Takuya Higashiyama

Background The major sites of distant metastases of papillary thyroid carcinoma (PTC) are the lung and bone; metastasis to the liver is rare. Although the postoperative serum thyroglobulin (Tg) level after total thyroidectomy is a good prognostic indicator for PTC when anti-thyroglobulin antibody (TgAb) is negative, the presence of TgAb interferes with the Tg assay, making serum Tg levels unreliable. Here we report a case of liver metastasis of PTC that presented with elevated serum levels of carbohydrate antigen 19-9 (CA19-9), which is usually a serum marker of pancreatic and gastrointestinal neoplasias. Case presentation A 69-year-old man was diagnosed with PTC and underwent total thyroidectomy 16 years ago. The patient's serum Tg levels increased progressively during follow-up and his serum TgAb was negative. Positron emission tomography (PET) and computed tomography (CT) revealed metastases of the lung, cervical spine, mediastinum and liver. The liver lesion was a solitary tumor measuring 4.0 cm in the greatest dimension. His serum CA19-9 level was very high (326 U/mL), and intrahepatic cholangiocarcinoma was suspected from the results of various examinations including gastrointestinal endoscopic imaging and CT. Laparoscopic partial liver resection for segment 4 was performed. The histopathological diagnosis was a metastatic liver tumor from PTC. The immunohistological examination revealed that the liver tumor was positive for CA19-9 and Tg. The primary PTC, recovered from paraffin-embedded specimen, was also positive for CA19-9. After the surgery, his serum CA19-9 level as well as serum Tg level markedly decreased. Conclusions We presented the first reported case of liver metastasis of a PTC presenting with elevated serum levels of CA19-9 after total thyroidectomy. This case suggests that the serum CA19-9 levels may serve as a surrogate marker for PTC in place of the serum Tg level in patients with positive serum TgAb if the PTC and/or the metastatic lesions are positive for CA19-9 staining.

Background: Our previous kinetic analyses of changes in the tumor volume (TV) of papillary thyroid microcarcinomas during active surveillance revealed that the tumors’ growth varied over time from rather rapid growth to shrinkage and that the hypothetical TV-doubling rates (DRs) before the patients’ presentation were much larger than their observed TV-DRs, indicating that rapid growth phases preceded their presentation. Whether this phenomenon also occurs in medullary thyroid carcinoma (MTC) was unknown. Methods: We retrospectively analyzed the cases of 46 MTC patients (18 hereditary, 28 sporadic; 9–80 years old at surgery, median 53.5 years; 19 males and 27 females) with elevated postoperative calcitonin (Ct) measured with the electrochemiluminescence immunoassay suggesting persistent disease. We calculated each patient’s Ct-DR and his/her hypothetical TV-DR, using the tumor size and age at surgery. Results: Ct-DRs (/year) after surgery were > 0.5, 0.1–0.5, − 0.1–0.1, and < − 0.1 in 9, 21, 12, and 4 patients, respectively (median 0.17). The hypothetical TV-DRs (/year) before surgery were > 1, 0.5–1.0, 0.1–0.5 and < 0.1 in 11, 21, 14, and 0 patients, respectively (median 0.60). The hypothetical TV-DR was higher than the observed Ct-DR in 41 of the 46 MTC patients and all 18 patients with hereditary MTC, suggesting that a rapid growth phase preceded surgery in these patients. Conclusions: In this series of MTC patients, the pre-surgery calculated hypothetical TV-DRs were significantly higher than the Ct-DRs observed post-surgery, suggesting that there were rapid growth periods before surgery in the vast majority of these MTC patients.

Background: The tumor–node–metastasis (TNM) classification system to categorized anaplastic thyroid cancer (ATC) was revised. Methods: The revised system was evaluated using a large database of ATC patients. Results: A total of 757 patients were analyzed. The proportion and median overall survival values (OS: months) for each T category were T1 (n = 8, 1.1%, 12.5), T2 (n = 43, 5.7%, 10.9), T3a (n = 117, 15.5%, 5.7), T3b (n = 438, 57.9%, 3.9), and T4 (n = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank p < 0.01). Sixty-three (58.3%) patients migrated from stage IV A to IV B by revision based on the existence of nodal involvement and 422 patients (55.7%) were stratified into stage IV B, without a worsening of their OS (6.1), leaving 45 patients (5.9%) in stage IV A with fair OS (15.8). The hazard ratios for the survival of the patients of stage IV B compared to stage IV A increased from 1.1 to 2.1 by the revision. No change was made for stage IV C (n = 290, 38.8%, 2.8). Conclusion: The revised TNM system clearly indicated the prognoses of ATC patients by extracting rare patients with fair prognoses as having stage IV A disease and categorized many heterogeneous patients in stage IV B.

For the differential diagnosis of medullary thyroid carcinoma (MTC) on thyroid nodules, ultrasound-guided fine-needle aspiration cytology is a useful and safe procedure, but its diagnostic accuracy is not high enough. As an ancillary method to accurately diagnose MTC, the calcitonin in fine-needle aspirate washout fluid (FNA-Ct) is used. However, no data are available about cut-off values of FNA-Ct using the currently available electrochemiluminescence immunoassay (ECLIA). We investigated 180 thyroid nodules in 141 patients. After smearing, the syringe and needle used for the FNA were rinsed with normal saline (0.5 mL). The calcitonin in the washout was measured by ECLIA. The FNA-Ct in the non-MTC nodules of MTC patients, non-MTC nodules of non-MTC patients, and MTC nodules were 10.6–2100 pg/mL (median 24.6 pg/mL), < 0.5–21.0 pg/mL (median < 0.5 pg/mL), and 94.9–4,070,000 pg/mL (median 177,000 pg/mL), respectively. A receiver operating characteristic analysis of the MTC nodules and the non-MTC nodules of the non-MTC patients indicated that the cut-off value was 21.0 pg/mL, leading to 100% sensitivity and 100% specificity. This is the first study to determine the cut-off value of FNA-Ct with an ECLIA, and we propose that the optimal cut-off value is 21.0 pg/mL.

