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 Table of Contents  
Year : 2019  |  Volume : 16  |  Issue : 3  |  Page : 128-136

A case-based approach to aggressive variants of papillary thyroid carcinoma with literature review

1 Department of Pathology, Governor Celestino Gallares Memorial Hospital, Tagbilaran City, Bohol, Philippines
2 Department of Pathology, Governor Celestino Gallares Memorial Hospital, Tagbilaran City, Bohol; Department of Pathology, MHAM College of Medicine, Cebu City, Philippines

Date of Submission10-Sep-2019
Date of Acceptance23-Oct-2019
Date of Web Publication18-Nov-2019

Correspondence Address:
Dr. Joseph Antoine Flordelis Chatto
Department of Pathology, Governor Celestino Gallares Memorial Hospital, Tagbilaran City, Bohol
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/trp.trp_37_19

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Papillary thyroid caarcinoma (PTC) is the most common thyroid and endocrine malignancy. Although considered to be indolent, aggressive variants have been identified, including the Tall Cell (TCV), Columnar Cell (CCV), Hobnail (HPTC) and Solid Variants (SVPTC). The objective of this study is to pre-operatively recognize the cytologic features of these variants. Four cases with final diagnoses of TCV, CCV, HPTC and SVPTC were reviewed and compared with Fine Needle Aspiration Biopsy (FNAB) smears. The first case is a 44-year-old female diagnosed with TCV pre-operatively through FNAB and was confirmed through tissue biopsy showing malignant glands in papillary formation with greater than 50% of tall cells. The second patient is a 54-year-old female with CCV showing stratified columnar cells with cytoplasmic supranuclear and subnuclear vacuoles. Third is a 57-year-old female with HPTC exhibiting eccentrically-located nuclei imparting a hobnail appearance with cellular dyscohesiveness. The fourth case is a 59-year-old female diagnosed with SVPTC showing predominantly solid sheets surrounded by thin, delicate fibrous stroma. They all have nuclear features of PTC. TCV, CCV, HPTC and SVPTC are related to extrathyroidal extension, angiolymphatic invasion, positive surgical margin and lymph node metastasis. FNAB is an important tool to recognize these variants preoperatively and plan for amore comprehensive management.

Keywords: Biologically aggressive papillary thyroid carcinoma, columnar cell variant, hobnail variant, papillary thyroid carcinoma, solid variant, tall cell variant

How to cite this article:
Chatto JA, Salillas AL. A case-based approach to aggressive variants of papillary thyroid carcinoma with literature review. Thyroid Res Pract 2019;16:128-36

How to cite this URL:
Chatto JA, Salillas AL. A case-based approach to aggressive variants of papillary thyroid carcinoma with literature review. Thyroid Res Pract [serial online] 2019 [cited 2022 Jun 30];16:128-36. Available from: https://www.thetrp.net/text.asp?2019/16/3/128/271156

  Introduction Top

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy accounting for 80%–90% of all thyroid malignancies. It is also the most common endocrine malignancy and makes up for 1% of all newly diagnosed cancers.[1] Most cases occur in adults between 20 and 50 years, with a female-to-male ratio of 4:1. PTC is diagnosed primarily by its nuclear features, such as the ovoid, ground glass nuclei with nuclear grooves and pseudoinclusions.[2] It usually has an indolent course with excellent prognosis and long-term survival rate.[3] However, the World Health Organization Classification of Tumours has recognized biologically aggressive variants of PTC, which have less favorable prognosis. These variants include tall cell (TCV), columnar cell (CCV), solid (SVPTC), and diffuse sclerosing. Another PTC subtype is the hobnail variant (HPTC), which is newly recognized, also with an aggressive clinical behavior, and was first described in 2010 by Asioli et al. These tumors are rare, and patients are reported to have poor clinical outcomes. Because of their clinical implications, any foci of such changes should be documented.[4] Here, we present cases of the tall cell, columnar cell, hobnail, and solid variants that were seen at the Governor Celestino Gallares Memorial Hospital in Bohol, Philippines. The aim of this study is to preoperatively recognize the cytologic features of these rare and aggressive PTC variants in order to plan for a more aggressive management.

