A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea.

BACKGROUND: In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC). METHODS: Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases. RESULTS: The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAFV600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27). CONCLUSIONS: The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

Analysis of RAS mutation in thyroid nodular hyperplasia and follicular neoplasm in a Korean population.

BACKGROUND: To investigate the difference in frequency of RAS mutations between nodular hyperplasia (NH), follicular thyroid adenomas (FTAs) and follicular thyroid carcinomas (FTCs) in a Korean population. METHODS: RAS mutations in 50 NH, 57 FTAs and 39 FTCs between January 2002 and May 2015 were analysed by pyrosequencing. RESULTS: Nine nodules of 50 NHs (18%), 18 nodules of 39 FTCs (46.2%) and 19 nodules of 57 FTAs (33.3%) harboured RAS mutations. Three FTCs and three FTAs showed two point mutations simultaneously. N-RAS codon 61 (n = 6 of 9, 66.7%) and H-RAS codon 61 (n = 3 of 9, 33.3%) were found in NHs. K-RAS codons 12-13, K-RAS codon 61, N-RAS codons 12-13 and H-RAS codons 12-13 were not found in NHs. N-RAS codon 61 (n = 7 of 21, 33.3%), K-RAS codons 12-13 (n = 6 of 21, 28.6%), H-RAS codon 61 (n = 4 of 21, 19.0%), K-RAS codon 61 (n = 3 of 21, 14.3%) and N-RAS codons 12-13 (n = 1 of 21, 4.7%) were found in FTCs, and N-RAS codon 61 (n = 10 of 22, 45.5%), K-RAS codons 12-13 (n = 5 of 22, 22.7%), H-RAS codon 61 (n = 5 of 22, 22.7%), K-RAS codon 61 (n = 1 of 22, 4.5%) and N-RAS codons 12-13 (n = 1 of 22, 4.5%) were observed in FTAs. CONCLUSIONS: The frequencies of RAS mutations among our Korean population were 18% in NHs, 46.2% in FTC and 33.3% in FTAs. N-RAS codon 61 was the most frequent mutation in NHs, FTCs and FTAs, and the frequency was not significantly different among the three groups. K-RAS codons 12-13 were the second most commonly involved site in FTCs and FTAs, whereas no mutation was detected at this site in NHs.

A case report of angioleiomyoma of uterus.

Angioleiomyoma (AL) is a very rare benign tumor that originates from smooth muscle cells and has thick walled vessels. It may be found throughout the body but more frequently occurs in the lower extremities and rarely develops in the head and other parts of the body. This paper presents a case report of giant AL detected in a 33-year-old woman who complained of severe anemia, menorrhagia, and palpable lower abdominal mass. The patient underwent myomectomy and was diagnosed with AL based on the pathological report of mass. The effective treatment for AL is either simple hysterectomy or angiomyomectomy depending on the patient's desire to preserve fertility and symptom.

Gene copy number variation and protein overexpression of EGFR and HER2 in distal extrahepatic cholangiocarcinoma.

EGFR and HER2 are among the most promising therapeutic targets in solid cancers. The expression status of EGFR and HER2 are associated with the prognosis, and with a number of clinicopathological factors, in many cancers. However, few studies have examined this association in distal extrahepatic cholangiocarcinoma (EHCC). Therefore, we investigated EGFR and HER2 protein expression and gene copy number variation (CNV) in distal EHCC. We also studied the association of these factors with clinicopathological parameters and prognosis. Immunostaining, using antibodies against EGFR and HER2, was performed on 84 cases of distal EHCC. All positive (3+) and equivocal (2+) EGFR and HER2 expression cases, together with randomly selected negative (1+ and 0) cases, were evaluated for EGFR and HER2 CNV. Among distal EHCC samples, 6.0% (n=5) were positive (3+) for EGFR expression and 6.0% (n=5) were equivocal (2+). HER2 expression was positively identified in 2.4% of samples (n=2), and was equivocal in 1.2% of samples (n=1). All cases of positive EGFR expression showed amplification (n=1) or high polysomy (n=4) involving the EGFR gene; three cases (60%) of equivocal EGFR expression showed high polysomy of the EGFR gene. All cases of positive or equivocal HER2 expression (n=3, 3.6%) showed amplification of the HER2 gene. In univariate analysis, EGFR expression and CNV were associated with shorter cancer-specific overall survival (p=0.003 and p=0.018, respectively). Multivariate analysis also showed that EGFR CNV was a significant prognostic factor in distal EHCC (p=0.015). Although further study is warranted, our findings suggest that EGFR expression and CNV are factors associated with poor prognosis, and that anticancer therapeutics against EGFR and HER2 receptors may be promising therapeutic options for patients with distal EHCC.

