Clinical characteristics and molecular pathology of skull ectopic thyroid cancer

Abstract

Thyroid cancer is very common, but skull ectopic thyroid cancer has not been reported in 50 years of literatures in foreign countries. There are only four cases of the skull ectopic thyroid cancer reported in more than 30 years of domestic literature including the cases in this report. This paper aims to investigate the clinical characteristics and possible molecular mechanisms of this rare disease. Five keywords of "thyroid gland", "ectopic thyroid", "thyroid cancer", "ectopic thyroid cancer" and "metastatic thyroid cancer" were included and 50 years of literatures in the PubMed-MEDLINE and Wanfang database were reviewed. By combining the test data of 2 cases of surgical patient tissue microarray specimens-molecular immunology pathology, the possible molecular mechanisms were analyzed and molecular regulation network diagram was drawn. The skull ectopic thyroid cancer has not been reported in 50 years of literatures in foreign countries and there are only four cases of the skull ectopic thyroid cancer reported in more than 30 years of domestic literature including the cases in this report. The molecular expressions of skull ectopic thyroid cancer, orthotopic thyroid cancer, and metastatic thyroid cancer were not the same: (I) AKT (P=0.012, 0.002) and mTOR (P=0.002, 0.004) were highly expressed in the skull ectopic thyroid cancer; (II) BRAF (P=0.029, 0.014) and ERK (P=0.002, 0.001) were highly expressed in orthotopic thyroid cancer; (III) MMP-9 (P=0.023, 0.016) was highly expressed in metastatic thyroid cancer. According to the molecular information base, the PI3K is predicted to be a key crossing gene of the above three signaling pathways, which showed no significant differences in these three thyroid cancers (P=0.692, 0.388, 0.227), but PI3K has regulation roles in the three signaling pathways of Akt/mTOR, MAPK, and NF-κB. PI3K gene is an important starting gene of thyroid cancers. After the canceration starts, due to the fact that the local microenvironments of thyroid cancers in different parts are different, the thyroid cancers are regulated by different signaling pathways. The ectopic thyroid cancer was correlated with Akt/mTOR pathway high expression; orthotopic thyroid was related with MAPK/BRAF/ERK signaling pathway high expression; and the metastatic thyroid cancer was related with NFkB/MMP9 high expression.

Keywords: Ectopic thyroid; ectopic thyroid carcinoma; metastatic thyroid carcinoma; molecular pathway; thyroid carcinoma.

Figure 1

Example 1: (A-C): figures before the first surgery and the observation of head CT and tumor section HE staining light microscope (scale: 20 µm; diagnosed as follicular thyroid carcinoma); (D-F): figures before the second surgery and the observation of head CT and tumor section HE staining light microscope (scale: 20 µm; diagnosed as follicular thyroid carcinoma); (G,I): figures before the neck thyroid gland surgery and the observation of MRI (the arrow points to the left lobe of the thyroid with abnormality signals) and HE staining light microscope of thyroid resection tissues (scale: 20 µm; diagnosed as thyroid nodules); (H) a neck photo with normal findings.

Figure 2

Example 2: (A,B) were preoperative brain MRI and CT respectively, the showed high signal of tumor shadow located in the right temporal region, and the tumor grew inside and outside the head and destroyed the skull; (C,D) were follow-up figures which respectively showed that the right tumorectomy surgery temporal region recovered well and the anterior cervical thyroid surgery region was also normal; (E,F) were the observation of pathological slice light microscopy respectively (HE ×400), which respectively showed that the head tumor was in line with the thyroid cancer, while the thyroid tumor was in line with the thyroid cell proliferative changes.

Figure 3

Immunohistochemistry light microscopy findings (partial ×400): row 1–5 were in situ normal thyroid gland, in situ nodular goiter, in situ papillary thyroid carcinoma, metastatic thyroid cancer and ectopic thyroid cancer, respectively; column 1–8 were PI3K, AKT, mTOR, BRAF, ERK, MMP-9, IKK, and NFκB, respectively.

Figure 4

Comparisons and statistics of different protein expression rates in tissue microarray.

Figure 5

Thyroid cancer-related signaling pathway relational graph.