Papillary Thyroid Carcinoma with Honeycomb-Like Growth: Clinicopathological Characteristics and Diagnostic Significance as a Novel Variant.

INTRODUCTION: We aimed to clarify the clinical and pathological characteristics of papillary thyroid carcinoma (PTC) with unique honeycomb-like growth (HLG) and discuss its diagnostic significance. METHODS: Among the 12,745 PTCs that were resected and histologically diagnosed, 28 PTC cases with HLG components (0.2%) were included. RESULTS: PTC-HLG was subclassified into pure (9 cases), which consisted of only HLG components, and mixed (19 cases), which consisted of conventional PTC and HLG components, types. HLG components were histologically characterized by (1) neoplastic cyst aggregation with intervening normal thyroid follicles, (2) the cyst wall composed of single-layered carcinoma cells, (3) low papillary growth, and (4) ball-like granulation tissues. Compared with the mixed type, the pure type occurred in older people (p < 0.05), had a smaller tumor size (p < 0.0001), was more interpreted as being benign by ultrasound (p < 0.05), and had a lower lymph node metastasis rate (p < 0.005). In the mixed type, 44.4% of conventional PTCs showed a Ki-67 labeling index of >5%. All and 10.5% of the mixed type showed lymph node and lung metastases, respectively. CONCLUSION: The pure type could be a nonaggressive variant of PTCs with a unique honeycomb growth pattern and tended to be clinically interpreted as benign. The mixed type is pathogenetically different from the pure type and is slightly aggressive compared with conventional PTCs.

Gauze blotting technique: a novel method to identify parathyroid glands during thyroid surgery without tissue damage.

Hypoparathyroidism is a major complication of thyroid surgery. To avoid this complication, visual identification of the parathyroid glands is essential. However, its effectiveness depends heavily on the surgeon's expertise. Here, we describe a novel method, the gauze blotting technique, to immunochemically identify the parathyroid glands during thyroid surgery. Twenty-three patients who underwent thyroid lobectomy were enrolled in this study; 16 and 7 had benign and malignant thyroid diseases, respectively. After visually identifying candidate nodules for the parathyroid gland, a piece of dry gauze (5 mm × 10 mm) was applied to each tissue until it was moistened by exudates from the tissue. Pieces of gauze were also applied to the thyroid gland and adipose tissue located away from the candidate nodules. The gauze was immersed in saline, and the intact PTH (i-PTH) level of the supernatant was measured. The median PTH level for the parathyroid glands was 1,060 pg/mL, which was significantly higher than that for the thyroid gland (34 pg/mL) and adipose tissue (28 pg/mL) (p < 0.001). The cut-off value to distinguish the parathyroid gland from other tissues was 68 pg/mL with a positive predictive value, negative predictive value, sensitivity, and specificity of 84.6%, 88.8%, 86.8%, and 86.7%, respectively. A value ≥250 pg/mL yielded a 100% positive predictive value. Our novel gauze blotting technique can identify the parathyroid glands without damaging tissues during thyroid surgery.

Clinical outcomes of follicular tumor of uncertain malignant potential of the thyroid: real-world data.

Thyroid tumors arising from follicular cells can generally be divided into malignant and benign tumors. However, some cases are difficult to clearly diagnose whether they are benign or malignant. Therefore, in the most recent version of World Health Organization (WHO) classification, some borderline lesions such as follicular tumor of uncertain malignant potential (FT-UMP), well-differentiated tumor of uncertain malignant potential (WDT-UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were proposed. In this study, we investigated the clinical aspects, including the prognosis, of FT-UMP patients. We investigated the clinical features of 339 patients with FT-UMP. On ultrasound, 68% of the tumors were diagnosed as intermediate, and only 5% of those tumors were diagnosed as malignant. On cytology, 40% of the tumors were diagnosed as follicular neoplasm, and only 1% of these were suspected to be or diagnosed as malignancy. The diagnosis was based on questionable capsular invasion for 332 patients, questionable vascular invasion for 2 patients, and both for 5 patients. Eighty-six percent of the tumors showed low cell proliferation activity. To date, five patients (1%) have shown distant recurrence during postoperative follow-up and underwent various treatments such as radioactive iodine therapy, orthopedic surgery, and denosumab injection. None of these patients have died due to thyroid carcinoma. Our findings suggest that FT-UMP is generally an indolent disease, but some patients show distant recurrence. Physicians should carefully follow patients, although it remains unknown how long they should be observed after surgery.

