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%.     

Sensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsy

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be extremely challenging and may be associated with false negative diagnoses. The purpose of this study was to determine the minimal cytologic criteria needed to identify FVPTC. We examined sixty-nine fine-needle aspiration (FNA) cases, processed with Diff-Quik and Papanicolaou stains, that were either diagnostic or suspicious of FVPTC. All cases had histologic confirmation. These cases included 29 FVPTC, 18 classic papillary thyroid carcinoma (PTC), 17 follicular neoplasm (6 adenomas, 10 carcinomas, 1 neoplasm NOS), 2 lymphocytic thyroiditis and 3 nodular goiter. Seven of the most commonly cited cytomorphologic features, including flat syncytial sheets, nuclear enlargement, fine chromatin, nuclear grooves, nuclear pseudoinclusions, and amount of colloid and cytoplasm, were evaluated. A diffuse distribution of fine chromatin, nuclear grooves, and colloid was seen more often in FVPTC than in follicular neoplasm (p<0.01). The combination of flat/syncytial sheets, nuclear enlargement, and fine chromatin was observed in all our cases of FVPTC, and is therefore considered a sensitive marker in detecting FVPTC. Logistic regression analysis revealed colloid to be the only positive predictor in favor of FVPTC over classic PTC.     

Fine-needle aspiration cytology diagnosis of colloid nodule versus follicular variant of papillary carcinoma of the thyroid

The cytologic differential diagnosis of colloid nodule (CN) and the follicular variant of papillary carcinoma (FVPC) is difficult with common morphologic features. To assess the utility of 18 cytologic morphometric parameters in the diagnosis of these thyroid lesions we evaluated 31 FNA samples that had histologic confirmation of the diagnoses. These 31 cases included 15 cases of CN, 8 cases of FVPC, and 8 cases of the usual variant of papillary carcinoma (UVPC) for reference values. For the morphometric analysis we used an Optimas 4.0 image analysis system. Comparing the CN group with the UVPC group revealed that eight of the parameters had statistically significant differences. The UVPC specimens were more cellular, less cohesive, had presence of papillary cellular groups more frequently, larger nuclei (UVPC: 109.33 ± 30.19 μm²; CN: 66.81 ± 15.02 μm2), higher nuclear to cytoplasmic (N/C) ratio, larger nucleoli, and present nuclear grooves and nuclear pseudoinclusions more frequently. The FVPC group differed from the CN group only in three parameters which included larger nuclei (98.49 ± 18.24 μm²), higher N/C ratio, and a more frequent presence of nuclear pseudoinclusions. When we compared these two variants of papillary carcinoma, we found that the UVPC specimens had less cellular cohesion, less preservation of the architectural polarity and a more frequent presence of papillary cellular groups than the FVPC. The FVPC can be differentiated from CN based on nuclear changes, which included a larger size, higher N/C ratio, and presence of pseudoinclusions. The absence of cellular cohesion and polarity combined with the presence of papillary groups are useful in separating the UVPC from the FVPC. A cutoff of 75 μm² should be used in separating benign from malignant nuclei. Diagn. Cytopathol. 1998;18:87–90. © 1998 Wiley-Liss, Inc.     

The fine-needle aspiration appearance of the follicular variant of thyroid papillary carcinoma: A report of three cases

The follicular variant of thyroid papillary carcinoma (FVTPC) is an uncommon neoplasm with the architectural features of a follicular lesion and the nuclear characteristics of a papillary carcinoma. The fine-needle aspiration (FNA) appearance is underreported in the literature. Three cases of histologically confirmed FVTPC that were aspirated prior to surgery are presented. Although the cytological features were suspicious or confirmatory of a low-grade thyroid carcinoma, they did not convey a specific diagnosis of the FVTPC. We suggest that this variant is recognizable as a neoplasm requiring surgical excision on FNA, but that the cytological appearance does not allow its specific diagnosis.     

The triage efficacy of fine needle aspiration biopsy for follicular variant of papillary thyroid carcinoma using the Bethesda reporting guidelines

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.     

Sonographic and cytologic differences of NIFTP from infiltrative or invasive encapsulated follicular variant of papillary thyroid carcinoma

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.     

Update on follicular variant of papillary thyroid carcinoma with an emphasis on new terminology: noninvasive follicular thyroid neoplasm with papillary-like nuclear features

The most common papillary thyroid carcinoma (PTC) variant is the follicular variant, representing ∼30% of all PTCs. The tumour is most common in middle aged (4th – 5th decades) women, who usually present with a single dominant nodule (about 3 cm). By definition, follicular architecture must be the dominant finding, while demonstrating the nuclear features of PTC. Papillary structures are <1% of volume, while necrosis, increased mitoses (>3/10 high power fields) and psammoma bodies are absent. The tumour category is divided into “encapsulated/well demarcated” and “invasive” types. The nuclear features include enlarged, elongated and overlapping nuclei; membrane irregularities (irregular contours, grooves and pseudoinclusions); chromatin clearing, margination and glassy nuclei. When the tumour is encapsulated/well demarcated without invasion, demonstrating the other inclusion and exclusion criteria, the new name of “Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features” (NIFTP) is used, a tumour that requires no additional treatment.     