  Case Reports Top

Case 1

The first patient is a 44-year-old female who presented with a 10-year history of a right anterior neck mass. On physical examination, a large goiter was noted in the right with no lymphadenopathies. FT4 was decreased while the FT3 and thyroid-stimulating hormone (TSH) were normal. Fine-needle aspiration biopsy (FNAB) was done, which revealed PTC, TCV. The smears showed neoplastic follicular cells in fragments, crowded groups, and rosettes with others scattered as single cells. Most of the tumor cells appeared tall and columnar with ovoid, pale nuclei and were arranged in a palisading pattern. Thick colloid lakes were also noted [Figure 1].
Figure 1: (a) Clusters and crowded groups of thyroid follicular cells with a papillary formation, ×10. (b) Tumor cells appear elongated with large, overlapping nuclei and nuclear grooves with abundant eosinophilic cytoplasm. (c) Tumor cells with elongated cytoplasm with nuclear overlapping and nuclear grooves, ×40

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Case 2

The second case is that of a 57-year-old female who presented with an 11-year history of a left thyroid neck mass with no other associated symptoms. Physical examination showed a large left thyroid mass. Thyroid function tests showed normal values. FNAB showed findings consistent with colloid goiter with hyperplastic change and cystic degeneration with papillary carcinoma not ruled out. The smears were reviewed and showed several irregular clusters of thyroid follicular cells with elongated cytoplasm and pleomorphic nuclei exhibiting pseudostratification [Figure 2]a and [Figure 2]b. Several cells show nuclear grooves and vague inclusions [Figure 2]c. Despite the rare nuclear features of PTC seen, the presence of the pseudostratified elongated cells with pleomorphic nuclei made us favor the diagnosis of PTC CCV.
Figure 2: Fine-needle aspiration biopsy showing (a and b) nuclear pseudostratification of thyroid follicular cells with eosinophilic cytoplasm, ×10. (c) Ovoid irregular nuclei with pseudostratification and occasional nuclear grooves, ×40

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Case 3

The third patient is a 54-year-old female presenting with a 10-year history of a left anterior neck mass with normal TSH. Sonography was done, which showed enlargement of the left thyroid with a hypoechoic solid mass. FNAB showed a follicular neoplasm in a background of a colloid goiter. A review of smears revealed medium-sized thyroid follicular cells arranged in branching cell groups. Some formed micropapillary and microfollicular structures while others were dispersed single cells with distinct “teardrop” cytoplasm, apically placed nuclei producing a surface bulge leading to a “comet cell” appearance [Figure 3]a, [Figure 3]b, [Figure 3]c. On higher magnification, the nuclei showed variable degrees of atypia with nuclear grooves and inclusions seen [Figure 3]d [Figure 3]e. Other areas showed single cells with abundant cytoplasm and sharp borders, which were aggregated in tile-like manner [Figure 3]f.
Figure 3: Fine-needle aspiration smears (a-c) the comet-like cell is shown with “teardrop” cytoplasm, ×10, ×40, ×100. (d and e) Soap bubble-like nuclear inclusions are recognizable, ×40, ×100. (f) Single cells with abundant cytoplasm and sharp borders aggregated in a tile-like manner, ×40

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Case 4

The fourth case is that of a 59-year-old euthyroid female who presented with a 3-year history of a left anterior neck mass. Ultrasound showed a 3.30 cm × 2.76 cm × 2.65 cm mass with architectural distortion. The mass was hypervascular to color flow with tributaries transecting in the enlarged mass. Smears were minimally cellular composed of benign thyrocytes admixed with atypical cells having ovoid, pale, and enlarged nuclei with few nuclear grooves and one indistinct intranuclear pseudoinclusion seen in a bloody background [Figure 4]a and [Figure 4]b.
Figure 4: Fine-needle aspiration smears (a) benign thyrocytes admixed with atypical cells showing ovoid, pale, and enlarged nuclei with few nuclear grooves. (b) One indistinct intranuclear pseudoinclusion seen in a bloody background

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Right subtotal thyroidectomy was subsequently performed on patient 1. The right subtotal thyroidectomy specimen weighed 150 g and was tan gray, rubbery, and smooth measuring 8 cm × 8 cm × 6 cm. On cut section, a solid, tan cream mass measuring 7 cm × 7 cm is seen [Figure 5].
Figure 5: (a and b) Right thyroid lobe

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The second patient underwent left thyroid lobectomy, and the specimen was sent to our laboratory for biopsy. The left thyroid lobe was tan gray, ovoid, and smooth measuring 5.5 cm × 4 cm × 3 cm [Figure 6]a. A well-defined, solid tan brown mass was seen on cut section measuring 3 cm × 2 cm [Figure 6]b.
Figure 6: (a and b) Left thyroid lobe. (b) Well-defined, solid tan brown mass was seen on cut section measuring 3 cm × 2 cm

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Total thyroidectomy was performed on the third patient. The specimen weighed 60 g. The left lobe was enlarged to 8.5 cm × 4 cm × 2.7 cm, and the section showed a well-delineated, white tan solid mass with the greatest dimension of 3.7 cm [Figure 7]. The right thyroid measured 3.7 cm × 3.2 × 0.7 cm. Cut section revealed brown areas with one focal cream tan, solid mass measuring 0.3 cm in the widest dimension.
Figure 7: Left thyroid lobe (Case 3)

