Search

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.

ALK-positive histiocytosis (APH) is a newly defined entity with specific histological features and a highly recurrent KIF5B-ALK gene fusion. APH is characterized by clonal proliferation of histiocytes and can present as either systemic or localized. It was first described in infants and then expanded to older children and adults. Although lung involvement has been shown in three systemic cases, localized lung lesions have not previously been reported. The ALK gene has many fusion partners in addition to KIF5B in APH. Here, we report a striking case of localized APH in the lung harboring a rare EML4-ALK rearrangement in a 52-year-old Chinese woman. Furthermore, we reviewed the previously published APH cases, analyzed the partner genes of the ALK fusions, and explored the role of patient ethnicity. We discovered a link between ethnicity and this rare disease.

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.

Objective. To evaluate the safety and efficacy of surgical ligation and endovascular embolization for the treatment of type II congenital extrahepatic portosystemic shunt (CEPS). Methods. In this retrospective study, 23 patients diagnosed with type II CEPS between March 2011 and April 2019 were divided into either a surgical group ( n = 13 ; 41.5 ± 19.9 years) or the interventional group ( n = 10 ; 44.9 ± 19.7 years). The surgical group underwent laparoscopic surgical ligation of the shunt alone or ligation of the shunt and splenic artery and/or vein. The interventional group underwent endovascular embolization using microcoils, detachable coils, and vascular plug. Results. All 23 patients received a one-step shunt closure, and their clinical symptoms were significantly improved within 3-month postprocedure and without recurrence during follow-up. The serum ammonia levels in both groups decreased after the procedure and dropped to normal level at 6- to 12-month postprocedure. Compared with baseline, the portal vein diameter in interventional group increased significantly at 3-, 6-, 12-, and 36-month postocclusion ( P = 0.01 for all). The procedure time was shorter in the interventional group ( 127.0 ± 43.2 minutes) than the surgical group ( 219.8 ± 56.7 minutes; P < 0.001 ). The intraoperative blood loss in the interventional group ( 32.0 ± 62.5 mL) was less than that in the surgical group ( 238.5 ± 396.9 mL; P = 0.001 ). Conclusion. Both surgical ligation and endovascular embolization are effective in the treatment of type II CEPS. Endovascular embolization has the advantages of shorter procedure time and less intraoperative blood loss. The ligation of the portosystemic shunt and splenic artery and vein is feasible with apparent safety, and it could avoid a second surgical treatment.

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.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.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 (P0.001, odds ratio = 16.899). The tumor sizes of the two FNA-negative level IIb metastatic lymph nodes were 0.4 mm and 3 mm.Level IIb lymph node dissection may be omitted in the treatment of N1b PTC patients if FNA to level II lymph nodes is negative.

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare lymphoma subtype. The present study investigated a refractory nodal ALK-positive LBCL case in a 28-year-old Chinese male. It was initially misdiagnosed as ALK-positive anaplastic large cell lymphoma; however, the patient's lesions relapsed and spread widely following a short remission for chemotherapy and the patient succumbed to the disease 3 months' post-autologous stem cell transplantation; thus, a revision was performed. Histologically, the tumor cells exhibited a characteristic immunoblastic morphology with marked cellular pleomorphism. All lesions shared the same immunoprofiles, including granular cytoplasmic ALK staining patterns and a lack of cell lineage-associated markers, with the exception of cluster of differentiation (CD)45 and CD4. CD30 expression was revealed to be negative and CD138 staining was observed to be positive, additionally, cytokeratin was expressed aberrantly in a relapsed tumor biopsy. Fluorescence in situ hybridization studies demonstrated breakage and extra copies of the ALK gene in ≥30% of cells. Final clarification was provided by the detection of immunoglobulin κ locus (IGK) gene rearrangement in clonality studies [but notimmunoglobulin heavy locus (IGH) and immunoglobulin λ locus (IGL) genes]. This aggressive entity requires distinct modalities of standard treatment, and may be ignored owing to its rarity in routine pathology laboratories. BIOMED-2 polymerase chain reaction assays, including for IGH, IGK and IGL genes, are essential for the detection of gene rearrangement.

