage. We hypothesize that this event is attributable to intra-thyroidal edema since no discrete hematoma is seen on imaging. Pre- and post-procedural ultrasound imaging is essential for detecting change in thyroid architecture. Recognition of this rare event is crucial when performing ultrasound guided thyroid FNA. (Figure Presented)

OBJECTIVE: The purpose of this study was to evaluate morphologic features predictive of benign thyroid nodules. MATERIALS AND METHODS: From a registry of the records of 1,232 fine-needle aspiration biopsies performed jointly by the cytology and radiology departments at a single institution between 2005 and 2007, the cases of 650 patients were identified for whom both a pathology report and ultrasound images were available. From the alphabetized list generated, the first 500 nodules were reviewed. We analyzed the accuracy of individual sonographic features and of 10 discrete recognizable morphologic patterns in the prediction of benign histologic findings. RESULTS: We found that grouping of thyroid nodules into reproducible patterns of morphology, or pattern recognition, rather than analysis of individual sonographic features, was extremely accurate in the identification of benign nodules. Four specific patterns were identified: spongiform configuration, cyst with colloid clot, giraffe pattern, and diffuse hyperechogenicity, which had a 100% specificity for benignity. In our series, identification of nodules with one of these four patterns could have obviated more than 60% of thyroid biopsies. CONCLUSION: Recognition of specific morphologic patterns is an accurate method of identifying benign thyroid nodules that do not require cytologic evaluation. Use of this approach may substantially decrease the number of unnecessary biopsy procedures

Enzyme replacement was introduced as treatment for non-neuronopathic Gaucher disease more than 15 years ago. To ensure the best use of this costly ultra-orphan agent, a systematic disease management approach has been proposed by an international panel; this includes the development, by consensus, of achievable treatment goals. Here we critically review these goals and monitoring guidelines and incorporate emerging experience of the disease in the therapeutic era, as well as contemporary clinical research. This review makes recommendations related specifically to the management of pregnancy; the appropriate use of splenectomy and bisphosphonate treatment; the relevance of biochemical markers to disease monitoring; and the use of semi-quantitative methods for assessing bone marrow infiltration. In addition, we identify key areas for development, including the requirement for a validated index of disease severity; the need to correlate widely used biomarkers with long-term disease outcomes, and the desirability of establishing agreed standards for monitoring of bone disease particularly in infants and children with Gaucher disease