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REVIEW ARTICLE
Year : 2013  |  Volume : 2  |  Issue : 4  |  Page : 231-234

Encapsulated Follicular variant of papillary thyroid carcinoma: Is histopathology a gold standard?


Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh, India

Date of Web Publication26-Nov-2013

Correspondence Address:
Chaganti Padmavathi Devi
Professor and Head Dept of Pathology Guntur Medical College, Guntur-522 004, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-8632.122155

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  Abstract 

The morphological features of encapsulated follicular variant of papillary thyroid carcinoma (FVPC) are reviewed and the controversies and diagnostic difficulties in the diagnosis of FVPC are discussed.

Keywords: Encapsulated, follicular variant, invasive, nuclear features, papillary, thyroid carcinoma


How to cite this article:
Devi CP, Devi KM, Akarsh M P, Kotakonda S. Encapsulated Follicular variant of papillary thyroid carcinoma: Is histopathology a gold standard?. J NTR Univ Health Sci 2013;2:231-4

How to cite this URL:
Devi CP, Devi KM, Akarsh M P, Kotakonda S. Encapsulated Follicular variant of papillary thyroid carcinoma: Is histopathology a gold standard?. J NTR Univ Health Sci [serial online] 2013 [cited 2020 Apr 4];2:231-4. Available from: http://www.jdrntruhs.org/text.asp?2013/2/4/231/122155


  Introduction Top


Follicular variant of papillary thyroid carcinoma (FVPC) was described by Crile and Hazard as alveolar variant of papillary thyroid carcinoma (PTC). [1] It was later confirmed by Lindsay in 1960. It was later defined by Chen and Rosai in 1977. [1] The author also assumed the biological behavior of these tumors might resemble PTC. [1] Hawk and Hazard studied 300 cases of PTC in 1976 and pointed out significant diagnostic difficulties. [1] Chen and Rosai emphasized the importance of nuclear features of PTC and showed that FVPC behaves in the same fashion as PTC. [2] Since then the FVPC is being diagnosed more frequently.

Tumors of thyroid which appear encapsulated on gross examination with folliculated pattern showing nuclear features of PTC on histology were diagnosed as encapsulated FVPC [Figure 1]. Encapsulated FVPC composed of follicles with capsular and vascular invasion are termed as 'invasive encapsulated FVPC'; whereas, encapsulated FVPC composed of follicles without capsular and vascular invasion are designated as 'noninvasive encapsulated FVPC'. According to Jeffery a diagnosis of FVPC cannot be made if the tumor shows more than 1% of papillary formations. [3] Cases of encapsulated variant of PTC posed difficulty in the diagnosis and Lloyd et al., showed there was a considerable variability in the diagnosis of FVPC. [4],[5] It was proposed that variability in the diagnosis of FVPC is due to lack of agreement on the criteria for making the diagnosis of FVPC. [4],[6]

The criteria applied for capsular invasion is complete infiltration of entire thickness of tumor capsule [Figure 2]. Tumor nests embedded within the tumor capsule and irregularity of the contour along the inner border of the capsule are not considered as capsular invasion. The criteria for vascular involvement is invasion of a vessel within or outside tumor capsule. The tumor in the blood vessel has to be covered by endothelium or attached to the vessel wall [Figure 3]. [3]
Figure 1: Thyroid tumor showing encapsulation

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Figure 2: Showing capsular infiltration

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Figure 3: Showing vascular infiltration; attachment of tumor to the endothelium

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The diagnosis of encapsulated FVPC is based solely on the presence of nuclear features of papillary carcinoma, nuclear clearing, overlapping, grooves, and pseudo inclusions [Figure 4]. [7]
Figure 4: Showing pale nuclei with stratifi catification

