Can cytology and the Thyroid Imaging, Reporting, and Data System (TI-RADS) identify noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) before surgery?

INTRODUCTION: In 2017, the American College of Radiology (ACR) created the Thyroid Imaging, Reporting, and Data System (TI-RADS) to select thyroid nodules for fine-needle aspiration (FNA). The objective of this study is to find out whether ACR TI-RADS is useful in triaging thyroid follicular cells with papillary-like nuclear features obtained by FNA to determine the extent of surgery. MATERIAL AND METHODS: The grayscale ultrasound of 76 noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 41 encapsulated (E), and 79 infiltrative (I) follicular variant (FV) of papillary thyroid carcinoma (PTC) were reviewed and assigned TI-RADS points and then suspicion levels. RESULTS: Of the 39 tumors with high suspicion level, 32 were IFVPTC, and seven were EFVPTC. Of the 137 tumors with moderate suspicion level, 47 were IFVPTC, 34 were EFVPTC, and 56 were NIFTP. Of the 19 tumors with mild suspicion level, all were NIFTP. The only tumor with no suspicion was an NIFTP. IFVPTC had a significantly higher suspicion level than EFVPTC and NIFTP (P < 0.0001). The difference in suspicion level between EFVPTC and NIFTP is not statistically significant. None of the cases of NIFTP in the study had a high suspicion level. CONCLUSIONS: The study demonstrates that cytology interpreted in the context of ACR TI-RADS suspicion levels can separate NIFTP from many IFVPTC and a few EFVPTC with overt invasion. PTC could be diagnosed in cytology if cells with papillary-like nuclear features derived from TR5 nodules. The nodules with TR4 or less that yield similar cells require surgical pathology to diagnose FVPTC with microscopic capsular or vascular invasions.

The role of the Milan System for Reporting Salivary Gland Cytopathology: A 5-year institutional experience.

BACKGROUND: Fine-needle aspiration (FNA) is widely accepted in the preoperative management of salivary gland lesions. The proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) aims to standardize reporting terminology. Studies regarding the risk of malignancy (ROM) for the proposed categories continue to evolve. The current retrospective study applied the MSRSGC to assess ROM for salivary gland lesions and focused on the "indeterminate" categories. METHODS: A total of 627 salivary gland FNA specimens obtained from 2011 through 2016 were retrieved, with follow-up available for 373 cases. The original diagnoses were recategorized using MSRSGC by 2 independent cytopathologists as: 1) non-diagnostic; 2) non-neoplastic; 3) atypia of undetermined significance (AUS); 4a) benign neoplasms; 4b) salivary gland neoplasm of uncertain malignant potential (SUMP); 5) suspicious for malignancy (SFM); and 6) malignant. The ROM and overall ROM for each diagnostic category were determined, with characterization of "indeterminate" (AUS, SUMP, and SFM) lesions. RESULTS: There was near-perfect agreement regarding categorization (626 of 627 cases; 99.8%) between the 2 cytopathologists, with discordance observed for 1 case. The sensitivity, specificity, negative predictive value, and positive predictive value of salivary gland FNA specimens at the study institution were 79%, 98%, 94%, and 92%, respectively. The ROM for non-diagnostic, non-neoplastic, benign neoplasms, AUS, SUMP, SFM, and malignant were 6.7%, 7.1%, 38.9%, 5.0%, 34.2%, 92.9%, and 92.3%, respectively. The indeterminate category had an overall ROM of 47.1%. CONCLUSIONS: The MSRSGC is a valuable tool that can help to standardize reporting and stratify cases preoperatively. Having a better understanding of the indeterminate diagnoses will help further refine risk classification criteria. Cancer Cytopathol 2018. © 2018 American Cancer Society.

