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At least 433 records · Page 24Linked to original sources

Regional lymph node metastasis in gastric cancer: evaluation with endoscopic US.

Endoscopic ultrasound (EUS) was performed in 83 patients with gastric cancer to evaluate regional lymph node metastasis. Histopathologic findings were compared with preoperative EUS findings in a total of 1,519 resected lymph nodes. In lymph node staging, the prevalence of metastatic adenopathy was 31.3% (26 of 83 patients); EUS had an accuracy of 83.1% (69 of 83 patients), sensitivity of 53.8% (14 of 26 patients), specificity of 96.5% (55 of 57 patients), positive predictive value of 87.5% (14 of 16 patients), and negative predictive value of 82.1% (55 of 67 patients). The greater the maximum diameter of the node with metastasis, or the larger the ratio of the metastatic area to the cross-sectional area of the node, the higher the detection rate. In tumors classified on the basis of depth of invasion according to the 1987 TNM system, the rate of detection of metastasis in individual nodes was 0% in pT1 tumors (none of five nodes), 20% in pT2 tumors (17 of 85 nodes), 29% in pT3 tumors (20 of 70 nodes), and 10% in pT4 tumors (three of 31 nodes). It is concluded that the most important use of EUS will be in diagnosis of regional lymph node metastasis.

Adolescent↗

Initial steps in lymph node metastasis formation in an experimental system: possible involvement of recognition by macrophage C-type lectins.

We used histological observations and experiments with fluorescent cell tracers to investigate the roles of tissue macrophages in recognition through a galactose/N-acetylgalactosamine-specific C-type lectin (mMGL) in lymph node metastasis formation by mouse ovarian tumor OV2944-HM-1 (HM-1) cells. Lymph node metastasis from subcutaneous sites was shown to be initiated by the entry of tumor cells into the subcapsular sinus of lymph nodes where mMGL-positive cells were mainly located. To investigate whether mMGL-positive cells contributed to host resistance against lymph node metastasis, we repeatedly treated mice bearing transplanted tumors with an mMGL-blocking monoclonal antibody that was known to inhibit mMGL binding to its ligands. The number of HM-1 cells recovered from lymph nodes 2 weeks after subcutaneous injections was significantly greater when the mice were treated with the blocking anti-mMGL antibody. These results suggested that mMGL-positive macrophages contributed to the host's defense against lymph node metastasis.

Animals↗

Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer.

BACKGROUND: The chemokine receptors CXCR4 and CCR7 have been suggested to play an important role in cancer invasion and metastasis. The expression of these receptors in human cervical cancer, however, has seldom been characterized. PATIENTS AND METHODS: We investigated the expression of CXCR4 and CCR7 in cervical cancer specimens and determined the association between their expression and the clinicopathological features observed, including patient outcome. RESULTS: CXCR4 expression was significantly higher in elderly patients (P=0.025); it was also significantly increased in patients with cancers displaying large tumor size (P=0.010), deep stromal invasion (P=0.0004), lymph-vascular space involvement (P=0.0002), or lymph node metastasis (P<0.0001). CCR7 expression was significantly higher in cases of squamous cell carcinomas (P=0.010) and in patients with cancers showing large tumor size (P<0.0001), deep stromal invasion (P<0.0001), vaginal invasion (P=0.047), lymph-vascular space involvement (P=0.012), or lymph node metastasis (P<0.0001). Logistic regression analysis revealed that deep stromal invasion (P=0.017) and CXCR4 (P=0.016) and CCR7 (P=0.022) expression were independent factors that influenced pelvic lymph node metastasis. The disease-free survival and overall survival (OS) rates of patients exhibiting both CXCR4 and CCR7 expression were significantly reduced (P<0.0001). In addition, the expression of both CXCR4 and CCR7 was an independent prognostic factor for OS (95% confidence interval=1.03-17.86; P=0.046). CONCLUSIONS: CXCR4 and CCR7 expression may be associated with lymph node metastasis; moreover, the expression of these receptors can serve as an indicator of poor prognosis in patients with cervical cancer.

Adult↗

Lymph-node metastasis in squamous cell carcinoma of the lip. A retrospective analysis of 105 cases.

