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2017, Cilt 56, Sayı 3, Sayfa(lar) 115-123
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Follicular variant of papillary thyroid carcinoma: Gray-scale and Doppler sonographic features
Tülay Öztürk1, Süha Süreyya Özbek1, Gülgün Demirpolat Kavukçu1, Yeşim Ertan2, Müge Tunçyürek2, Ali Veral2, Deniz Nart2, Recep Gökhan İçöz3, Mehmet Mahir Akyıldız3, Özer Makay3
1Ege University Faculty of Medicine, Department of Radiology, İzmir, Turkey
2Ege University Faculty of Medicine, Department of Pathology, İzmir, Turkey
3Ege University Faculty of Medicine, Department of Surgery, İzmir, Turkey
Keywords: Thyroid carcinoma, papillary thyroid carcinoma, follicular variant, Doppler
Abstract
Aim: The aim of this study was to present the sonographic characteristics of follicular variant of papillary thyroid carcinoma (FVPTC) related to different forms of the thyroid nodules, including those without a capsule. Another purpose was to analyze the color Doppler ultrasonography (CDUS) features of this unique tumor, which have not been intensively studied in previous works.

Materials and Methods: Twenty-two thyroid nodules (male/female: 17/5; mean age±SD: 42±16 years; range: 17-70) diagnosed with FVPTC were included in this study. The sonographic and Doppler features of the nodules were analyzed retrospectively. The intranodular pattern of vascularity was categorized with regard to the presence of perinodular and/or intranodular vascular signals, as well as a “spoke-and-wheel” appearance.

Results: The length of the nodules varied from 6 to 55 mm. Most of nodules were purely solid (77.3%), isoechoic (59.1%) or hypoechoic (31.8%) and had an oval shape (72.7%), well-defined margins (68.2%) and a peripheral hypoechoic halo (68.2%). Thirty-one percent of the nodules had a lobulated shape with microlobulated margins or an irregular configuration with ill-defined margins. Encapsulated FVPTCs had a peripheral hypoechoic halo and well-defined margins, whereas infiltrative cases exhibited the opposite characteristics. No calcification was observed in 72.7% of the nodules. Perinodular and predominantly peripheral intranodular hypervascularity was observed in 14 nodules (66.7%) and was the dominant pattern of vascularity in most of the encapsulated FVPTCs, unlike the infiltrative FVPTCs.

Conclusion: Diagnosis of FVPTC should always be considered when large thyroid nodules with predominantly solid echo-texture and other sonographic features that suggest benignity and nodular hypervascularity are observe.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Disscussion
  • Conclusion
  • References
  • Introduction
    The most common malignancy of the thyroid gland is papillary thyroid carcinoma (PTC). Multiple variants of PTC have been reported with distinct histopathological features. The follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common variant and comprises 9-22% of all PTC nodules1. As a unique tumor, FVPTC presents with dual histopathologic characteristics. In addition to having specific nuclear features that suggest the diagnosis of PTC, FVPTC also presents with a predominant follicular pattern mimicking other follicular neoplasms2. FVPTC is seen relatively frequently in younger populations and tends to form larger thyroid nodules. Local lymph node metastasis is rarer than PTC, whereas the clinicopathologic features are relatively favorable3. Liu et al.4 reported lower rates of extrathyroideal extension, positive margins and regional lymph node metastasis in patients with the encapsulated form, and no distant metastasis or recurrence of this form was observed in their series.

