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.     

A review of the cytomorphological features of NIFTP

Follicular variant of papillary thyroid carcinoma (FVPTC), including encapsulated (E-FVPTC) and infiltrative (I-FVPTC) forms, account for approximately 30% of all PTC. These subtypes demonstrate different biological behavior and molecular profiles when compared to classical PTC. E-FVPTC has low regional recurrence and metastatic potential with a biological behavior similar to that of follicular adenoma. In 2015, a multidisciplinary panel of experts revised the diagnostic terminology for cases of noninvasive E-FVPTC to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). NIFTP was morphologically defined as a noninvasive follicular patterned neoplasm with nuclear features of PTC and scant nuclear pseudo-inclusions, specifically excluding papillary structures and psammoma bodies. The employment of NIFTP diagnostically has significantly impacted fine needle aspiration (FNA) diagnosis and the associated risk of malignancy employed in reporting thyroid FNA specimens. The emerging literature suggests specific cytomorphologic features more frequently encountered with NIFTP compared to cases of I-FVPTC. This article reviews the cytology literature regarding NIFTP and discusses the significance of this new entity in the practice of thyroid cytopathology.     

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.     

Follicular thyroid lesions coexisting with Hashimoto's thyroiditis: incidence and possible sources of diagnostic errors

Our objectives were to study the types and incidence of thyroid follicular lesions coexisting with Hashimoto's thyroiditis (HT), the pitfalls in their cytodiagnosis, and the effect on management. All cases of HT diagnosed by fine-needle aspiration (FNA) and/or histology over a 7-yr period were retrospectively studied. HT coexisted with follicular adenoma (FA) in 6 cases, follicular variant of papillary carcinoma (FVPC) in 1 case, and goitrous nodule (GN) in 2 cases. The overall incidence rates of thyroid neoplasm and goitrous nodules coexistent with HT were 15% and 3.5%, respectively. A preoperative FNA diagnosis was available in 10 histologically proven cases of HT. A false-positive diagnosis of follicular neoplasm (FN) that led to unnecessary thyroidectomies was given in 3 cases. In 2 of these, the cytological diagnosis was HT with the possibility of coexisting FN, and in the third case, the cytological finding of HT was misinterpreted as FN. The main causes of these diagnostic pitfalls were the presence of hyperplastic follicular cells with nuclear pleomorphism, a paucity of lymphoid cells in burned-out HT, and lack of ones exposure. Nuclear pleomorphism was observed in none of the follicular adenomas. FNA diagnosed accurately the coexisting lesions in 6 cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by 85.7%, with no false-negative results. Indeed, aspiration on and around the thyroid nodule helps in sampling HT. However, HT may dominate the smear and obscure neoplasia. This can be avoided if the procedure is performed by the pathologist and the aspiration is done on the nodule only. The overlapping cytological features of FN and HT were the main causes of false-positive results. This can be reduced by avoiding the diagnosis of FN in the presence of follicular-cell pleomorphism and/or moderate to excessive numbers of lymphoid cells, provided proper aspiration technique is maintained.     

Distinguishing tall cell variant of papillary thyroid carcinoma from usual variant of papillary thyroid carcinoma in cytologic specimens

Tall cell variant (TCV) is an aggressive form of papillary thyroid carcinoma (PTC), usually associated with higher local recurrence and distant metastasis. Some authors have suggested that TCV can be effectively diagnosed on thyroid fine-needle aspiration (FNA); this diagnosis may help clinicians plan a more effective treatment regimen. The objective of this study was to compare the FNA specimens of TCV with those of usual variant of PTC (UV-PTC) and to define a set of distinguishing cytologic features. Thirty FNA specimens of histologically proven TCV were compared with 32 FNA specimens of histologically proven UV-PTC. All specimens were evaluated for the following features: papillary groups (PG), elongated/tall cells (EL/TC), oncocytic cytoplasm (OC), distinct cell borders (DCB), prominent central nucleoli (PCN), intranuclear grooves (NG), and intranuclear inclusions (NI). These features were semiquantitatively measured on a sliding scale of 0-4 in both air-dried Diff-Quik-stained and ethanol-fixed Papanicolaou-stained preparations. TCV showed distinctive cytologic features, which can distinguish them from UV-PTC. These included EL/TC, OC, and DCB and were also found to be statistically significant (P < 0.0001). No significant differences were noted for PG and NG. The NIs in TCV cases were qualitatively different than those in UV-PTC. In TCV there were multiple inclusions within the same nucleus imparting a "soap bubble appearance" to the nucleus. This feature was seen in almost all cases of TCV and was rarely seen in usual PTC. On the basis of the above-mentioned cytologic features, TCV can be distinguished from usual PTC in FNA specimens.     

Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations

The follicular variant (FV) of papillary thyroid carcinoma is characterized by a follicular growth pattern and cytologic features of papillary carcinoma. ret/PTC rearrangements are common in classic papillary thyroid carcinoma (PTC) and PAX8-PPAR gamma and ras mutations in follicular thyroid carcinoma. Their prevalence in FV has not been established. We studied these genetic alterations and clinical-pathologic features in 30 FV cases and compared those with 46 non-FV papillary carcinomas. FV cases revealed 1 ret/PTC rearrangement (3%) and 13 ras mutations (43%). Non-FV cases harbored 13 ret/PTC (28%) (P = .006) and no ras mutations (P = .0002). No PAX8-PPAR gamma was found in either group. FV cases demonstrated a significantly higher prevalence of tumor encapsulation, angiovascular invasion, and poorly differentiated areas and a lower rate of lymph node metastases. These data indicate that the FV of papillary carcinoma has a distinct set of molecular alterations and is characterized by a high frequency of ras point mutations.     

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.     

Can cytomorphology differentiate between benign nodules and tumors arising in Graves' disease?

Fine-needle aspiration (FNA) specimens from thyroid nodules arising in Graves' disease (GD) can pose diagnostic difficulties because the cytomorphologic changes in GD may mimic nuclear features of papillary thyroid carcinoma (PTC). In addition, treatment of GD patients with radioactive iodine (RAI) may cause significant cytologic atypia, further increasing the diagnostic difficulty. From March 1999 to April 2002, a total of 14 hypofunctioning nodules in 9 patients with GD underwent FNA; 3 patients had received RAI treatment. Three cases were diagnosed as suspicious for PTC and 11 as benign. Three patients with the diagnosis of suspicious for PTC on FNA underwent surgery and were found to have papillary carcinoma. We assessed all cases to find key cytologic features that can differentiate between nodules with reactive/reparative nuclear atypia from PTC arising in GD. The cytologic features assessed included cellularity, amount of colloid, monotony of the cell population, oncocytic features, cell crowding, lymphocytic infiltration, nuclear elongation, nuclear grooves, pale powdery chromatin, presence of small eccentric nucleoli, and random nuclear atypia. Each feature was semiquantitatively graded on a sliding scale of 0 to 4, with 0 representing absence and 4 representing a predominance of the feature. The mean value of each feature was calculated and the benign and malignant lesions were compared using the unpaired t-test. Four features were found to be statistically significant in the diagnosis of PTC as compared to the benign nodules in GD. The nuclei of PTC in GD show prominent nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli. All other features studied were not found to be statistically significant. There does exist an overlap between the cytologic features of benign nodules and PTC arising in GD. However, adherence to strict diagnostic criteria (nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli) can enable the diagnosis of PTC arising in GD.     