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The fourth patient underwent left thyroid lobectomy with isthmusectomy. The left lobe was tan brown, ovoid, and firm measuring 7 cm × 5 cm × 3 cm. Cut section showed a solitary cream, well-defined mass measuring 7 cm in the greatest dimension [Figure 8].
Figure 8: Left thyroid lobe (Case 4)

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Microscopic examination of case 1 showed malignant glands in papillary formation predominantly (>50%) lined by a single layer of tall cells with abundant eosinophilic cytoplasm. The heights of these cells are at least three times their width. On higher magnification, the nuclei were enlarged and elongated, crowded, and overlapping with multiple nuclear grooves [Figure 9].
Figure 9: Right thyroid mass. (a and b) Malignant glands in papillary formation lined by a single layer of tall cells with eosinophilic cytoplasm, ×10. (c and d) The nuclei are enlarged and elongated, crowded, and overlapping with multiple nuclear grooves, ×40

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Case 2 revealed a malignant thyroid neoplasm in papillary formation lined by stratified columnar cells, predominantly with clear cytoplasm. Supranuclear and subnuclear vacuoles are also seen in the cytoplasm [Figure 10]a and [Figure 10]b. Higher magnification showed nuclear crowding and overlapping with occasional nuclear grooves and pseudoinclusions noted in some of the tumor cells [Figure 10]c and [Figure 10]d.
Figure 10: Left thyroid mass. (a) Malignant glands with a combination of tall columnar cells with pseudostratified nuclei as well as cell with follicular architecture, ×4. (b) Pseudostratified columnar cells with supranuclear and subnuclear cytoplasmic vacuoles, ×40. (c and d) Pseudostratified columnar cells with hyperchromatic nuclei, ×10 and × 40

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On microscopic examination of the third case, the left thyroid mass showed a tumor with a papillary growth pattern and variably sized follicles [Figure 11]a. Some of the tumor cell nuclei were eccentrically located showing a bulging of the nuclei at the tip of the cell imparting a hobnail appearance [Figure 11]b. Loss of cellular cohesiveness was evidently leading to cell detachment [Figure 11]c. On higher magnification, both the papillae and neoplastic follicles were mostly lined by cuboidal-to-elongated cells with abundant, well-defined cytoplasmic borders. There are few nuclei showing multiple “soap bubble” intranuclear inclusions. Greater than 30% of the malignant cells with hobnail features form micropapillary structures without fibrovascular cores. Concomitant tall cells/oncocytic cells were also identified [Figure 11]d. A diagnosis hobnail variant of PTC was given. The right thyroid mass revealed a micropapillary thyroid carcinoma [Figure 12].
Figure 11: Left thyroid mass. (a) Thin arborizing papillae with prominent hobnail cells, ×10. (b) Hobnail cells, ×40. (c) Loss of cellular cohesiveness resulting in tufts of detaching cells, ×10. (d) Tall and oncocytic cells lining micropapillae without fibrovascular core, ×40

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Figure 12: Papillary microcarcinoma in the right lobe, ×10

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Histosection of the fourth case showed a malignant tumor composed of solid sheets of neoplastic follicular cells surrounded by thin, delicate fibrous stroma [Figure 13]a. Higher magnification revealed mild-to-moderate nuclear pleomorphism with scanty cytoplasm. Nuclear grooves and pseudoinclusions are also noted [Figure 13]b. Some areas are arranged in trabeculae, while others have tall cell and microfollicular patterns. Necrosis is absent [Figure 13]c and d].
Figure 13: (a) Malignant tumor composed of solid sheets of neoplastic follicular cells surrounded by thin, delicate fibrous stroma (b) Higher magnification showing mild-to-moderate nuclear pleomorphism with scanty cytoplasm (c) Tumor cells with tall cell and (d) microfollicular patterns

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A final diagnosis of PTC, TCV is made for case 1. The patient complains of tumor recurrence at the right lobe 1 year after the surgery. PTC, CCV was the final diagnosis for the second case. There is no recurrence 1 year after the surgery. The third patient was diagnosed with PTC, hobnail variant and is lost to follow-up. The final diagnosis of the fourth case was PTC, solid variant. The patient is still due for follow-up.

  Discussion Top

We presented four of the so-called biologically aggressive and rare variants of PTC. The TCV of PTC, first described by Hawk and Hazard in 1976, is uncommon and occurs in 1%–12% of all PTC but is notably increasing in incidence worldwide.[5],[6],[7],[8],[9],[10] The CCV comprises about 0.2% of all PTC cases and was first described by Evans in 1986 who initially described two cases of clinically aggressive cases that commonly occur in men. He also described four cases of encapsulated variants, which occurred in women.[11] The HPTC is newly recognized and was first described by Asioli et al. in 2010.[12],[13],[14] Furthermore, the solid variant accounts for approximately 3% of PTC cases. Greater than 30% of which are survivors of the Chernobyl incident.[15],[16],[17],[18],[19]