    FVPTC, especially the encapsulated form, presents with benign imaging features as in follicular adenomas and carcinomas, with which it has similar genetic alterations and biological behavior. These facts account for why diagnosing encapsulated FVPTC and differentiating it from other tumors with a follicular pattern is a difficult task, both in cytological and sonographic studies, unlike the infiltrative form that has a more malignant appearance5. The reported and relatively benign findings in the literature related to FVPTC are most likely due to the encapsulated form6-8. In this study, we aimed to present the ultrasonographic characteristics of FVPTC related to different forms of the thyroid nodules, including those without a capsule. Another purpose was to analyze the color Doppler ultrasonography (CDUS) features of this unique tumor, which have not been intensively studied in previous work.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Disscussion
  • Conclusion
  • References
  • Methods
    This study was approved by the local research ethics committee. Twenty-two patients with the histopathologic diagnosis of FVPTC were retrospectively evaluated. Only the largest FVPTC (“dominant FVPTC” in case of multiplicity) in each patient was enrolled in the study. The size, echogenicity, homogeneity, shape and marginal patterns, the presence or absence of any peripheral halo, internal structure, cystic component or calcification was noted. In addition, the pattern of vascularity was categorized with respect to the presence and degree of perinodular and/or intranodular vascular signals. The nodules exhibiting circumscribing perinodular vessels with multiple centripetal vascular branches were accepted to have a “spoke-and-wheel” appearance in accordance with the relevant literature9.

    The US examinations were performed between 2006 and 2013 using one of three high-resolution Doppler US units (Sonoline Antares, Acuson Antares, Acuson S2000; all by Siemens Medical Solutions USA Inc., Mountain View CA, USA) equipped with tissue harmonic and spatial compound imaging technologies. The examinations were carried out using the following high-resolution, multiple linear-array transducers: VFX 9-4 (4-9 MHz), VFX 13–5 (5-13 MHz), 14L5 (5-14 MHz), 18L6 HD (5.5-18 MHz). All examinations were performed by the same radiologist (SSO), with more than 20 years of experience on medical US applications.

    Sixteen of the 22 patients underwent US guided fine-needle aspiration biopsy (FNAB) before surgery. All patients underwent total thyroidectomy based on the results of preoperative tests, intraoperative exploration and frozen section analysis10. The nodules were subdivided into three forms as encapsulated, if the nodule was surrounded by a capsule; circumscribed, if the nodule was non-encapsulated and non-infiltrative; infiltrative, if the nodule was non-encapsulated but yielded signs of infiltration to adjacent thyroid parenchyma.

    Intraclass correlation coefficient (ICC) was used to evaluate the agreement between the sonographic and histopathologic measurements of the longest diameter of each nodule. For this purpose, intraclass correlation coefficient according to the two-way mixed effects model was calculated.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Disscussion
  • Conclusion
  • References
  • Results
    Twenty two thyroid nodules in 22 patients (male/female: 17/5; mean age±SD: 42±16) with the histopathologic diagnosis of FVPTC constituted the study group. The demographic characteristics of the patients, the time interval between the final US examination and surgery, and the pathological data of FVPTC nodules were summarized in Table-1.


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    Table 1: The Demographic, Surgical and Pathological (Dominant FVPTC) Data of the Patients With the Diagnosis of FVPTC.

    US guided FNAB was performed in 16 (72.7%) patients before surgery. Cytopathologic diagnosis was benign in 8 nodules (50% of those biopsied), “non-diagnostic” in two nodules, “suspicious for PTC” in five nodules and “malignant” in one nodule. Although some nodules had a cytopathologic diagnosis of benignity, all patients in the series underwent surgical excision due to suspicious sonographic findings and/or some cytopathological details.

    On histological examination, all nodules had classical nuclear features of PTC with a predominantly follicular growth pattern, suggesting the diagnosis of FVPTC (Figure-1).


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    Figure 1: FVPTC in a 47 year-old female patient. a) Longitudinal sonogram of left thyroid lobe shows a 10-mm-long, minimally heterogeneous, hypoechoic, solid nodule with well-defined margins and hypoecoic halo. b) Macroscopic view of the related thyroidectomy specimen demonstrates the nodule to be a solid nodule with well-defined margins and close similarity to its sonographic appearance. c) Photomicrograph displays the tumor (T) with a marked capsule (arrows) and adjacent non-neoplastic tissue (N). d) A high-power view demonstrates a predominantly follicular pattern with follicular structures, in addition to characteristic nuclear features of PTC such as dense, pink-staining colloid (arrows), neoplastic irregular, clear nuclei with grooves and micronucleolus (arrowheads).