During 1975-87, 105 patients with squamous cell carcinoma (SCC) of the lip were surgically treated. All patients underwent radical resection of the tumor. Only the patients with palpable lymph nodes had a simultaneous neck dissection. All patients were followed up for at least 5 years. Of the 80 patients without palpable lymph nodes, only three developed lymph-node metastasis. Of the 25 patients with palpable lymph nodes who underwent modified neck dissection, four had recurrence of lymph-node metastasis at a different level. The over-all 5-year survival rate was 97%. The survival rate for patients with lymph-node metastasis was 88%.

Aged↗

[Clinical and pathological related factors of occult cervical lymph node metastasis in squamous cell carcinoma of tongue].

BACKGROUND & OBJECTIVE: Some clinical and histopathological features of squamous cell carcinoma of tongue (TSCC) were closely associated with occult cervical lymph node metastasis (OCLNM). This study was designed to investigate the correlation between occult cervical lymph node metastasis in squamous cell carcinoma of tongue and the clinicopathological indexes of primary tumor tissue. METHODS: Thirty-five TSCC patients with OCLNM treated in Cancer Center, Sun Yat-sen University from 1988 to 1996 were enrolled. According to random principle, 35 TSCC patients without OCLNM at the same period were selected. Tumor deepness was measured and pathological parameters were assessed under microscope. RESULTS: The rates of OCLNM in group of infiltrative plus ulcerative type, group of infiltrative type, group of ulcerative type and group of exogenous type were 70.37%, 41.67%, 40.00%, and 27.27%, respectively; the rates of OCLNM in T1, T2, and T4 were 44.00%, 43.48%, and 62.64%, respectively. The rates of OCLNM in groups of tumor deepness < 4 mm, 4-7.9 mm, and > or = 8 mm were 14.29%, 61.54%, and 88.89%, respectively. The rates of OCLNM in groups of response of peritumoral lymphocyte +, ++ and +++ were 73.68%, 58.62%, and 18.18%, respectively. The rates of OCLNM in groups of with vascular invasion and without vascular invasion were 85.71% and 46.03%, respectively. The rates of OCLNM in groups of well, moderate, and poor differentiation were 52.63%, 42.31%, and 66.67%, respectively. The rates of OCLNM in groups of invasive patterns of type I, type II, type III, and type IV were 40.90%, 50.00%, 52.00%, and 80.00%, respectively. Univariate analysis indicated that OCLNM in TSCC was closely associated with gross appearance of primary tumor, tumor deepness, response degree of peritumoral lymphocyte and vascular invasion (P < 0.05), but was not associated with T stage, pathological differentiation, and invasion way (P > 0.05); Logistic multivariate analysis manifested that only tumor deepness and response degree of peritumoral lymphocyte significantly correlated with OCLNM in TSCC. CONCLUSION: There was significant correlation between gross appearance of primary tumor, tumor deepness, response degree of peritumoral lymphocyte and vascular invasion and OCLNM in TSCC. These parameters can be used to predict occult cervical lymph node metastasis in TSCC.

Adult↗

The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer.

BACKGROUND: The aim of the present study was to evaluate the diagnostic utility of levels of circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9 (MMP-9), and VEGF and to verify that the combination assay of these circulating factors is a clinically useful indicator to predict the presence of lymph node metastasis in non-small cell lung cancer (NSCLC). METHODS: A series of 78 patients who underwent surgery for NSCLC was used in this study. Serum VEGF-C and VEGF and plasma MMP-9 levels were analyzed with enzyme-linked immunosorbent assay (ELISA) kits. Logistic regression models were used to analyze the influence of VEGF-C, MMP, and VEGF levels on the probability of presence or absence of lymph node metastasis. RESULTS: Patients with lymph node metastasis had higher serum VEGF- C, VEGF, and plasma MMP-9 concentrations than did those without metastasis (VEGF-C, P = .0004; VEGF, P = .001). Serum VEGF- C reached a sensitivity of 85% and specificity of 68% when a cutoff value of 1762.0 pg/mL was applied, while VEGF reached 80% sensitivity and 59% specificity at 316.8 pg/mL. MMP-9 reached a sensitivity of 63% and specificity of 75% when a cutoff value of 51.4 ng/mL was applied. In the ROC curve analysis, VEGF-C (0.761) had the biggest areas under the ROC curve, followed by MMP-9 (0.723) and VEGF (0.694). Combination assay of three markers had higher sensitivity and specificity for prediction than single-marker assays (AUC = 0.837). CONCLUSIONS: This study has confirmed that combination assay of three markers to determine VEGF-C, MMP-9, and VEGF expression in circulation detects lymph node metastasis in NSCLC with higher accuracy than single-marker assays.

