Effect of high-dose vitamin C on renal ischemia-reperfusion injury.

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

Trouble-makers in cytologic interpretation of the uterine cervix.

The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.

Prognostic factors of breast phyllodes tumors.

BACKGROUND: Phyllodes tumor (PT) is a relatively rare breast tumor, accounting for <1% of all breast tumors. MAIN BODY: Adjuvant therapy with chemotherapy or radiation therapy, other than surgical excision, has not been established yet. PT, similar to other breast tumors, is classified as benign, borderline, and malignant according to the World Health Organization classification system, depending on stromal cellularity, stromal atypia, mitotic activity, stromal overgrowth, and tumor border. However, this histological grading system cannot effectively or fully reflect the clinical prognosis of PT. Several studies have investigated prognostic factors for PT as some PTs recur or metastasize to distant sites, and thus, prediction of prognosis is clinically imperative. CONCLUSION: This review discusses clinicopathological factors, immunohistochemical markers, and molecular factors that have been investigated in previous studies to have an impact on the clinical prognosis of PT.

Cell Component and Function of Tumor Microenvironment in Thyroid Cancer.

Thyroid cancer is the most common cancer in the endocrine system. Most thyroid cancers have good prognosis, but some of them are resistant to treatment or show aggressive behavior. Like other tumors, thyroid cancers harbor tumor microenvironment (TME) composed of cancer associated fibroblasts (CAF) and immune cells. Autoimmune lymphocytic thyroiditis can occur in the thyroid, and it may be associated with cancer development. TME is involved in tumor progression through various mechanisms: (1) CAF is involved in tumor progression through cell proliferation and extracellular matrix (ECM) remodeling; and (2) immune cells are involved in tumor progression through cell proliferation, angiogenesis, epithelial mesenchymal transformation (EMT), and immune suppression. These events are activated by various cytokines, chemokines, and metabolites secreted from cells that comprise TME. This review is focused on how CAF and immune cells, two important cell components of thyroid cancer TME, are involved in tumor progression, and will explore their potential as therapeutic targets.

PAX2, PAX8, and PR are correlated with ovarian seromucinous borderline tumor with endometriosis.

BACKGROUND: Ovarian "seromucinous carcinoma" has been recently removed in 2020 5th Edition of WHO classification of Female Genital Tumors and is considered as a subtype of endometrioid carcinoma with mucinous differentiation, while "seromucinous borderline tumor" remains and exists as a distinct entity. Both diseases may be considered as no more same lineage. However, ovarian seromucinous borderline tumor (SMBT) is also one of the endometriosis-related neoplasm of ovary similar to endometrioid tumor, featuring that about 50% of ovarian SMBTs combine endometriosis. The present study was aimed to investigate whether the ovarian SMBTs are different in clinical features and molecular patterns, according to the presence of combined endometriosis. RESULTS: There were no statistical differences in clinical findings between two groups. There was also no significant difference in pregnancy outcomes and recurrence between two groups. In immunohistochemical patterns, there was a statistically significant difference in PAX2 and PAX8 expression between in ovarian SMBT with or without endometriosis (P = 0.016, P < 0.001). Only a few cases of ovarian SMBT with endometriosis showed expression of PAX2 and conversely, most of the cases showed expression of PAX8. PR positivity was more prominent in ovarian SMBT with endometriosis than without endometriosis (P = 0.018), although there was no difference in positive ER expression. There were no statistical differences in WT1, CK20 and CDX2 expressions between two groups. CONCLUSIONS: Ovarian SMBT with endometriosis did not clinically differ from that without endometriosis. However, the molecular patterns were different between two groups and ovarian SMBT with endometriosis is close to endometrioid tumor types unlike SMBT without endometriosis. Further, a direct comparison study between seromucinous borderline tumor and endometrioid borderline tumor is needed with a gene profiling study to prove their relationship.

Additional Excision Biopsy in Patients With Atypical Ductal Hyperplasia at Ultrasound-guided Vacuum-assisted Breast Biopsy.

