Head & Neck Case Review
A 19-year-old female presented with a rapidly enlarging 7.5 cm left-sided thyroid mass. Multiple, bilateral pulmonary nodules measuring up to 2 cm were present on CT scan, consistent with metastatic disease. She underwent total thyroidectomy and left neck dissection followed by radioactive iodine ablation. Images from the thyroid resection are shown below.
Q1. Which gene is most likely to harbor a mutation in this patient’s tumor?
- A. BRAF
- B. DICER1
- C. RAS
- D. TERT
Q2. The prognosis for this tumor type is better in young people than in older adults.
- A. True
- B. False
Poorly Differentiated Thyroid Carcinoma.
Poorly differentiated thyroid carcinoma (PDTC) is a clinically aggressive follicular cell derived neoplasm that represents approximately 1% of all thyroid malignancies. The 10-year patient survival (60-70%) is intermediate between differentiated and anaplastic thyroid carcinomas.
The most widely accepted definition of PDTC is the laid out in the Turin criteria, which were adopted by the World Health Organization Classification of Tumours of the Endocrine Organs in 2017. According to the Turin criteria, PDTC is defined as a tumor with solid, trabecular, or insular growth that lacks papillary nuclear features and has at least one of the following: ≥ 3 mitoses per 10 high power fields, tumor necrosis, or convoluted nuclei. There is some evidence that the Turin criteria can be applied to Hurthle cell (oncocytic) tumors as well.
The overwhelming majority of PDTCs occur in older adults (mean patient age of 60 years); they are exceedingly rare in childhood or adolescence. However, PDTCs that do occur in younger persons have unique features. They primarily affect teenagers and frequently harbor DICER1 mutations, which may be associated with hereditary DICER1 syndrome in a subset of cases. DICER1 mutations are very rare in adult PDTC, which often harbor driver mutations common in differentiated thyroid carcinomas (BRAF, NRAS, etc…). These mutations have not been found in pediatric PDTC.
While the prognosis of differentiated thyroid carcinoma is more favorable in younger persons compared to older adults, the same is not true for PDTC. PDTC in the young (< 21 years) is still an aggressive tumor type. Although data is limited, survival rates are likely similar to those in older adults. Prognostic features remain to be characterized but disease extent may be important. Large tumor size and extrathyroidal extension with positive resection margins may be associated with worse outcomes compared to more limited tumors or tumors with encapsulation.
- Asioli S, Erickson LA, Righi A, et al. Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression. Mod. Pathol. 2010;23:1269–1278.
- Ibrahimpasic T, Ghossein R, Carlson DL, et al. Outcomes in patients with poorly differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 2014;99:1245–1252.
- Volante M, Collini P, Nikiforov YE, et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am. J. Surg. Pathol. 2007;31:1256–1264.
- Tallini G, Asioli S, Aubert S, et al. Poorly differentiated thyroid carcinoma. In: WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon: International Agency for Research on Cancer; 2017.
- Chernock RD, Rivera B, Borrelli N, Hill DA, Fahiminiya S, Shah T, Chong AS, Aqil B, Mehrad M, Giordano TJ, Sheridan R, Rutter MM, Dehner LP, Foulkes WD, Nikiforov YE. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Mod. Pathol. Epub ahead of print.
- Hill DA, Ivanovich J, Priest JR, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science 2009;325:965.
Q1 = B. DICER1
Q2 = B. False
Rebecca Chernock, M.D.
Department of Pathology and Immunology
Washington University in St. Louis