Follicular Variant of Papillary Thyroid Carcinoma: Accuracy of FNA Diagnosis and Implications for Patient Management

Follicular variant of papillary thyroid carcinoma (FVPTC) creates a continuous diagnostic dilemma among pathologists because of the paucity of nuclear changes of papillary carcinoma and overlapping features with benign and other neoplastic follicular lesions. Current guidelines for the management of thyroid nodules recommend surgery for confirmed PTC, suspicious for PTC, and follicular neoplasm cases, while further immediate diagnostic studies or treatment are not routinely required if the nodule is benign on cytology. This study is designed to determine the accuracy of cytology in the diagnosis of FVPTC, based on the Bethesda classification system, and determine the implications for patient management based on the current recommendation. Based on a retrospective review of cytologic diagnoses between January 2008 and December 2011, thyroid fine needle aspiration (FNA) cytology specimens with subsequent surgical intervention and a final diagnosis of FVPTC were selected. The cytologic diagnoses were compared with the final diagnoses, and the percentage of cases contributing to the final diagnosis of FVPTC was calculated for each diagnostic category. Triage efficiency and diagnostic accuracy were calculated. One hundred and fifty-two cases with histologic confirmation of FVPTC were identified (representing 128 patients—101 female, 27 male). All patients had undergone either lobectomy with completion thyroidectomy or total thyroidectomy. The cytologic diagnosis of “positive for malignancy” accounted for only 27 % of the final histologic diagnosis of FVPTC, while suspicious for carcinoma, follicular neoplasm, follicular lesion of undetermined significance, and benign accounted for 11, 23, 23, and 16 % of the final diagnosis of FVPTC, respectively. Only 18 % of the 55 cases tested were positive for BRAF mutation. The subtle nuclear features of FVPTC pose challenges for an accurate diagnosis. Therefore, a better approach is to triage these cases for surgical intervention and/or further evaluation of the particular nodule. Our triage efficacy for FVPTC was 84 %; however, the diagnostic accuracy of PTC was 38 %. A negative diagnosis on FNA has diagnostic and management implications for up to 16 % of cases because they may have no further immediate diagnostic studies or treatment. BRAF mutation analysis provides minimal effect on diagnostic accuracy.     

Nuclear crease as a cytodiagnostic feature of papillary thyroid carcinoma in fine-needle aspiration biopsies

Nuclear crease or grooving was found to be a diagnostic feature of papillary thyroid carcinoma (PTC) in fine-needle aspiration (FNA) biopsies. The FNA biopsies of 37 cases of PTC, 50 cases of multinodular goiter, and 50 cases of follicular neoplasms (45 follicular adenomas and five follicular carcinomas) were examined. The diagnosis was histologically verified in all the cases. The nuclear crease was found to be present in 34 of 37 cases of PTC and in two of five cases of follicular carcinoma. There was no nuclear crease in any of the other cases examined. Thus, it is concluded that the nuclear crease is a fairly constant and characteristic feature of PTC in FNA biopsies and can be used as a valuable diagnostic criterion.     

Cytopathologic features of medullary carcinoma of the thyroid

Medullary carcinoma of the thyroid (MCT) presents a varied but characteristic cytologic pattern in cellular samples obtained by fine-needle aspiration (FNA) biopsy. In our experience with 17 cases of MCT, ten were identified by cytologic examination. One was acellular. The remaining six were typed as undifferentiated carcinoma (three cases), follicular variant of papillary carcinoma (one case), and cellular adenoma (two cases). Four Hürthle cell tumors and four papillary carcinomas were incorrectly typed as MCT. There was one false positive. Careful consideration of the listed cytologic features should make the FNA biopsy diagnosis of MCT of satisfactory sensitivity for the evaluation of "cold" thyroid nodules. Specificity may be considerably improved by using immunoperoxidase stain for calcitonin granules and/or by large-needle biopsy.     

