Deep learning prediction model for central lymph node metastasis in papillary thyroid microcarcinoma based on cytology.

Controversy exists regarding whether patients with low-risk papillary thyroid microcarcinoma (PTMC) should undergo surgery or active surveillance; the inaccuracy of the preoperative clinical lymph node status assessment is one of the primary factors contributing to the controversy. It is imperative to accurately predict the lymph node status of PTMC before surgery. We selected 208 preoperative fine-needle aspiration (FNA) liquid-based preparations of PTMC as our research objects; all of these instances underwent lymph node dissection and, aside from lymph node status, were consistent with low-risk PTMC. We separated them into two groups according to whether the postoperative pathology showed central lymph node metastases. The deep learning model was expected to predict, based on the preoperative thyroid FNA liquid-based preparation, whether PTMC was accompanied by central lymph node metastases. Our deep learning model attained a sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and accuracy of 78.9% (15/19), 73.9% (17/23), 71.4% (15/21), 81.0% (17/21), and 76.2% (32/42), respectively. The area under the receiver operating characteristic curve (value was 0.8503. The predictive performance of the deep learning model was superior to that of the traditional clinical evaluation, and further analysis revealed the cell morphologies that played key roles in model prediction. Our study suggests that the deep learning model based on preoperative thyroid FNA liquid-based preparation is a reliable strategy for predicting central lymph node metastases in thyroid micropapillary carcinoma, and its performance surpasses that of traditional clinical examination.

Pathologic complete response after neoadjuvant v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibition combined with immunotherapy therapy for anaplastic thyroid carcinoma: a case report and literature review.

Anaplastic thyroid carcinoma (ATC) is a highly malignant tumor with invasive nature. Most patients present with locally advanced and/or distant metastatic diseases that are difficult to treat. We report a case of a previously inoperable patient with v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutated ATC. After a trial of neoadjuvant Dabrafenib/Trametinib with immunotherapy, the tumor became operable, and surgical pathology indicated a pathologic complete response (pCR). We also reviewed cases from the literature that utilized neoadjuvant BRAF-directed therapy in ATCs. These cases emphasize that BRAF-and immune-directed therapy is a feasible option in patients with inoperable ATC and may lead to improved outcomes.

3cDe-Net: a cervical cancer cell detection network based on an improved backbone network and multiscale feature fusion.

BACKGROUND: Cervical cancer cell detection is an essential means of cervical cancer screening. However, for thin-prep cytology test (TCT)-based images, the detection accuracies of traditional computer-aided detection algorithms are typically low due to the overlapping of cells with blurred cytoplasmic boundaries. Some typical deep learning-based detection methods, e.g., ResNets and Inception-V3, are not always efficient for cervical images due to the differences between cervical cancer cell images and natural images. As a result, these traditional networks are difficult to directly apply to the clinical practice of cervical cancer screening. METHOD: We propose a cervical cancer cell detection network (3cDe-Net) based on an improved backbone network and multiscale feature fusion; the proposed network consists of the backbone network and a detection head. In the backbone network, a dilated convolution and a group convolution are introduced to improve the resolution and expression ability of the model. In the detection head, multiscale features are obtained based on a feature pyramid fusion network to ensure the accurate capture of small cells; then, based on the Faster region-based convolutional neural network (R-CNN), adaptive cervical cancer cell anchors are generated via unsupervised clustering. Furthermore, a new balanced L1-based loss function is defined, which reduces the unbalanced sample contribution loss. RESULT: Baselines including ResNet-50, ResNet-101, Inception-v3, ResNet-152 and the feature concatenation network are used on two different datasets (the Data-T and Herlev datasets), and the final quantitative results show the effectiveness of the proposed dilated convolution ResNet (DC-ResNet) backbone network. Furthermore, experiments conducted on both datasets show that the proposed 3cDe-Net, based on the optimal anchors, the defined new loss function, and DC-ResNet, outperforms existing methods and achieves a mean average precision (mAP) of 50.4%. By performing a horizontal comparison of the cells on an image, the category and location information of cancer cells can be obtained concurrently. CONCLUSION: The proposed 3cDe-Net can detect cancer cells and their locations on multicell pictures. The model directly processes and analyses samples at the picture level rather than at the cellular level, which is more efficient. In clinical settings, the mechanical workloads of doctors can be reduced, and their focus can be placed on higher-level review work.