B-cell to T-cell ratio as a novel indicator in flow cytometry in the diagnosis of thyroid lymphoma.

Preoperative flow cytometry is recommended to prove the monoclonality and confirm the diagnosis of thyroid lymphoma. However, lymphoma cases without light chain restriction may also have monoclonality. The aim of our study was to identify a novel marker for thyroid lymphomas using aspirated materials for flow cytometry. We retrospectively analyzed 26 patients with primary thyroid lymphomas and 16 patients with benign lymphoproliferative lesions. The materials for flow cytometry were obtained by fine-needle aspiration cytology using a 22-gauge needle under ultrasound guidance. Light chain restriction was defined as a κ to λ ratio of less than 0.5 or more than 3.0. According to the light chain-positive rate, 25% or less and more than 25% were classified as the low and high light chain-positive rate groups, respectively. B-cell predominance was defined as a CD19 to CD4 ratio (B- to T-cell ratio) of more than 2.0. B-cell predominance was more frequently observed in lymphomas (88.5%) than in benign lymphoproliferative lesions (25.0%; p < 0.001). Light chain restriction based on the κ/λ ratio was detected in 69.2% of lymphomas, but not in benign lymphoproliferative lesions. Among lymphomas belonging to the low light chain-positive rate group, 88.9% did not exhibit light chain restriction and B-cell predominance was present. In contrast, benign lymphoproliferative lesions with B-cell predominance were not detected in the low light chain-positive rate group. B-cell predominance was a useful indicator for diagnosing thyroid lymphoma in the low light chain-positive rate group without light chain restriction.

Evaluation of E-Cadherin and ß-Catenin Immunoreactivity for Determining Undifferentiated Cells in Anaplastic Thyroid Carcinoma.

INTRODUCTION: An immunohistochemical study has occasionally been performed to diagnose anaplastic thyroid carcinoma (ATC). However, antibodies to confirm the undifferentiated nature of ATC have not yet been evaluated. The aim of this study was to evaluate E-cadherin and ß-catenin expressions in immunoreactivity to determine undifferentiated carcinoma cells in the diagnosis of ATC. METHODS: We immunohistochemically examined 29 ATCs, 30 poorly differentiated thyroid carcinomas (PDTCs), 22 well-differentiated thyroid carcinomas (WDTCs), and 3 squamous cell carcinomas. Antibodies for thyroid transcription factor-1 (TTF-1), paired-box gene 8 (PAX8), ß-catenin, and E-cadherin were used. RESULTS: All WDTCs tested positive for TTF-1, PAX8, and E-cadherin. The positive rates of TTF-1, PAX8, and E-cadherin were 93.3, 93.3, and 100%, respectively, in PDTCs and 17.2, 51.7, and 10.3%, respectively, in ATCs. WDTC expressed the lateral cell membrane staining for ß-catenin and E-cadherin, whereas PDTC showed circumferential cell membranous expression (fishnet pattern). ß-catenin cell membrane expression in ATCs is lost or discontinuous. Carcinoma cells with ß-catenin nuclear expression without cell membranous expression were scattered in 72.4% of ATCs but were not observed in the other carcinomas. CONCLUSION: We propose 3 immunohistochemical findings to determine undifferentiated carcinoma cells in the diagnosis of ATC: (1) ß-catenin nuclear expression with no or reduced cell membranous expression, (2) the loss or discontinuous pattern of E-cadherin expression, and (3) the loss of PAX8 nuclear expression.

Histological alterations following fine-needle aspiration for parathyroid adenoma: Incidence and diagnostic problems.

This study aimed to clarify the histological alterations following fine-needle aspiration for parathyroid adenoma and discuss the occurrence of diagnostic problems. Among the 392 patients with parathyroid adenoma who underwent resection, fine-needle aspiration was performed for 21 (5.1%) parathyroid adenoma nodules. Histological findings that were significantly more frequent in cases that underwent fine-needle aspiration were considered histological alterations following fine-needle aspiration for parathyroid adenoma, including the following six findings: thick fibrous capsule (71.4%), multilayered fibrous capsules (14.3%), capsular pseudo-invasion (42.9%), fibrous bands (57.1%), hemosiderin deposition (14.3%), and tumor implantation (14.3%). Eighteen parathyroid adenoma nodules (85.7%) exhibited one or more of the six findings. Tumor cells and adipocytes entrapped within the thick fibrous capsule were occasionally observed. The fibrous bands were frequently connected to the thick fibrous capsule. The number of passes, duration between fine-needle aspiration and resection, tumor size, and purpose of fine-needle aspiration were not related to the incidence of histological findings. Because of the histological alterations following fine-needle aspiration for parathyroid adenoma that can be easily mistaken for signs of atypical adenoma or parathyroid carcinoma, we recommend that the six findings be excluded from pathological findings indicating atypical adenoma or parathyroid carcinoma in patients with preoperative fine-needle aspiration.