BACKGROUND/AIM: We conducted this single-center, retrospective study to identify predictors of upgrading to malignancy and to discuss the necessity of additional excision biopsy in patients who were diagnosed with atypical ductal hyperplasia (ADH) at ultrasound (US)-guided vacuum-assisted breast biopsy (VABB) based on our 18-year, single-center experience. PATIENTS AND METHODS: The current study was conducted in a total of 12,160 patients who were evaluated at our medical institution during an 18-year period between January of 2003 and December of 2020. We included the patients who were diagnosed with ADH at US-guided VABB using the Mammotome® (Devicor Medical Products, Inc., Cincinnati, OH, USA). We therefore included a total of 114 patients (n=114) with ADH in the current study. RESULTS: Of 114 eligible patients, 36 underwent additional excision biopsy and the remaining 78 did not. Of these 36 patients, 15 were found to have an upgrading to malignancy at a rate of upgrading of 41.7%. These include 7 cases (46.6%) of low-grade ductal carcinoma in situ (DCIS), 3 cases (20.0%) of intermediate grade DCIS, 1 case (6.7%) of microinvasive DCIS, 3 cases (20.0%) of multifocal lobular carcinoma in situ, and 1 case (6.7%) of mucinous carcinoma. Finally, only suspicious microcalcification on mammography was a significant predictor of upgrading to malignancy (p=0.023). CONCLUSION: An additional excision biopsy is recommended to reduce the rate of upgrading to malignancy in patients who were diagnosed with ADH through a US-guided VABB.

Digital Dermatopathology and Its Application to Mohs Micrographic Surgery.

Digital pathology is being gradually adopted in hospitals due to technological advances. We propose that digital pathology can be used in Mohs micrographic surgery (Mohs surgery) to precisely check residual tumor cells in frozen tumor margin tissues. This would aid surgeons and pathologists in accurately recording tumor margins and give patients the benefit of shorter operation time.

Glucose Metabolism and Glucose Transporters in Breast Cancer.

Breast cancer is the most common malignancy in women worldwide and is associated with high mortality rates despite the continuously advancing treatment strategies. Glucose is essential for cancer cell metabolism owing to the Warburg effect. During the process of glucose metabolism, various glycolytic metabolites, such as serine and glycine metabolites, are produced and other metabolic pathways, such as the pentose phosphate pathway (PPP), are associated with the process. Glucose is transported into the cell by glucose transporters, such as GLUT. Breast cancer shows high expressions of glucose metabolism-related enzymes and GLUT, which are also related to breast cancer prognosis. Triple negative breast cancer (TNBC), which is a high-grade breast cancer, is especially dependent on glucose metabolism. Breast cancer also harbors various stromal cells such as cancer-associated fibroblasts and immune cells as tumor microenvironment, and there exists a metabolic interaction between these stromal cells and breast cancer cells as explained by the reverse Warburg effect. Breast cancer is heterogeneous, and, consequently, its metabolic status is also diverse, which is especially affected by the molecular subtype, progression stage, and metastatic site. In this review, we will focus on glucose metabolism and glucose transporters in breast cancer, and we will additionally discuss their potential applications as cancer imaging tracers and treatment targets.

The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis.

The morbidity and mortality of breast cancer is mostly due to a distant metastasis, especially to the bone. Many factors may be responsible for bone metastasis in breast cancer, but interactions between tumor cells and other surrounding types of cells, and cytokines secreted by both, are expected to play the most important role. Bone marrow adipocyte (BMA) is one of the cell types comprising the bone, and adipokine is one of the cytokines secreted by both breast cancer cells and BMAs. These BMAs and adipokines are known to be responsible for cancer progression, and this review is focused on how BMAs and adipokines work in the process of breast cancer bone metastasis. Their potential as suppressive targets for bone metastasis is also explored in this review.

Clinical experience of uterine smooth muscle tumor of uncertain malignant potential in two gynecological centers: Oncological and obstetrical aspects.