Clinically, patients with TCV tend to be older than those with classic PTC (cPTC), with an age range of 41–66 (mean of 50.1).[2],[7],[10] The study conducted by Wang et al. indicates that females are predominantly affected, with a female-to-male ratio of 2.9–1.[6] However, male patients tend to have more advanced disease when diagnosed at an older age.[7] TCV is also found to be more prevalent in patients with Graves' disease.[20] The same is true for CCV and HPTC which occur mostly in females and in older individuals.[20],[21],[22] HPTC commonly occurs in women, with an average age ranging from 28 to 78 years, and patients usually present with neck mass and cervical lymphadenopathy.[12] In stark contrast to the other variants, SVPTC tends to occur in children with no sex predilection.[16],[17],[19] Although rare, it may still occur in adults, as seen in our case. Our four patients are 44-, 54-, 57-, and 59-year-old females. The mean tumor diameters of the four variants are comparable to the tumor size in the classic variant (3 cm).[7],[23],[24] The largest tumor size in our cases is that of TCV (7 cm) and SVPTC (7 cm) followed by HPTC (3.7 cm) and CCV (3 cm). In a study by Michels in 2007 on 674 PTC cases, TCV cases were significantly bigger, more often bilateral and/or multifocal, and more widely invasive with more frequent extrathyroidal extension and a higher grade.[25] Ultrasound findings of these variants mostly show hypoechoic nodules with or without extrathyroidal extension.[6],[26] The solid variant may also exhibit intranodular vascularity.[18]

On cytology, the tumor cells of TCV appear elongated (three times as high than wide) with ample eosinophilic cytoplasm. Cytoplasmic membranes are sharp, which distinctly delineate one cell from the other. The nuclei are variably sized with striking features of PTC and abundant intranuclear pseudoinclusions. Characteristic soap bubble-like inclusions have been reported. Squamous metaplasia may also be appreciated.[5],[6],[10],[27] The diagnosis of CCV based on FNA remains to be challenging because the typical nuclear features of PTC, such as the ground glass nuclei, nuclear grooves, and intranuclear pseudoinclusions, are not consistently present. Nuclear pseudostratification may be seen and its presence should alert the cytopathologist.[28] Recently, the cytological features of HPTC have been reported as comet-like cells, representing the cytological counterpart of the histological hobnailing.[29] The cytologic features of 18 cases of SVPTC were analyzed by Higuchi et al., and majority of them showed solid clusters as well as small papillary clusters in conjunction with a clean background.[16] Giorgadze et al. reported three cytomorphologic patterns from a study of 13 cases, namely cohesive, syncytial-type tissue fragments; microfollicles/trabeculae; and dyshesive single cells. The limitation, in this case, is the bloody aspirate due to the hypervascular nature of the tumor.[18]

Histologically, TCV shows papillary growth, but a trabecular low-power appearance may be appreciated. It consists of cells that have a height of two to three times the width with eosinophilic cytoplasm, basally oriented nuclei, and the classic features of PTC.[6],[7],[8],[25] Necrosis and mitosis are more common due to the larger size.[30] This variant is still poorly defined because of the variability of the height of these tumor cells depending on the plane of section, presence of tall cells in other PTC variants, and different diagnostic criteria.[2],[7] Our patient's tumor is composed of >50% tall cells with basally oriented nuclei and with features of PTC. Currently, there is no standard definition concerning the proportion of tall cells required to allow a diagnosis of TC PTC.[7],[10],[25],[31] The 2004 World Health Organization classification defines this variant as composed predominantly of cells whose heights are at least three times their widths.[2] Nonetheless, there is still a debate as to the percentage of tall cells necessary to make a diagnosis with multiple recommendations ranging from 30% to 70%. Several studies have demonstrated previously diagnosed cases of cPTC reclassified as TCV after being reviewed by endocrine pathologists.[6] In the study by Beninato et al. on 34 cases of TCV or PTC with tall cell features (TCFs) in 2013, the incidence of extrathyroidal extension, angiolymphatic invasion, positive surgical margin, and lymph node metastases was already increased in tumors with at least 10% tall cells.[8] The demographic and clinicopathologic characteristics of PTC with TCFs (10%–50% tall cells) and TCV of PTC (>50% tall cells) were compared by Oh et al. and were noted to be the same. However, these tumors were significantly more aggressive than cPTC.[3]

