Cytologic Features of Focal Papillary Thyroid Carcinoma Arising within Follicular Adenoma: A Masked Cytomorphologic Analysis of 17 Cases

Background/Objective: Focal papillary thyroid carcinoma (PTC) arising within a follicular adenoma (PTCFA) represents a clinically significant, but rare, histopathologic subset of papillary carcinomas whose cytologic features have not been well described. This uncommon presentation of PTC may contribute to a subset of thyroid aspirates interpreted as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS). Study Design: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA' on corresponding surgical excision were identified from the archival records of 2 large academic medical centers. A control group of 40 FNAB comprised of 20 follicular adenomas (FA) and 20 PTC was identified (based on the corresponding surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a masked fashion and scored for a series of 31 cytomorphologic features. The intraclass correlation between diagnostic categories and overall agreement between cytopathologists was statistically evaluated. Results: Aspirates of PTCFA were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and 'malignant' (n = 1). On masked review, the most common cytomorphologic features of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a papillary architecture were absent in 85 and 88% of the cases, respectively. Relative to the 2 control groups, the PTCFA cases demonstrated overlapping features between FA and PTC for the majority of the 31 examined cytomorphologic features. Conclusion: PTCFA represent a rare subset of PTC that is difficult to recognize as PTC by FNAB. Most cases exhibit overlapping features between a benign thyroid nodule and conventional PTC, and they are often interpreted as 'AUS/FLUS'.     

Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and "grooves." Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma.     

Papillary thyroid carcinoma and its variants in fine needle aspiration smears. A cytomorphologic study with special reference to tall cell variant

OBJECTIVE: To study the fine needle aspiration (FNA) cytologic features of papillary thyroid carcinoma (PTC) with special reference to its tall cell variant (TCV), which is the most aggressive of the variants. STUDY DESIGN: Fifty-four PTC cases were classified into variants, and the frequency of well-known morphologic criteria was determined. Four parameters were quantitatively analyzed based on a study of 200 consecutive neoplastic follicular cells: shape of cells, color of cytoplasm, intranuclear cytoplasmic inclusion (INCI) and nuclear grooves. RESULTS: The PTC cases included 6 TCV (> or = 30% tall cells), 8 cases with a significant tall cell component (sig. TCC) having 10-29% tall cells, 17 usual variant (UV), 17 follicular variant (FV) and 6 miscellaneous variants. TCV differed significantly from UV and FV in having a higher tall cell count, higher count of cells with reddish cytoplasm and INCI, and higher frequency of cases with lymphocytic infiltration. PTC (with significant tall cell component [TCC]) differed significantly from TCV with regard to tall cell count and lymphocytic infiltration, from UV with respect to tall cell count and monolayered sheets, and from FV with respect to tall cells, INCI, grooved nuclei, acinar formation, fire-flare appearance and giant cells. CONCLUSION: TCV was cytologically distinct from other variants. The biologic behavior of PTC cases with significant TCC, which morphologically seem to be a group intermediate between TCV on the one hand and UV and FV on the other, however, needs to be carefully monitored.     

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation.Methods: Thyroid surgery cases at a single institution from 2005–2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings.Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology.Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy.Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound     

Risk of Malignancy in Thyroid Cytology: The Impact of The Reclassification of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)

Objective: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We aimed to compare the risk of malignancy (ROM) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) on fine-needle aspiration cytology (FNAC), before and after the reclassification, in a large cohort of patients.Methods: We analyzed 5,625 consecutive FNAC samples performed in 2012–2014 and selected category III (atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS]), IV (follicular neoplasm [FN]/suspicious for a follicular neoplasm [SFN]), V (suspicious for malignancy [SFM]), and VI (malignant) of the BSRTC. We reviewed the histology of operated patients and compared ROM before and after the introduction of the NIFTP category.Results: A total of 772 patients were identified and 45% underwent surgery (n = 348). There were 180 cases of AUS/FLUS (10 NIFTP), 114 cases of FN/SFN (2 NIFTP), 29 cases of SFM (3 NIFTP), and 25 cases of BSRTC VI (no NIFTP). Exclusion of NIFTP from malignant lesions resulted in a relative and absolute decrease in the ROM in AUS/FLUS (15.2% and 5.5%, respectively), FN/SFN (7.6% and 1.8%, respectively) and SFM (14.2% and 10.3%, respectively) categories. Among the NIFTP patients, 93% underwent total thyroidectomy and 20% received radioiodine.Conclusion: Reclassification of noninvasive EFVPTC as NIFTP resulted in a decrease in overall ROM, and the BSRTC categories most affected were III and V.Abbreviations: AUS = atypia of undetermined significance; BSRTC = Bethesda System for Reporting Thyroid Cytopathology; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; FNAC = fine-needle aspiration cytology; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma; ROM = risk of malignancy; SFM = suspicious for malignancy; SFN = suspicious for a follicular neoplasm     

Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis

Objective: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection. Study Design: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant. Results: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01). Conclusions: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis.     