How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery-Risk stratification of papillary thyroid carcinoma in young patients.

Current histopathological diagnosis methods cannot distinguish the two types of thyroid carcinoma: clinically significant carcinomas with a potential risk of recurrence, metastasis, and cancer death, and clinically insignificant carcinomas with a slow growth rate. Both thyroid tumors are diagnosed as "carcinoma" in current pathology practice. The clinician usually recommends surgery to the patient and the patient often accepts it because of cancer terminology. The treatment for these clinically insignificant carcinomas does not benefit the patient and negatively impacts society. The author proposed risk stratification of thyroid tumors using the growth rate (Ki-67 labeling index), which accurately differentiates four prognostically relevant risk groups based on the Ki-67 labeling index, ≥30%, ≥10 and <30%, >5 and <10%, and ≤5%. Indolent thyroid tumors with an excellent prognosis have the following four features: young age, early-stage (T1-2 M0), curatively treated, and low proliferation index (Ki-67 labeling index of ≤5%), and are unlikely to recur, metastasize, or cause cancer death. Accurate identification of these indolent tumors helps clinicians select more conservative treatments to avoid unnecessary aggressive (total thyroidectomy followed by radio-active iodine) treatments. Clinicians can alleviate the fears of patients by confirming these four features, including the low proliferation rate, in a pathology report immediately after surgery when patients are most concerned.

Feasibility of Augmented Reality-Guided Transjugular Intrahepatic Portosystemic Shunt.

PURPOSE: To investigate an augmented reality (AR)-guided endovascular puncture to facilitate successful transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: An AR navigation system for TIPS was designed. Three-dimensional (3D) liver models including portal and hepatic vein anatomy were extracted from preoperative CT images. The 3D models, intraoperative subjects, and electromagnetic tracking information of the puncture needles were integrated through the system calibration. In the AR head-mounted display, the 3D models were overlaid on the subjects, which was a liver phantom in the first phase and live beagle dogs in the second phase. One life-size liver phantom and 9 beagle dogs were used in the experiments. Imaging after puncture was performed to validate whether the needle tip accessed the target hepatic vein successfully. RESULTS: Endovascular punctures of the portal vein of the liver phantom were repeated 30 times under the guidance of the AR system, and the puncture needle successfully accessed the target vein during each attempt. In the experiments of live canine subjects, the punctures were successful in 2 attempts in 7 beagle dogs and in 1 attempt in the remaining 2 dogs. The puncture time of needle from hepatic vein to portal vein was 5-10 s in the phantom experiments and 10-30 s in the canine experiments. CONCLUSIONS: The feasibility of AR-based navigation facilitating accurate and successful portal vein access in preclinical models of TIPS was validated.

[Clinicopathologic characteristics and histogenesis of mucinous tumor of peritoneum].

