Two Sequences Variations of the E768D Mutation Found in Familial Medullary Thyroid Carcinomas

Medullary thyroid cancer or MTC is present in sporadic form (75% of cases) and in familial form (25% of cases), in this latter situation, the MTC is a part of Multiple Endocrine Neoplasia type 2 (MEN 2). The MEN2 is divided into MEN2A, MEN2B and FMTC or isolated familial MTC. The MEN2 are rare hereditary disease, transmitted as an autosomal dominant mode, linked to mutations of the RET gene. The discovery of a mutation in the RET proto-oncogene by molecular biology techniques in a index case of MTC confirms the diagnosis of familial and allows the genetic testing of healthy clinically related index case: those who carry the genetic mutation, will be offered prophylactic thyroidectomy before any biological or clinical manifestation. The genetic analysis of the RET gene was performed by PCR / sequencing. The E768D mutation was found in the exon 13 of the RET gene in 2 differences sequences forms (GAG/GAC et GAG/GAT). This mutation, already described, found in the FMTC.

Unusual case of medullary thyroid cancer

Medullary thyroid carcinomas make up 9,4% of all cancers of the thyroid gland [1]. We can divide them into sporadic and familial form. Sporadic forms are most common. The rest of medullary thyroid carcinomas are familial forms which in most cases are associated with MEN2a and MEN2b syndromes. If neoplasm is associated with MEN2a or MEN2b syndromes, other tumors can occur: pheochromocytoma or adenomas of parathyroids glands. Medullary thyroid carcinoma typically occurs as a solid tumor in the thyroid region of the neck. It can produce also: pain in thyroid region, dysphagia, hoarseness, cervical lymphadenopathy. These symptoms are caused by infiltration of adjacent tissues by neoplasm and by metastases to cervical lymph nodes. It is very rare that there is no tumor in the thyroid region, when a patient complains about signs associated with infiltration of the tumor, but in some cases lymphadenopathy can be the first sign of medullary thyroid carcinoma [2]. Rarer than that there is no tumor in thyroid gland visualized in CT scans when there are signs of cervical lymphadenopathy. In this case report we present the patient with metastases of the medullary thyroid carcinoma to the neck and no other findings in physical examination and additional testing.

DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbor somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been identified as a reliable predictor of aggressive behavior and development of lymph node metastases, a possible correlation of DLL3 expression with the presence of stromal desmoplasia was of particular interest. 59 paraffin-embedded samples of sporadic MTC with (44 cases) and without (15 cases) stromal desmoplasia and known lymph node status were included. DLL3 expression was determined by immunohistochemistry; no expression (0%), low expression (1–49%) and high expression (≥50%) were correlated with clinicopathological data. The proportion of DLL3 positivity was significantly correlated with both stromal desmoplasia (P < 0.0001) and lymph node metastases (P < 0.0001). MTC without stromal desmoplasia consistently lack DLL3 expression. This is the first study to focus on MTC regarding DLL3 expression and the relationship to various factors. Our results demonstrate that expression of DLL3 in MTC represents a reliable surrogate marker for stromal desmoplasia and lymph node metastases and might be an indicator for aggressive clinical behavior. DLL3 expression in ≥50% of tumor cells virtually excludes MTC without stromal desmoplasia. DLL3 was discussed as a potential therapeutic target in malignant tumors of other locations with positive immunohistochemical reaction and might therefore be a new therapeutic option in MTC, as well.

Ultrasonographic characteristics of medullary thyroid carcinoma according to nodule size: application of the Korean Thyroid Imaging Reporting and Data System and American Thyroid Association guidelines

Background Few studies have categorized ultrasound (US) findings of various sized medullary thyroid carcinomas (MTCs) according to updated guidelines. Purpose To evaluate and compare the differences in US findings of MTC according to nodule size, using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and American Thyroid Association (ATA) guidelines. Material and Methods The study included 119 patients with 129 MTC nodules, which were surgically confirmed at our institution between March 1999 and September 2017. Nodules were divided into large (≥1.0 cm) and small (<1.0 cm) groups. US images were analyzed according to the K-TIRADS and ATA guidelines. The differences in US characteristics between small and large nodules were compared using Fisher’s exact or Chi-square tests. Results Of 129 MTC nodules, 84 (65.1%) were large nodules and 45 (34.9%) were small nodules. According to the nodule size, small MTC nodules were classified more commonly as high suspicion by K-TIRADS and ATA (95.6% and 93.3%, respectively) ( P < 0.001), but presented neither cystic change, isoechogenicity, nor low suspicion category by K-TIRADS and ATA. In contrast, large MTC nodules showed more frequently cystic change (15.5%), isoechogenicity (16.7%), smooth margins (50%), or low or intermediate suspicion US features by K-TIRADS and ATA (59.6% and 36.0%, respectively) (all P values < 0.001). Conclusion Most small MTC nodules are classified as high suspicion on US, whereas large MTC nodules are diagnosed more frequently as low or intermediate suspicion by K-TIRADS and ATA.