Pathologic basis of the sonographic differences between thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Ultrasonography is pivotal in triage thyroid biopsy in the era after the identification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This pictorial essay illustrates the pathologic basis of the sonographic features that distinguish NIFTP from thyroid cancers. In this study, we present the correlations of ultrasonography to ×1 histopathology to assess shape and margin characteristics. Markedly hypoechoic nodules correlate to microfollicular/solid nodules, while isoechoic/hyperechoic thyroid nodules correlate to normofollicular/macrofollicular nodules. The ultrasound findings of NIFTP and minimally invasive encapsulated thyroid cancers are similar. Both are well-circumscribed, oval-to-round nodules with regular margins. Blurred or microlobulated margins indicate infiltrating tumors, while lobulated margins are characteristic of expansile tumors. Overtly invasive encapsulated tumors are characterized by oval-to-round nodules with irregular or lobulated margins. The ultrasound findings for infiltrative thyroid cancers show at least one of the following malignant features: marked hypoechoicity, taller-than-wide shape, microcalcifications, and blurred or microlobulated margins.

Sonographic and cytologic differences of NIFTP from infiltrative or invasive encapsulated follicular variant of papillary thyroid carcinoma: A Review of 179 Cases.

We reclassified 179 cases of the follicular variant (FV) of papillary thyroid carcinoma (PTC) into 72 (40.2%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 37 (20.7%) encapsulated FVPTC with invasion (EFVPTC), and 70 (39.1%) infiltrative FVPTC (IFVPTC) without a capsule. In the NIFTP group, 5.6% cytology were hypercellular and the remainder low to moderate cellularity. PTC nuclei were absent in 18%, focally present in 37.5%, and diffusely present in 44.4%. In the EFVPTC group, 8.1% cytology were hypercellular and the reminder low to moderate cellularity. PTC nuclei were absent in 24.3%, focally present in 29.7% and diffusely present in 45.9%. In IFVPTC group, 24.3% cytology were hypercellular and the reminder low to moderate cellularity. PTC nuclei were diffusely present in 88.6% and focally present in 11.4%. The ultrasound findings for NIFTP and minimally invasive EFVPTC typically demonstrated a circumscribed oval/round nodule with a hypoechoic rim, and the Doppler was mostly hypervascular. The ultrasound findings for overtly invasive EFVPTC typically showed a round/oval nodule with irregular margins and the Doppler was mostly hypervascular. The ultrasound findings for IFVPTC group showed at least one of the malignant gray-scale features: markedly hypoechoic, taller-than-wide, microcalcifications or blurred margins. The Doppler in this group was mostly avascular. An algorithm is proposed to triage thyroid FNA based on different scenarios of the sampled cells, interpreted in the context of ultrasound features with histology outcomes. Five composite ultrasound-cytology-histology figures illustrate NIFTP, IFVPTC, and IFVPTC with intratumoral fibrosis, microfollicular EFVPTC and normofollicular EFVPTC. Diagn. Cytopathol. 2017;45:533-541. © 2017 Wiley Periodicals, Inc.

Most Thyroid Cancers Detected by Sonography Lack Intranodular Vascularity on Color Doppler Imaging: Review of the Literature and Sonographic-Pathologic Correlations for 698 Thyroid Neoplasms.

OBJECTIVES: This study investigated the controversy of whether hypervascularity on color Doppler sonography correlates with thyroid malignancy by reviewing the literature and sonographic-pathologic correlation. METHODS: Over a 20-year period, 698 thyroid nodules had color Doppler and histopathologic data. Intranodular vascularity was graded 0 to 3+, and histopathologic findings were recorded. RESULTS: The data were collected from 698 patients (557 women and 141 men) with a mean age of 48 years (range, 16-87 years). Of the 698 neoplasms, 425 were malignant (mean size, 1.7 cm; range, 0.4-9 cm; 150 ≤1 cm), and 273 were benign. The carcinomas included 391 papillary, 12 Hürthle cell, 9 medullary, 6 follicular, 5 poorly differentiated, and 2 anaplastic. The grading of intranodular vascularity was 0 in 63.3%, 1+ in 12.9%, 2+ in 6.6%, and 3+ in 17.4%. Among thyroid carcinomas, follicular carcinoma and the encapsulated subtype of the follicular variant of papillary carcinoma had significantly higher intranodular vascularity than the rest (P < .0001). Benign neoplasms included 226 follicular adenoma/adenomatoid nodules (mean size, 3.2 cm; range, 1.2-8.0 cm), 42 Hürthle cell adenoma/adenomatoid nodules (mean size, 2.6 cm; range, 0.8-5.5 cm), and 5 hyalinizing trabecular adenomas (mean size, 2.4 cm; range, 0.6-6.0 cm; 4 ≤1 cm). The grading of intranodular vascularity was 0 in 6.9%, 1+ in 12.1%, 2+ in 2.6%, and 3+ in 78.4%. Intranodular hypervascularity was associated with adenoma/adenomatoid thyroid nodules, whereas a lack of vascularity was related to thyroid carcinomas (P < .0001). CONCLUSIONS: Most sonographically detected thyroid cancers lack intranodular vascularity, and most hypervascular thyroid nodules are adenoma/adenomatoid nodules, the encapsulated subtype of the follicular variant of papillary carcinoma, or follicular carcinomas.

