Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis

Abstract Objective.—To describe and document tumor-to-tumor metastases in the thyroid gland. Methods and Results.—In this series we describe 3 cases of tumor-to-tumor metastasis in which the recipient tumor was a follicular variant of papillary thyroid carcinoma. The donor tumors and sites were small cell carcinoma of the lung, neuroendocrine carcinoma probably of pancreatic origin with initial presentation as liver metastasis, and clear cell carcinoma of the kidney with metastasis to liver and pancreas. The donor tumor cells infiltrated the substance of the follicular variant of papillary thyroid carcinoma, the nontumorous thyroid parenchyma, and the lymphovascular spaces. Small cell carcinoma and neuroendocrine carcinoma showed positive reactivity for neuroendocrine markers and were negative for thyroglobulin and calcitonin. The follicular variant of papillary thyroid carcinoma showed positivity with thyroglobulin and cytokeratin 19. Conclusions.—Although tumor-to-tumor metastases in thyroid gland are exceedingly rare, one should be aware of this phenomenon as the metastatic lesion may simulate a thyroid primary. History of a previous tumor and immunohistochemical stains can be helpful in distinguishing between primary and metastatic thyroid neoplasms.

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Tumor-to-tumor metastasis: Lung adenocarcinoma metastasizing to a follicular variant of papillary thyroid carcinoma

Pathology International ◽

10.1111/j.1440-1827.2011.02679.x ◽

2011 ◽

Vol 61 (7) ◽

pp. 435-441 ◽

Cited By ~ 18

Author(s):

Kazuki Hashimoto ◽

Hidetaka Yamamoto ◽

Takafumi Nakano ◽

Minako Oyama ◽

Hideki Shiratsuchi ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Lung Adenocarcinoma ◽

Tumor Metastasis ◽

Papillary Thyroid ◽

Follicular Variant ◽

Tumor To Tumor Metastasis

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Correlation between B-RAFV600E mutation and clinico–pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature

Endocrine Related Cancer ◽

10.1677/erc.1.01086 ◽

2006 ◽

Vol 13 (2) ◽

pp. 455-464 ◽

Cited By ~ 154

Author(s):

L Fugazzola ◽

E Puxeddu ◽

N Avenia ◽

C Romei ◽

V Cirello ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Mutational Analysis ◽

Direct Sequencing ◽

Older Age ◽

Age At Diagnosis ◽

Papillary Thyroid ◽

Genetic Event ◽

Single Stranded Conformational Polymorphism ◽

Pathologic Features

Recently, a somatic point mutation of the B-RAF gene (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence variable among different series. Since discordant data on the clinico-pathologic features of B-RAF mutated PTC are present in the literature, the aim of the present co-operative study was to establish the prevalence of this genetic alteration and to perform a genotype–phenotype correlation in a large cohort of patients with PTC. To this purpose, a series of 260 sporadic PTCs with different histological variants were included in the study. The mutational analysis of the B-RAF gene was performed either by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing. Statistical analyses were obtained by means of χ2/Fisher’s exact test and t-test. Overall, a heterozygous T > A transversion at nucleotide 1799 (V600E) was found in 99 out of 260 PTCs (38%). According to the histological type of the tumor, the B-RAF V600E mutation was present in 48.3% of cases of classic PTCs (85 out of 176), in 17.6% (nine out of 51) of follicular variants of PTCs, in 21.7% (five out of 23) in other PTC variants and in none of the ten poorly differentiated tumors. B-RAF V600E was significantly associated with the classic variant of PTC (P = 0.0001) and with an older age at diagnosis (P = 0.01). No statistically significant correlation was found among the presence of B-RAF V600E and gender, tumor node metastasis (TNM), multicentricity of the tumor, stage at diagnosis and outcome. In conclusion, the present study reports the prevalence of B-RAF V600E (38%) in the largest series of sporadic PTCs, including 260 cases from three different Italian referring centers. This prevalence is similar to that calculated by pooling together all data previously reported, 39.6% (759 out of 1914 cases), thus indicating that the prevalence of this genetic event lies around 38–40%. Furthermore, B-RAF V600E was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated PTC variants. A significant association of B-RAF mutation was also found with an older age at diagnosis, the mutation being very rare in childhood and adolescent PTCs. Finally, no correlation was found with a poorer prognosis and a worse outcome after a median follow-up of 72 months.

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Preoperative RAS Mutational Analysis Is of Great Value in Predicting Follicular Variant of Papillary Thyroid Carcinoma

BioMed Research International ◽

10.1155/2015/697068 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Tae Sook Hwang ◽

Wook Youn Kim ◽

Hye Seung Han ◽

So Dug Lim ◽

Wan-Seop Kim ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Thyroid Nodules ◽

Mutational Analysis ◽

Braf V600e ◽

Papillary Thyroid ◽

Follicular Variant ◽

Ras Mutation ◽

Ras Mutations ◽

Codon 61

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n=57), BRAF K601E (n=11), or RAS (n=64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

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Mutational Analysis of the APC Gene in Cribriform-Morula Variant of Papillary Thyroid Carcinoma

World Journal of Surgery ◽

10.1007/s00268-005-0368-3 ◽

2006 ◽

Vol 30 (5) ◽

pp. 775-779 ◽

Cited By ~ 36

Author(s):

Shinya Uchino ◽

Shiro Noguchi ◽

Hiroto Yamashita ◽

Hiroyuki Yamashita ◽

Shin Watanabe ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Mutational Analysis ◽

Apc Gene ◽

Papillary Thyroid

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Hyperfunctioning Papillary Thyroid Carcinoma with a BRAF Mutation: The First Case Report and a Literature Review

European Thyroid Journal ◽

10.1159/000513552 ◽

2021 ◽

pp. 1-6

Author(s):