    The longest diameter of the 21 dominant FVPTC nodules ranged between 8 and 50 mm (20±11 mm; mean±SD). The longest diameter of a FVPTC nodule which had been excised in another medical center and consulted by our pathology department was not available. The dominant FVPTC nodules had an average longest diameter of 23±12 mm (mean±SD; ranging from 6 to 55 mm) according to preoperative US examination. These measurements correlated perfectly with those obtained during histopathologic evaluations. The ICC between the sonographic and histopathologic measurements of the longest diameters of the nodules was 0.952 (95% CI, 0.865-0.983) indicating high level of agreement. The histopathologic evaluation of 22 nodule specimens revealed a capsule surrounding 15 of the FVPTC nodules (68.2%, “encapsulated form”). Three of the seven nodules without a capsule had circumscribed margins, one of which had focal and minimal peritumoral infiltration (all accepted as “circumscribed form”). The remaining four FVPTCs had invaded the adjacent thyroid parenchyma in an infiltrative pattern (“infiltrative form”).

    In 9 patients, there were additional foci of malignant nodules in the thyroid gland (Table-1). Eight of them were shown to have FVPTC nodule(s) that were smaller than the dominant FVPTC nodule, with one case having an extra focus of PTC in the classical type. The remaining patient had a classical type PTC in addition to a FVPTC nodule.

    Gray-scale US and CDUS features were summarized in Table-2,3 and 4. Inner structure was purely solid in 77.3% and heterogeneous in 63.6% of the nodules (Figure-2).


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    Table 2: The Sonographic Data of Dominant FVPTC Nodules in the Series.


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    Table 3: General Overview of Gray-Scale Sonographic Features of Dominant FVPTC Nodules.


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    Table 4: General Overview of Doppler Sonographic Features of Dominant FVPTC Nodules.*

    Cystic components of small size were present in only 5 nodules. Although two thirds of the nodules had an oval shape, well-defined margins and peripheral hypoechoic halo (Figure-2,3), there were nodules that had a lobulated shape with microlobulated margins or irregular configuration with ill-defined margins (Figure-4,5).


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    Figure 4: Course calcified foci in a FVPTC of a 31-year-old female patient. a) Longitudinal sonogram of right lobe demonstrates a 15-mm-long, dominantly isoechoic nodule with mixed echotexture, microlobulated borders and foci of coarse calcification (arrow). b) Color Doppler US image of the same nodule yields perinodular and predominantly peripheral intranodular hypervascularization.


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    Figure 5: An infiltrative FVPTC nodule in a 70 year-old female patient. Longitudinal sonogram of left thyroid lobe demonstrates an irregular solid nodule with a long diameter of 21 mm, ill-defined margins, microcalcified foci (arrow) and rare vascular signals in its peripheral regions.

    Most of the observed nodules were isoechoic or hypoechoic compared to the normal thyroid parenchyma. Nearly 72.7% of the nodules had no calcification, whereas coarse calcification were observed in three nodules and microcalcific foci in three nodules (Figure-4,5). Only one dominant FVPTC nodule in the series was shown to have an anteroposterior diameter greater than its transverse diameter. On CDUS examination, peri- and intranodular vascular signals were demonstrated in 21 nodules. Apparent perinodular and predominantly peripheral intranodular hypervascularity was observed in 14 nodules (66.7%) (Figure-3,4). A “spoke-and-wheel” appearance was demonstrated in 9 nodules (Figure-2). The remaining 7 nodules (33.3%) were shown to exhibit rare perinodular and peripherally located intranodular vascular signals.

    The sonographic features demonstrated in different forms of FVPTC are presented and compared in Table-5. Although there were exceptions in each group, the encapsulated FVPTCs typically had a peripheral hypoechoic halo and well-defined margins, whereas the infiltrative FVPTCs exhibited the opposite characteristics. The majority of the encapsulated FVPTCs, and all of the circumscribed nodules were oval in shape and isoechoic in internal appearance, contrary to the infiltrative nodules. All of the FVPTCs in the series were completely solid, except for 5 encapsulated nodules with small cystic components.