CCV is composed of pseudostratified columnar cells, which may contain supranuclear and subnuclear cytoplasmic vacuoles that are reminiscent of early secretory endometrium, which are seen in our patient.[2],[20],[24] Overall morphology may resemble adenocarcinoma of the endometrium or gastrointestinal tract. The nuclei are hyperchromatic with the characteristic large clear nuclei of the classic papillary carcinoma only focally present. The cytoplasm is eosinophilic and tapering. Papillary, follicular, trabecular, and solid growth patterns are seen as well.[2],[20],[22] As observed by Wenig et al. from 16 cases, multiple growth patterns can occur in one tumor, but the defining histologic criterion of CCV is the presence of nuclear stratification.[24] The WHO Classification of Tumours did not specify the percentage of columnar cells required to make the diagnosis of CCV. Ferreiro et al. state that at least 50% columnar cells should be present, whereas Wenig et al. adopted 70% based on their study of 16 cases.[24],[32] Ito et al. did a study in 2008 subclassifying 1521 PTC s into the various histological variants and found that CCV comprised 0.4% of these cases.[33] HPTC is composed of variably sized complex papillary structures without fibrovascular core and are lined by cells with increased nucleocytoplasmic ratios and apically placed nuclei producing a surface bulge (hobnail appearance).[12] According to Bellevicine et al., typical features of HPTC include the presence of hobnail and papillary or micropapillary cytoarchitectural patterns, single teardrop cells similar to comet-like cells, high nucleocytoplasmic ratio, and severe crowding, all of which were seen in our case.[29]

The criteria for the diagnosis of SVPTC include predominantly (>70%) solid growth pattern of the primary tumor, retention of nuclear features of PTC, and absence of necrosis.[2],[34] In the review of 20 patients by Nikiforov, all tumors had between 70% and 100% solid growth with nests of tumor surrounded by thin rim of fibrotic stroma in 11 cases and by broad fibrotic bands with extensive fibrosis in nine cases. All cases showed an abundant cytoplasm with nuclear features of classical PTC.[34] This morphologic architecture is similar to our case with 80% solid pattern surrounded by thin fibrotic stroma in the absence of necrosis.

The immunohistochemical features of TCV are similar to cPTC. The tumor cells are positive for HBME, cytokeratin-19, galectin-3, CD15, and EMA.[10] They may also be positive for p53, C-Met, MUC1, and type IV collagenase overexpression.[6],[15] For CCV, CDX2 is selectively expressed and can be used to distinguish from other variants.[20],[35],[36] There are no specific immunohistochemical stains in HPTC. However, thyroglobulin, TTF-1, HBME-1, and p53 are positive in all cases, and there is a membrane staining for β-catenin and E-cadherin.[12],[37] Because one of the primary differential diagnoses for SVPTC is medullary carcinoma, thyroglobulin, TTF-1, and calcitonin should be performed, wherein SVPTC is positive for the former two and negative for the latter.[17]

Although also seen in cPTC, the frequency of BRAF mutation is higher in TCV, CCV, and HPTC, which is a molecular marker related to aggressive tumor behavior.[6],[7],[13],[20],[38],[39] Contrary to the other aggressive variant, SVPTC is most frequently associated with RET/PTC3 rearrangements.[34],[36] Molecular and immunohistochemical studies were not done on our patients due to the unavailability of these tests in our institution.

Most cases of PTC are managed by standard total thyroidectomy. However, in some variants with more aggressive behaviors, the correct recognition on preoperative FNA is useful for suggesting a more intensive neck surgery.[34] Because of local invasion, neck dissection and irradiation tended to be more frequently performed in TCV patients.[25] Studies recommend total thyroidectomy with routine prophylactic central lymph node dissection.[6] Moreover, Wang et al. recommend radioactive iodine therapy for all patients regardless of the tumor size as well as a more aggressive postoperative thyrotropin suppression therapy.[6] If newly diagnosed patients with TCV has undergone partial thyroidectomy, they should return for a completion thyroidectomy and central neck dissection followed by radioactive iodine ablation of residual tissue, as recommended by Jalisi et al. If total thyroidectomy was already performed initially, then the patients should return for radioactive iodine ablation.[40] Subtotal thyroidectomy was performed on our first case despite the preoperative FNAB diagnosis of TCV. A more aggressive surgical management may have prevented the patient's present recurrence of tumor. Similarly, total thyroidectomy with central compartment neck dissection, lymphadenectomy, and/or resection of invaded surrounding structures followed by postoperative radioactive iodine is also recommended for CCV.[21] Because SVPTC is considered to be more aggressive than cPTC, total thyroidectomy with appropriate lymph node dissection is recommended.[41] Another literature states that tumors limited to the thyroid can be managed conservatively, whereas tumors extending outside the boundaries of the thyroid need a more aggressive therapy.[25] Some studies also suggest the use of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography for staging and surveillance of patients with aggressive subtypes of thyroid cancer.[42] For the second, third, and fourth cases, the aggressive variants (CCV, HPTC, and SVPTC) were not diagnosed on preoperative FNAB. Had they been recognized earlier, the patients would have benefited from a more appropriate surgical approach.