Cytohistology of papillary carcinoid and emerging concept of pulmonary neuroendocrine neoplasms.

This timely review starts by reporting the clinical, cytologic and histologic features of a morphologic variant of pulmonary carcinoid tumor forming exclusively of papillae. This growth pattern is so rare that it was not included in 2014 WHO classification of pulmonary neuroendocrine neoplasms. The current concept is reviewed, and example of spindle cell carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma are illustrated with fine needle aspiration cytology, surgical and clinical follow-up. Finally, the new findings in cell biology and molecular biology that led to the emerging concept that carcinoids and high-grade neuroendocrine lung carcinomas are separate biological entities are reviewed and summarized in a tumorigenic module.

Fine-needle aspiration cytology of the solid variant of papillary thyroid carcinoma: a study of 13 cases with clinical, histologic, and ultrasound correlations.

BACKGROUND: The solid variant of papillary thyroid carcinoma (SVPTC) comprises approximately 3% of thyroid cancers, and there are conflicting reports about its behavior in the literature. The cytology of SVPTC is limited to 3 single case reports, a review article, and a monograph. We present the first cytologic study of SVPTC. METHODS: Fine-needle aspiration smears obtained with ultrasound guidance from 13 patients with histologically pure SVPTC were reviewed, and the cytologic features recorded. Ultrasound images were retrieved from radiology and were correlated with low-power histology images. Intratumor vascularity on Doppler imaging was correlated with cellularity in cytology samples. RESULTS: Three cytomorphologic patterns of SVPTC were identified: cohesive, syncytial-type tissue fragments; microfollicles/trabeculae; and dyshesive single cells. All 3 SVPTCs in the first group were encapsulated without invasion. Two of 6 SVPTCs in the second group had a single lymph node metastasis; 4 were encapsulated, and 2 had pushing borders. Ultrasound images in the first and second SVPTC groups were similar, with the majority revealing a well defined, solid nodule with minimal intranodular vascularity. All 4 SVPTCs in the third group had infiltrative borders; and, with the exception of one 0.8-cm tumor, all had multiple lymph node metastases. Ultrasound in the third group revealed irregular borders. RET/PTC1 and RET/PTC3 mutations were found in 2 cases of the third group. CONCLUSIONS: SVPTCs are heterogeneous tumors. The cohesive, syncytial tissue-fragment pattern can be recognized as SVPTC in smears and is associated with encapsulation and indolent behavior. The microfollicular/trabecular pattern is indistinguishable from that of the follicular variant of papillary thyroid carcinoma and has intermediate behavior. The dyshesive single-cell pattern correlates with infiltrative tumor growth and may not be unique to SVPTC.

Amyloid-rich low grade adenocarcinoma of the parotid: fine-needle aspiration cytology with histologic correlations.