The authors describe an aptasensor for visual and fluorescent detection of lysozyme via an inner filter effect (IFE). The assay is based on the fact that red gold nanoparticles (AuNPs) act as powerful absorbers of the green fluorescence of CdTe because of spectral overlap. If the lysozyme-binding aptamer is adsorbed onto the surface of the AuNPs, the salt-induced aggregation of AuNPs (that leads to a color change from red to blue) does not occur and the IFE remains efficient. If lysozyme is present, it will bind the aptamer and thereby prevent its adsorption on the AuNPs. As a result, the salt-triggered aggregation of the AuNPs will occur. Consequently, color will change from red to blue, and green fluorescence will pop up because the IFE is suppressed. Under optimum conditions, fluorescence is linearly related to lysozyme concentration in the 1.0 nM to 20 nM concentration range, with a 0.55 nM limit of detection. The method is perceived to be of wider applicability in that it may be used to design other visual and fluorescent assays if appropriate aptamers are available.

The aim of the present study is to investigate the relationship between urinary-type plasminogen activator (uPA) expression and clinicopathological features in papillary thyroid carcinoma (PTC) and to determine the signal transduction of PTC cells in vitro. PTC tissues from 42 patients were analyzed for the expression of uPA and the BRAF(V600E) mutation. BCPAP, a PTC cell line harboring the BRAF(V600E) mutation, was used to study MAPK signaling. PCR and direct sequencing were applied to analyze BRAF(V600E) mutation status. uPA mRNA expression was measured using a quantitative RT-PCR method, and uPA protein was localized using an immunohistochemical method. The ERK protein status was detected by Western blot analysis. uPA gene expression was significantly increased in PTC tissues as compared to the corresponding non-tumor tissues. Furthermore, the up-regulation of uPA mRNAs was correlated with high-risk clinicopathological features, including extrathyroid invasion, loss of cellular polarity/cohesiveness, and the BRAF(V600E) mutation. Marked dephosphorylation of ERK1/2 and down-regulation of uPA expression were detected when BCPAP was treated with a MEK inhibitor, U0126. MEK inhibitors might be a potential treatment strategy for aggressive PTC with BRAF(V600E) through inhibition of uPA expression.

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.

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 (34βE12), 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.

Periostin is an extracellular matrix protein. Five isoforms of human periostin cDNA have been reported, but the expression of periostin isoforms in the human thyroid tissue is by far unknown. A group of primer sets were designed to amplify the full length of cDNA sequence of periostin. Using human thyroid carcinoma and their paired non-neoplastic tissues together with anaplastic thyroid carcinoma cell lines, we examined the presence of periostin cDNA isoforms by RT-PCR and direct DNA sequence analysis. We identified eight coexisting cDNA isoforms in all the tissue samples and cell lines. Three of them were unique to this study. Especially two of them haven't been previously reported in any species. The eight periostin isoforms differ in the C-terminus from exon XII to exon XXI where alternative splicing usually happens. This is the first report that demonstrates all the eight isoforms of periostin cDNA expressed in the human thyroid gland and identifies three novel isoforms.

Summary Background & aims We examined the effects of a coffee preparation on liver fibrosis induced by carbon tetrachloride (CCl 4 ) and explored the possible mechanisms. Methods Rats were divided randomly into four groups: control, CCl 4 , and two coffee preparation groups. Except for the control group, liver fibrosis was induced in male Sprague–Dawley (SD) rats by subcutaneous injection with 40% CCl 4 twice a week for 8 weeks. At the same time, a coffee preparation (300 mg/kg and 150 mg/kg) was administered to the two coffee preparation groups intragastrically once daily. Results Upon pathological examination, a coffee preparation treatment significantly reduced liver damage and symptoms of liver fibrosis. The mRNA expression of collagen I, collagen III, bcl-2, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) were markedly increased by CCl 4 treatment but suppressed by a coffee preparation treatment. Whereas compared with the CCl 4 group, the mRNA expression of Bax was increased in the coffee preparation group. The protein expression of Bax and bcl-2 were confirmed by western blot. Intragastric administration of a coffee preparation reduced the protein expression of α-smooth muscle actin (α-SMA) and the glucose-regulated proteins (GRP) 78 and 94 in rats increased by CCl 4 . Conclusions Our data indicate that a coffee preparation can efficiently inhibit CCl 4 -induced liver fibrosis in rats. The coffee preparation may therefore be a potential functional food for preventing liver fibrosis.