Shinsuke Shinkai ◽

Kenji Ohba ◽

Kennichi Kakudo ◽

Takayuki Iwaki ◽

Yoshihiro Mimura ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Reference Range ◽

Mutational Analysis ◽

Thyroid Tissue ◽

Braf V600e ◽

Histopathological Diagnosis ◽

Thyroid Function Tests ◽

Papillary Thyroid ◽

First Case

Introduction: Hyperfunctioning papillary thyroid carcinoma (PTC) is rare and consequently, little information on its molecular etiology is available. Although BRAF V600E (BRAF c.1799T>A, p.V600E) is a prominent oncogene in PTC, its mutation has not yet been reported in hyperfunctioning PTC. Case Presentation: Ultrasonography detected a 26-mm nodule in the right lobe of the thyroid gland of a 48-year-old man. Thyroid function tests indicated that he was hyperthyroid with a TSH level of 0.01 mIU/L (reference range: 0.05–5.00) and a free thyroxine level of 23.2 pmol/L (reference range: 11.6–21.9). TSHR autoantibodies were <0.8 IU/L (reference value: <2.0 IU/L). The 99mTc thyroid scintigram revealed a round, right-sided focus of tracer uptake by the nodule with a decreased uptake in the remainder of the gland. The patient underwent total thyroidectomy because fine-needle aspiration cytology revealed a malignancy. The histopathological diagnosis was conventional PTC. Subsequent mutational analysis of BRAF (exon 15), TSHR (exons 1–10), GNAS (exons 7–10), EZH1 (exon 16), KRAS, NRAS, HRAS (codons 12, 13, and 61), and TERT promoter (C250T and C228T) identified a heterozygous point mutation in BRAF V600E in a tumor tissue sample. In addition, we identified a TSHR D727E polymorphism (TSHR c.2181C>G, p.D727E) in both the tumor and the surrounding normal thyroid tissue. Discussion and Conclusions: We report a case of hyperfunctioning PTC with a BRAF V600E mutation for the first time. Our literature search yielded 16 cases of hyperfunctioning thyroid carcinoma in which a mutational analysis was conducted. We identified TSHR mutations in 13 of these cases. One case revealed a combination of TSHR and KRAS mutations; the other case revealed a TSHR mutation with a PAX8/PPARG rearrangement. These findings suggest that the concomitant activation of oncogenes (in addition to constitutive activation of the TSHR-cyclic AMP cascade) are associated with the malignant phenotype in hyperfunctioning thyroid nodules.

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Mutational analysis of metastatic lymph nodes from papillary thyroid carcinoma in adult and pediatric patients

Surgery ◽

10.1016/j.surg.2016.10.002 ◽

2017 ◽

Vol 161 (1) ◽

pp. 176-187 ◽

Cited By ~ 3

Author(s):

Alexander L. Shifrin ◽

Michele Fischer ◽

Trevor Paul ◽

Brian Erler ◽

Katherine Gheysens ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Lymph Nodes ◽

Pediatric Patients ◽

Mutational Analysis ◽

Papillary Thyroid ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph

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SUN-LB78 Hyperfunctioning Papillary Thyroid Carcinoma With a BRAF Mutation

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2109 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Shinsuke Shinkai ◽

Kenji Ohba ◽

Akio Matsushita ◽

Go Kuroda ◽

Yuki Sakai ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Braf Mutation ◽

Reference Range ◽

Mutational Analysis ◽

Color Doppler ◽

Driver Mutations ◽

Histopathological Diagnosis ◽

Thyroid Function Tests ◽

Papillary Thyroid

Abstract Background: Hyperfunctioning papillary thyroid carcinoma (PTC) is a rare tumor and accounts for less than 0.1% of all thyroid tumors. Information about its driver mutations is limited. Our literature search yielded 16 cases wherein a mutational analysis was conducted. Thyrotropin receptor (TSHR) mutations were identified in 11 of these cases. One case revealed a combination of TSHR and KRAS mutations. No mutations were identified in the other four cases. BRAFV600E is a prominent oncogene in PTC; however, hyperfunctioning PTC with this mutation has not yet been reported. Clinical Case: In a 48-year-old man, ultrasonography (US) during an annual medical checkup revealed a nodule at the right lobe of the thyroid gland. He visited the outpatient clinic for further evaluation. Thyroid function tests indicated that he was hyperthyroid with TSH level of 0.01 mIU/L (reference range: 0.05-5.00), free thyroxine level of 1.8 ng/dL (reference range: 0.9-1.7), and free triiodothyronine level of 4.3 pg/mL (reference range: 2.3-4.0). Serum thyroglobulin was 62.1 ng/mL (reference range: <33.7) and TSHR autoantibodies (TRAb) was <0.8 IU/L (reference range: <2.0 IU/L). B-mode US revealed a hypoechoic, heterogeneous nodule with largest diameter of 25 mm, and it had a jagged border and microcalcification. Color Doppler US revealed increased intranodular vascularity. The 99mTc thyroid scintigram revealed a round, right-sided focus of tracer uptake by the nodule with suppression in the remainder of the gland. These findings were consistent with an autonomously-functioning thyroid nodule. The patient underwent total thyroidectomy because fine-needle aspiration cytology revealed a malignant cytological diagnosis. The histopathological diagnosis of the patient was PTC, tall cell variant, pT2, pEx0, pN1b, and M0. Subsequent mutational analysis of BRAF (exon 15), TSHR (exons 9 and 10), GNAS (exons 7-10), KRAS, NRAS, HRAS (codons 12, 13, and 61), and TERT promoter (C250T and C228T) only identified a heterozygous point mutation in BRAFV600E in tissue samples. Conclusion: We report for the first time a case of hyperfunctioning papillary thyroid carcinoma with a BRAF mutation.

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