The Use of the Bethesda System for Reporting Thyroid Cytopathology in Korea: A Nationwide Multicenter Survey by the Korean Society of Endocrine Pathologists.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized the reporting of thyroid cytology specimens. The objective of the current study was to evaluate the nationwide usage of TBSRTC and assess the malignancy rates in each category of TBSRTC in Korea. METHODS: Questionnaire surveys were used for data collection on the fine needle aspiration (FNA) of thyroid nodules at 74 institutes in 2012. The incidences and follow-up malignancy rates of each category diagnosed from January to December, 2011, in each institute were also collected and analyzed. RESULTS: Sixty out of 74 institutes answering the surveys reported the results of thyroid FNA in accordance with TBSRTC. The average malignancy rates for resected cases in 15 institutes were as follows: nondiagnostic, 45.6%; benign, 16.5%; atypical of undetermined significance, 68.8%; suspicious for follicular neoplasm (SFN), 30.2%; suspicious for malignancy, 97.5%; malignancy, 99.7%. CONCLUSIONS: More than 80% of Korean institutes were using TBSRTC as of 2012. All malignancy rates other than the SFN and malignancy categories were higher than those reported by other countries. Therefore, the guidelines for treating patients with thyroid nodules in Korea should be revisited based on the malignancy rates reported in this study.

Clear cell neuroendocrine tumor of the pancreas in von Hippel-Lindau disease: a case report and literature review.

Clear cell neuroendocrine tumor (NET) of the pancreas is found in von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type I (MEN I), and sporadic form. Clear cell NETs are often misdiagnosed as metastatic renal cell carcinoma. A 47-year-old woman with VHL was found to have a mass in the pancreatic tail and two masses in the right kidney with two cysts. A distal pancreatectomy and right radical nephrectomy were performed. The pancreatic lesion was a well-circumscribed, golden-yellow solid mass, which was lobulated by septal fibrosis. Microscopically, the tumor consisted of entirely of clear cells with prominent nucleoli. The tumor cell nests were separated by collagen fibrosis. Immunohistochemical studies were positive for the neuroendocrine markers and vimentin. Synchronous kidney tumors were clear cell renal cell carcinoma and cystic renal cell carcinoma. Those with syndrome are younger than those without syndrome. Sporadic tumors have larger size and higher grade than those of VHL and MEN I. Stromal sclerosis is frequently observed in VHL, compared with the other two groups. In the absence of a documented genetic profile and family history, awareness of these features should help us to diagnose clear cell pancreatic NETs resembling metastatic renal cell carcinoma.

Endotracheal Leiomyoma Mimicking Malignancy on 18F-FDG PET/CT in a Patient With Papillary Thyroid Carcinoma.

Endotracheal leiomyoma is a rare benign lesion, accounting for approximately 1% of tracheal tumors, and generally occurs in the lower respiratory tract. Because its growth causes airway obstruction symptom, surgical treatment is generally suggested after detection. We report a case with leiomyoma of the cervical endotracheal space showing intense FDG uptake on F-FDG PET/CT mimicking malignancy in a 79-year-old woman with papillary thyroid carcinoma.

Papillary Thyroid Carcinoma Arising Within a Follicular Adenoma: A Case Report, Ultrasound Features, and Considerations.

Papillary thyroid carcinoma (PTC) arising within a follicular adenoma is an exceptionally rare histopathological subtype that shows the nuclear features of PTC within a benign-appearing, circumscribed follicular adenoma. Although it is clinically significant because of its malignant nature, its ultrasonographic features have not been described previously. A 26-year-old man presented with a heterogeneous isoechoic solid nodule with a marked hypoechoic solid focus and a low echoic peripheral rim in the right thyroid gland on ultrasonography. On color Doppler images, markedly increased vascularity was seen in the hypoechoic solid component. An ultrasound-guided gun biopsy suggested a follicular neoplasm. In the evaluation of a hemithyroidectomy specimen, thyroid follicles and a thin fibrous capsule were seen, which favored a follicular adenoma with tumor cells in a focal area indicating papillary carcinoma. Here, we report a case of PTC arising within a follicular adenoma and discuss possible considerations in thyroid ultrasonographic examinations.

Neural Axis Metastasis from Metachronous Pulmonary Basaloid Carcinoma Developed after Chemotherapy & Radiation Therapy of Uterine Cervical Carcinoma.