Amyloid deposits are unexpected in salivary gland tumors. A 60-year-old woman presented with a 1.8 cm, slow-growing parotid mass. Both fine-needle aspiration and frozen section were misinterpreted as pleomorphic adenoma. The final pathology was amyloid-rich low grade adenocarcinoma of the parotid gland. The aspirates consisted of three components: mucin, amyloid, and tumor cells. The mucin was unusually thick, stringy, and metachromatic. The amyloid presented as innumerable concretions scattered solitarily or in small jigsaw puzzle-like aggregates, individually wrapped by tumor cells. The tumor cells had bland oval nuclei and scant-to-abundant cytoplasm, arranged in loosely cohesive small sheets. On histology, the tumor cells were arranged in interconnecting monolayered glands of a wide range of size with small patches of cellular regions composed of plump tumor cells. As the luminal mucin and amyloid deposits enlarged, the lining tumor cells became thin and flat. The glandular lumen molded amyloid concretions into different shapes and sizes. Atrophic or pyknotic tumor cells outlined the amyloid concretions with concentric laminations, reminiscent of corpora amylacea. Alcian blue positive luminal mucin, associated with newly formed amyloid, was present in mucinous regions of the tumor. This is the first description of cytologic features of amyloid-rich low grade adenocarcinoma of the parotid and the second case in the pathology literature. The literature of amyloid-rich tumors was reviewed and the implication of the presence of abundant amyloid on the death of tumor cells suggested.

Cribriform morular variant of papillary thyroid carcinoma: clinical and cytomorphological features on fine-needle aspiration.

BACKGROUND: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor that may arise in patients with familial adenomatous polyposis (FAP), although sporadic instances of this tumor have been reported. When it arises in FAP, CMV-PTC may present before colonic manifestations are apparent, so proper identification and classification are essential for prompt assessment of the colonic disease status and genetic and familial counseling. METHODS: Nine cases of PTC with cribriform morular cytomorphology were identified at 2 large tertiary-care hospitals; 6 were true CMV-PTC with positive ß-catenin and 3 were CMV-like PTC with negative ß-catenin. A review of the cytomorphology and a cytology-histology correlation were performed. RESULTS: Only 1 patient presented with a known history of FAP. Patients presented with a median age of 41 years (range 19-64 years). There was a clear female predilection; 8 of 9 patients (89%) were female. All cases demonstrated the classical nuclear and architectural features of PTC. In addition, the most salient features were large tissue fragments with cribriform architecture and dense cellular morules. The elongated cellular shape of the tumor cells led to the misclassification of one tumor as a tall-cell variant of PTC on the FNA material. CONCLUSION: CMV-PTC or CMV-like PTC demonstrate cytomorphological features that overlap with classic PTC. ß-Catenin immunostaining plays an important role in making a definitive diagnosis.

Cytological features of clear cell thyroid tumors, including a papillary thyroid carcinoma with prominent hobnail features.

Primary thyroid tumors with extensive clear cell changes are extremely rare. More than 10,000 ultrasound-guided thyroid fine needle aspirations examined over a period of 17 years by the first author, only one of the 530 (<0.2%) papillary thyroid carcinomas (PTCs) and three of the 42 (7.1%) follicular thyroid carcinomas (FTCs) had extensive cytoplasmic clearing. Thyroidectomies were performed for these cases at four different hospitals in New York City. Final pathology was available for review in each of the four cases. Histology showed a 1.5-cm PTC with prominent hobnail features and clear cell change in a 31-year-old woman, a 4.3-cm FTC without angioinvasion in a 31-year-old woman, a 4.5-cm angioinvasive FTC in a 45-year-old man, and a 2-cm FTC with extensive angioinvasion in a 41-year-old woman with McCune-Albright syndrome (previously published). On ultrasound, the FTCs were solid circumscribed nodules and the PTC had an irregular margin. In these cases, the etiology for the cytoplasmic clearing included accumulation of glycogen in the PTC, accumulation of vesicles in two of the FTCs, and accumulation of lipid droplets in a FTC with extensive angioinvasion. Review of the cytologic literature showed 17 cases of follicular-derived thyroid tumors with extensive clear cell change. To the best of our knowledge, this is the first cytologic report of PTC with hobnail features and extensive clear cell change.

Encapsulated follicular variant of papillary thyroid carcinoma: fine-needle aspiration with ultrasound and histologic correlation of 41 cases.

