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  • Author: Mitsuyoshi Hirokawa x
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Kaoru Kobayashi Kuma Hospital, Kobe City, Hyogo, Japan

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Mitsuyoshi Hirokawa Kuma Hospital, Kobe City, Hyogo, Japan

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Tomonori Yabuta Kuma Hospital, Kobe City, Hyogo, Japan

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Mitsuhiro Fukushima Kuma Hospital, Kobe City, Hyogo, Japan

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Minoru Kihara Kuma Hospital, Kobe City, Hyogo, Japan

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Yuuki Takamura Kuma Hospital, Kobe City, Hyogo, Japan

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Yasuhiro Ito Kuma Hospital, Kobe City, Hyogo, Japan

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Akihiro Miya Kuma Hospital, Kobe City, Hyogo, Japan

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Nobuyuki Amino Kuma Hospital, Kobe City, Hyogo, Japan

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Akira Miyauchi Kuma Hospital, Kobe City, Hyogo, Japan

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Background: Thyroid nodules with cystic content or mixed sponge-like aspect on ultrasonography and a concordant cytology are strongly predictive of benignity. Objectives: We present 8 patients with honeycomb-like papillary thyroid carcinoma with multiple small cysts on ultrasonography. Methods: The patients were 6 women and 2 men aged between 30 and 57 years. The tumors of these patients showed honeycomb-like multiple small cysts that were aggregated in some area of the thyroid gland on ultrasonography. Histopathological examination indicated a well-differentiated type of papillary thyroid carcinoma with multiple small cysts and a small solid lesion. The cysts were lined with papillary carcinoma cells, and normal thyroid tissue lay between the cysts. Results: There is a peculiar type of papillary thyroid carcinoma that histopathologically shows honeycomb-like multiple small cysts in the thyroid gland. Ultrasonography can be used to identify characteristic features of honeycomb-like multiple small cysts in the thyroid gland in such patients. Conclusions: One should be aware of this peculiar type of papillary thyroid carcinoma with honeycomb-like multiple small cysts on ultrasonography, although thyroid nodules with cystic lesions are generally regarded as benign in clinical management.

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Eijun Nishihara Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Yoshitaka Hobo ASKA Pharmamedical Co., Ltd. Fujisawa, Japan

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Akira Miyauchi Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Yasuhiro Ito Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Miyoko Higuchi Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Mitsuyoshi Hirokawa Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Mitsuru Ito Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Shuji Fukata Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Mitsushige Nishikawa Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Takashi Akamizu Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Objective

This study aimed to elucidate disproportionately low serum thyroglobulin (Tg) values in Tg antibody (TgAb)-positive patients with structural recurrence of papillary thyroid carcinoma (PTC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Design

A retrospective study was performed on 176 patients in whom Tg and TgAb levels were measured between 2016 and 2021. Several comprehensive analyses of Tg-LC-MS/MS with an electrochemiluminescence immunoassay for Tg (Tg-ECLIA) were conducted using serum samples.

Methods

TgAb-positive patients who underwent total thyroidectomy with multiple lung metastases due to PTC were evaluated using Tg-LC-MS/MS and Tg-ECLIA. Tg expression in lymph node metastases and metastatic lesions was evaluated by immunohistochemistry and Tg levels of aspiration washouts were also evaluated. Two in vitro assays were performed to elucidate TgAb interference.

Results

Tg concentrations of negative TgAb in both assays were similar (R2= 0.99; n  = 52). Patients with structural recurrence showed higher Tg values with Tg-LC-MS/MS than with Tg-ECLIA. The undetectable proportion was significantly lower with Tg-LC-MS/MS (31.6%, 6/19) than with Tg-ECLIA (68.4%, 13/19; P  = 0.023). The spike-recovery rate and Tg concentrations determined by the serum mixture text (n  = 29) were significantly reduced to 75.0% (118.3–88.7%) and 81.3% (107.0–87.0%), respectively, with TgAb using Tg-ECLIA (both P  < 0.001) confirming assay interference but not using Tg-LC-MS/MS (91.8–92.3%, P  = 0.77 and 98.4–100.8%, P  = 0.18, respectively).