Sonographic Features Of Multifocal Papillary Thyroid Carcinomas

Objective: It is uncertain whether papillary thyroid carcinomas (PTCs) of the same subtype display similar sonographic features. This retrospective analysis of pre-operative sonographic and pathologic findings aimed to assess whether PTCs of the same subtype share sonographic features.Methods: Before undergoing thyroid surgery, 137 patients underwent ultrasound (US) examination. A single radiologist used a picture archiving and communication system and pathologic reports to investigate all sonographic features of the largest and second largest PTCs. Additionally, the radiologist evaluated the similarity of sonographic features between primary (largest), secondary (second largest), and daughter (secondary with same subtype as the primary) PTCs.Results: Of the 137 PTC patients, 48 (35.0%) had multiple PTCs; however, 5 had no US images of the secondary PTC. Of the 43 secondary PTCs with US images, 9 (20.9%) secondary PTCs were of a different subtype than the primary PTC and revealed sonographic features that differed from those of the primary PTC. Of the 48 patients with multiple PTCs, the subtype was the same in the primary and secondary PTCs in 34 (70.8%) patients. Of the 34 daughter PTCs, 32 (94.1%) had sonographic features similar to those of the primary PTC, whereas 2 (5.9%) showed different sonographic features than the primary PTC. There was no significant difference between primary and daughter PTCs in the size, location, sonographic features, or Korean Thyroid Imaging Reporting and Data System category (P>.05).Conclusion: Daughter PTCs show similar sonographic features as the primary PTC.Abbreviations: K-TIRADS = Korean Thyroid Imaging Reporting and Data System; PTC = papillary thyroid carcinoma; US = ultrasound     

Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level

Objective: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes.Methods: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated.Results: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC.Conclusion: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels.Abbreviations: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma     

BRAF Mutation Analysis of Fine-Needle Aspiration Biopsies of Papillary Thyroid Carcinoma: Impact on Diagnosis and Prognosis

Objective: The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis. Study Design: FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used in this study. DNA was extracted from archival cytology slides. Mutation analysis was performed by standard sequencing and locked nucleic acid-PCR/sequencing. Results: The BRAF V600E mutation was present in 46% of cases, but it was absent in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases. Recurrence was significantly more frequent (p = 0.006) in cases with BRAF mutations and 54% of these cases presented with stage 2 or higher. Conclusion: The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence. BRAF mutation analysis did not provide a significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or atypical in our institution.     

Cytopathology of non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants

Objective

Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well‐defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features.

Methods

Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC‐FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared.

Results

There were 23 NIFTP cases, 18 FVPTC and 8 PTC‐FP. A microfollicle‐predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC‐FP showed high‐grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003).

Conclusion

NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC‐FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology.

     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Thyroseq®V2.0 Molecular Testing: A Cost-Effective Approach for the Evaluation of Indeterminate Thyroid Nodules

Objective: Approximately 15 to 30% of thyroid nodules have indeterminate cytology. Many of these nodules are treated surgically, but only 5 to 30% are malignant. Molecular testing can further narrow the risk of malignancy of these nodules. Our objective was to assess the cost effectiveness of ThyroSeq®V2.0 compared to diagnostic thyroidectomy for the evaluation of indeterminate nodules.Methods: Cytology and histopathology slides of Bethesda category III and IV (suspicious for follicular neoplasia [SFN]) nodules obtained between January 1, 2014 and November 30, 2016 were re-reviewed by 2 endocrine cytopathologists. Costs for a diagnostic approach using ThyroSeq® were calculated and compared to those of diagnostic thyroidectomy.Results: We included 8 Bethesda category III nodules that underwent ThyroSeq® and 8 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 4 were positive for mutations and underwent thyroid surgery. The average cost per nodule evaluated was $14,669 using ThyroSeq®, compared to $23,338 for diagnostic thyroid surgery. The cost per thyroid cancer case detected was $58,674 using ThyroSeq® compared to $62,233 for diagnostic thyroid surgery. We included 13 nodules Bethesda category IV that underwent ThyroSeq® and 11 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 6 were positive for mutation and underwent thyroid surgery. The average costs per nodule evaluated were $14,641 using ThyroSeq® and $24,345 using diagnostic thyroidectomy. The cost per thyroid cancer case detected was $31,721 when using ThyroSeq® compared to $53,560 for diagnostic thyroidectomy.Conclusion: The use of ThyroSeq® in our institution is cost effective compared to diagnostic thyroid surgery for the evaluation of Bethesda categories III and IV (SFN) nodules.Abbreviations: FNA = fine-needle aspiration; GEC = gene expression classifier; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid cancer; SFN = suspicious for follicular neoplasia     

IS MEASUREMENT OF CIRCULATING TUMOR DNA OF DIAGNOSTIC USE IN PATIENTS WITH THYROID NODULES?

