Multi-slice Computer Tomography (MSCT) Analysis of Benign and Malignant Nodules in Patients With Chronic Lymphocytic Thyroiditis
- MSCT features is useful in differentiate the benign and malignant nodules in CLT patients.
- MSCT is superior than plain CT scan in nodule diagnosis in CLT patients
- MSCT may apply as an important diagnostic modality in the clinical practice.
Objective To assess the clinical significance of Multi-slice Computer Tomography(MSCT) by comparing the MSCT feature of benign and malignant nodules in patients with chronic lymphocytic thyroiditis(CLT).
Methods MSCT findings, including the size, solid percentage, calcification, margin, capsule, anteroposterior–transverse ratio as well as the mode and the degree of enhancement of 137 thyroid nodules in 127 patients with CLT were retrospectively analyzed. Furthermore, the correlation between MSCT finding and pathological results, the differences of MSCT finding between benign and malignant nodules were also analyzed.
Results The complete solid was found in 77.5% (31/40) of malignant nodules while 32 nodules of dominant cystic components were all benign (P<0.05). Compared with the benign nodules, the microcalcification and internal calcification were more frequently presented in the maglinant nodules (P<0.05). The MSCT features such as ill-defined margin, absence of capsule or incomplete capsule or homogeneous enhancement were more likely to present in the malignant nodules(P<0.05). In addition, no significant difference was found on solid percentages from the value of plain CT scan, value of arterial phase and value of venous phase between benign and malignant nodules (P>0.05).
Conclusions MSCT features is useful in differentiate the benign and malignant nodules in CLT patients. MSCT may apply as an important diagnostic modality in the clinical practice.
Key Words: Multi-slice Computer Tomography (MSCT), benign and malignant nodules, chronic lymphocytic thyroiditis(CLT)
Chronic lymphocytic thyroiditis(CLT), also known as Hashimoto thyroiditis, is the most common thyroiditis disease in the clinic with a typical clinical presentation of diffuse and infiltration of lymphocytes in the thyroid and the formation of lymphoid follicles.(1-2) In the past, surgery is rare used in CLT treatment because CLT is thought as a diffuse lesion. However, the nodules which formed due to CLT itself or with thyroid nodules are usually found in the patients. In China, about one third of the patients presented with nodules were treated with surgery, and the incidence of thyroid cancer is significantly higher in CLT patients than that in non-CLT patients.(3) The application of computer tomography(CT) is restricted in differentiating the thyroid nodules and diagnosing diffuse CLT and few reports is focus on the CT features of the CLT with nodules. (4) We reported here is about comparison analysis of the benign and malignant nodules in the patients with CLT using multi-slice computer tomography(MSCT) and tried to explore the different CT features between these two kind of nodules to expand the clinical value of the MSCT.
Subjects and methods
A total of 127 patients who diagnosed with thyroid nodules by palpation or B-mode ultrasound from January 2005 to December 2013 were enrolled in the study. Patients were included in the study if their cytology samples were evaluated as CTL with benign or malignant nodules.All the patients were performed with MSCT plain and enhanced scan on the thyroid. The male/Female was 10/117. The median age was 52 yrs (range 19-77 yrs).
The patients were required to place in supine position with hyperextend neck. All CT scans were obtained using a MSCT scanner (LightspeedPro 32 CT; General Electric, Milwaukee, WI) with the following parameters: 2.5-mm section thickness and section slice, and 30-35 seconds scan delay at arterial phase while 50-60 seconds scan delay during parenchyma tissue. The scanning range was planned in a craniocaudal direction from the superior border of hyoid to aorta arch including the entire thyroid mass (mean coverage, 250 mm). Each patient received 100 mL of nonionic contrast material (iohexol [Omnipaque 300, GE Healthcare]) through an 18-gauge needle placed in a peripheral arm vein at a rate of 2.5-3 mL/s and dose of 1.5 mL/kg. Axial images were reconstructed at 1.25-mm increments at the end of the scan and then coronal section was reconstructed.