Adult↗

Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma.

AIMS: One important step in tumour invasion is the penetration of the basement membrane. Matrix metalloproteinases (MMPs) play a key role in the migration of normal and malignant cells through the basement membrane. The aim of this study was to investigate correlations between matrix metalloproteinase 2 (MMP-2) immunoreactivity and currently used classification systems and possible relationships between lymph node metastasis and MMP-2 expression. METHODS AND RESULTS: This prospective study analysed specimens obtained from 114 gastric cancer patients (mean age 64 years; range 33-86 years) who underwent gastrectomy with extended lymphadenectomy. All specimens were categorized according to UICC classification, WHO classification, tumour differentiation, Laurén classification, Ming classification and Goseki classification. Formalin-fixed paraffin-embedded tumour specimens were stained using an avidin-biotin complex peroxidase assay. MMP-2 expression in the tumour epithelium was studied by immunohistochemistry with semiquantitative (score 0-3) evaluation. The MMP-2 staining pattern was positive (score 1-3) in 93 (81.6%) specimens and negative (score 0) in 21 (18.4%) samples. No significant correlations were found between MMP-2 expression and other variables such as age, tumour differentiation, WHO, Lauren, Goseki, and Ming classifications. In contrast, the intensity of MMP-2 staining in tumour cells correlated significantly with depth of tumour infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), and UICC stage. CONCLUSIONS: Expression of MMP-2 is strongly associated with tumour progression and lymph node metastasis in gastric cancer. Therefore MMP-2 staining may be clinically useful as predictor of tumour progression, especially for lymph node metastasis.

Adult↗

Genetic alterations related to lymph node metastasis and peritoneal dissemination in epithelial ovarian cancers.

Genetic alterations are assumed to be necessary for the development and progression of ovarian cancer. However, the genetic alterations that occur during lymph node metastasis and peritoneal dissemination are poorly understood. In the present study, we used comparative genomic hybridization to detect genetic alterations in 30 tumors from patients with primary ovarian cancers and analyzed the associations of these genetic alterations with clinical stage and surgical pathological factors, such as histological grade, lymph node metastasis, and peritoneal dissemination. The total number of genetic alterations per tumor ranged from 0 to 39, with an average of 17.7 alterations per tumor. Among the genetic alterations in ovarian cancers, gains on chromosomes 8q and 3q and losses on chromosomes 17p, 18q, and 4q were observed frequently. Although the difference in total numbers of genetic alterations between early-stage tumors and advanced-stage tumors was not significant, the difference was significant when high-grade cancers were compared with low-grade cancers. Eight regions on seven chromosomes showed genetic alterations related to lymph node metastasis or peritoneal dissemination. Gain at 11q13-q14 and loss at 17q11.2-q21 were related not only to lymph node metastasis and peritoneal dissemination but also to clinical stage and histological grade.

Chromosomes, Human, Pair 11↗

Increased expression of valosin-containing protein (p97) is associated with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma.