Potential role of mobile rapid on-site evaluation® in thyroid fine-needle aspiration cytology to reduce delayed repeated aspiration.

Rapid on-site evaluation of fine-needle aspiration cytology is time-consuming and requires specialized cytopathology staff. Mobile Rose® is a newly developed device for rapid on-site evaluation of fine-needle aspiration cytology. This study aimed to investigate the potential role of Mobile Rose® in reducing delayed repeated aspiration of the thyroid. A total of 120 cytological samples were collected and observed using Mobile Rose® after fine-needle aspiration cytology between September and October 2020, with immediate assessment of minimal or no cell clusters after conventional smear preparation. After qualifying and scoring, needle washout materials were prepared using the BD CytoRichTM method and correlated with cytology results. The average turn-around time of Mobile Rose® was found to be 1.5 minutes. Sensitivity, specificity, positive predictive value, and negative predictive value were 94.4%, 100%, 100%, and 57.1%, respectively. False-negative results were attributed to small aggregates of cells that were difficult to distinguish from the background and artifacts. Mobile Rose® may represent an important innovation for rapid on-site evaluation that is fast, has high diagnostic performance, does not require the presence of specialized cytology staff, and can reduce delayed repeated aspiration of the thyroid gland. However, further minor improvements and confirmation are required.

Evaluation of the diagnostic utility of the aminotransferase/lactate dehydrogenase ratio for the suspension of tissue specimens during thyroid surgery for the identification of parathyroid tissue.

Identification of the parathyroid glands during surgery is crucial for preventing postoperative hypoparathyroidism. Kikumori et al. reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio for the saline suspension of a suspicious tissue can differentiate parathyroid tissue from other tissues. The aim of this study was to evaluate the utility of this method and investigate the appropriate time for measurement. We obtained 465 tissue specimens during thyroidectomy of 102 patients with papillary thyroid carcinoma (PTC), and 422 specimens (129 parathyroid, 92 PTC, and 201 other tissues) with measurable AST and LDH were analyzed. Small pieces of the tissues were immersed in saline and sent for measurement of AST and LDH. The assay was performed immediately after thyroidectomy for 245 specimens (the same-day group) and during the next morning for the remaining 177 specimens (the next-day group). The accuracy of diagnosing parathyroid tissue was significantly better in the same-day group than in the next-day group. A cut-off value of 0.18 gave the best diagnostic precision, with an area under the receiver operating characteristic curve of 0.95 and 88.7% sensitivity and specificity in the same-day group. When the cut-off value was set to 0.20, the specificity for excluding carcinomatous tissues was 100%. When measured on the day of the surgery, the AST/LDH ratio for the saline suspension of the surgical specimens is useful for discriminating parathyroid tissues from other tissues. This method can be utilized at most hospitals where intraoperative frozen sections or rapid parathyroid hormone assays are not available.

Needle Tract Implantation Following Fine-Needle Aspiration of Thyroid Cancer.

BACKGROUND: Needle tract implantation (NTI) can occur after thyroid fine-needle aspiration cytology (FNAC). To date, no studies enrolling a large number of patients and studying the cumulative incidence (CI) of NTI have been published. This study analyzed the clinicopathological features of NTI and calculated the CI. METHODS: A total of 11,745 patients who underwent first FNAC, resection for thyroid carcinomas and related lymph node metastases, and postoperative ultrasonography in Kuma Hospital between 2006 and 2017 were evaluated. NTI was defined as macroscopically visible and/or sonographically detected recurrent tumors at the sites of the previous aspiration. Lymphovascular invasion and/or nodal metastasis were excluded. RESULTS: We found 22 NTI-THY (originated from aspiration of thyroid tumors) and 8 NTI-LN (originating from lymph nodes) cases with CI of 0.15% and 0.37%, and 0.37% and 0.58% at 5 and 10 years after FNAC, respectively. A large percentage (53%) of cases are presented as more aggressive histologic subtypes than their original tumors. Of these NTI patients, 4 (12.1%) died of disease and 10 (33.3%) developed distant metastases but remained alive with stable disease, three (9.1%) developed local recurrences, and the remaining 15 (10%) were free of recurrence. CONCLUSIONS: We demonstrated for the first time the CI and detailed clinicopathological features of thyroid NTI associated with possible histological transformation. Despite the low CI, the risk of death and distant metastases increase manifold in NTI patients than that in patients without recurrence. Therefore, NTI could be an important prognostic variable and impact patient survival.