  Summary Top

PTC is the most common thyroid and endocrine malignancy. We presented four of the so-called aggressive variants of PTC. TCV has a 4.5 times greater risk of recurrence compared to cPTC.[8],[43] It is associated with extrathyroidal extension, angiolymphatic invasion, positive surgical margin, lymph node metastasis, multifocality, distant metastasis, higher TNM stage, and higher mortality.[6],[7],[8],[31],[43],[44],[45],[46] Similarly, CCV cases show advanced local growth and extrathyroidal extension and tend to show a more aggressive clinical behavior.[2],[30] It was suggested that the variant be divided into circumscribed and widely invasive subtypes, corresponding to indolent and aggressive clinical behavior, respectively.[2],[20],[24],[47] The patient with columnar cell tumor variant has not recurred 1 year after the surgery compared to our patient with TCV. This could be attributed to the fact that the mass was encapsulated, which would mean a better prognosis. To the present time, only a few cases of PTC with prominent hobnail features have been described and most of them had aggressive behaviors.[29],[48],[49] Concomitant TCFs and others with small foci of undifferentiated (anaplastic) thyroid carcinomas were seen in some reported cases.[13] Comparably, our patient exhibited coexisting tall/oncocytic cells along with >30% hobnail features forming micropapillary structures. SVPTC is also associated with a slightly higher frequency of distant metastasis and less favorable prognosis compared to the cPTC. However, it has a better prognosis than poorly differentiated thyroid carcinoma.[22],[34],[50] In a review of 200 patients who underwent surgery for PTC by Sebastian et al., the variants showing the worst prognosis were TCV and SVPTC and poorly differentiated.[51]

Take-home message

The rare and aggressive variants of PTC pose a greater potential for invasion with poor clinical outcome. Thus, preoperative recognition of its features by FNAB is important in order to plan for a more appropriate management. These patients should also be closely monitored for recurrence.

  Conclusion Top

It is essential to identify the aggressive variants of PTC because they frequently present with a more unfavorable clinical outcome than the cPTC. FNAB is an important tool to recognize these variants preoperatively and plan for a more comprehensive management. For these cases, various literature recommend total thyroidectomy with central neck dissection followed by radioactive iodine ablation of residual tissue.