Objective: Circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA), is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detecting thyroid malignancy in patients with thyroid nodules.Methods: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, 1-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules. The ctDNA panel consisted of 96-mutations in 9 cancer driver genes. The primary outcome measures were the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of our ctDNA panel for the diagnosis of thyroid malignancy as determined by pathologic and/or molecular tissue examination.Results: Results from 10 subjects could not be determined due to inadequate volume or technical issues. The final classifications of the thyroid nodules were 13 malignant and 43 benign lesions. A KRAS G12V mutation was detected in the plasma of 1 patient with stage IVA papillary carcinoma whose tissue contained the same mutation. Two of the 43 patients with benign lesions also had ctDNA detected, giving a sensitivity of 7.7%, specificity of 95.35%, PPV of 33.33%, and NPV of 77.35%. There were no significant differences between benign or malignant lesions in cfDNA levels.Conclusion: Neither cfDNA measurements nor our panel of ctDNA mutations are sensitive or specific enough to provide valuable information over FNAB. An expanded panel and the inclusion of proteomics may improve sensitivity and specificity for thyroid cancer detection.Abbreviations: cfDNA = cell-free DNA; ctDNA = circulating tumor DNA; FNAB = fine-needle aspiration biopsy; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features     

Statistical Comparison of Afirma Gsc and Afirma Gec Outcomes in a Community Endocrine Surgical Practice: Early Findings

Objective: The Veracyte Afirma Gene Expression Classifier (GEC) has been the most widely used negative predictive value molecular classifier for indeterminate cytology thyroid nodules since January 2011. To improve the specificity and further reduce unnecessary thyroid surgeries, a second-generation assay (Afirma Genetic Sequence Classifier &lsqb;GSC]) was released for clinical use in August 2017. We report 11 months of clinical outcomes experience with the GSC and compare them to our 6.5-year experience with the GEC.Methods: We searched our practice registry for FNAB nodules with Afirma results from January 2011through June 2018. GEC versus GSC results were compared overall, in oncocytic and nononcocytic aspirates and by pathologic outcomes.Results: GSC identified less indeterminate cytology nodules as suspicious (38.8%; 54/139) when compared to GEC (58.4%; 281/481). There was a decrease of in the percentage of oncocytic fine-needle aspiration thyroid biopsy (FNAB) subjects classified as suspicious in the GSC group, with 86 of 104 oncocytic indeterminates (82.7%) classified as suspicious by GEC and 12 of 34 (35.3%) classified as suspicious by GSC. The surgery rate in patients with oncocytic aspirates fell from 56% in the GEC group to 31% in the GSC-evaluated group (45%). Pathology analysis demonstrated a false-negative percentage for an incomplete surgical group of 9.5% for GEC and 1.2% for GSC.Conclusion: Our GSC data suggest that the GSC further reduces surgery in indeterminate thyroid nodules by improving the specificity of Afirma technology without compromising sensitivity. A primary determinant for this change is a significant improvement in the specificity of the Afirma GSC test in oncocytic FNAB aspirates.Abbreviations: FNAB = fine-needle aspiration biopsy; GEC = Gene Expression Classifier; GSC = Genetic Sequence Classifier     

Preoperative and Postoperative Evaluation of Thyroid Disease in Patients Undergoing Surgical Treatment of Primary Hyperparathyroidism

ObjectiveTo evaluate the occurrence of thyroid disease in patients undergoing parathyroidectomy for primary hyperparathyroidism.MethodsIn this case series, records of all patients with a diagnosis of primary hyperparathyroidism who underwent parathyroidectomy between January 2005 and December 2008 in our clinic were analyzed retrospectively. Preoperatively, all patients were evaluated with ultrasonography and parathyroid scintigraphy; when needed, thyroid scintigraphy and ultrasound-guided fine-needle aspiration biopsy (FNAB) were used. All patients underwent standard neck exploration. Postoperative histopathologic findings of thyroid tissue were classified as nodular/ multinodular hyperplasia, Hashimoto thyroiditis, papillary thyroid carcinoma, or normal.ResultsFifty-one women and 9 men were included. In the 60 patients, preoperative ultrasonography revealed thyroiditis (without nodules) in 13 (22%), a solitary nodule in 9 (15%) (coexistent with thyroiditis in 7 patients), multinodular goiter in 24 (40%) (coexistent with thyroiditis in 5 patients), and normal findings in 14 (23%). Rates of thyroiditis and nodular goiter were 42% and 55%, respectively. Collectively, prevalence of thyroid disease was 77%. Total thyroidectomy was performed in 27 patients, and hemithyroidectomy was performed in 15 patients. Indications for total thyroidectomy were nondiagnostic or suspicious FNAB results in 5 patients, hyperthyroidism in 4 patients, ultrasonography findings in 11 patients, and intraoperatively recognized suspicious nodularity in 7 patients. Postoperatively, thyroid carcinoma was diagnosed in 9 patients (15%).ConclusionsThyroid disease, particularly thyroid carcinoma, is common in patients with primary hyperparathyroidism. This association should be considered when selecting the surgical procedure. Intraoperative evaluation of the thyroid is as important as preoperative evaluation with ultrasonography and FNAB in patients with thyroid disease and primary hyperparathyroidism. (Endocr Pract. 2010;16:7-13)     