OBJECTIVE: To investigate the clinicopathologic characteristics, prognosis and histologic origin of the mucinous tumor of the peritoneum. METHODS: According to 2010 WHO classification of tumours of the digestive system, 34 cases diagnosed as "pseudomyxoma peritonei (PMP) " were reevaluated and divided into low grade and high grade. Immunohistochemistry was applied to investigate the expression of SATB2 and the histologic origin of the mucinous tumor of the peritoneum, using antibodies against SATB2, CK7, CK20 and CDX-2. The relationship between clinicopathologic characteristics and prognosis of the low grade and high grade tumors were analyzed. RESULTS: Twenty five patients had low grade mucinous tumors (two of them were no cell type), nine patients had high grade mucinous tumors. There was no significant difference between low grade and high grade mucinous tumors in age, sex, recurrence and organs involvement (P>0.05). Thirty patients were followed up, the overall survival rates of patients with low grade and high grade mucinous tumors were 13/21 (61.9%) and 3/9, respectively. The median survival time was 74 and 24 months in low and high grade patients, and the difference was statistically significant (P=0.002).Immunohistochemistry showed the expression rates of CDX-2, CK20, and CK7 in totally 32 cases (excluding 2 cases of no cell type) were 30/32(93.8%), 31/32 (96.9%), and 3/16, respectively; the expression rates of CDX-2, CK20, and CK7 in 16 cases with distinct primary site were 15, 16, and 1, respectively; fifteen of 16 cases of tumors of unknown primary site were positive for CDX-2 and CK20, two of the them were positive for CK7. There was no difference in the expression of CDX-2, CK20 and CK7 between tumors with distinct primary site and tumors with unknown primary site (P>0.05). The expression rate of SATB2 in the cases was 56.3% (18/32), excluding 2 cases of no cell type. There was no significant difference between low grade and high grade tumors in the expression of SATB2 [15/23(65.2%) vs 3/9, P=0.102], also SATB2 was not related to the prognosis of the tumor (P=0.786). CONCLUSION: The prognosis of the mucinous tumor of the peritoneum was significantly different between low grade and high grade according to WHO 2010 classification, and most mucinous tumor of the peritoneum originated from the appendix.

Combination kinase inhibitors and immunotherapy for unresectable anaplastic thyroid carcinoma: A retrospective single-center study.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is rare but has a very poor prognosis. New therapeutic options such as multikinase inhibitors and selective tyrosine kinase inhibitors have revolutionized the treatment of ATC, with immunotherapy also showing encouraging effects. This study evaluated the efficacy and safety of kinase inhibitors combined with an anti-PD-1 inhibitor as first-line treatment, as well as in the neoadjuvant setting for patients with unresectable ATC. MATERIALS & METHODS: This retrospective single-center study recruited consecutive patients with stage IVB and IVC ATC who received first-line kinase inhibitors plus immunotherapy between June 2021 and June 2023. The patients were treated with either selective or multi-kinase inhibitors (dabrafenib/trametinib, lenvatinib, or anlotinib) in combination with one immune checkpoint inhibitor (pembrolizumab, sintilimab, or camrelizumab). The endpoints included overall survival (OS), progression-free survival (PFS), response evaluation, and feasibility of R0/R1 resection. RESULTS: Eighteen patients were included in this analysis. The median OS (mOS) was 14.0 months and the 12-month survival rate was 55.6 %. The mOS in BRAF V600E mutated ATC was not reached, significantly longer than non-BRAF V600E mutated ATC (4.0 months [95 %CI, 1.1-6.9], p = 0.049). Among evaluable patients, 5 achieved a complete response (CR) and 6 patients achieved partial response (PR). The best ORR was 61.1 %. Surgical resection was feasible in 7/18 (38.9 %) patients. One grade 5 adverse event (AE) occurred. Most AEs were well tolerated. CONCLUSIONS: Combination kinase inhibitors with immunotherapy as first-line therapy are safe and effective for the treatment of unresectable ATC, especially with BRAF V600E mutation.

Exploring prognostic values of DNA ploidy, stroma-tumor fraction and nucleotyping in stage II colon cancer patients.

PURPOSE: To assess the prognostic value of three novel biomarkers, DNA ploidy, stroma-tumor fraction, and nucleotyping, seeking for more accurate stratification in stage II colon cancer. METHODS: A total of 417 patients with complete follow up information were enrolled in this study and divided into three clinical risk groups. IHC was performed to examine MSI status. DNA ploidy, stroma and nucleotyping were estimated using automated digital imaging system. Kaplan-Meier survival curves, Cox proportional hazards regression models, and correlation analyses were carried out to process our data. RESULTS: In the whole cohort of stage II colon cancer, nucleotyping and DNA ploidy were significant prognostic factors on OS in univariate analyses. The combination of nucleotyping and DNA ploidy signified superior OS and DFS. Difference was not significant between low-stroma and high-stroma patients. In multivariable analyses, nucleotyping and the combination of nucleotyping and DNA ploidy were proven the dominant contributory factors for OS. In the low-risk group, we found the combination of nucleotyping and DNA ploidy as the independent prognostic factor statistically significant in both univariate and multivariable, while in the high-risk group, the nucleotyping. CONCLUSIONS: Our study has proven nucleotyping and the combination of DNA ploidy and nucleotyping as independent prognostic indicators, thus expanding the application of nucleotyping as a predictor from high risk stage II colon cancer to whole risks.