BACKGROUND: Valosin-containing protein (VCP, also known as p97) exhibits antiapoptotic function and metastasis by activation of nuclear factor kappa-B signaling pathway. Our previous study showed that VCP expression level correlated with prognosis of hepatocellular and gastric carcinoma. In the present study, association of VCP expression with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma (PDAC) was examined. METHODS: VCP expression in 83 patients (46 males and 37 females) of ages ranging from 43 to 80 (median, 66) years who had undergone curative surgery for primary PDAC was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker or equal to (low expression) or stronger (high expression) than that in noncancerous ductal tissue. RESULTS: Thirty-two tumors (38.6%) and 51 tumors (61.4%) were classified as low-VCP-expressing and high-VCP-expressing tumors, respectively. VCP expression correlated significantly with lymph node metastasis (P <.01) but not with various clinicopathologic factors, including age, gender, and histologic differentiation. Multivariate analysis revealed VCP expression as an independent prognosticator for both disease-free and overall survival, along with histologic differentiation, T stage of pathologic tumor-node-metastasis (pTNM) classification, and lymph node metastasis. Furthermore, VCP expression was a prognosticator for disease-free and overall survival in each relatively early stage (I or II) and advanced stage (III) group of pTNM classification. CONCLUSIONS: Our results indicate the potential usefulness of VCP expression as a marker of metastasis and overall prognosis of PDAC.

Adenosine Triphosphatases↗

Expression of vascular endothelial growth factor C and its correlation with lymph node metastasis in colorectal carcinoma.

To study the expression of vascular endothelial growth factor C (VEGF-C) in colorectal carcinoma and its relationship with lymph node metastasis, the expression of VEGF-C protein in colorectal carcinoma tissues obtained from 94 patients who underwent radical resection was immunohistochemically detected. Meanwhile, the expression of VEGF-C mRNA in 4 colorectal carcinoma cell lines was examined by reverse transcription polymerase chain reaction (RT-PCR). VEGF-C protein was found to be expressed in 53.2% of patients. The expression was more frequently detected in tumors with lymph node metastasis than in those without metastasis (P<0.01), and there was significant correlation between its expression and lymphatic invasion, TNM stage (P<0.01). However, no significant correlation was found between its expression and the age, gender, tumor location, depth of invasion and vascular invasion. 2 of the 4 colorectal carcinoma cell lines, including LoVo and LoVo-5FU, expressed VEGF-C mRNA. The expression of VEGF-C is closely related to lymph node metastasis, and it might take part in the tumor lymphangiogenesis.

Adenocarcinoma↗

Predictors of axillary lymph node metastasis in T1 breast carcinoma.

This study was designed to determine the predictors of axillary lymph node metastasis in T1a (< or =0.5 cm), T1b (>0.5 cm and < or =1.0 cm), and T1c (>1.0 cm and < or =2.0 cm) breast cancers. The charts of 204 patients who underwent axillary lymph node dissections for T1 breast carcinomas at our institution were reviewed. Of these, 23 (11%) patients had T1a cancers, 55 (27%) patients had T1b cancers, and 126 (62%) patients were diagnosed with T1c lesions. Fifty patients (24.5%) had axillary node metastases. Of those with T1a lesions, one (4.3%) patient had axillary node involvement, compared with 9 (16.4%) patients with T1b and 40 (31.7%) patients with T1c lesions. Nodal involvement was significantly increased in T1c cancer compared with either T1a (odds ratio = 8.24; P < 0.05) or T1b (odds ratio = 2.73; P < 0.05). Similar results were found in tumors with grade 3 nuclear pleomorphism (odds ratio = 10.45 versus grade 1 and 3.46 versus grade 2; P < 0.05). The presence of lymphovascular invasion was also associated with an increased likelihood of nodal involvement (odds ratio = 3.15; P < 0.05). Predictors of axillary lymph node metastasis in T1 breast carcinomas include increasing tumor size, grade 3 nuclear pleomorphism, and the presence of lymphovascular invasion. These predictors may have a role in stratifying patients with T1 breast carcinomas into subgroups that may benefit from less invasive methods of evaluating axillary lymph node status.

Axilla↗

A model for the study of lymph node metastasis from oral carcinoma by serial transplantation of metastatic tumor in hamsters.

A new model of lymph node metastasis was successfully established by serial transplantation of a metastatic tumor to the submandibular lymph node from a chemically induced squamous cell carcinoma of the tongue into the buccal pouch in hamsters. Tongue carcinomas were induced by application of a 0.5% solution of 9,10-dimethyl-1,2-benzanthracene (DMBA) in acetone. The tongue tumors and metastatic tumors to the submandibular lymph nodes were transplanted to the buccal pouch of recipient hamsters. In the first generation, lymph node metastases were found only in hamsters that received a metastatic tumor. The metastatic tumors to the lymph nodes were maintained by serial transplantation into the buccal pouch from metastatic sites until the eleventh generation. The incidence of lymph node metastasis exceeded 90% in animals after the ninth generation.