Conclusions

TgAb had no effect on the Tg-LC-MS/MS assay but yielded 19–25% lower values in Tg-ECLIA. Tg-LC-MS/MS is preferable for monitoring serum Tg levels in TgAb-positive patients, although those with structural recurrence often had disproportionally low Tg values.

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Akira Miyauchi Departments of Surgery, Kuma Hospital, Kobe, Japan

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Takumi Kudo Departments of Internal Medicine, Kuma Hospital, Kobe, Japan

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Mitsuyoshi Hirokawa Departments of Pathology, Kuma Hospital, Kobe, Japan

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Yasuhiro Ito Departments of Surgery, Kuma Hospital, Kobe, Japan

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Minoru Kihara Departments of Surgery, Kuma Hospital, Kobe, Japan

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Takuya Higashiyama Departments of Surgery, Kuma Hospital, Kobe, Japan

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Tomonori Yabuta Departments of Surgery, Kuma Hospital, Kobe, Japan

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Hiroo Masuoka Departments of Surgery, Kuma Hospital, Kobe, Japan

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Hisakazu Shindo Departments of Surgery, Kuma Hospital, Kobe, Japan

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Kaoru Kobayashi Departments of Surgery, Kuma Hospital, Kobe, Japan

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Akihiro Miya Departments of Surgery, Kuma Hospital, Kobe, Japan

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Background: We previously reported that the Ki-67 labeling index (LI) in primary tumors and the thyroglobulin (Tg)-doubling time (DT) were potent prognostic indicators in patients with papillary thyroid carcinoma (PTC). Objectives: To elucidate the relationship between these two factors. Methods: A total of 390 patients with PTC who underwent total thyroidectomy between 1998 and 2004 and in whom the Tg-DT was calculated were enrolled. We determined the Ki-67 LI in primary tumors and compared these values with the patients' clinicopathological factors, postoperative Tg status, Tg-DT, and prognosis. Tg status was categorized by postoperative serum Tg values: biochemically persistent disease (BPD), equivocal state, and biochemical remission. Results: The Ki-67 LI was ≤5% in 312 patients (80%), 5%-10% in 48 patients (12%), and >10% in 30 patients (8%). Ki-67 LI was significantly associated with BPD (p < 0.0001). The proportion of BPD patients increased with the higher Ki-67 LI category: 24, 67, and 87%, respectively. The Ki-67 LI had a significant inverse correlation with the Tg-DT (Spearman's ρ = −0.5267, p < 0.0001). Of the 378 patients without distant metastasis at surgery, 68 patients had recurrence, and 6 of the 390 patients died of PTC during the follow-up (mean 88 months). On multivariate analyses, the Ki-67 LI remained an independent predictor of disease-free survival and disease-specific survival when Tg-DT and Tg status were excluded from the analyses. Conclusions: Evaluation of the Ki-67 LI in primary tumors may allow the prediction of the postoperative Tg status, Tg-DT and prognosis of patients with PTC.

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Kaoru Kobayashi Kuma Hospital, Kobe, Japan

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Hisashi Ota Kuma Hospital, Kobe, Japan

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Mitsuyoshi Hirokawa Kuma Hospital, Kobe, Japan

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Tomonori Yabuta Kuma Hospital, Kobe, Japan

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Mitsuhiro Fukushima Kuma Hospital, Kobe, Japan

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Hiroo Masuoka Kuma Hospital, Kobe, Japan

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Takuya Higashiyama Kuma Hospital, Kobe, Japan

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Minoru Kihara Kuma Hospital, Kobe, Japan

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Yasuhiro Ito Kuma Hospital, Kobe, Japan

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Akihiro Miya Kuma Hospital, Kobe, Japan

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Akira Miyauchi Kuma Hospital, Kobe, Japan

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Background: It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. Case Description: Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a “nodule in nodule” appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a “nodule in nodule” appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. Conclusion: A small number of patients with follicular carcinomas or follicular neoplasms may present with a “nodule in nodule” appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis.

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