Double blind analysis was performed in all the CT images. The CT features was recorded as follow: (1) Solid vs. cystic percentage: Solid (More than 95% solid percentage), 50-95% Solid, Cystic(1-49% Solid); (2) Calcification: a Morphology: Micro(diameter≤2 mm) or Macro(diameter>2 mm) or eggshell(arc-shaped or semi arc-shaped) or Mixed(coexist with multiple calcification focus), b position: internal or peripheral; (3)Margins: Well-defined or ill defined (4) Capsule: Intact or incomplete or unclear and none; (5) Enhancement : Complete cystic or homogeneous enhancement or heterogeneous enhancement;(6) Lesion size: Max dimension of the lesion (7) anteroposterior and transverse ratio (8) Enhancement degree: measure the net value of artery or venous phase of the lesion and used the plain scan as the reference value. The measurement of the CT value should avoid regions presented with cystic change, necrosis, calcification and vessels.
All the statistical analysis were performed with SPSS 17.0 software (Illinois, US). Chi square was used to assess on count data. Student t test was used for measurement data after homogeneity test of variance. P<0.05 was considered as statistical significant.
Patient demography and pathological feature of the lesions
There were 10 males and 117 females in our study. The median age was 52 yrs (range 19-77 yrs). The male/Female ratio was 1:11.7.
A total of 40 cases of CLT with malignant nodules were observed. Among them, 26 with papillary cancer (Figure 1A-B)(One combined with microcarcinoma), 10 with microcarcinoma, 2 with medullary cancer (Figure 2A-B), and 1 with lymphoma (Figure 3A-B). Among 26 papillary cancer, 3 combined with follicular adenocarcinoma, 1 combined with medullary cancer and follicular adenocarcinoma, and 5 combined with microcarcinoma and follicular adenocarcinoma. In addition, 87 CLT with benign nodules were observed, including 63 cases of follicular adenocarcinoma (Figure 4A-B), 7 cases of nodules goiter (Figure 5A-B) and 17 cases of nodules hyperplasia (Figure 6A-B). One malignant and nine benign nodules were found in 10 malignant cases with bilateral resection and were divided into benign and malignant group, respectively. The max nodule among multiple nodules in the benign group was used for comparison of CT feature and pathology analysis. According to the above described rules, 97 nodules and 40 nodules were divided into benign and malignant group, respectively.
Comparison of Benign and Malignant Nodules Within CLT
The solid percentage, the morphology and position of the calcification, margins, capsule and enhancement between benign and malignant group showed significant difference (p<0.05). Most of the nodules in benign group present solid constitute, macro or eggshell or mixed calcification morphology, the heterogeneous enhancement and no significant difference was found (p>0.05)(Table 1). Most of the nodules in malignant group showed solid constitute (31/40, 77.5%) and none of the nodules was cystic constitute. 33% of the cystic constitute was found in benign nodules(32/97). The calcification incidence in malignant group was 37.5%, 22.5% was micro calcification, 88.2% was internal calcification (Figure 2A). 21.6% calcification was found in benign nodules and 81.0% was located in margin of the nodules (Figure 5A). Most of the benign nodules have well-defined (76.3%) and intact capsule(63.9%)(Figure 4A). Most of the malignant nodules have ill-defined margin (75.0%), unclear (65.0%)(Figure 2A) or incomplete(27.5%) capsule and 7 of them presented features of incomplete enhanced ring (Figure 1A). Among the heterogeneous benign nodules, 16 were peninsula enhancement which has irregular low density area in the periphery region or obvious enhanced nodules in the central region. While 7 in the malignant group presented with peninsula enhancement. No significant difference was found between benign and malignant nodules (χ2=0.020, p=0.886). Among the homogeneous nodules, the incidence of malignant nodules (55.0%) was significantly higher than the benign nodules (25.8%)(p<0.05). Thirty-two cystic nodules were all benign and 21 were incomplete enhancement and 3 cases of complete calcification were microcarcinoma among them. The size of the benign nodules was significantly larger than the malignant nodules. The anteroposterior and transverse ratio between two group showed no difference (p>0.05)(Table 2). The remaining 76 benign nodules and 37 malignant nodules (Above 21 nodules were excluded) were processed with plain CT scan on the parachyma tissue. And no significant difference was found on net value of artery or venous phase(p>0.05)(Table 2).