A rare case of BRAF V600E-mutated epithelioid glioblastoma with a sarcomatous component.

Epithelioid glioblastoma is a rare subtype of glioblastoma, but the coexistence of a sarcomatous component is even rarer. An 80-year-old woman was admitted to our hospital with somnolence. Magnetic resonance imaging revealed a cystic lesion with a solid component in the left temporal-parietal lobe. Histopathological examination of the resected tumor revealed three components; namely, typical glioblastoma, sarcomatous and epithelioid components at a ratio of about 5:3:2. All components were immunohistochemically positive for vimentin and mutated BRAF (V600E) and showed focal expression of glial fibrillary acidic protein and cytokeratin AE1/AE3, but they were negative for isocitrate dehydrogenase 1. Genetic analysis revealed that both the sarcomatous and epithelioid components harbored BRAF T1799A (V600E) mutation and homozygous deletion of cyclin-dependent kinase inhibitor 2A/B. We diagnosed this tumor as epithelial glioblastoma with a sarcomatous component. Our results indicate that even when the epithelial component is not dominant, immunohistochemical and genetic investigation of BRAF mutations is useful for the diagnosis of glioblastoma subtypes. In particular, although the prognosis of epithelial glioblastoma is poor, potentially effective targeted therapies for BRAF V600E-mutated tumors are available.

Prevalence and diagnostic significance of noninvasive follicular thyroid neoplasm with papillary-like nuclear features among tumors previously diagnosed as follicular adenoma: a single-institutional study in Japan.

The incidence of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in papillary thyroid carcinoma (PTC) is significantly lower in Asian countries than Western countries; however, the difference remains unexplained. This study aimed to evaluate the incidence of NIFTP in tumors diagnosed as follicular adenoma (FA) in a Japanese institution and discuss the significance of NIFTP. In this study, 44 tumors were investigated, which were histologically diagnosed as FA at the Kuma Hospital in 2008. Of the 44 tumors, 13 (29.5%) were revised as NIFTP. In the remaining 31 tumors, the FA diagnosis was reconfirmed. On aspiration cytology, most of the NIFTPs were categorized into follicular neoplasm or suspicious for a follicular neoplasm. On histological examination, 9 (29.0%) of 31 FA nodules showed a nuclear score of 1. Twelve (92.3%) of 13 NIFTP nodules showed a nuclear score of 2, and the remaining nodule had a nuclear score of 3. No metastasis of FA or NIFTP was detected. There were no evidences of distant metastasis during follow-up. This is the first study to describe that NIFTP is more frequently included in tumors diagnosed as FA rather than PTC in Japan. As clinical management of FA and NIFTP is the same, in Japan, there is no reason to distinguish between FA and NIFTP. Conclusively, the necessity of using the disease entity "NIFTP" is not found in Japan.

Case report: exceptionally rapid growth character of hobnail variant of papillary thyroid carcinoma: a report of four cases.

The newest WHO classification adopts hobnail variant as an aggressive variant of papillary thyroid carcinoma (PTC). We here report four cases (ages 70-76 years, all females) with hobnail variant PTC treated at Kuma Hospital. Their lesions were cytologically diagnosed as PTC before surgery, but not as hobnail variant. All patients underwent a total thyroidectomy with central node dissection, and two patients also underwent therapeutic lateral node dissection. The clinical courses of three of the patients were very eventful. One patient showed recurrence to lymph nodes in the lateral compartment only 5 months after the initial surgery. In the initial surgery, one patient had a 36-mm lymph node metastasis in the lateral compartment, which was diagnosed as hobnail variant on pathology; 9 months post-surgery, metastases to the ipsilateral lateral lymph node, lung, and bone were newly detected. Her lung metastasis grew rapidly; its tumor volume-doubling time was 0.15 years and its tumor-doubling rate was 6.67/year. One patient underwent annual ultrasound examinations as postoperative follow-up after hemithyroidectomy for a benign nodule, but a 35-mm nodule diagnosed as PTC on cytology and lateral node metastases appeared within a short period, and she underwent a second surgery. Both the primary lesion and lymph nodes were diagnosed as hobnail variant by postoperative pathology. Three of the four patients showed exceptionally rapid growth of primary and/or metastatic/recurred lesions, indicating that patients with the hobnail variant should undergo very close and careful post-operative observation.