Encapsulated papillary thyroid carcinoma, follicular variant: a misnomer

Papillary thyroid carcinoma (PTC) has long been diagnosed based on its unique nuclear features (PTC-N); however, significant observer discrepancies have been reported in the diagnosis of encapsulated follicular patterned lesions (EnFPLs), because the threshold of PTC-N is subjective. An equivocal PTC-N may often occur in non-invasive EnFPLs and benign/malignant disagreements often create serious problems for patients' treatment. This review collects recent publications focusing on the so-called encapsulated follicular variant of papillary thyroid carcinoma (EnFVPTC) and tries to emphasize problems in the histopathological diagnosis of this spectrum of tumors, which covers encapsulated common-type PTC (EncPTC), EnFVPTC, well-differentiated tumor of uncertain malignant potential (WDT-UMP), follicular adenoma (FA) with equivocal PTC-N and minimally invasive follicular carcinoma (mFTC). We propose that EnFVPTC and other EnFPLs with equivocal PTC-N should be classified into a unified category of borderline malignancy, such as well-differentiated tumor of uncertain behavior (WDT-UB), based on their homogeneous excellent outcome. It is suggested that the unified nomenclature of these lesions may be helpful to reduce significant observer disagreements in diagnosis, because complete agreement in the diagnosis of an EncPTC, EnFVPTC or FA by all pathologists may be not possible for this problematic group of tumors. In conclusion, a malignant diagnosis of EnFVPTC should not be used to cover this spectrum of tumors until uncertainty about the nature of this lesion is settled, whether it is benign, precancerous or malignant.     

Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma

The accurate diagnosis of differentiated thyroid tumors is very important for clinical management of patients. The histopathological distinction between some types of differentiated thyroid tumors can be very difficult even for experienced pathologists. We used immunohistochemical markers from published data obtained from DNA expression profiling, tissue microarray analysis, and immunohistochemistry to analyze a series of 157 thyroid tumors and 5 normal thyroids. These analyses showed that several antibodies were useful in distinguishing follicular adenomas from follicular variant of papillary thyroid carcinomas including HBME-1, CITED 1, galectin-3, cytokeratin 19, and S100A4 (p<0.0001). A combination of markers consisting of a panel of HBME-1, galectin-3, and CK19 or a panel of HBME-1, CITED1, and galectin-3 was usually most effective in distinguishing follicular adenoma from follicular variant of papillary thyroid carcinoma. Because individual tumors may not express some of these markers, the use of a panel of antibodies is recommended. These results indicate that some individual antibodies or a panel of antibodies combined with histopathological analysis can be useful in separating follicular adenoma (FA) from follicular variant of papillary thyroid carcinoma (FVPTC).     

Thyroid follicular neoplasm: Analysis by fine needle aspiration cytology,frozen section,and histopathology

We performed a retrospective analysis of follicular neoplasm data obtained from frozen section examinations of thyroid nodules. A total of 5,660 patients underwent preoperative neck ultrasonography and fine‐needle aspiration cytology (FNAC), surgical treatment, and follow‐up at a medical institute. Patients with papillary thyroid microcarcinoma were excluded from this study. In 971 cases, frozen section examination was performed during the surgical treatment of follicular neoplasm that was diagnosed via FNAC. Thyroid malignancies were histologically confirmed in 25.1% of cases (244/971). Among the patients with papillary thyroid carcinoma, 45 were diagnosed with the follicular variant of papillary thyroid carcinomas (27.4%). The diagnostic sensitivity of frozen section for the nonfollicular variant of papillary thyroid carcinoma was better than that for the follicular variant of papillary thyroid carcinoma (89.1% versus 78.9%; P = 0.1023). For 12 cases the diagnosis was atypical follicular adenomas. The diagnostic accuracy of frozen section in cases of follicular neoplasm was 76.9% with a sensitivity of 84.8% and a specificity of 98.9%. In conclusion, our analysis revealed high rates of accuracy when using frozen tissue sections for early diagnosis and treatment of follicular neoplasm; thus, an early decision to extent of surgery prevents a risky follow‐up surgery. Diagn. Cytopathol. 2010;38:801‐805. © 2009 Wiley‐Liss, Inc.     