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It is suggested that the typical ground glass nuclei should be seen more than occasionally to call a tumor as PTC. [7] Plain vesicular nuclei are seen in many benign and malignant lesions of thyroid which should not be considered for diagnosis. The follicular cells in the vicinity of lymphocytic thyroiditis also show nuclear clearing with occasional nuclear grooves giving a suspicion of FVPC. [8] In these cases, the criteria for the diagnosis of FVPC are very fine powdery chromatin giving the appearance of nuclear clearing, nuclear grooves, nuclear overlapping, crowding, nuclear membrane irregularity, and nuclear enlargement. [9]

Chan proposed that the following criteria for the diagnosis of FVPC which included ovoid nuclei, crowded nuclei, clear nuclei, intranuclear grooves, and inclusions. [10] Psammoma bodies and secondary features like elongated irregularly shaped follicles, dark staining colloid, and multinucleated histiocytes in the lumen of the follicles are also taken into consideration. [9] However, the criteria which are mostly relied upon are in the decreasing order of frequency, nuclear clearing, very fine powdery chromatin, nuclear grooves, nuclear overlapping, nuclear membrane irregularity, and nuclear enlargement; and the secondary features like chromatin margination, distorted follicular architecture, and fibrosis or sclerosis. [6] It is found that the criteria for the diagnosis of papillary carcinoma are variable and the most common feature consistently seen was nuclear enlargement. Others have found a considerable interobserver variability. So a term well-differentiated thyroid tumor of uncertain malignant potential was used for the tumors with follicular pattern without convincing nuclear features. [9]

Livolsi and Baloch have classified FVPC into six histological variants based on growth patterns and distribution of nuclear features. [9]

Type 1: Cases which are uncapsulated and invasive tumors which do not pose diagnostic difficulty are included in this category. This lesion resembles papillary carcinoma, but there are no papillae and the lesion is completely composed of follicular patterns with the nuclei showing definitive features of papillary carcinoma. These case show lymphatic invasion with multifocal growth in the thyroid and metastasize to lymph nodes. [4],[11]

Type 2-5: These are encapsulated tumors with capsular and vascular invasion, but the diagnostic dilemma in these cases is whether to name them as follicular or papillary carcinoma. [4],[11] These tumors are classified under papillary carcinoma if the nuclear features are present diffusely or in multiple locations within the same tumor [Figure 4]. The area that shows the best nuclear features is in the periphery of the tumor closest to the tumor capsule.

Among these categories, type 2 shows encapsulated invasive tumors with classical features of PTC distributed in diffuse fashion.

Type 3 shows encapsulated invasive tumors with classical or unconvincing features of PTC which show multifocal distribution.

Type 4 shows encapsulated noninvasive tumors with classical and diffuse features of PTC.

Type 5 includes encapsulated noninvasive tumors with classical or unconvincing features of PTC with multifocal distribution.

Type 6 includes cases of follicular adenoma (FA) of thyroid if sub centimeter of the area show nuclear features of papillary carcinoma of thyroid then the lesion is designated as papillary microcarcinoma in FA. [11]

Encapsulated FVPTC without invasion showing nuclear features of PTC in a multifocal pattern, but do not show all characteristic features are classified as well-differentiated tumor of uncertain malignant potential. [12],[13]

Immunohistochemical (IHC) markers including, high molecular weight cytokeratin, cytokeratin 19, vimentin, HBME1, CD 57, CD 15, and CD 44 are expressed in FVPTC; but these are also reported less frequently in benign thyroid lesions and are not conclusive enough to discriminate between PTC and FVPTC. [14] CD 57 positivity was observed in 95% of cases of PTC, 27% of follicular adenomas, and 10% of colloid nodules. [15] CD 56 was positive in all follicular lesions except in PTC and it is a negative diagnostic marker for cases of PTC.(16) Its positivity in benign lesions is 93%, whereas in malignancy is 5%. [16]

As the IHC is less sensitive, light microscopy remains the gold standard for the diagnosis of FVPC presently. [6]