Flow cytometric, gene rearrangement, and karyotypic analyses of 110 cases of primary thyroid lymphoma: a single-institutional experience in Japan.

Ancillary studies for primary nodal lymphomas have been well documented; however, studies of primary thyroid lymphoma (PTL) are limited. Here, we aimed to clarify the clinicopathological, flow cytometric, gene rearrangement, and karyotypic characteristics of PTL by investigation of a large series at a single institute. We performed flow cytometric, IgH rearrangement, and karyotypic analyses of 110 PTL tissues surgically resected at Kuma Hospital between January 2012 and April 2017. All PTLs were of B-cell origin, including mucosa-associated lymphoid tissue lymphoma (MALTL; 89 patients, 80.9%), diffuse large B-cell lymphoma (DLBCL; 18 patients, 16.4%), and follicular lymphoma (FL; three patients, 2.7%). In 96 (87.3%) patients, anti-thyroid antibodies were positive. For flow cytometry using aspirated and resected materials, light chain restriction was observed in 73.7% and 69.2% of examined cases, respectively. Heavy chain JH DNA rearrangement was observed in 65.4% of PTLs (58.1% of MALTL cases, 100% of DLBCL cases, and 100% of FL cases). Chromosomal abnormalities were detected in 49.0% of PTLs, and translocation was most frequently detected (24.0%), followed by addition (20.8%) and trisomy (18.8%). The most frequent (9.4%) karyotype was t(3;14)(q27;q32). Both FLs harbored t(14;18)(q32;q21), and the karyotype was not detected in patients with MALTL and DLBCL. The negative rate for all three examinations was 3.8%. We concluded that thyroid MALTL was cytogenetically different from that in other organs. Our results suggested that pre-operative flow cytometry analysis using aspirated materials was as reliable as that using resected materials.

Optimal needle size for thyroid fine needle aspiration cytology.

Concerning the needle size for thyroid fine needle aspiration cytology (FNAC), 25-27-gauge needles are generally used in Western countries. However, in Japan, the use of larger needles (21-22-gauge needles) is common. The aim of our study was to determine the optimal needle size for thyroid FNAC. We performed ultrasound-guided FNAC for 200 thyroid nodules in 200 patients using two different-sized needles (22 and 25 gauge). For each nodule, two passes with the different-sized needles were performed. The order of needle sizes was reversed for the second group of 100 nodules. The second aspiration was more painful than the first, regardless of the needle size. An association with more severe blood contamination was more frequently observed with the use of 22-gauge needles (32.0%) than with the use of 25-gauge needles (17.5%) and in the second aspiration (37.5%) than in the initial aspiration (12.0%). The initial aspiration samples were more cellular than the second aspiration samples. Regarding the unsatisfactory and malignancy detection rates, there was no statistical difference between the needles. In three of seven markedly calcified nodules, it was difficult to insert 25-gauge needles into the nodules. In terms of the diagnostic accuracy and pain, either needle size can be used. We recommend using 22-gauge needles for markedly calcified nodules because 25-gauge needles bend more easily in such cases. We demonstrated that the initial aspiration tended to obtain more cellular samples and to be less contaminated. Thus, the initial aspiration is more important and should be closely attended.

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto's thyroiditis.