FNA diagnosis of a metastatic papillary thyroid carcinoma arising from a previously unknown follicular variant of papillary thyroid microcarcinoma

While metastatic tumors to bone or lymph nodes from previously known primaries are often successfully diagnosed via fine‐needle aspiration (FNA), a metastatic deposit in a patient with no previously known cancer may pose a diagnostic dilemma. Here, we present a case of metastatic papillary thyroid carcinoma that presented initially as a large pelvic bone mass. FNA was performed on this mass. The diagnosis was challenging due the fact that the tumor did not display the classic nuclear features associated with papillary thyroid carcinoma, instead the nuclear morphology was in keeping with a follicular thyroid carcinoma. Given the patient's concurrent, unremarkable thyroid imaging studies the final diagnosis required an extensive immunohistochemical work‐up. Diagn. Cytopathol. 2014;42:711–715. © 2013 Wiley Periodicals, Inc.     

Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology

Mixed medullary-follicular carcinoma (MMFC) of thyroid is an extremely rare tumor, characterized by coexistence of morphological and immunohistochemical features of both medullary carcinoma and follicular (or papillary) carcinoma. We herein present fine needle aspiration (FNA) findings of a histology-confirmed MMFC along with a review of literature. The patient was a 64-year-old woman who had a history of Hashimoto's thyroiditis and presented with enlargement of preexisting right thyroid nodule. An US-guided FNA of the thyroid nodule was performed and conventional smears were prepared. A cytologic diagnosis of "positive for malignancy, consistent with medullary thyroid carcinoma (MTC)" was rendered based on the presence of features characteristic for MTC, and the absence of components of follicular neoplasm (adenoma and carcinoma) or papillary carcinoma. However, microscopic examination of the follow-up total thyroidectomy specimen with the aid of immunocytochemical study detected minor portion of follicular carcinoma in addition to MTC. A histologic diagnosis of MMFC was then established. While specific identification of MMFC by FNA may be difficult, it should be emphasized that adequate sampling in conjunction with the proper immunostaining panel could have highlighted the different aspects of the mixed tumor.     

Papillary thyroid carcinoma with an adenoid cystic pattern: report of a case with fine-needle aspiration cytology and immunocytochemistry

Although fine-needle aspiration (FNA) cytologic features of conventional papillary thyroid carcinoma (PTC) and some of its variants have been documented in the literature, PTC with an adenoid cystic pattern has not so far been described. A 35-year-old woman presented with solitary cold nodule in the right lobe of thyroid. FNA smears from the nodule showed features of PTC such as papilliform clusters, monolayered sheets, psammoma bodies, increased frequency of nuclear grooves, and intranuclear cytoplasmic inclusions. In addition, there were areas of follicular formation and light-pink to deep-purple hyaline globules with a laminated appearance and surrounded by neoplastic cells, reminiscent of adenoid cystic carcinoma. These globules were present in 53% of the follicles. Immunocytochemical staining for thyroglobulin yielded positive cytoplasmic reaction in the neoplastic cells. Histopathology of the thyroidectomy specimen confirmed the cytodiagnosis of PTC. The hyaline globules were present focally and were light pink to deep purple with a laminated appearance resembling psamomma bodies. The colloid and follicular cells were positive for thyroglobulin but the hyaline globules were negative. Von Kossa staining for calcium revealed positive reaction in the psamomma bodies and some of the hyaline globules, indicating that the globules may be the beginning of psammoma bodies. Thus, FNA cytology was useful in diagnosing an unusual variant of PTC.     

Incidence of neoplasia in Hashimoto's thyroiditis: A fine-needle aspiration study

There is a recognized association between Hashimoto's thyroiditis (HT) and thyroid neoplasms. We reviewed fine-needle aspirations (FNAs) from 90 patients with HT to assess the contribution of this procedure. For seven patients, FNA showed HT and follicular neoplasm (n = 6) or HT and papillary carcinoma (n = 1). Eighteen patients underwent thyroid resection. Three patients had follicular adenomas which were not detected by FNA, one patient had papillary carcinoma confirmed, and six patients with follicular neoplasm by FNA were negative for tumor. Thus, 4% of our patients had confirmed neoplasms, an incidence lower than usually reported. One reason for the lower rate of neoplasia in our series was misinterpretation of follicular neoplasia in the background of HT. The cytologic changes in the hyperplastic follicular and metaplastic oncocytic epithelium are similar to those seen in follicular neoplasm. Our study suggests that these processes may be indistinguishable, and thus, in the presence of HT, the diagnosis of follicular neoplasm probably should not be rendered. Diagn Cytopathol 1996;14:38–42. © 1996 Wiley-Liss, Inc.     

Synchronous papillary thyroid carcinoma and follicular thyroid carcinoma: case report and review of literature

Collision tumor is a term denoting two histologically distinct tumor types occuring at the same anatomic site, which is a rare clinical entity. In the thyroid gland, collision tumors are rare. Here we report a case of the synchronous occurrence of follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). The current case report describes a 40-year-old woman with synchronous FTC and PTC. Pathologists and surgeons should be aware of collision tumors to avoid possible misdiagnosis.