9,10-Dimethyl-1,2-benzanthracene↗

[The relationship between vascular endothelial growth factor, microvascular density, lymph node metastasis and prognosis of breast carcinoma].

OBJECTIVE: To investigate the relationship between vascular endothelial growth factor (VEGF) microvascular density (MVD), lymph node metastasis and prognosis of breast carcinoma (BC). METHODS: VEGF protein expression and MVD in 92 cases of BC and VEGF mRNA expression in part of the cases were studied by immunohistochemistry methods and reverse-transcription polymerase chain reaction (RT-PCR) technique. RESULTS: VEGF mRNA expression in BC tumor tissues were higher than those in adjacent normal tissues. Increment of both VEGF(121) and VEGF(165) showed significant difference (P < 0.05 approximately 0.01). In addition, VEGF(145) expression was also observed in BC. There was a close positive correlation between VEGF and MVD (r = 0.702, P < 0.01). VEGF protein expression and MVD correlated significantly with lymph node metastasis and tumor relapse (P < 0.05 approximately 0.01). The time period of relapse-free-survival (RFS) in the patient group with high VEGF expression and MVD was significantly lower than RFS in the group with low VEGF expression and MVD (P < 0.01). CONCLUSION: VEGF is highly related to angiogenesis of BC. The increase of VEGF and MVD may promote lymph node metastasis and relapse of BC. VEGF and MVD may have prognostic value in RFS of BC patients.

Adult↗

Long-term survival of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement.

We report the case of a very rare 6-year disease-free survivor of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement. A 76-year-old female with liver dysfunction was referred to our institution. Contrast-enhanced computed tomography showed a 5-cm low-density tumor with irregular marginal enhancement in the left and caudate lobes of the liver. Cholangiography revealed complete obstruction of the left hepatic bile duct. Angiography showed obstruction of the left branch of the portal vein. Metastasis to the hilar lymph nodes was disclosed at surgery. The patient underwent left hepatectomy with caudate lobectomy, resection of the extrahepatic bile duct, and lymphadenectomy. The total vascular exclusion of the liver was used for hepatectomy and reconstruction of the portal vein. Microscopically, the tumor was a poorly differentiated adenocarcinoma with many infiltrating lymphocytes, and extensive necrosis was present within the tumor. The experience gained in the present case suggests that aggressive surgery may be a potential approach to provide a hope of long-term survival for patients with intrahepatic cholangiocarcinoma despite the presence of regional lymph node metastasis and vascular invasion.

Aged↗

Tumour budding at the deepest invasive margin correlates with lymph node metastasis in submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2.

In the past few years, tumour budding at the invasive margin has been reported as a new risk factor for lymph node metastasis in advanced colorectal cancers, but it is sometimes difficult to detect tumour budding in submucosal colorectal cancer by haematoxylin and eosin staining. We immunohistochemically examined tumour budding at the deepest invasive margin of 56 surgically resected submucosal colorectal carcinomas using anticytokeratin antibody CAM5.2, furthermore checked by AE1/AE3, and determined the relation between tumour budding and clinicopathological factors. Moreover, we used the monoclonal antibody D2-40 for immunohistochemistry to detect lymphatic involvement. Tumour budding was detected in 42 cases (75.0%), and the budding-positive group showed a significantly higher rate of lymph node metastasis (including isolated tumour cells) (16/42 vs 0/14; P=0.004) than the budding-negative group. The sensitivity and negative predictive value of tumour budding alone for lymph node metastasis were superior to those of lymphatic invasion alone. Furthermore, the specificity and positive predictive value of the combination of either lymphatic invasion or tumour budding were superior to those of lymphatic invasion alone. Tumour budding detected immunohistochemically by using CAM5.2 is a newly found risk factor for lymph node metastasis and may help to avoid oversurgery in the future.