Management of Patients With Low-Risk Papillary Thyroid Carcinoma

ObjectiveTo define a rational, cost-effective, simple approach to managing most patients with papillary thyroid cancer (PTC) who are at low-risk of either cause-specific mortality or tumor recurrence.MethodsTaking advantage of the collective experience of a cohort of 2512 patients with PTC who had initial definitive treatment at the Mayo Clinic in Rochester, Minnesota, between 1940 and 2000, a 5-step approach to the management of low-risk PTC has been devised. This program is based on appropriate preoperative ultrasound localization of neck disease and potentially curative surgery consisting of near-total or total thyroidectomy, with appropriate neck nodal exploration and resection.ResultsThe emphasis of the present program is on the extent of initial surgery, where optimal care is ascribed to a near-total thyroidectomy with curative intent and appropriate neck nodal resection as predicated by appropriate preoperative ultrasonography evaluation of regional lymph nodes. Radioiodine remnant ablation (RRA) is not applicable to patients with PTC who are defined on the day of definitive initial surgery to be at low risk as defined by a metastasis, age, completeness of resection, invasion, and size (MACIS) score of less than 6.ConclusionThe outlook for patients with low-risk PTC is very optimistic, with rates at 30 postoperative years of only 1% for cause-specific mortality and less than 15% for tumor recurrence at any site. The long-term results obtained by potentially curative bilateral resection, appropriate regional lymph nodal excision, and selective use of RRA are excellent. Realistically improving these acceptably low rates for cause-specific mortality and tumor recurrence may be difficult. (Endocr Pract. 2007;13:521-533)     

Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.     

Hyalinizing trabecular tumor in a background of lymphocytic thyroiditis: a challenging neoplasm of the thyroid

ObjectiveTo describe a case of hyalinizing trabecular tumor (HTT) in a background of lymphocytic thyroiditis that was misdiagnosed as papillary thyroid carcinoma (PTC) based on fine-needle aspiration (FNA) cytologic findings and overtreated with total thyroidectomy.MethodsWe present a case report, including the imaging and pathologic findings, of a 68-year-old woman who presented with a multinodular goiter that was suspicious for PTC.ResultsOn the basis of FNA cytologic findings, she underwent a total thyroidectomy, and histologic examination of the thyroid gland revealed HTT in a background of lymphocytic thyroiditis. Radioiodine treatment was not administered because of the tumor’s low risk profile. No metastatic foci were established under nonsuppressive levothyroxine therapy after 3 years of follow-up.ConclusionsHTT is a challenging entity because of the uncertainty of its nature, the diagnostic challenges,and the mimicry of other types of thyroid tumors. In order to avoid overtreatment, endocrinologists and thyroid surgeons should be aware of the features of HTT, and suspicious cases should be evaluated by experienced cytopathologists. (Endocr Pract. 2011;17:e140-e143)     

Nuclear grooves in the aspiration cytology of papillary carcinoma of the thyroid

Nuclear grooving has recently been shown to be a useful morphologic feature in the diagnosis of papillary carcinoma of the thyroid in tissue sections and imprint smears. In order to assess the diagnostic value of nuclear grooving in cytologic specimens, the presence of this feature was evaluated in fine needle aspirates from 20 papillary carcinomas of the thyroid, 10 follicular adenomas, 3 follicular carcinomas, 1 medullary carcinoma, 10 nodular goiters and 4 cases of Hashimoto's thyroiditis. In each case, 30 random high-power fields (HPFs), or all fields in less cellular smears, were examined, and the percentage of the fields in which nuclear grooving could be seen was recorded. Seventeen of 20 papillary carcinomas (85%) showed nuclear grooves in more than 25% of the HPFs examined; in the remaining three cases, grooves were observed in less than 25% of the HPFs. In control cases (all other thyroid lesions), nuclear grooves either were absent or were present in less than 25% of the HPFs examined. These findings suggest that nuclear grooving, when seen in abundance, can be considered a reliable criterion for the diagnosis of papillary carcinoma in fine needle aspiration cytology of the thyroid. The presence of occasional grooves, however, should be regarded as a nonspecific finding.