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    Table 5: The Comparison of US Findings in FVPTC Nodules With and Without Capsule.

    Forty percent of the encapsulated FVPTCs and two of the three circumscribed FVPTCs had a homogeneous echo texture, whereas all of the infiltrative legions were heterogeneous. Rare microcalcific foci were demonstrated in one of the 12 encapsulated FVPTCs and in half of the infiltrative FVPTCs. Coarse calcifications were observed in only 3 encapsulated FVPTCs within the whole series. Perinodular and predominantly peripheral intranodular hypervascularity was the dominant pattern of vascularity in 64% of the encapsulated FVPTCs and in all of the circumscribed nodules. On the other hand, half of the infiltrative FVPTCs exhibited a similar vascularity, whereas the remaining half had rare perinodular and peripheral intranodular vascular signals. Only one of the infiltrative FVPTCs was demonstrated to have a “spoke-and-wheel” pattern of vascularization, whereas nearly half of the encapsulated nodules and all of the circumscribed nodules exhibited this appearance.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Disscussion
  • Conclusion
  • References
  • Discussion
    It was reported that marked hypoechogenicity, microlobulated or irregular margins, foci of microcalcification, a taller-than-wide shape, signs of invasion to surrounding tissue, local lymphadenopathies, and rich intranodular vascularity at CDUS were suggestive for malignancy in thyroid nodules6-8.

    Although the sensitivity of these US features is relatively high for papillary and medullary carcinomas, follicular neoplasms and FVPTCs tend to display US characteristics often common to benign nodules, including a solid echo-texture, circumscribed margins, hypoechoic halo and oval shape. Microcalcifications are not regularly demonstrated in follicular tumors or FVPTC11. Recently, the misleading “benign” US appearance of FVPTC was held responsible for the delay of clinical suspicion of FVPTC (12). Also in our series, the majority of FVPTC nodules presented with features suggesting a false diagnosis of benignity. The exceptions were the three nodules with irregular shape and ill-defined margins. The remaining carcinomas, however, had a completely benign appearance. Therefore, there is a strong need to develop other US parameters for clinical practice.

    Typically, nodules with a follicular pattern tend to present with relatively large nodules12. Indeed, the nodules in our series were large with a mean long-diameter of 23 mm, reaching up to 55 mm. It was noteworthy that only one of 22 dominant FVPTC nodules had an anteroposterior diameter larger than its transverse dimension. The results of this study are in contradiction to the claim that the “taller-than-wider-sign” has the highest diagnostic odds ratio for malignancy13. Another remarkable and common feature of the FVPTC nodules in our series was the relatively dominant solid texture with regard to their huge dimensions. FVPTC nodules were completely solid in 77% of our cases and had only tiny cystic components in the remaining ones, suggestive of a follicular pattern. Nodules of a follicular nature often lack cystic elements or have very small cystic components relative to their large body14,15. That notable observation of predominantly solid content was valid for not only the encapsulated or circumscribed FVPTCs but also the infiltrative nodules in our series.

    In a recent review, moderate, rich, predominant, or exclusive internal flow on CDUS of thyroid follicular neoplasms (FN) were grouped and designated as “predominant internal flow” pattern. This pattern was considered indicative of malignancy. It was reported that the overall sensitivity of CDUS was 85% 16. De Nicola et al. reported a significant and positive association between a predominantly central flow and malignancy in thyroid FNs 17. Flow patterns of cases in these two studies show similarities to our cases described as having perinodular and predominantly peripheral intranodular flow patterns. We believe that the diversity regarding vascularity patterns is due to its description and that our classification of flow patterns is more detailed and sensitive. In the majority of our FVPTC cases, hypervascularization in the nodules was apparent, with a perinodular and predominantly peripheral intranodular distribution of vessels. It was noteworthy to observe the distribution of peripheral vessels with centripetal branches resulting in a “spoke-and-wheel” appearance in half of the nodules evaluated by CDUS, similar to that previously described for follicular tumors 9.