CT2X-IRA: CT to x-ray image registration agent using domain-cross multi-scale-stride deep reinforcement learning.

Objective.In computer-assisted minimally invasive surgery, the intraoperative x-ray image is enhanced by overlapping it with a preoperative CT volume to improve visualization of vital anatomical structures. Therefore, accurate and robust 3D/2D registration of CT volume and x-ray image is highly desired in clinical practices. However, previous registration methods were prone to initial misalignments and struggled with local minima, leading to issues of low accuracy and vulnerability.Approach.To improve registration performance, we propose a novel CT/x-ray image registration agent (CT2X-IRA) within a task-driven deep reinforcement learning framework, which contains three key strategies: (1) a multi-scale-stride learning mechanism provides multi-scale feature representation and flexible action step size, establishing fast and globally optimal convergence of the registration task. (2) A domain adaptation module reduces the domain gap between the x-ray image and digitally reconstructed radiograph projected from the CT volume, decreasing the sensitivity and uncertainty of the similarity measurement. (3) A weighted reward function facilitates CT2X-IRA in searching for the optimal transformation parameters, improving the estimation accuracy of out-of-plane transformation parameters under large initial misalignments.Main results.We evaluate the proposed CT2X-IRA on both the public and private clinical datasets, achieving target registration errors of 2.13 mm and 2.33 mm with the computation time of 1.5 s and 1.1 s, respectively, showing an accurate and fast workflow for CT/x-ray image rigid registration.Significance.The proposed CT2X-IRA obtains the accurate and robust 3D/2D registration of CT and x-ray images, suggesting its potential significance in clinical applications.

Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease.

A form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In conclusion, IgG4 Hashimoto's thyroiditis presents histopathological features quite distinct from its non-IgG4 counterpart.

Encapsulated papillary thyroid carcinoma, follicular variant: a misnomer.

Papillary thyroid carcinoma (PTC) has long been diagnosed based on its unique nuclear features (PTC-N); however, significant observer discrepancies have been reported in the diagnosis of encapsulated follicular patterned lesions (EnFPLs), because the threshold of PTC-N is subjective. An equivocal PTC-N may often occur in non-invasive EnFPLs and benign/malignant disagreements often create serious problems for patients' treatment. This review collects recent publications focusing on the so-called encapsulated follicular variant of papillary thyroid carcinoma (EnFVPTC) and tries to emphasize problems in the histopathological diagnosis of this spectrum of tumors, which covers encapsulated common-type PTC (EncPTC), EnFVPTC, well-differentiated tumor of uncertain malignant potential (WDT-UMP), follicular adenoma (FA) with equivocal PTC-N and minimally invasive follicular carcinoma (mFTC). We propose that EnFVPTC and other EnFPLs with equivocal PTC-N should be classified into a unified category of borderline malignancy, such as well-differentiated tumor of uncertain behavior (WDT-UB), based on their homogeneous excellent outcome. It is suggested that the unified nomenclature of these lesions may be helpful to reduce significant observer disagreements in diagnosis, because complete agreement in the diagnosis of an EncPTC, EnFVPTC or FA by all pathologists may be not possible for this problematic group of tumors. In conclusion, a malignant diagnosis of EnFVPTC should not be used to cover this spectrum of tumors until uncertainty about the nature of this lesion is settled, whether it is benign, precancerous or malignant.

Classification of thyroid follicular cell tumors: with special reference to borderline lesions.