Background: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive malignancy, with a median survival of less than 6 months due to rapid progression and resistance to multimodal therapies. Effective treatment strategies have not been identified. A prospective clinical study was performed to objectively evaluate outcomes of treatment with paclitaxel. Methods: An investigator-initiated, multicenter, nonrandomized, open-label, single-arm study to evaluate the feasibility and efficacy of weekly paclitaxel (80 mg/m ² ) administration for patients with pathologically confirmed ATC was conducted in a nationwide organization. Results: Feasibility was analyzed in 56 patients. More than one course of treatment was performed in 52 (93%) patients retaining sufficient dose intensity (>84%). No patient had to terminate the treatment because of an adverse event. The median overall survival was 6.7 months [confidence interval 4.4–9.0]. The 6-month survival was 54%. Among the 42 patients with an evaluable lesion, none demonstrated complete remission, 9 (21%) showed partial remission, 22 (52%) achieved stable disease, and 8 (19%) exhibited progressive disease; 3 did not complete the initial treatment course. The objective response rate was 21%, and the clinical benefit rate was 73%. The median time to progression was 1.6 months. Statistically, no additional effect of concomitant radiation was demonstrated in 6 patients receiving combined therapy. Eight patients, in whom a complete post-treatment surgical removal of the tumor was feasible, survived significantly longer (median 7.6 months [CI 8.1–23.0]) than the other 34 patients in whom the tumor could not be completely removed after chemotherapy (5.4 months [CI 3.0–7.8], p = 0.018). Summary: The study demonstrates objective and accurate information concerning the feasibility and efficacy of a standardized treatment with weekly paclitaxel administration for ATC patients. Conclusions: Weekly paclitaxel administration for ATC patients can be of clinical benefit in a neo-adjuvant setting.

Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, often demonstrating resistance to multimodal therapeutic approaches. The median survival of ATC patients after initial diagnosis was reported to be < 6 months due to the rapid progression of disease by dissemination and/or invasion. There have been several reports describing possible effective chemotherapies, but these studies might be biased by the nature of retrospective accumulations of clinical experiences, and thus reliable data concerning the efficacies of the treatment efforts are required. In 2009, we established the research organization Anaplastic Carcinoma Research Consortium Japan (ATCCJ) to investigate this highly malignant disease. Using this nationwide organization, we conducted a prospective clinical study to investigate the feasibility, safeness, and efficacy of chemotherapy with weekly paclitaxel for ATC patients. This trial is registered on the clinical trials site of the University Hospital Medical Information Network Clinical Trials Registry Web site (UMIN000008574). The study was started in 2012, and enrollment was closed in March 2014 after accumulating 71 patients from 28 registered institutes. The follow-up data will be available in April 2015. Important information concerning the management of this disease is expected to be revealed by this study. The concept and design of the study are described herein.

Patients with metastases to the thyroid from renal cell carcinoma (RCC) that need surgical management are not many and unfamiliar to clinicians and thyroid endocrinologists. Therefore, little information is available on ultrasonographic features of metastatic carcinoma in the thyroid. The strategic value of ultrasound in preoperative surgical planning for patients with thyroid nodules has become increasingly appreciated. The purposes of this article are to clarify the ultrasound characteristics of metastatic carcinoma to the thyroid from RCC by evaluating many patients in one institute, and to investigate the role of ultrasonography in preoperative diagnosis. Ten patients with these carcinomas who had undergone surgical management were investigated clinically and ultrasonographically. Ultrasonographic features to be evaluated were the form of involvement in the thyroid, size, shape, pattern, calcifications, vascularity, and tumor thrombus. Clinical features were previous history of RCC, serum thyroglobulin levels, cytology, preoperative diagnosis, and surgery. Ultrasonographic features of these carcinomas were more likely to involve a solitary, irregular, and solid without calcifications, and prominent intra-tumoral vascularity and tumor thrombus in the vein. These patients tended to be older, and to have relatively late recurrence in the thyroid, RCC in the right kidney as the primary site, and relatively low serum thyroglobulin levels. Metastatic carcinomas to the thyroid from RCC presented highly characteristic features on ultrasonography. These ultrasonographic features combined with cytological findings and previous medical history of RCC can provide the optimal process for the preoperative diagnosis of such patients.

We report a case of familial adenomatous polyposis( FAP) presenting with thyroid cancer. A 24-year-old woman, on histological examination, was diagnosed as having the cribriform-morular variant of papillary thyroid carcinoma, which is known to be associated with FAP. Therefore, she underwent colonoscopy, and FAP was diagnosed. In addition, abdominal computed tomography( CT) scans revealed a tumor, approximately 12 cm in diameter, in the right lower abdomen. After total thyroidectomy, total proctocolectomy and excision of the tumor arising from the mesentery of the small intestines were performed. The histological diagnosis was FAP with a desmoid tumor arising from the mesentery.