Adenocarcinoma↗

[Development of an experimental model for spontaneous lymph node metastasis of human esophageal carcinoma in nude mice--histopathological analysis].

Three human squamous cell carcinoma cell lines (HPL-EsC-1-K, -S, and -M) originated from a male patient with esophageal carcinoma were established and were studied on their tumorigenic and metastatic properties in nude mice. All cell lines grew in the hind foot pads following subcutaneous inoculation and produced popliteal lymph node metastasis dose (2-8 x 10(6)/mouse)-dependently. Based on the histopathological findings on serial sections of the lymph nodes, the stages of lymph node invasion by cancer cells were classified into 4 stages (St. 0-III). The time course of lymph node metastasis of EsC-K cells were examined. Advanced stage of metastasis increased according to the time elapsed after tumor cell inoculation. Incidence of metastasis of EsC-K cells were not affected by host factors such as sex differences, anti-asialo GM1 antibody treatment on the hosts. Today, there are few experimental models for studies on spontaneous lymph node metastasis of human carcinomas. This experimental model provides a useful research tool for studies on the biology and therapy for lymph node metastasis of esophageal cancer.

Animals↗

Enhanced efficacy of bleomycin adsorbed on silica particles against lymph node metastasis in patients with esophageal cancer: a pilot study.

BACKGROUND: Lymph node metastases occur very frequently and extensively in patients with esophageal cancer. The aim of this pilot study was to try the targeting chemotherapy for lymph node metastases by use of bleomycin adsorbed on silica particles (BLM-SI). METHODS: BLM-SI or bleomycin solution (BLM-SOL) was injected into the submucosa of the esophageal wall by means of endoscopy 3 days before operation in 16 patients with middle thoracic esophageal cancer. The distribution of bleomycin in the regional lymph nodes and surrounding connective tissues was studied. RESULTS: When BLM-SI was administered, bleomycin activity was found in both the regional lymph nodes and connective tissues, not only in the mediastinal region but also in the cervical and abdominal region. Bleomycin activity was significantly higher in all regions after BLM-SI administration than after BLM-SOL administration. Degenerative or necrotic changes were microscopically observed in 11 of 36 lymph nodes with metastatic foci. Bleomycin activity in the blood was significantly lower after BLM-SI was administered than after BLM-SOL. Serious systemic side effects except for fever were not observed in any patients. CONCLUSIONS: These results indicate that BLM-SI could be a useful treatment modality for targeting lymph node metastasis of esophageal cancer without serious side effects.

Adsorption↗

Immunostaining for ret oncogene proteins in papillary thyroid carcinoma: a correlation of ret immunoreactivity and potential of lymph node metastasis.

Ret oncogenes, particularly Ret/PTC, have been associated with the potential of local invasion of papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the correlation between the Ret oncogene expression and the potential of lymph node metastasis of PTC. A total of 107 PTC were microscopically reviewed to identify areas of infiltrating carcinoma (IC). IC was defined as tumor cells disposed in a haphazard pattern and in lobules, nests, follicles, or single cells within a desmoplastic or sclerotic stroma. All cases were submitted to immunostaining for Ret oncogene. There were 36 noninfiltrating PTC with lymph node metastasis in 1 case and 71 infiltrating PTC with lymph node metastasis in 40 cases. For non-PTC, the positive immunoreactivity was often weak to moderate and focal. For infiltrating PTC with IC, the IC displayed strong immunoreactivity. The noninfiltrating component of PTC with IC usually showed stronger reactivity than PTC without an infiltrating component. Furthermore, 36 of 40 metastatic PTC in lymph node were immunoreactive. Three follicular adenomas with areas of scar caused by fine-needle aspiration biopsy were not immunoreactive for Ret. In view of the high potential of infiltrating PTC for lymph node metastasis, distinction of this type of carcinoma from its noninfiltrating form is clinically important. Because immunoreactivity for Ret is usually positive in areas of infiltrating PTC and is often negative or focally positive in noninfiltrating PTC, immunostaining for Ret is helpful to identify infiltrating PTC and distinguish it from changes caused by fine-needle aspiration biopsy in benign thyroid lesions.

Adult↗