OBJECTIVE: The encapsulated follicular variant of papillary carcinoma (FVPC) was recently reported to have genetic alterations and biological behavior closer to follicular adenoma/carcinoma than classic papillary carcinoma and unencapsulated FVPC. The objective of this study is to alert cytologists to this new subtype and to report our experience. STUDY DESIGN: Cytology of 41 cases of surgery-proven encapsulated FVPC was reviewed and correlated with histopathology and ultrasound findings. These cases were collected over 19 years from 188 aspirates reported as 'suspicious or atypical, cannot exclude FVPC' and from 245 aspirates reported as follicular neoplasm. RESULTS: Thirteen aspirates had diffusely atypical nuclei, 20 aspirates had mixed normal and atypical nuclei, and 8 aspirates had no atypical nuclei. On histology, papillary nuclei were distributed focally in the second and third groups. Crowded, oval, clear nuclei occurred in nearly 80% of the cases, nuclear grooves occurred in 12.2%, and nuclear pseudoinclusions occurred in 4.9%. Capsular invasion without angioinvasion was present in 30% of encapsulated FVPCs, with angioinvasion in 17.5% and lymph node metastasis in 7.5%. Most encapsulated FVPCs were benign-appearing on ultrasound with round-to-oval, circumscribed nodules with a hypoechoic rim. CONCLUSIONS: Encapsulated FVPC is more difficult to recognize on fine-needle aspiration and ultrasound than unencapsulated FVPC.

Adenomatoid nodules are the main cause for discrepant histology in 234 thyroid fine-needle aspirates reported as follicular neoplasm.

According to several large studies, the surgical pathologist renders a non-neoplastic diagnosis in ∼20-40% of thyroid fine-needle aspiration (FNA) cases reported as follicular neoplasm. This study analyzes the cause of this poor correlation between cytology and histology. Cases consisting of oncocytic (Hurthle) cells were excluded from study. During the study period from January 1996 to April 2010, histologic follow-up was available for 234 of 670 cases (34.9%) reported as follicular neoplasm on ultrasound-guided thyroid FNA. Sonographic and Doppler data were available in all cases and included nodule location, size, echogenicity, and vascularity. Of the 234 aspirates with follow-up, surgical pathology reported 130 cases (55.6%) of follicular adenoma, 15 cases (6.4%) of follicular carcinoma, 14 cases (6.1%) of follicular variant of papillary carcinoma, and 75 cases (32.3%) of nodular goiter. Recuts of those index nodules reported as nodular goiter were examined independently by two pathologists using the 2× objective lens. Adenomatoid nodule was defined as an insufficiently encapsulated "blue" nodule of increased nuclear density when compared with the surrounding thyroid. Of the 75 cases reported as nodular goiter, 60 index nodules (80%) fulfilled the described criteria for adenomatoid nodule, while 15 did not. In conclusion, adenomatoid nodules are the main cause of poor histologic correlation with follicular neoplasm reported by FNA. If "increased nuclear density at scanning magnification" were adopted by surgical pathologists as the major diagnostic criterion for follicular adenoma rather than encapsulation, noncorrelated cases would be reduced from 32 to 6.4%.

Large cell carcinoma of the lacrimal gland diagnosed by fine needle aspiration biopsy.

A 67-year-old man presented with a 6-month history of a malignant appearing left lacrimal gland mass. Fine needle aspiration biopsy was performed in the office, diagnosing the mass as large cell carcinoma (LCCA) of the lacrimal gland. This represents the second reported case of LCCA of the lacrimal gland and details the potential for FNA biopsy to successfully yield the diagnosis. LCCA of the lacrimal gland is rare, but should be considered in cases of malignant lacrimal gland neoplasms.

Fine-needle aspiration of mucin-producing thyroid tumors.