Future directions

In our setting, molecular testing is rarely done and the diagnosis as well as management is mostly based on the histomorphologic features of the tumor. In the advent of targeted therapy, we should aspire to make molecular profiling a part of the work-up for PTC to assure that the appropriate treatment modality is given.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ozgursoy OB, Eisele DW, Tufano RP. The prognostic implications from molecular testing of thyroid cancer. Otolaryngol Clin North Am 2014;47:595-607.  Back to cited text no. 1
LiVolsi VA, Albores-Saavedra J, Asa SL, Baloch ZW, Sobrinho-Simoes M, Wenig B, et al. Papillary Carcinoma In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (Eds). World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of the Endocrine Organs. IARC Press: Lyon 2004. p. 57-66.  Back to cited text no. 2
Oh WJ, Lee YS, Cho U, Bae JS, Lee S, Kim MH, et al. Classic papillary thyroid carcinoma with tall cell features and tall cell variant have similar clinicopathologic features. Korean J Pathol 2014;48:201-8.  Back to cited text no. 3
Poller DN, Johnson SJ. Recent developments in the pathology of thyroid cancer. Clin Oncol (R Coll Radiol) 2017;29:278-82.  Back to cited text no. 4
de Matos PS. Thyroid epithelial tumors. Diagn Histopathol 2008;14:236-46.  Back to cited text no. 5
Wang X, Cheng W, Liu C, Li J. Tall cell variant of papillary thyroid carcinoma: Current evidence on clinicopathologic features and molecular biology. Oncotarget 2016;7:40792-9.  Back to cited text no. 6
Villar-Taibo R, Peteiro-González D, Cabezas-Agrícola JM, Aliyev E, Barreiro-Morandeira F, Ruiz-Ponte C, et al. Aggressiveness of the tall cell variant of papillary thyroid carcinoma is independent of the tumor size and patient age. Oncol Lett 2017;13:3501-7.  Back to cited text no. 7
Beninato T, Scognamiglio T, Kleiman DA, Uccelli A, Vaca D, Fahey TJ 3rd, et al. Ten percent tall cells confer the aggressive features of the tall cell variant of papillary thyroid carcinoma. Surgery 2013;154:1331-6.  Back to cited text no. 8
Olson M, Maleki Z. Tall cell variant of papillary thyroid carcinoma: Cytomorphologic features in thyroid FNA. J Am Soc Cytopathol 2012;8:S64.  Back to cited text no. 9
Sadow P, Hunt J. Update on clinically important variants of papillary thyroid carcinoma. Diagn Histopathol 2010;17:106-13.  Back to cited text no. 10
Baloch ZW, LiVolsi VA. Unusual tumors of the thyroid gland. Endocrinol Metab Clin North Am 2008;37:297-310, 7.  Back to cited text no. 11
Asioli S, Erickson LA, Sebo TJ, Zhang J, Jin L, Thompson GB, et al. Papillary thyroid carcinoma with prominent hobnail features: A new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of eight cases. Am J Surg Pathol 2010;34:44-52.  Back to cited text no. 12
Lubitz CC, Economopoulos KP, Pawlak AC, Lynch K, Dias-Santagata D, Faquin WC, et al. Hobnail variant of papillary thyroid carcinoma: An institutional case series and molecular profile. Thyroid 2014;24:958-65.  Back to cited text no. 13
Motosugi U, Murata S, Nagata K, Yasuda M, Shimizu M. Thyroid papillary carcinoma with micropapillary and hobnail growth pattern: A histological variant with intermediate malignancy? Thyroid 2009;19:535-7.  Back to cited text no. 14
Li W, Sun D, Ming H, Zhang G, Tan J. A rare case report of very low thyroglobulin and a negative whole-body scan in a patient with a solid variant of papillary thyroid carcinoma with distant metastases. Medicine (Baltimore) 2017;96:e6086.  Back to cited text no. 15
Higuchi M, Hirokawa M, Suzuki A, Takada N, Yamao N, Kuma S, et al. Cytological features of solid variants of papillary thyroid carcinoma: A fine needle aspiration cytology study of 18 cases. Cytopathology 2017;28:268-72.  Back to cited text no. 16
Abdul Rahman WF, Md Hashim MN, Win TT, Bakrin IH. Solid variant of papillary thyroid carcinoma in a 14-year-old girl. BMJ Case Rep 2013;2013:bcr2013010001.  Back to cited text no. 17
Giorgadze TA, Scognamiglio T, Yang GC. Fine-needle aspiration cytology of the solid variant of papillary thyroid carcinoma: A study of 13 cases with clinical, histologic, and ultrasound correlations. Cancer Cytopathol 2015;123:71-81.  Back to cited text no. 18
Damle N, Ramya S, Bal C, Durgapal P. Solid variant of papillary carcinoma thyroid in a child with no history of radiation exposure. Indian J Nucl Med 2011;26:196-8.  Back to cited text no. 19
[PUBMED]  [Full text]  
Sak SD. Variants of papillary thyroid carcinoma: Multiple faces of a familiar tumor. Turk Patoloji Derg 2015;31 Suppl 1:34-47.  Back to cited text no. 20
Pradeep HD, Chandrasingha PC, Kannangara KR, Epitakaduwa EK, Fernando RF. Columnar cell variant of papillary thyroid carcinoma a rare and clinically aggressive variant. Sri Lanka J Surg 2015;33:44-5.  Back to cited text no. 21
Nirupama M, Kini H, Kini A. Cytomorphology of columnar cell variant of papillary thyroid carcinoma- a case report. Int J Sci Publ 2013;3:1-2.  Back to cited text no. 22
Asioli S, Erickson LA, Righi A, Lloyd RV. Papillary thyroid carcinoma with hobnail features: Histopathologic criteria to predict aggressive behavior. Hum Pathol 2013;44:320-8.  Back to cited text no. 23
Wenig BM, Thompson LD, Adair CF, Shmookler B, Heffess CS. Thyroid papillary carcinoma of columnar cell type: A clinicopathologic study of 16 cases. Cancer 1998;82:740-53.  Back to cited text no. 24