OBJECTIVES: To evaluate the clinical characteristics and obstetrical and oncological outcomes of patients with uterine smooth muscle tumors of uncertain malignant potential (STUMP) and analyze the risk factors for recurrence. STUDY DESIGN: A retrospective cohort study was performed at two gynecological centers using data collected between January 2008 and August 2018. All the patients enrolled were diagnosed with STUMP and had been followed up for at least 6 months. The patients' characteristics, treatment methods, recurrence rate, and subsequent pregnancy outcomes were evaluated. RESULTS: The mean age of the 62 patients was 36.1 ±â€¯9.1 years (median 35, range 20-55 years) and mean follow-up duration was 36.3 ±â€¯26.8 months (29.5, 6-130). All the patients were of premenopausal status. Fourteen patients (22.6 %) were initially treated by hysterectomy and 48 (77.4 %) by myomectomy. During the study period, three patients (4.8 %) experienced recurrence. However, there was no statistical difference between myomectomy and hysterectomy in terms of the rate of recurrence of STUMP or sarcoma, and all patients survived even after recurrence. Multivariate analysis revealed that a history of previous myomectomy was the sole independent risk factor for recurrence (odds ratio = 51.071; 95 % confidence interval = 2.743-950.726; p = 0.008). Subsequent pregnancies were successful in 10 of 19 women (52.6 %) who tried to conceive. Two of them had ongoing pregnancies at the time of last follow-up; the remaining eight women experienced a total of 14 subsequent pregnancies. CONCLUSIONS: The recurrence rate of STUMP was similar between hysterectomy and myomectomy. Therefore, fertility sparing myomectomy can be considered in women diagnosed with STUMP with close monitoring.

Expression of proteins related to autotaxin-lysophosphatidate signaling in thyroid tumors.

BACKGROUND: We aimed to investigate the expression of proteins related with autotaxin (ATX)-lysophosphatidate (LPA) signaling and the clinical implications in primary and metastatic thyroid tumors. METHODS: We constructed tissue microarrays with 545 primary thyroid tumors [338 papillary thyroid carcinoma (PTC), 111 follicular carcinoma (FC), 69 medullary carcinoma (MC), 23 poorly differentiated carcinoma (PDC), and four anaplastic carcinoma (AC)]. Immunohistochemical stains for proteins related to ATX-LPA signaling (e.g., ATX, LPA1, LPA2, and LPA3) were performed. RESULTS: The expression of ATX was highest in MC, while the LPA1 expression was higher in PDC and AC, and the expression of LPA2 and LPA3 was highest in PTC (p < 0.001). Additionally, the expression of ATX, LPA1, and LPA2 was higher in conventional-type PTC than in follicular-variant PTC (p < 0.05). PTC with BRAF V600E mutation showed higher expression of ATX, LPA1, LPA2, and LPA3 than PTC without BRAF V600E mutation (p < 0.001). In univariate analysis, ATX positivity (p = 0.005) and LPA1 positivity (p = 0.014) were correlated with shorter overall survival in PTC. CONCLUSION: Proteins related to the ATX-LPA axis showed different levels of expression in primary thyroid tumors according to subtype.

Protective Effect of Ethyl Pyruvate against Myocardial Ischemia Reperfusion Injury through Regulations of ROS-Related NLRP3 Inflammasome Activation.

Emerging evidence indicates the pronounced role of inflammasome activation linked to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. Ethyl pyruvate (EP) is an antioxidant and conveys myocardial protection against I/R injury, while the exact mechanisms remain elusive. We aimed to investigate the effect of EP on myocardial I/R injury through mechanisms related to ROS and inflammasome regulation. The rats were randomly assigned to four groups: (1) sham, (2) I/R-control (IRC), (3) EP-pretreatment + I/R, and (4) I/R + EP-posttreatment. I/R was induced by a 30 min ligation of the left anterior descending artery followed by 4 h of reperfusion. EP (50 mg/kg) was administered intraperitoneally at 1 h before ischemia (pretreatment) or upon reperfusion (posttreatment). Both pre- and post-EP treatment resulted in significant reductions in myocardial infarct size (by 34% and 31%, respectively) and neutrophil infiltration. I/R-induced myocardial expressions of NADPH oxidase-4, carnitine palmitoyltransferase 1A, and thioredoxin-interacting protein (TXNIP) were mitigated by EP. EP treatment was associated with diminished inflammasome activation (NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like protein, and caspase-1) and interleukin-1ß induced by I/R. I/R-induced phosphorylation of ERK and p38 were also mitigated with EP treatments. In H9c2 cells, hypoxia-induced TXNIP and NLRP3 expressions were inhibited by EP and to a lesser degree by U0126 (MEK inhibitor) and SB203580 (p38 inhibitor) as well. EP's downstream protective mechanisms in myocardial I/R injury would include mitigation of ROS-mediated NLRP3 inflammasome upregulation and its associated pathways, partly via inhibition of hypoxia-induced phosphorylation of ERK and p38.