    In the literature, the sensitivity of FNAB for diagnosis of PTC was reported to be between 75 and 94%, whereas the sensitivity of FNAB for diagnosis of FVPTC was low, varying from 25 to 37% 18-22. Cytological diagnosis of FVPTC with FNAB is more difficult than that of PTC nodules, not only because of overlapping cytomorphological features of benign and malignant follicular cells but also due to relatively small areas suggesting PTC components with focal areas of characteristic nuclear features 22-26. The authors also emphasized the importance of awareness for the possibility of FVPTC, particularly in large thyroid nodules, even in the setting of a benign FNAB 26. The aforementioned literature data also accounts for the false-negative “benign” results in 8 of the 16 nodules that had undergone cytological examination in our series, with only one of them being diagnosed as “malignant”.

    The major limitations of the presented study include the limited number and spectrum of the pathologic subvariants in the study group, as well as the study’s retrospective design. Due to the relative scarcity of this specific pathologic entity, the instances of the FVPTCs, and especially those without capsule, are far from being adequate for a reliable statistical analysis and a solid conclusion. Such instances would be of greater significance in the case of a prospective and larger study in which the sonographic features of different forms of FVPTC nodules were compared not only to each other but also to those of other thyroid malignancies.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
  • Conclusion
  • References
  • Conclusion
    Although some subvariants may have apparent malignant US features, FVPTC nodules appear to have gray-scale and Doppler sonographic features largely identical with those of follicular thyroid neoplasms in most cases, probably due to their unique clinical and histopathological characteristics. Diagnosis of FVPTC should always be considered probable among other pathologies with a follicular pattern when large thyroid nodules with completely or predominantly solid echotexture, in addition to other typical US features suggesting benignity, are observed. The presence of perinodular and intranodular hypervascularization, especially with an accompanying “spoke-and-wheel” appearance, may further support the diagnosis.

    Acknowledgement
    We thank Timur Kose from the Biostatistics Department of Ege University Faculty of Medicine, for his statistical advice and help.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
  • Conclusion
  • References
  • References

    1) Jogai S, Adesina AO, Temmim L, Al-Jassar A, Amir T, Amanguno HG. Follicular variant of papillary thyroid carcinoma: A cytological study. Cytopathology 2004;15(4):212-6.

    2) Wreesmann VB, Ghossein RA, Hezel M, et al. Follicular variant of papillary thyroid carcinoma: Genoma-wide appraisal of a controversial entity. Genes Chromosomes Cancer 2004;40(4):355-64.

    3) Salajegheh A, Petcu EB, Smith RA, Lam AK. Follicular variant of papillary thyroid carcinoma: A diagnostic challenge for clinicians and pathologists. Postgrad Med J 2008;84(988):78-82.

    4) Liu J, Singh B, Tallini G, et al. Follicular variant of papillary thyroid carcinoma: A clinicopathologic study of a problematic entity. Cancer 2006;107(6):1255-64.

    5) Yang GC, Fried K, Yakoushina TV, Schreiner AM. Encapsulated follicular variant of papillary thyroid carcinoma: Fine-needle aspiration with ultrasound and histologic correlation of 41 cases. Acta Cytol 2013;57(1):26-32.

    6) Moon WJ, Jung SL, Lee JH, et al. Benign and malignant thyroid nodules: US differentiation-multicenter retrospective study. Radiology 2008;247(3):762-70.

    7) Takashima S, Fukuda H, Nomura N, Kishimoto H, Kim T, Kobayashi T. Thyroid nodules: Re-evaluation with ultrasound. J Clin Ultrasound 1995;23(3):179-84.

    8) Hegedüs L. Clinical practice. The thyroid nodule. N Engl J Med 2004;351(17):1764-71.

    9) Solbiati L, Charboneau JW, Reading CC, James EM, Hay ID. The Thyroid Gland. In: Rumack CM, Wilson SR, Charboneau JW, Levine D, editors. Diagnostic Ultrasound 4th ed. Philadelphia: Elsevier Mosby; 2011:708-49.