We report the case of a common type papillary thyroid carcinoma (PTC) patient who developed early recurrence and persistent disease even after ablation therapy. The patient was an 80-year-old man that was incidentally found to have a mass lesion in the left lower lobe of his thyroid. A total thyroidectomy and a left side modified radical neck dissection were performed; histological examination revealed a common type PTC. The patient underwent lymph node dissection twice for recurrence and (131)I-Na ablations for fluctuated elevation of serum thyroglobulin. The resected tumor and recurrence in lymph nodes revealed non-solid type papillary carcinoma with mixed features of less well-differentiated morphology, which we suggest included loss of cellular polarity/cohesiveness, tall cells and columnar cells. Immunohistochemistry revealed high a MIB-1 labeling index (15-20%) in both the primary tumor and the metastatic tumor in the lymph nodes. p53 immunoreaction was found positive at very low level (

Prognostic analyses of thyroid carcinomas of follicular cell origin were carried out on patients treated at Kuma Hospital, Kobe, Japan. A new histopathological classification based on the prognostic evidence is proposed in this study, and it is applicable to the patients treated curatively. Major histological types of papillary carcinoma, follicular carcinoma and poorly differentiated carcinoma were combined into one single entity of follicular cell adenocarcinoma because (i) they have the same cell origin (follicular cell); (ii) clear-cut separation of papillary and follicular carcinoma is not always possible, and 10 year cause-specific survival was essentially similar when the patients were treated curatively; and (iii) poorly differentiated carcinoma usually has a background of either papillary or follicular carcinoma. This adenocarcinoma together with undifferentiated carcinoma was stratified into four prognostic groups using pure morphological criteria of the degree of cellular differentiation and histological grade. They are termed well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, poorly differentiated carcinoma and undifferentiated carcinoma of the thyroid. The 10 year disease-free survival rates were 86.3-93.1%, 65.4-78.7%, and 43.0-53.8%, and 0%, respectively. The 10 year cause-specific survival rates were 97.2-100%, 91.5-97.4%, and 71.2-80.0%, and 0%, respectively.

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.

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 (34βE12), 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.

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.

Two hundred and sixty-three cases of primary human papillary thyroid carcinoma (PTC) were analyzed. All cases met the following parameters: tumor size > or = 10 mm, no distant metastasis at presentation, and no coexistence of other histological type. The histological features of the solid/trabecular component, encapsulation, tall/columnar cell component and loss of polarity/cohesiveness were utilized to subclassify the 263 cases of PTC into five groups: solid type (15.6%), encapsulated group (9.5%), tall/columnar cell group (7.2%), micropapillary/discohesive group (19.8%) and not-otherwise-specified group (47.9%). We focused on the latter four non-solid groups and compared their prognosis with the solid type. The tall/columnar cell group showed the worst disease-free survival rate (DFS) analyzed by the Kaplan-Meier method, followed by the micropapillary/discohesive group. The not-otherwise-specified group and encapsulated group showed a better DFS rate than the solid type. Cancer-related death was noted in the tall/columnar cell group (21.1%) and micropapillary/discohesive group (3.8%), but not in the other groups. The four non-solid histological groups were further categorized into two prognostic groups: high-risk group (including tall/columnar cell group and micropapillary/discohesive group); and low-risk group (including encapsulated group and not-otherwise-specified group). Their 10-year disease-free survival rates were 78.7% and 93.1%, respectively. In the present study, histological grouping was significantly correlated with prognosis in the multivariate analysis according to the Cox proportional hazards regression model in addition to clinical parameters of extrathyroid invasion and gross lymph node metastasis, which predicts the patient outcome in terms of tumor recurrence and cancer-related death more precisely.