Michels JJ, Jacques M, Henry-Amar M, Bardet S. Prevalence and prognostic significance of tall cell variant of papillary thyroid carcinoma. Hum Pathol 2007;38:212-9.  Back to cited text no. 25
Shin JH. Ultrasonographic imaging of papillary thyroid carcinoma variants. Ultrasonography 2017;36:103-10.  Back to cited text no. 26
Baloch ZW, LiVolsi VA. Fine-needle aspiration of the thyroid: Today and tomorrow. Best Pract Res Clin Endocrinol Metab 2008;22:929-39.  Back to cited text no. 27
Dowerah S, Borgohian M, Manta A. Columnar cell type of thyroid papillary carcinoma: The diagnostic challenges. Eur J Pharm Med Res 2016;3:568-72.  Back to cited text no. 28
Bellevicine C, Cozzolino I, Malapelle U, Zeppa P, Troncone G. Cytological and molecular features of papillary thyroid carcinoma with prominent hobnail features: A case report. Acta Cytol 2012;56:560-4.  Back to cited text no. 29
Lloyd RV, Buehler D, Khanafshar E. Papillary thyroid carcinoma variants. Head Neck Pathol 2011;5:51-6.  Back to cited text no. 30
Dettmer MS, Schmitt A, Steinert H, Capper D, Moch H, Komminoth P, et al. Tall cell papillary thyroid carcinoma: New diagnostic criteria and mutations in BRAF and TERT. Endocr Relat Cancer 2015;22:419-29.  Back to cited text no. 31
Ferreiro JA, Hay ID, Lloyd RV. Columnar cell carcinoma of the thyroid: Report of three additional cases. Hum Pathol 1996;27:1156-60.  Back to cited text no. 32
Ito Y, Hirokawa M, Uruno T, Kihara M, Higashiyama T, Takamura Y, et al. Prevalence and biologic behavior of variants of papillary thyroid carcinoma: Experience at a single institution. Pathology 2008;40:617-22.  Back to cited text no. 33
Nikiforov YE, Erickson LA, Nikiforova MN, Caudill CM, Lloyd RV. Solid variant of papillary thyroid carcinoma: Incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior. Am J Surg Pathol 2001;25:1478-84.  Back to cited text no. 34
Enriquez ML, Baloch ZW, Montone KT, Zhang PJ, LiVolsi VA. CDX2 expression in columnar cell variant of papillary thyroid carcinoma. Am J Clin Pathol 2012;137:722-6.  Back to cited text no. 35
Baloch ZW, LiVolsi VA. Special types of thyroid carcinoma. Histopathology 2018;72:40-52.  Back to cited text no. 36
Asioli S, Maletta F, Pagni F, Pacchioni D, Vanzati A, Mariani S, et al. Cytomorphologic and molecular features of hobnail variant of papillary thyroid carcinoma: Case series and literature review. Diagn Cytopathol 2014;42:78-84.  Back to cited text no. 37
Chernock R. Immunohistochemistry of thyroid gland carcinomas: Clinical utility and diagnostic pitfalls. Diagn Histopathol 2016;22:184-90.  Back to cited text no. 38
Morandi L, Righi A, Maletta F, Rucci P, Pagni F, Gallo M, et al. Somatic mutation profiling of hobnail variant of papillary thyroid carcinoma. Endocr Relat Cancer 2017;24:107-17.  Back to cited text no. 39
Jalisi S, Ainsworth T, Lavalley M. Prognostic outcomes of tall cell variant papillary thyroid cancer: A meta-analysis. J Thyroid Res 2010;2010:325602.  Back to cited text no. 40
Silver CE, Owen RP, Rodrigo JP, Rinaldo A, Devaney KO, Ferlito A, et al. Aggressive variants of papillary thyroid carcinoma. Head Neck 2011;33:1052-9.  Back to cited text no. 41
Vadrucci M, Serio G, Baroli A.18 F-FDG PET/CT-guided clinical management of the rare aggressive “Columnar-cell” variant of papillary thyroid cancer. Endocrinol Metab (Seoul) 2016;31:343-4.  Back to cited text no. 42
Girardi FM, Barra MB, Zettler CG. Variants of papillary thyroid carcinoma: Association with histopathological prognostic factors. Braz J Otorhinolaryngol 2013;79:738-44.  Back to cited text no. 43
Liu Z, Zeng W, Chen T, Guo Y, Zhang C, Liu C, et al. Acomparison of the clinicopathological features and prognoses of the classical and the tall cell variant of papillary thyroid cancer: A meta-analysis. Oncotarget 2017;8:6222-32.  Back to cited text no. 44
Calangiu C, Simionescu C, Stepan A, Parnov M, Cercelaru L. The assessment of prognostic histopatholgical parameters depending on histological patterns of papillary thyroid carcinoma. Curr Health Sci J 2014;40:37-41.  Back to cited text no. 45
Siddiqui AA, Olansky L, Sawh RN, Tierney WM. Pancreatic metastasis of tall cell variant of papillary thyroid carcinoma: Diagnosis by endoscopic ultrasound-guided fine needle aspiration. JOP 2006;7:417-22.  Back to cited text no. 46
Chen JH, Faquin WC, Lloyd RV, Nosé V. Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma. Mod Pathol 2011;24:739-49.  Back to cited text no. 47
Baloch Z, LiVolsi VA, Tondon R. Aggressive variants of follicular cell derived thyroid carcinoma; the so called 'real thyroid carcinomas'. J Clin Pathol 2013;66:733-43.  Back to cited text no. 48
Lilo MT, Bishop JA, Ali SZ. Hobnail variant of papillary thyroid carcinoma: A case with an unusual presentation. Diagn Cytopathol 2017;45:754-6.  Back to cited text no. 49
Vuong HG, Odate T, Duong UN, Mochizuki K, Nakazawa T, Katoh R, et al. Prognostic importance of solid variant papillary thyroid carcinoma: A systematic review and meta-analysis. Head Neck 2018;40:1588-97.  Back to cited text no. 50
Sebastian SO, Gonzalez JM, Paricio PP, Perez JS, Flores DP, Madrona AP, et al. Papillary thyroid carcinoma: Prognostic index for survival including the histological variety. Arch Surg 2000;135:272-7.  Back to cited text no. 51


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]


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