The metastatic potential of encapsulated FVPC may be low but not infrequent. [9] According to Jeffery, the metastatic potential of FVPC to lymph nodes is 65%; whereas, for encapsulated FVPC is 5% and lymph nodal metastasis of encapsulated FVPC is similar to follicular carcinoma. [3] If FVPC measures more than 1.5 cm, completion thyroidectomy followed by radioactive iodine therapy is advocated. [7] In cases of noninvasive encapsulated variant of FVPC, adverse outcomes are less and in these cases invasion is the main determinant of malignant behavior but not nuclear features. [3] Cases of noninvasive encapsulated FVPC can be managed by lobectomy alone. [3],[7] According to Rosai et al., larger follow-up of these cases is needed. [11]


  Conclusion Top


FVPC has to be diagnosed based on histopathological features especially nuclear features of PTC. Diagnostic difficulties arise when the nuclear features are incomplete and borderline. IHC markers including both positive and negative markers are not 100% sensitive for FVPC and light microscopy remains the gold standard for the diagnosis of FVPC.

 
  References Top

1.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;84:78-82.  Back to cited text no. 1
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2.Baloch ZW, Livolsi VA. Follicular - patterned lesions of the thyroid. Am J Clin Pathol 2002;117:143-50.  Back to cited text no. 2
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3.Liu J, Singh B, Tullini G, Curlson DL, Katabi N, Shaha A, et al. Follicular variant of papillary thyroid carcinoma A clinicopathological study of a problamatic entity. Cancer 2006;6:1255-64.  Back to cited text no. 3
    
4.Lloyd RV, Erickson LA, Casey MB, Lam KY, Lohse CM, Asa SL, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 2004;28:1336-40.  Back to cited text no. 4
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5.Renshaw AA, Gould EW. Why there is tendency to over overdiagnose the follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 2002;117:19-21.  Back to cited text no. 5
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6.Elsheikh TM, Asa SL, Chan JK. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol 2008;130:736-44.  Back to cited text no. 6
    
7.Ghossein R. Problems and controversies in the histopathology of thyroid carcinomas of follicular cell origin. Arch Pathol lab Med 2009;133:683-91.  Back to cited text no. 7
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8.Baloch JW, Livolsi VA. Etiology and significance of the optically clear nucleus. Endocr Pathol 2002;13:289-99.  Back to cited text no. 8
    
9.Livolsi VA, Baloch ZW. Many faces of follicular variant of papillary thyroid carcinoma. Pathol Case Rev 2009;14:214-8.  Back to cited text no. 9
    
10.Chen KT, Rosai J. Follicular variant of thyroid papillary carcinoma; A clinicopathologic study of six cases. Am J Surg Pathol 1977;1:123-30.  Back to cited text no. 10
    
11.Rosai J, Carcangui ML, DeLelli RA. Tumors of the thyroid gland. 3 rd series [Fascicle5] Washington: Armed forces institute of Pathology; 1992.  Back to cited text no. 11
    
12.Zhu Z, Gandhi M, Nikiforova M. Molecular profile and clinical pathologic features of the follicular variant of papillary thyroid carcinoma: An unusually high prevalence of ras mutations. Am J clin pathol 2003:120:71-7.  Back to cited text no. 12
    
13.Inaba M, Umemura S, Satoh H. Expression of RET in follicular cell -derived tumors of the thyroid gland: Prevalence and implication of morphological type. Pathol Int 2003;53:146-53.  Back to cited text no. 13
    
14.Chan JK. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary carcinoma of thyroid. Am J Clin Pathol 2002;117:16-8.  Back to cited text no. 14
    
15.Khan A, Baker SP, Patwardhan NA, Pullman JM. CD 57 [leu-7] expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma. Virchows Arch 1998;432:427-32.  Back to cited text no. 15
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16.Shahebrahimi K, Madani SH, Fazaeli AR, Khazaei S. Diagnostic value of CD 56 and nm 23 markers in papillary thyroid carcinoma. Indian J Pathol Microbiol 2013;56:2-5.  Back to cited text no. 16
[PUBMED]  Medknow Journal  


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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