Nuclear grooves: A useful criterion in the cytopathologic diagnosis of papillary thyroid carcinoma

A recent report emphasized the usefulness of the grooved nucleus as a diagnostic criterion of papillary thyroid carcinoma (PTC) in histopathologic material. The present study was undertaken to evaluate whether grooved nuclei can serve as an additional diagnostic criterion for PTC in cytologic material obtained by fine-needle aspiration (FNA). Slides from 124 consecutive thyroid FNAs were reviewed. Specimens included 11 PTCs, one follicular carcinoma, six follicular adenomas, eight follicular neoplasms not otherwise specified, 10 cases of chronic thyroiditis, and 88 colloid nodules/adenomatous goiters. Among the PTC cases, grooved nuclei were found in all 11 (100%), intranuclear inclusions in nine (82%), papillary fragments in seven (64%), and psammoma bodies in two (18%). Nuclear grooves were also observed in two of the 113 non-PTC cases (1.8%), both of which were colloid nodules, one with extensive Hurthle-cell change. The grooved nuclei were best identified on Papanicolaou-stained material. They were inconspicuous and difficult to identify in air-dried Diff-Quik-stained material. It appears that the recognition of grooved nuclei among tumor cells is a valuable diagnostic feature of PTC in cytologic material stained with polychromatic Papani-colaou stain.     

Paraganglioma‐like medullary thyroid carcinoma: A case report and literature review

Medullary thyroid carcinoma (MTC) accounts for 3%‐5% of all thyroid malignancies. Most MTC can be diagnosed by their typical cytologic and histologic morphology and immunohistochemical features. However, some rare variants of MTC may pose diagnostic difficulties on both cytology and histology. Paraganglioma‐like MTC (PLMTC) is a rare, but widely recognized variant of MTC. PLMTC is known to share morphological and architectural similarities with paraganglioma, hyalinizing trabecular tumor, and carcinomas of thyroid follicular cell origin, such as follicular carcinoma and follicular variant of papillary thyroid carcinoma. The combination of clinicopathologic features and a battery of immunohistochemical markers is essential for making a correct diagnosis. Herein, we report one case of PLMTC with both cytologic and histologic features and review the clinicopathologic features of previously reported cases.     

Follicular neoplasm of the thyroid—vanishing cytologic diagnosis?

The significance of making a diagnosis of follicular neoplasm on fine needle aspiration (FNA) biopsy remains a controversial issue, considering that the diagnosis of follicular carcinoma is based on histological criteria and the significantly decreasing incidence of follicular carcinoma in the general population. On FNA the main differential diagnoses of follicular neoplasm includes follicular variant of papillary carcinoma (FVPC), follicular adenoma, follicular carcinoma and benign solitary nodule occurring in a goiter. Several studies have looked at immunohistochemical and molecular markers to distinguish benign from malignant lesions but none of them have proved to be infallible. Although, FVPC is a distinct entity from the follicular neoplasm group, it is not always possible to separate it from the other follicular lesions because of overlapping cytologic features and often-sporadic presence of nuclear features, follicular variant of papillary carcinoma remains the main pitfall in a diagnosis of follicular neoplasm. Since a significant number of cases that are malignant on follow-up are usually FVPC, consequently, follicular neoplasm is an essential diagnostic consideration on FNA. In addition, follicular carcinoma, despite a decreasing incidence continues to be a real entity. Therefore, it is essential that follicular neoplasm continue to be part of our diagnostic repertoire.     

Ultrasound-guided fine-needle aspiration biopsy of the thyroid: role of on-site assessment and multiple cytologic preparations

Several studies have shown that ultrasound guidance can serve as a valuable aid in improving the diagnostic yield of fine-needle aspiration (FNA) biopsy of thyroid nodules. In this study, we evaluated the combined impact of ultrasound-guidance, rapid on-site evaluation of FNA specimens, and different cytologic preparations (fresh and alcohol-fixed smears, Millipore filter) and staining methods (Diff-Quik and Papanicolaou stains) on the diagnostic yield of thyroid FNA. Ultrasound-guided FNA was performed on 282 patients (313 cases) between November 1997 and April 1999. The diagnostic categories included: benign (198 cases, 63.2%); indeterminate (42 cases, 13.4%); suspicious for follicular variant of papillary carcinoma (26 cases, 8.3%), malignant (32 cases, 10.1%); and nondiagnostic (15 cases, 5%). The nondiagnostic cases also included 6 cystic lesions without any solid component and 3 thyroid-bed aspirations. After excluding these, the nondiagnostic rate was only 2%. Histological follow-up was available in 77 (77/313) cases. The concordance rate between cytological and histological diagnosis was 100% in malignant, 67% in suspicious, and 56% in indeterminate cases. All cases with histologic follow-up were selected to evaluate the independent diagnostic efficacy of each aforementioned cytologic staining method. A definite diagnosis could be made solely on the basis of air-dried, Diff-Quik-stained preparations in 50 (65%), alcohol-fixed, Papanicolaou stained smears in 68 (88%), and Millipore filter preparations in 70 (91%) cases. We conclude that ultrasound-guided FNA combined with on-site evaluation and different cytologic preparations can significantly improve the diagnostic accuracy of thyroid FNA specimens.     

Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.     

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.     

Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion.

No single cytologic feature is specifically diagnostic for papillary thyroid carcinoma. We report herein the presence of swirl-like cellular aggregates in fine needle aspirates of papillary thyroid carcinoma but not in other thyroid entities. Cellular swirls are defined as concentrically organized aggregates of tumor cells in which many of the most peripherally situated cells have ovoid rather than round nuclei that are oriented perpendicular to the radius of the swirl. One hundred Papanicolaou- and/or Diff-Quik-stained FNAs of the thyroid diagnosed as papillary carcinoma, including seven fine needle aspirates of cervical lymph nodes showing metastatic papillary carcinoma, with or without cell blocks, were reviewed for the presence of cellular swirls. An additional 100 thyroid FNAs, similarly stained and prepared, diagnosed as nodular goiter, Hashimoto's thyroiditis and follicular neoplasm were also reviewed for the presence of cellular swirls. Cellular swirls were easily observed at screening magnification and confirmed at high magnification. Seventeen of 100 FNAs (17%) of papillary carcinoma contained cellular swirls. No cases diagnosed as nodular goiter, Hashimoto's thyroiditis or follicular neoplasm contained these structures. Thirteen cases with swirls had histologic follow-up. These comprised seven papillary carcinomas with classical histopathology, two designated 'differentiated papillary carcinoma,' two with follicular variant histopathology; one with a minor component of follicular variant histopathology; one papillary carcinoma metastatic to a cervical lymph node with classic histopathology. Swirls occurred in cases with relatively little pleomorphism, or in well-differentiated regions of papillary carcinoma that also displayed less well-differentiated components. Cellular swirls are a finding that is highly specific to papillary thyroid carcinoma. They are easily seen at screening magnification. Their presence in a FNA specimen may be helpful in cases where classic criteria for papillary thyroid carcinoma are scarce, particularly in well-differentiated papillary thyroid carcinoma. While the size and scope of this study are insufficient to conclude that cellular swirls alone are diagnostic of papillary thyroid carcinoma in the absence of other criteria, we believe these structures should be added to the list of diagnostic criteria.     

Cribriform‐morular variant of papillary thyroid carcinoma—Cytological and immunocytochemical findings of 18 cases

The purpose of this article was to describe cytologic findings of cribriform‐morular variant of papillary thyroid carcinoma (CMV‐PTC) in detail, to review previously reported cases, and to emphasize the diagnostic significance of this subtype. We examined 19 ultrasound‐guided fine needle aspiration (FNA) specimens from 18 CMV‐PTC patients. Cytologic features of CMV‐PTC were as follows, (1) hypercellularity, (2) papillary arrangement composed of tall columnar cells, (3) cribriform pattern, (4) morules, (5) spindle cells, (6) obscure ground‐glass nuclei, (7) peculiar nuclear clearing (PNC), (8) foamy or hemosiderin‐laden histiocytes, (9) hyaline materials, (10) absence of colloid in the background. The nuclear and cytoplasmic immunoreactivity of beta‐catenin and biotin‐positive PNC can indicate CMV‐PTC. We believe that cytologic diagnosis of CMV‐PTC is possible and it may lead to the early detection of polyposis coli. Diagn. Cytopathol. 2010;38:890–896. © 2010 Wiley‐Liss, Inc.