Aya Ebina

Risk-adapted management of papillary thyroid carcinoma according to our own risk group classification system: Is thyroid lobectomy the treatment of choice for low-risk patients?

BACKGROUND Our original system for risk group classification for predicting cause-specific death from papillary thyroid carcinoma (PTC) defined patients with distant metastasis and older patients (≥ 50 years) with either massive extrathyroidal extension or large (≥ 3 cm) lymph node metastasis as high risk; all others are low risk. For unilateral, low-risk PTC, the extent of thyroidectomy (less-than-total thyroidectomy vs total or near-total thyroidectomy) has been determined based on the choice of the patient since 2005. PATIENTS Of 1,187 patients who underwent initial thyroidectomy for PTC (tumor size [T] >1 cm) between 1993 and 2010, 967 (82%) were classified as low risk. Among low-risk patients, 791 (82%) underwent less than total thyroidectomy. RESULTS The 10-year cause-specific survival and disease-free survival rates did not differ between patients who underwent total thyroidectomy versus less than total thyroidectomy (cause-specific survival, 99% vs 99% [P = .61]; disease-free survival, 91% vs 87% [P = .90]). Age ≥ 60 years, T ≥ 3 cm, and lymph node metastases >3 cm represented significant risk factors for distant recurrence. CONCLUSION The favorable overall survival of low-risk patients, regardless of the extent of thyroidectomy, supports patient autonomy in treatment-related decision making. Low-risk patients possessing risk factors for distant recurrence would be likely to benefit from total thyroidectomy followed by radioactive iodine.

A Clinical Study of Pharyngolaryngectomy with Total Esophagectomy: Postoperative Complications, Countermeasures, and Prognoses.

Objective Patients with advanced hypopharyngeal or cervical esophageal cancer have a comparatively high risk of also developing thoracic esophageal cancer. Pharyngolaryngectomy with total esophagectomy is highly invasive, and few reports about it exist. We examined the postoperative complications and respective countermeasures and prognoses of patients who underwent pharyngolaryngectomy with total esophagectomy. Study Design Case series with chart review. Setting Department of Head and Neck Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan. Subjects and Methods We examined the postoperative complications and respective countermeasures and prognoses of 40 patients who underwent pharyngolaryngectomy with total esophagectomy in our hospital. Results Postoperative complications were observed in 23 patients (57.5%) and consisted of 8 groups: tracheal region necrosis in 5 patients; neck abscess formation/wound infection in 5; fistula in 4; tracheostomy suture leakage in 2; ileus in 2; lymphorrhea in 2; pulmonary complications in 2; and other complications, including hemothorax, tracheoinnominate artery fistula, temporary cardiac arrest due to intraoperative mediastinum operation, methicillin-resistant Staphylococcus aureus enteritis, and sepsis, in 1 patient each. A lethal complication—brachiocephalic vein hemorrhage due to tracheostomy suture leakage and hemorrhagic shock due to tracheoinnominate artery fistula—occurred in 2 (5%) patients. The crude 5-year survival rate was 48.6%. Conclusions Serious postoperative complications were related to tracheostomaplasty. Although pharyngolaryngectomy with total esophagectomy is highly invasive, we believe that our outlined treatment method is the most appropriate for cases of advanced hypopharyngeal or cervical esophageal cancer that also requires concurrent surgery for esophageal cancer.

Molecular alterations of coexisting thyroid papillary carcinoma and anaplastic carcinoma: identification of TERT mutation as an independent risk factor for transformation

Thyroid papillary carcinoma is the most common endocrine neoplasm and generally carries a favorable prognosis. However, a small subset of papillary carcinomas transforms into anaplastic carcinoma, an undifferentiated cancer with a dismal prognosis. Recent studies using next-generation sequencing revealed the genomic landscape of papillary carcinoma and anaplastic carcinoma. However, risk factors for anaplastic transformation in papillary carcinoma remain obscure. In the present study, we investigated molecular alterations of papillary carcinoma and anaplastic carcinoma components in 27 tumors in which anaplastic carcinoma coexisted with antecedent papillary carcinoma. We conducted direct sequencing for BRAF, TERT promoter and PIK3CA, and immunohistochemistry for p53, TTF-1 and subunits of the SWI/SNF complex (ARID1A, ARID1B, ATRX, SMARCA2, SMARCA4, SMARCB1, and PBRM1). BRAFV600E and TERT promoter mutated at the rate of 90% and 95%, respectively, and these mutational statuses were almost identical between the papillary carcinoma and anaplastic carcinoma components. PIK3CA mutation was positive in 33% of our samples with a heterogeneous mutation pattern of the papillary carcinoma and anaplastic carcinoma components. Aberrant expression of p53 and loss of TTF-1 were present in 63 and 59%, respectively, and these two alterations were confined to the anaplastic carcinoma components. There was a loss of the SWI/SNF complex in a subset of the tumors with a heterogeneous pattern of the papillary carcinoma and anaplastic carcinoma components: SMARCA4 in 4% and PBRM1 in 4%. In a multivariate comparison between the antecedent papillary carcinoma components and control papillary carcinomas without anaplastic transformation, TERT promoter mutation was independently associated with anaplastic transformation. Collectively, papillary carcinoma-derived anaplastic carcinomas are characterized by BRAF and TERT promoter mutations, and these mutations occur prior to anaplastic transformation. Alterations of PIK3CA and the SWI/SNF complex are relatively rare and temporally heterogeneous. Of note, a papillary carcinoma harboring TERT promoter mutation is at higher risk for anaplastic transformation.

Stromal tiny black dots, like “sugar-coated”, of von Kossa stain is a diagnostic clue to hyalinizing trabecular tumor of the thyroid gland: Kossa-positive dots of thyroid HTT

Hyalinizing trabecular tumor (HTT) is a rare low‐grade tumor, and a prominent feature is the basement membranous stroma. We assume that such characteristic stromal findings of HTT are related to calcium deposition, and examined HTT samples by von Kossa special staining. There has been no report describing von Kossa special staining for such stroma. We collected 12 cases of HTT and 30 cases of papillary thyroid carcinoma (PTC) that had matched age, gender, tumor size, and surgical procedure characteristics as a control group. We compared the staining pattern and degree of von Kossa positivity between HTT and PTC, and a grading system of von Kossa stain was adopted to highlight differences between them. On von Kossa staining, all HTT revealed many tiny black dots around vessels in the hyalinized stroma, like “sugar‐coated”, and a high degree of calcium deposition in most cases, whereas PTC showed sparse stromal calcification in some cases. The degree of von Kossa staining was significantly different between the two groups. This is the first report describing abundant tiny black dots, like a “sugar‐coated” appearance, of von Kossa stain in HTT. Here, we propose this finding can be a useful diagnostic clue to HTT.

Intrathyroidal epithelial thymoma: carcinoma showing thymus-like differentiation mimicking squamous cell carcinoma of the thyroid.

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