The expressions of autotaxin-lysophosphatidate signaling-related proteins in metastatic breast cancer.

PURPOSE: We evaluated the expression of autotaxin-lysophosphatidate signaling-related proteins and the clinical implications for metastatic breast cancer. METHODS: We constructed tissue microarrays (TMA) with 126 cases of metastatic breast cancer [31 (24.6%) bone metastases, 36 (28.6%) brain metastases, 11 (8.7%) liver metastases, and 48 (38.1%) lung metastasis], and we conducted immunohistochemical staining for the autotoxin-lysophosphatidate signaling-related proteins ATX, LPA1, LPA2, and LPA3. RESULTS: Stromal ATX (P = 0.006) and LPA1 (P < 0.001) were differently expressed according to their metastatic organ; stromal ATX showed high expression in bone metastasis, and LPA1 showed high expression in liver and lung metastases. Stromal ATX positivity was higher than others in luminal A type tumors (P = 0.035), and stromal LPA3 positivity was correlated with a high Ki-67 labeling index (LI) (P = 0.005). In univariate analysis, tumoral LPA3 negativity was correlated with shorter overall survival (OS) (P = 0.015) in metastatic breast cancer. When analyzed according to the metastatic sites, tumoral LPA3 negativity was correlated with shorter OS (P = 0.010) in lung metastasis, whereas stromal LPA3 negativity was correlated with shorter OS (P = 0.026) in brain metastasis. In multivariate Cox analysis, tumoral LPA3 negativity was an independent poor prognostic factor (HR = 2.311, 95% CI: 1.029-5.191, P = 0.043). CONCLUSION: Among autotoxin-lysophosphatidate signaling-related proteins, stromal ATX was highly expressed in bone metastases, and LPA1 was highly expressed in liver and lung metastases. Tumoral LPA3 might be a prognostic factor in metastatic breast cancer.

Recurrence Rates and Characteristics of Phyllodes Tumors Diagnosed by Ultrasound-guided Vacuum-assisted Breast Biopsy (VABB).

BACKGROUND/AIM: Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. PATIENTS AND METHODS: Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. RESULTS: Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). CONCLUSION: Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those <3 cm, can be safely monitored with ultrasonography instead of performing immediate re-excision.

Effects of Post Ischemia-Reperfusion Treatment with Trimetazidine on Renal Injury in Rats: Insights on Delayed Renal Fibrosis Progression.

Even after recovery from acute kidney injury, glomeruli remain vulnerable to further injury by way of interstitial fibrosis. This study is aimed at elucidating the effects of post ischemia-reperfusion (I/R) treatment with trimetazidine on the progression to renal fibrosis as well as short- and intermediate-term aspects. Trimetazidine 3 mg/kg or 0.9% saline was given intraperitoneally once upon reperfusion or daily thereafter for 5 d or 8 w. Renal histologic changes and related signaling proteins were assessed. After 24 h, post I/R treatment with trimetazidine significantly reduced serum blood urea nitrogen and creatinine levels and tubular injury accompanied with upregulation of hypoxia-inducible factor- (HIF-) 1α, vascular endothelial growth factor (VEGF), and Bcl-2 expression. After 5 d, post I/R treatment with trimetazidine reduced renal tubular cell necrosis and apoptosis with upregulation of HIF-1α-VEGF and tissue inhibitors of metalloproteinase activities, attenuation of matrix metalloproteinase activities, and alteration of the ratio of Bax to Bcl-2 levels. After 8 w, however, post I/R treatment with trimetazidine did not modify the progression of renal fibrosis. In conclusion, post I/R treatment with trimetazidine allows ischemic kidneys to regain renal function and structure more rapidly compared to nontreated kidneys, but not enough to resolute renal fibrosis in long-term aspect.

Clinicopathological Analysis of Ultrasound-guided Vacuum-assisted Breast Biopsy for the Diagnosis and Treatment of Breast Disease.