Multiple primary or secondary malignancies after anticancer therapy were recently reported to be increasing in frequency. The authors describe a case of metachronous metastatic pulmonary basaloid carcinoma to the central nervous system that was discovered after chemotherapy and radiation therapy for cervical uterine carcinoma. Two different types of cancer developed within some interval. There's the possibility that a secondary pulmonary neoplasm developed after the chemotherapy and radiotherapy conducted as cervical cancer treatment.

EGFR, COX2, p-AKT expression and PIK3CA mutation in distal extrahepatic bile duct carcinoma.

Distal extrahepatic bile duct (EBD) carcinoma is a rare but highly aggressive malignant neoplasm. Some in vitro studies have shown that EGFR and PI3K-Akt pathway play an important role in the carcinogenesis of bile duct carcinoma. The aim of the present study is to investigate the expression of EGFR, p-AKT, and COX-2 and the mutation of PIK3CA in distal EBD carcinoma and evaluate the association with clinicopathological factors. Ninety cases of distal extrahepatic bile duct (EBD) carcinoma specimens were studied. Immunohistochemistry (IHC) using antibodies against EGFR, p-AKT, and COX-2 was performed on TMA blocks. The PIK3CA mutation was evaluated using the PNAClamp Detection Kit from DNA samples extracted from formalin fixed, paraffin embedded tissue. EGFR expression of distal EBD carcinomas was 61.9%, 26.2%, 6.0% and 6.0% in the negative, weakly positive, moderately positive, and strongly positive groups, respectively. Positive EGFR expression showed significant relationships with high T stage (p = 0.024). In Kaplan-Meier analysis, EGFR expression was associated with shorter cancer-specific overall survival (p = 0.005). Multivariate analysis also showed that moderate or strong (2+ or 3+) EGFR expression was a significant prognostic factor in distal EBD carcinoma: HR 5.286; p = 0.001. Ninety cases of EBD carcinoma tissue were analysed for hotspot mutations (exon 9 and 20) in the PIK3CA gene. Only one mutation was detected: a missense mutation of H1047 at exon 20. The expression levels of p-AKT and COX-2 showed no association with any clinicopathological parameters, including survival rate. Moderate and strong EGFR expressions demonstrate a direct link to poor prognosis. Although further study is warranted to understand the clinicopathological significance, our finding suggests EGFR is a useful prognostic marker of patients with distal EBD carcinoma. A low prevalence of PIK3CA mutation exists in the distal EBD carcinoma of Korean patients, indicating that mutation screening may not be useful in determining prognosis or in formulating a treatment response to targeted inhibition in Korea.

The Diffuse Sclerosing Variant of Papillary Thyroid Cancer Presenting as Innumerable Diffuse Microcalcifications in Underlying Adolescent Hashimoto's Thyroiditis: A Case Report.

Hashimoto's thyroiditis is the most common diffuse thyroid disease and is characterized by diffuse lymphocytic infiltration. However, the ultrasonographic findings of papillary thyroid carcinomas that arise from Hashimoto's thyroiditis in the pediatric and adolescent population are not well known.We report a rare ultrasonographic finding in a 22-year-old woman diagnosed with the diffuse sclerosing variant of papillary thyroid carcinoma that arose from underlying Hashimoto's thyroiditis: innumerable diffuse microcalcifications instead of a typical malignant-appearing nodule.

Papillary Thyroid Carcinoma Arising in Children and Adolescent Hashimoto's Thyroiditis: Ultrasonographic and Pathologic Findings.

Objectives. We compared the ultrasonography and pathology features of papillary thyroid carcinoma (PTC) in pediatric and adolescents with Hashimoto's thyroiditis (HT) with those of non-HT patients. Materials and Methods. Eleven patients who were surgically confirmed to have pediatric or adolescent PTC from 2006 to 2014 were included in this study. We retrospectively analyzed the preoperative ultrasonography and pathology features of PTC arising in HT and non-HT patients. Results. On ultrasonography, thyroid gland was lobulated and enlarged, with many scattered microcalcifications in four of five HT patients. Four of six non-HT patients had suspicious masses with calcifications. The diffuse sclerosing variant of PTC (DSVPTC) was found in three of five HT patients, but none in non-HT patients. Macroscopic or microscopic extrathyroidal extension was evident in all of the HT patients and four of the non-HT patients. Neck lymph node metastases were in all HT patients and five of non-HT patients. Conclusions. Three of five PTCs in pediatric and adolescent HT patients were DSVPTC, whereas all PTCs of the non-HT patients were classic type. On ultrasonography, thyroid gland was diffusely enlarged with scattered microcalcifications in four of five HT patients. All five HT cases had aggressive disease, including extrathyroidal extension and cervical lymph node metastases.