Hashimoto's thyroiditis with heavy lymphoplasmacytic infiltration is a common comorbidity of immunoglobulin G4 (IgG4)-related thyroiditis and Warthin-like papillary thyroid carcinoma (WL-PTC). We hypothesized that WL-PTC may have a strong association with IgG4-related thyroiditis. To validate this hypothesis, we clinically and immunohistochemically studied 17 WL-PTC cases. Fourteen patients (82.4%) had anti-thyroglobulin antibody and were confirmed to have Hashimoto's thyroiditis through microscopic analysis. Among them, five (29.4%) had disease consistent with IgG4-related thyroiditis but did not exhibit a "storiform" pattern or obliterative phlebitis. IgG4-related diseases were not found in other organs. No cases with serum IgG4 level of >135 mg/dL were noted. A total of 94.1% of WL-PTC cases had IgG4-positive plasma cells (+PCs) in the stroma, and cases with rich IgG4+PCs were more frequently associated with Hashimoto's thyroiditis than those with poor IgG4+PCs. In this study, all three cases without Hashimoto's thyroiditis had poor IgG4+PCs, and one of them did not exhibit IgG4+PCs in the stroma of WL-PTC and Hashimoto's thyroiditis. Nodal metastatic lesions were seen in eight cases, all of which were not WL-PTC. As such, we should consider that the Hashimoto's disease with rich IgG4+PCs seen in our cases is representative of non-IgG4-related disease and not IgG4-related disease involving multiple organs. This study is the first to demonstrate the presence of IgG4+PCs in the stroma of WL-PTC. We concluded that the appearance of IgG4+PCs in the stroma of WL-PTC may be related to Hashimoto's thyroiditis with rich IgG4+PC.

Derivation of thyroid lymphoepithelial cysts from follicular cells.

The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts. On ultrasound, half of thyroid lymphoepithelial cysts were interpreted as calcified nodules regardless of no calcification. Thyroid lymphoepithelial cysts and squamous metaplasia tended to be located in the central and lower portions of the thyroid, while solid cell nests were located in the upper and central portions (p < 0.05). In 95.2% of patients with thyroid lymphoepithelial cysts and all patients with squamous metaplasia, lesions were histologically associated with chronic thyroiditis forming lymph follicles. Hashimoto's disease was serologically confirmed in 18 patients with lymphoepithelial cysts (85.7%) and 10 patients with squamous metaplasia (76.9%). Immunohistochemically, lymphoepithelial cysts showed nuclear positivity for PAX8, thyroid transcription factor 1, and p63. One lateral cervical cyst (7.1%) showed positive staining for PAX8, while solid cell nests were PAX8-negative. In three (14.3%) cases of thyroid lymphoepithelial cysts, squamous cells located on the superficial layer were focally and weakly positive for CEA. We concluded that thyroid lymphoepithelial cysts originate from follicular cells and are unrelated to solid cell nests and lateral cervical cysts arising from branchial-derived remnants.

Utility of monoclonal PAX8 antibody for distinguishing intrathyroid thymic carcinoma from follicular cell-derived thyroid carcinoma.

Follicular cell-derived thyroid carcinomas, including thyroid squamous cell carcinomas (SCCs) and anaplastic carcinomas, are immunoreactive for paired-box gene 8 (PAX8), while non-follicular cell-derived thyroid carcinomas stain negative for the PAX8 antibody. Intrathyroid thymic carcinoma (ITTC) arising from the intrathyroidal ectopic thymus exhibits moderate-to-strong nuclear reactivity for polyclonal PAX8. This is difficult to understand given that PAX8 is not associated with embryonic thymic development. We aimed to determine the diagnostic significance of monoclonal PAX8 antibody in distinguishing ITTCs from follicular cell-derived thyroid carcinomas. Ten ITTCs, 14 poorly differentiated thyroid carcinomas (PDTCs), 14 thyroid SCCs, 7 thymic tissue specimens, 7 thymomas, and 1 thymic carcinoma were analyzed using antibodies against polyclonal and monoclonal PAX8, thyroid transcription factor-1, p63, and CD5. Four ITTCs (40.0%) stained positive for polyclonal PAX8; none stained positive for monoclonal PAX8. All PDTCs and 92.9% of SCCs were immunoreactive for both polyclonal and monoclonal PAX8. All PDTCs, 46.2% of SCCs, and none of the ITTCs were immunoreactive for thyroid transcription factor-1. Eight ITTCs (80.0%), but none of the PDTCs and SCCs, were immunoreactive for CD5. We are the first to show that ITTCs stain negative for monoclonal PAX8. Monoclonal PAX8 is a more reliable marker than polyclonal PAX8 for determining follicular cell origin. We conclude that monoclonal PAX8 is a useful marker for distinguishing ITTCs from PDTCs and SCCs. Monoclonal PAX8 negativity is additional evidence in support of ITTCs not being follicular cell-derived thyroid carcinomas, but having a thymic origin.

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia distinct from the salivary type.