OBJECTIVE: Mucin-producing thyroid tumors are extremely rare. Nonetheless, we have encountered three such cases in fine-needle aspiration. We report the cytologic and histologic findings and review the literature. STUDY DESIGN: Cytologic features were studied on direct smears using Romanovsky stain to detect background substance and Papanicolaou stain to analyze nuclear and cytoplasmic features. The cytologic features were correlated with histology. Mucin was demonstrated by mucicarmine, Alcian Blue/PAS, and Alcian Blue (pH 2.5). RESULTS: The cytologic features related to mucin include: (1) thick luminal mucin globules and signet ring cells aspirated from an 83-year-old woman with a 3-cm signet ring cell follicular adenoma, (2) abundant fluffy mucin containing signet ring cells in cohesive fragments aspirated from a 75-year-old man with the bilateral signet ring cell follicular variant of papillary carcinoma, which is the first case in the English literature, and (3) abundant thin mucoid mucin aspirated from the lymph node of an 86-year-old woman with a 5-cm mucinous poorly differentiated thyroid carcinoma. CONCLUSION: The occurrence of mucin in thyroid fine-needle aspiration does not necessarily indicate metastasis, and the presence of mucin in cervical lymph nodes does not exclude the thyroid gland as a possible primary.

Histiocytic sarcoma with interdigitating dendritic cell differentiation: a case report with fine needle aspiration cytology and review of literature.

A hybrid histiocytic sarcoma-interdigitating dendritic cell sarcoma was found in a small perinephric lymph node of an asymptomatic 80-year-old man, who presented a year ago with two small foci of lung metastasis found during routine chest X-ray. Fine needle aspiration cytology demonstrated interconnecting long and thin cell processes radiating from dendrite-like neoplastic cells with oval, enlongated, reniform, and irregular nuclei with vesicular chromatin and distinct nucleoli. Histology showed spindled epitheliod and histiocytic cells with abundant, slightly eosinophilic cytoplasm with indistinct cell borders and forming fascicles in a vague storiform pattern with interspersed T-lymphocytes. Immunohistochemically, the neoplastic cells were strongly positive for histiocytic markers: CD163, CD68, lysozyme, and PU.1, as well as strongly positive for dendritic cell markers: S100 and fascin, but were negative for CD1a (Langerhans cell marker), CD21/CD35 (follicular dendritic cell markers), B-cell, and T cell markers. This case is compared to the four hybrid histiocytic-dendritic sarcomas reported since 1983.

Cystic papillary thyroid carcinoma in fine needle aspiration may represent a subset of the encapsulated variant in WHO classification.

This study audits the reliability of ultrasound-guided fine needle aspiration (FNA) in excluding papillary thyroid carcinoma (PTC) in thyroid cysts containing mural nodules, and investigates the histological counterpart of cystic PTC diagnosed on FNA. Using a 10-5 MHz ultrasound probe and a 27-gauge needle, solid portions of thyroid nodules were sampled and assessed immediately using both Diff-Quik and Ultrafast Papanicolaou stains. Unlike usual PTCs that demonstrate hypercellularity, the aspirates of cystic PTC showed low cellularity and consisted of papillae with atypical nuclei scattered in abundant thin colloid. Over a period of 13 years, histological follow-up was obtained from 11 women and 6 men in whom cystic PTC was reported on FNA. This represented 4.4% of 383 cases of PTC reported and 0.25% of all thyroid FNAs performed. In all 17 cases, histopathology showed encapsulated PTC in various stages of cystic degeneration. Sonography correlated well with histopathology, where findings ranged from cysts with small mural nodules to solid nodules with pockets of thin colloid. In 87 patients with thyroid cysts containing mural nodules, FNA findings were benign, as was clinical follow-up that ranged from 1 to 12 years. In conclusion, ultrasound-guided FNA, if performed in the manner described, can reliably distinguish cystic PTC from a benign cyst with a mural nodule. Cystic PTC on FNA in this series correlates to a subset of the encapsulated variant of PTC, an entity described in the 1988 WHO Histological Typing of Thyroid Tumours in the good prognostic category.

Medullary thyroid carcinoma presenting as rectangular cell type on fine-needle aspiration.

Medullary thyroid carcinoma typically presents as dyscohesive plasmacytoid, spindled, or polygonal cells on fine-needle aspiration smears. We recently encountered a case of sporadic medullary thyroid carcinoma that presented as a hypercellular aspirate composed of cohesive aggregates of rectangle-shaped cells. The case was mistakenly reported as a hypercellular follicular neoplasm on cytology. Subsequent thyroidectomy revealed medullary carcinoma. We draw attention to this distinctive rectangular cell type as an additional morphology for medullary thyroid carcinoma.