We propose a new classification of thyroid follicular cell tumors which is correlated with patient's prognosis. It is unique as to two new categories: borderline malignancy between benign and malignant, and moderately differentiated adenocarcinoma (MDA) as a differentiation classification to stratify tumor aggressiveness. As to diagnostic criteria, we recommend invasiveness (capsular and vascular invasion) to separate benign and malignant and it should not be based on presence or absence of papillary thyroid carcinoma (PTC) type nuclear features (PTC-N). Thus borderline malignancy in our new classification includes some of the formerly malignant tumors and they are 1) papillary microcarcinoma, 2) encapsulated conventional PTC (EncPTC), 3) encapsulated follicular variant PTC (EnFVPTC), 4) well differentiated tumor of uncertain malignant potential (WDT-UMP), 5) follicular tumors of uncertain malignant potential (FT-UMP), and 6) capsular invasion only follicular thyroid carcinoma (FTC). Review of the literature revealed that those thyroid tumors have consistently excellent outcome. Well differentiated follicular cell adenocarcinoma (WDA) in our classification includes common type PTC and low-risk follicular carcinoma (FTC). They are invasive (diffuse infiltrative) common type PTC and minimally invasive type FTC with less than 4 foci of angioinvasion. Moderately differentiated follicular cell adenocarcinoma (MDA) includes FTC with angioinvasion (more than 4), aggressive variants of PTC, such as tall cell, columnar cell, solid, loss of cellular polarity/cohesiveness (hobnail) variants and encapsulated carcinoma with high grade histology. Poorly differentiated carcinoma (PDC) includes PDC of WHO definition, insular carcinoma, tumors with minor anaplastic transformation and tumors with distant metastasis at presentation.

Level IIb neck dissection guided by fine-needle aspiration for N1b papillary thyroid carcinoma.

BACKGROUND: The extent of neck dissection for patients with papillary thyroid carcinoma (PTC) metastasis in lateral cervical lymph nodes is still debated. Studies aiming to omit level IIb were generally based on postoperative histopathologic information. The purpose of this study was to evaluate the predictive value of fine-needle aspiration (FNA) for level II lymph nodes in identifying candidates for neck dissection sparing level IIb before surgery. METHODS: We prospectively enrolled 156 consecutive previously untreated PTC patients with lateral neck metastases who were subjected to 178 therapeutic lateral neck dissections (including level IIa, IIb, III, IV, and Vb) between June 2018 and August 2021. Ultrasound-guided FNA of suspicious lymph nodes at level II was preoperatively performed. The cytology of FNA and thyroglobulin (Tg) washout concentration with other clinical predictors was analyzed for lymph node metastases at level IIb. RESULTS: Preoperative ultrasonography revealed suspicious lymph nodes at level II in 118 cases, and fifty were positive on FNA results. Metastasis at level IIb was seen in 17 (9.6%) of the postoperative specimens. By univariate analysis, the rate of level IIb metastasis was significantly higher in patients with FNA-positive lymph nodes at level II (P<0.001, odds ratio = 16.899). The tumor sizes of the two FNA-negative level IIb metastatic lymph nodes were 0.4 mm and 3 mm. CONCLUSIONS: Level IIb lymph node dissection may be omitted in the treatment of N1b PTC patients if FNA to level II lymph nodes is negative.

Using Whole Slide Gray Value Map to Predict HER2 Expression and FISH Status in Breast Cancer.

Accurate detection of HER2 expression through immunohistochemistry (IHC) is of great clinical significance in the treatment of breast cancer. However, manual interpretation of HER2 is challenging, due to the interobserver variability among pathologists. We sought to explore a deep learning method to predict HER2 expression level and gene status based on a Whole Slide Image (WSI) of the HER2 IHC section. When applied to 228 invasive breast carcinoma of no special type (IBC-NST) DAB-stained slides, our GrayMap+ convolutional neural network (CNN) model accurately classified HER2 IHC level with mean accuracy 0.952 ± 0.029 and predicted HER2 FISH status with mean accuracy 0.921 ± 0.029. Our result also demonstrated strong consistency in HER2 expression score between our system and experienced pathologists (intraclass correlation coefficient (ICC) = 0.903, Cohen's κ = 0.875). The discordant cases were found to be largely caused by high intra-tumor staining heterogeneity in the HER2 IHC group and low copy number in the HER2 FISH group.