    10) Makay O, Icoz G, Gurcu B, et al. The ongoing debate in thyroid surgery: should frozen section analysis be omitted? Endocr J 2007;54(3):385-90.

    11) Yoon JH, Kim EK, Hong SW, Kwak JY, Kim MJ. Sonographic features of the follicular variant of papillary thyroid carcinoma. J Ultrasound Med 2008;27(10):1431-7.

    12) Ozdemir D, Ersoy R, Cuhaci N, et al. Classical and follicular variant papillary thyroid carcinoma: Comparison of clinical, ultrasonographical, cytological, and histopathological features in 444 patients. Endocr Pathol 2011;22(2):58-65.

    13) Brito JP, Gionfriddo MR, Al Nofal A, et al. The accuracy of thyroid nodule ultrasound to predict thyroid cancer: Systematic review and meta-analysis. J Clin Endocrinol Metab 2014;99(4):1253-63.

    14) Fukunari N, Nagahama M, Sugino K, Mimura T, Ito K, Ito K. Clinical evaluation of color Doppler imaging for the differential diagnosis of thyroid follicular lesions. World J Surg 2004;28(12):1261-5.

    15) Müller HW, Schröder S, Schneider C, Seifert G. Sonographic tissue characterization in thyroid gland diagnosis. A correlation between sonography and histology. Klin Wochenschr 1985;63(15):706-10.

    16) Iared W, Shigueoka DC, Cristófoli JC, et al. Use of color Doppler ultrasonography for the prediction of malignancy in follicular thyroid neoplasms: Systematic review and meta-analysis. J Ultrasound Med 2010;29(3):419-25.

    17) Nicola HD, Szejnfeld J, Logullo AF, Wolosker AMB, Souza LRMF, Chiferi V Jr. Flow pattern and vascular resistive index as predictors of malignancy risk in thyroid follicular neoplasms. J Ultrasound Med 2005;24(7):897-904.

    18) Chen H, Zeiger MA, Clark DP, Westra WH, Udelsman R. Papillary carcinoma of the thyroid: Can operative management be based solely on fine-needle aspiration? J Am Coll Surg 1997;184(6):605-10.

    19) Tielens ET, Sherman SI, Hruban RH, Ladenson PW. Follicular variant of papillary thyroid carcinoma: A clinicopathologic study. Cancer 1994;73(2):424-31.

    20) Kini SR, Miller JM, Hamburger JI, Smith MJ. Cytopathology of papillary carcinoma of the thyroid by fine needle aspiration. Acta Cytol 1980;24(6):511-21.

    21) Kesmodel SB, Terhune KP, Canter RJ, et al. The diagnostic dilemma of follicular variant of papillary thyroid carcinoma. Surgery 2003;134(6):1005-12.

    22) Lin HS, Komisar A, Opher E, Blaugrund SM. Follicular variant of papillary carcinoma: The diagnostic limitations of preoperative fine-needle aspiration and intraoperative frozen section evaluation. Laryngoscope 2000;110(9):1431-6.

    23) Lang BH, Lo CY, Chan WF, Lam AK, Wan KY. Classical and follicular variant of papillary thyroid carcinoma: A comparative study on clinicopathologic features and long-term outcome. World J Surg 2006;30(5):752-8.

    24) Suster S. Thyroid tumors with a follicular growth pattern: Problems in differential diagnosis. Arch Pathol Lab Med 2006;130(7):984-8.

    25) Baloch ZW, Sack MJ, Yu GH, Li Volsi VA, Gupta PK. Fine needle aspiration of thyroid: an institutional experience. Thyroid 1998;8(7):565-9.

    26) Mehanna R, Murphy M, McCarthy J, et al. False negatives in thyroid cytology: Impact of large nodule size and follicular variant of papillary carcinoma Laryngoscope 2013;123(5):1305-9.

  • Top
  • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
  • Conclusion
  • References
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