Persistent Vocal Fold Granuloma Following Superficial PAAG Injection Laryngoplasty: A Case Report.

The injection material polyacrylamide hydrogel (PAAG; Ferrosan, Søborg, Denmark) is often used as space filler for soft-tissue defects. PAAG is a suitable alternative to the materials used for injection laryngoplasty. Over the past decade, 427 patients have undergone injection laryngoplasty in our clinic using PAAG, and no major complications, such as material migration or foreign body granuloma, were identified. Here, we report the case of the first woman to undergo laryngomicrosurgery to remove a vocal fold granuloma that developed after a superficial injection laryngoplasty performed 4 years previously.

Submucosal Tunneling Endoscopic Resection of a Leiomyoma Originating from the Muscularis Propria of the Gastric Cardia (with Video).

While endoscopic submucosal dissection (ESD) is widely used to treat gastrointestinal tumors, it is rarely used for subepithelial tumors (SETs) originating from the muscularis propria of the esophagus and gastric cardia because of the risk of perforation and problems with inadequate space and field of view during procedures. Submucosal tunneling endoscopic resection (STER) is a new therapeutic method for treating SETs in specific locations in the esophagus and stomach. This technique is highly skill-dependent, using a mucosal flap that covers a deeper part of the gut wall, but is safe and minimally invasive compared with conventional endoscopic approaches such as ESD in SETs originating from the muscularis propria.We report a patient who underwent STER to remove a SET located at the gastric cardia. The patient recovered without any complications. We believe that our case shows the efficacy and safety of the STER technique for patients with a SET originating from the muscularis propria.

Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman.

Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results.

Uterine Serous Adenocarcinoma in an Elderly Postmenopausal Woman: Clinically Misdiagnosed as Uterine Cervix Cancer.

Uterine serous adenocarcinoma (USC) is rare and invasive cancer. This cancer is more often reported in the ovary, the fallopian tube, and the endometrium than uterine cervix. No matter where the tumor is located, the tumor exhibits similar histological characteristics. So when uterine cancer is proven to be serous adenocarcinoma, it is necessary to see if the tumor originated from ovary or endometrium and invaded the cervix. We report a case of a 73-year-old postmenopausal woman with USC arising near the internal os of endocervical canal, clinically misdiagnosed as uterine cervix cancer.

A solitary large radioiodine accumulative lung lesion in high-dose 131i therapeutic scan: bronchial atresia with mucocele.

We reported a large radioiodine accumulative lung lesion on I therapeutic whole-body scan performed in a 50-year-old woman for thyroid cancer ablation therapy. Previously, her chest radiography and contrast-enhanced chest CT images showed bronchial atresia in the left upper lobar bronchus and mucus-filled dilated distal bronchus. Bronchial mucocele was confirmed by CT-guided percutaneous transthoracic needle aspiration. Bronchial atresia is a rare congenital abnormality associated with the mucocele.

Metastasis of colon cancer to medullary thyroid carcinoma: a case report.

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

Retrieval rate and accuracy of ultrasound-guided 14-G semi-automated core needle biopsy of breast microcalcifications.

OBJECTIVE: To evaluate the retrieval rate and accuracy of ultrasound (US)-guided 14-G semi-automated core needle biopsy (CNB) for microcalcifications in the breast. MATERIALS AND METHODS: US-guided 14-G semi-automated CNB procedures and specimen radiography were performed for 33 cases of suspicious microcalcifications apparent on sonography. The accuracy of 14-G semi-automated CNB and radiology-pathology concordance were analyzed and the microcalcification characteristics between groups with successful and failed retrieval were compared. RESULTS: Thirty lesions were successfully retrieved and the microcalcification retrieval rate was 90.9% (30/33). Thirty lesions were successfully retrieved. Twenty five were finally diagnosed as malignant (10 invasive ductal carcinoma, 15 ductal carcinoma in situ [DCIS]) and five as benign. After surgery and mammographic follow-up, the 25 malignant lesions comprised 12 invasive ductal carcinoma and 13 DCIS. Three lesions in the failed retrieval group (one DCIS and two benign) were finally diagnosed as two DCIS and one benign after surgery. The accuracy of 14-G semi-automated CNB was 90.9% (30/33) because of two DCIS underestimates and one false-negative diagnosis. The discordance rate was significantly higher in the failed retrieval group than in the successful retrieval group (66.7% vs. 6.7%; p < 0.05). Punctate calcifications were significantly more common in the failed retrieval group than in the successful retrieval group (66.7% vs. 3.7%; p < 0.05). CONCLUSION: US-guided 14-G semi-automated CNB could be a useful procedure for suspicious microcalcifications in the breast those are apparent on sonography.