We report three cases of thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE), which is an extremely rare variant of mucoepidermoid carcinoma (MEC). The aims of this report were to describe the clinicopathological findings, including results from immunohistochemical and fluorescence in situ hybridization analysis of thyroid SMECE, as well as to discuss the distinction between thyroid SMECE and its salivary counterpart. The cases included a 63-year-old female, a 44-year-old male, and a 66-year-old female, with all patients presenting with Hashimoto's thyroiditis. Nodal metastasis was not found in any of the three cases. Neither regional recurrences nor distant metastases were found in any patient during the follow-up, which was 20 years, 3 years, and 18 months, respectively. Histologically, tumors were composed of epidermoid carcinoma cells, intermediate type carcinoma cells, and goblet cell-type mucus-secreting carcinoma cells, with all tumors displaying a sclerotic stroma with eosinophilic and lymphocytic infiltration. The formation of eosinophilic abscess in the tumor nests that might be a novel characteristic finding of SMECE was observed. Immunohistochemically, the carcinoma cells were positive for cytokeratin 34ßE12, TTF-1, and PAX8, but negative for thyroglobulin. In two cases, increased IgG4-positive plasma cells were observed. Mastermind-like transcriptional coactivator 2 (MAML2), according to fluorescence in situ hybridization, was intact in all cases. In conclusion, thyroid SMECE has favorable outcomes and seems to be genetically different from salivary MEC. This is the first report to describe the presence of increased IgG4-positive plasma cells in the stroma of SMECE.

Impact of the modification of the diagnostic criteria in the 2017 Bethesda System for Reporting Thyroid Cytopathology: a report of a single institution in Japan.

The Bethesda System for Reporting Thyroid Cytopathology has recently been revised in 2017 (TBSRTC 2017). This study aimed to evaluate the impact of modifying the diagnostic criteria in TBSRTC 2017 at a single institute. We retrospectively reviewed cytological specimens of 10,399 thyroid nodules submitted for thyroid fine-needle aspiration cytology. Among them, 56 atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) nodules, 16 suspicious for malignancy (SFM) nodules, and 8 malignant nodules were re-categorized into follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN). The incidence of FN/SFN was increased by 0.8%, while that of AUS/FLUS, SFM, and malignant nodule was decreased by 0.5%, 0.2%, and 0.1%, respectively. In nine (60%) of the 15 nodules that were re-classified from AUS/FLUS to FN/SFN nodules and re-aspiration was performed, it was possible to judge whether they were benign or malignant. Of the 24 patients with FN/SFN nodules originally diagnosed with SFM or malignant, 16 were followed up without surgical resection. In conclusion, TBSRTC 2017 only caused minor changes in the incidence of each diagnostic category. TBSRTC 2017 was revised to avoid false positives owing to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) that account for >10% of papillary thyroid carcinomas; however, it is not necessary in low frequency NIFTP institutes or countries. In Japan, we propose active surveillance as an accepted option for clinically managing AUS/FLUS, FN/SFN, SFM, or malignant nodules having favorable benign clinical findings or being part of the low-risk group.

Cytoplasmic Lipid Accumulation Characteristic of the Cribriform Variant of Papillary Thyroid Carcinoma.

OBJECTIVE: The purpose of this study was to clarify the diagnostic significance of cytoplasmic lipid accumulation (CLIA) in the cribriform variant of papillary thyroid carcinoma (CV-PTC). METHODS: We performed a histological, immunohistochemical, and cytological examination of 35 CV-PTC cases at the Kuma Hospital. CLIA was defined as bubble-like multivacuolation in cytoplasm with distinct cell border. We also examined 100 conventional PTC (con-PTC) cases as controls. RESULTS: Histological analysis showed the presence of carcinoma cells with CLIA in 60.0% of CV-PTC and 5.0% of con-PTC cases. The vacuoles tended to distribute in the subnuclear portion of carcinoma cells showing papillary growth. They were positive for oil red O staining and adipophilin. The carcinoma cells without the vacuoles showed a subnuclear dot-like expression for adipophilin in CV-PTC cases, but not in the con-PTC cases. Cytological analysis showed CLIA in 17 (54.8%) of the 31 CV-PTC cases, but not in the con-PTC cases. CONCLUSION: This is the first study to report the presence of carcinoma cells with CLIA in CV-PTC. The subnuclear dot-like expression of adipophilin may be characteristic of CV-PTC. These findings might be related to degenerative changes occurring in CV-PTC.