Faculty Bibliography

Background: Despite their common occurrence on fine-needle aspiration (FNA) biopsies, Hurthle cell lesions often pose diagnostic challenges. The associated molecular alterations are also not well understood. The goal of this study was to delineate the molecular profile of Hurthle cell lesions classified as Bethesda categories III or IV (atypia of undetermined significance (AUS) or suspicious for follicular neoplasm (SFN)) on FNA and to correlate this molecular profile with surgical resection findings. Design: 140 of 575 FNA's diagnosed as AUS or SFN were Hurthle cell lesions, of which 130 had Thyroseq molecular tests; 21/130 had surgical follow-up and the remaining 109/130 cases were lost to follow-up or considered clinically benign. Results: A majority of the Hurthle cell AUS or SFN had negative Thyroseq results (65%). The most prevalent mutations involved the RAS gene (19%). The remaining mutations each involved fewer than 4% of the cases. On surgical follow-up, 29% (6/21) were benign follicular neoplasms (5/6 were Hurthle type) with a variety of associated mutations. 24% (5/21) were non-neoplastic on surgical excision, including Hashimoto's thyroiditis with no mutations and nodular hyperplasia with KRAS or NRAS mutation. Another 24% (5/21) had non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) with different associated mutations. Finally, 24% (5/21) were malignant on surgical excision including Hurthle variant of follicular carcinoma with a variety of associated mutations, invasive follicular-variant of papillary thyroid carcinoma with NRAS mutation and an incidental papillary thyroid microcarcinoma (micro PTC) with KRAS mutations (Table 1). One micro PTC and three NIFTP cases had marked associated Hashimoto's thyroiditis in the surgical specimens. Conclusions: Our study shows the majority of Hurthle cell lesions diagnosed as AUS or SFN on thyroid FNA biopsies have no molecular alterations. Among the molecular alteration identified in Hurthle cell lesions, RAS mutations were the most prevalent; however, they were equally associated with benign lesions, NIFTP and malignant tumors. Therefore, they may not be useful in pre-surgical management decisions. The number of remaining molecular alterations was too small for significant analysis. Interestingly, almost half of the NIFTP and micro PTC cases had a background of Hashimoto's thyroiditis which may have masked the true nature of the lesions during FNA evaluation. (Table Presented)

Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound-guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette-like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.

BACKGROUND: Differentiating parathyroid and thyroid lesions can be challenging because of considerable morphologic overlap and anatomic proximity. Therefore, the authors sought to identify characteristic morphologic patterns and useful adjunct tests to distinguish these 2 entities. METHODS: A search was conducted in the study institution database for clinically indeterminate thyroid nodules from 2000 through 2016 with an emphasis on confirmed parathyroid nodules. Pathology reports, slides, ancillary studies, molecular analysis, and clinical and radiologic data were retrieved. RESULTS: A total of 143 cases of clinically indeterminate thyroid nodules were identified; 34 of these were confirmed parathyroid nodules. Three cytologic patterns were identified: 1) oncocytic cell pattern (9 cases; 26%); 2) follicular lesion of undetermined significance-like/papillary-like pattern (14 cases; 41%); and 3) nonspecific endocrine cell clusters (11 cases; 32%). Bare oval nuclei (100%), nuclear overlap (88%), crowded sheets (88%), and intracytoplasmic vacuoles (62%) were observed. Ten cases (29%) demonstrated positive immunostaining for parathyroid hormone (PTH), 7 cases (21%) demonstrated a positive PTH assay, and 9 cases (26%) had PTH detected by ThyroSeq v.2. The remaining 8 cases were morphologically either indeterminate or suggestive of parathyroid origin. The cytologic diagnosis was confirmed clinically (20 cases) or surgically (14 cases). Based on cytology alone, 8 cases initially were diagnosed as thyroid tissue and amended to parathyroid lesion after ancillary studies were performed, including 5 cases based on ThyroSeq v.2 results alone. CONCLUSIONS: Lesions with follicular lesion of undetermined significance-like or oncocytic features are prone to misdiagnosis. The current study identified distinct cytologic patterns in parathyroid lesions suggestive of parathyroid origin, which, together with PTH immunostains or assay, molecular studies, or sestamibi scans, aid in distinguishing parathyroid from thyroid lesions. Cancer (Cancer Cytopathol) 2017. (c) 2017 American Cancer Society.

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)

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

BACKGROUND: An elevated CD4/CD8 T-cell ratio on flow cytometry (FCM) analysis has been reported in the literature to be associated with Hodgkin lymphoma (HL). The purpose of our study was to determine the diagnostic significance of an elevated CD4/CD8 ratio in lymph node fine needle aspiration (FNA) specimens. DESIGN: Between 1996 and 2002, out of 837 lymph node FNAs submitted for flow cytometry analysis, 85 cases showed an elevated CD4/CD8 ratio, defined as greater than or equal to 4, without definitive evidence of a lymphoproliferative disorder. The cytologic diagnoses of these 85 cases were grouped into four categories: reactive, atypical, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Histologic follow-up was available in 17/85 (20%) of the cases. RESULTS: 5 of the 64 cases in which FCM and cytology did not reveal evidence of a lymphoproliferative disease had tissue follow-up because of persistent lymphadenopathy and high clinical suspicion. 3/5 (60%) confirmed the diagnosis of reactive lymphadenopathy. The two remaining cases (40%) were positive for lymphoma (1HL, 1NHL). 8/15 cases called atypical on cytology had histologic follow-up. 7/8 (87.5%) cases were positive for lymphoma (3HL, 4NHL). 3/4 cases called HL on cytology had tissue follow-up and all 3 (100%) confirmed the diagnosis of HL. One case diagnosed as NHL on cytology was found to be a diffuse large B-cell lymphoma. In summary, out of 17 cases with histologic follow-up 4/17 (24%) were reactive with CD4/CD8 T-cell ratio of 4.1-29, 7/17 (41%) were HLs with CD4/CD8 T-cell ratio of 5.3-11, and 6/17 (35%) were NHLs with CD4/CD8 T-cell ratio of 4.2-14. CONCLUSION: An elevated CD4/CD8 ratio on FCM is a nonspecific finding which may be seen in both reactive and lymphoproliferative disorders. The cytomorphologic features of the smear are more relevant than the sole flow cytometric finding of an elevated CD4/CD8 ratio