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer.

Background: Adenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC. Methods: We applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information. Results: A total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity. Conclusion: This study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.

Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population.

Immunotherapy shows prospects in treating advanced medullary thyroid carcinoma although controversial reports are present. Recently, histological grading has been applied to medullary thyroid carcinoma by the Ki-67 index, mitotic figures, and tumor necrosis. However, the interrelation of PD-L1 expression, the Ki-67 index, and major genetic alterations of sporadic medullary thyroid carcinoma has not been fully reported. We examined the expression of PD-L1 (SP142 and 22C3) and the Ki-67 index immunohistologically and detected the major genetic alterations by next-generation sequencing in a cohort of sporadic medullary thyroid carcinomas, studied their survival impact, and discussed their interrelation. We identified that a high Ki-67 index (> 2%) and positive RET M918T mutation were correlated with poor disease-free survival but were not correlated with PD-L1 expression. All PD-L1 positive tumors were RET M918T mutation negative, and PD-L1 expression was positively correlated with HRAS mutation. The Ki-67 index was correlated with neither PD-L1 expression nor major genetic alterations. Our results indicate that immunotherapy targeting PD-L1/PD-1 might be more effective for patients with sporadic medullary thyroid carcinoma harboring HRAS mutations.

Retinoid X receptor γ up-regulation is correlated with dedifferentiation of tumor cells and lymph node metastasis in papillary thyroid carcinoma.

The expression of retinoid X receptor γ (RXRγ) and the clinicopathological parameters of total 69 patients with papillary thyroid carcinoma (PTC) larger than 1 cm were examined. The PTCs were classified into two groups according to the presence of loss of cellular polarity/cohesiveness (LOP/C). The expression of RXRγ mRNA was examined by reverse transcriptase polymerase chain reaction and quantitative real-time PCR. The RXRγ mRNA up-regulation was found to be positively correlated with extrathyroid invasion (r = 0.293, P = 0.019), advanced tumor stage (r = 0.318, P = 0.016) and lymph node metastasis (LNM) (r = 0.338, P = 0.005), as well as LOP/C (r = 0.345, P = 0.004), which was proposed as a histological characteristic of poor cellular differentiation. The RXRγ mRNA expression, as well as extrathyroid invasion, LOP/C and advanced tumor stage, was further confirmed to be one of the independent predictive factors (Odds ratio: 6.545; 95% confidence interval: 1.575-27.208) of LNM using multivariate analysis. These results suggest that RXRγ may play a role in the dedifferentiation and metastasis of PTC.

Squamous cell components in a thyroid follicular adenoma: significant evidence of follicular cell origin by histomorphological, immunohistochemical and molecular analyses.

Squamous cells in the thyroid appear in a variety of conditions, including adenomatous goiters, malignant neoplasms, inflammatory diseases, and embryonic remnants. However the origin of the squamous cells is still under dispute. Here we report a case of an encapsulated follicular cell tumor consisting of follicular cells, basaloid squamous cells, and morphologically intermediate cells. The patient was a 66-year-old man presenting with a progressively enlarged painless lump in the right side of his neck. A solid tumor with encapsulation in the right lobe was confirmed by simple right lobe thyroid lobectomy. This tumor demonstrated heterogeneous immunoreactions for Ki-67, thyroglobulin, thyroid transcription factor-1, and pan-cytokeratin (AE1/AE3), in that the intermediate cells had intermediate immunoreactivity between follicular and basaloid squamous cells. p63 was positive in the periphery layer of tumor cell nests of the intermediate and squamous cells. A completely negative immunoreaction was noted for high molecular weight cytokeratin (34ßE12), calcitonin, CEA, p53, CD5, and rearranged in transformation (RET). Mutational analysis of BRAF and RAS were negative. These results strongly suggest that this tumor is a follicular adenoma, and that the squamous component originated from follicular cells undergoing squamous metaplasia. The patient has been disease free more than 40 months after surgery.