BACKGROUND/AIM: To evaluate the usefulness and safety of vacuum-assisted breast biopsy (VABB) for breast lesion diagnosis and treatment. PATIENTS AND METHODS: Clinical and histopathological data of 8,748 patients, who underwent 11,221 VABB procedures were analyzed. RESULTS: Most patients (58.2%) were <40 years old. Most lesions (39.6%) were 0.6-1.0 cm in diameter while 3.2% were ≥3.0 cm; fibroadenomas were the most common (46.6%). Eight (14% of 57) cases of atypical ductal hyperplasia were underestimated. The positive predictive values (PPVs) of breast imaging reporting and data system (BI-RADS) ultrasound category were 0.6%, 3.4%, 34.8%, 66.2%, and 93.8% for category 3, 4a, 4b, 4c, and 5 lesions, respectively. The mean number of core specimens was 9.5±8.8; the mean procedure time was 3.4±2.7 min. No residual lesions were found in 94.4% of the 7,480 patients. CONCLUSION: VABB could replace ultrasound-guided core biopsy and surgical excisional biopsy for the diagnosis of breast disease and the treatment of benign breast lesions.

Male Infertility Associated with a Supernumerary Marker Chromosome.

A marker chromosome (mar) is a structurally abnormal chromosome in which no part can be identified. The significance of a marker varies, depending on the material contained within the marker. Very few reports have been published of marker chromosomes associated with male infertility. Here, we report the case of an infertile man with a rare variant of a marker chromosome of a mos 47,XY,+mar[25]/46,XY[25] karyotype.

The Intraoperative Immunohistochemical Staining of CD56 and CK19 Improves Surgical Decision for Thyroid Follicular Lesions.

BACKGROUND: When differential diagnosis is difficult in thyroid follicular lesions with overlapping histological features, the immunohistochemical staining can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of thyroid follicular lesion and explore the possible gains and limitations of the practice. METHODS: Eighty-six nodules of 79 patients whose intraoperative frozen sections were selected as the control group, and 53 nodules of 48 patients whose intraoperative frozen sections were subject to rapid immunohistochemistry were selected as the study group. RESULTS: Five nodules (6%) in the control group were diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study group, six nodules (11%) were follicular neoplasm and none were deferred. Three nodules (4%) in the control group showed diagnostic discrepancy between the frozen and permanent diagnoses, but none in the study group. The average turnaround time for the frozen diagnosis of the control group was 24 minutes, whereas it was 54 minutes for the study group. CONCLUSIONS: Intraoperative rapid immunohistochemical stains significantly decreased the diagnostic discrepancy in this study. Considering the adverse effects of indefinite frozen diagnosis or discrepancy with permanent diagnoses, the intraoperative rapid immunohistochemical stain can help to accurately diagnose and hence provide guidance to surgical treatment.

Combined Oral Medroxyprogesterone/Levonorgestrel-Intrauterine System Treatment for Women With Grade 2 Stage IA Endometrial Cancer.

OBJECTIVE: The aim of this study was to evaluate the oncologic and pregnancy outcomes of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment in young women with grade 2-differentiated stage IA endometrial adenocarcinoma who wish to preserve fertility. METHODS: We retrospectively reviewed the medical records of patients with grade 2 stage IA endometrial adenocarcinoma who had received fertility-sparing treatment at CHA Gangnam Medical Center between 2011 and 2015. All of the patients were treated with combined oral MPA (500 mg/d)/LNG-IUS, and follow-up dilatation and curettage were performed every 3 months. RESULTS: A total of 5 patients were included in the study. The mean age was 30.4 ± 5.3 years (range, 25-39 years). After a mean treatment duration of 11.0 ± 6.2 months (range, 6-18 months), complete response (CR) was shown in 3 of the 5 patients, with partial response (PR) in the other 2 patients. One case of recurrence was reported 14 months after achieving CR. This patient was treated again with combined oral MPA/LNG-IUS and achieved CR by 6 months. The average follow-up period was 44.4 ± 26.2 months (range, 12-71 months). There were no cases of progressive disease. No treatment-related complications arose. CONCLUSIONS: Combined oral MPA/LNG-IUS treatment is considered to be a reasonably effective fertility-sparing treatment of grade 2 stage IA endometrial cancer. Although our results are encouraging, it is preliminary and should be considered with experienced oncologists in well-defined protocol and with close follow-up.

Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report.

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.