CLT is a kind of autoimmune disease featured by thyroid antigen response and lymphocytes infiltration by T and B cells. It is firstly reported by Hashimoto in 1912 and also named as Hashimoto thyroiditis (HT). CLT often occurs in the female and most of the patients are middle-young people. The median age of the patients was 52 yrs and the Male/Female ratio was 1:11.7, which is consistent with previous description. Some of the studies showed that CLT is closely related with the primary thyroid lymphoma(5) and increased risk of papillary cancer and microcarcinoma can be found in CLT patients(6-7). Among the 74 cases of CLT with nodules, 28.4% were malignant (40/127) and most of them were papillary cancer (26/40, 65.0%) and microcarcinoma (11/40, 27.5%). Although the combination of ultrasound examination with serum assessment can improve the sensitivity and specificity in malignant thyroid diagnosis,(8) lacking of the sonographic features on prediction value with high sensitivity and high positive in thyroid makes it difficult to differentiate the CLT with nodules while the hyper-variability on serum examination and half of the CTL was misdiagnosed.(1-2) Thyroid biopsy with fine needle before operation is another examination to identify the thyroid carcinoma.(8-10) However, Yang et al conducted a trial enrolled with 1100 patients and found that only 75% of the specificity was found by thyroid biopsy. Recently, the application of MSCT in thyroid diagnosis leads to the improvement on both specificity and sensitivity in thyroid nodules characterization.(11-12)
Here, we found the size of benign nodules is significant larger than the malignant nodules and this was because the higher incidence of microcarcinoma(27.5%) and timely operation on the suspected carcinoma. The nodules in the malignant group were complete solid or solid dominant and no cystic was found. This is because homogeneous distribution of the cancer cells and the adequate blood supply could reduce the liquid necrosis. 33.0% of cystic were found in the benign group and this may be related with the hyaline degeneration, bleeding, necrosis and hematoma absorbing. Moon et al suggested the sonographic diagnosis showed a specificity of 91.4%-92.5% when anteroposterior and transverse ratio ≥1. The explanation may because expansive growth in benign nodules while infiltration was found in malignant nodules. Here, we didn’t find a significant difference on CT analysis between benign and malignant nodules when anteroposterior and transverse ratio ≥1. The different conclusion made by CT and ultrasound may due to the pressure will be added when performing the ultrasound examination. Most of the benign nodules were soft and easy to transform under the pressure, therefore, the anteroposterior and transverse ratio <1 could be conducted. Most of the malignant nodules were parachyma with hard property and the effect of pressure is minimal.
We also tried to identify whether the margin was well-defined and the capsule was intact. Compared with the normal thyroid nodules, lower density thyroids and inferior contrast were observed in the CLT patients due to the uptake of the iohexol. Therefore it is hard to distinguish the different using plain scan. And the enhanced scan in CLT patients can help to find out the nodules. The pathology base of thyroid nodules is the presence of hyperplasia change in epithelial constitute of the nodules or one or multiple nodules constituted by eosnophils; Cystic change in the nodules, cystic wall constituted by fibrous tissue, lymphocytes and infiltration of the lymphocytes with lymphatic follicle presented in the cystic wall and periphery tissue, combined with well- or ill-defined margin.(13) Since the adequate blood supply of CLT tissue and tissue adenocarcinoma was under stress, most of the nodules have intact capsule and well-defined margin, there is a low density intact ring presented as mosaic or halo sign.(14) The goiter is a disease of hyperplasia. The hyperplasia nodules are isolated by fibrous tissue due to long-term thyroid enlargement and the follicle hyperplasia. Also a large amount of colloid was found in the hyperplastic follicles and psudo-capsule can be found around the nodules. Plain CT scan can only produce ill-defined thyroid outline or uneven thickness and intact capsule while enhanced CT can produce well defined thyroid outline. Most of the malignant nodules had ill-defined margin (75.0%), absence of capsule or unclear capsule (65%), incomplete pseudo-capsule (27.5%) and presented with incomplete enhanced ring feature. The pathological basis of the ill-defined margin around the cancer tissue was due to infiltration growth, invasion, extracapsule extension of the tumor tissue to the surrounding adeno-tissue. Tan et al suggested peninsular like enhancement is one of the features in diagnosing thyroid papillary cancer.(15) We didn’t observe a significant difference between benign and malignant group. Irregular necrosis and remaining cancer tissues were presented in both thyroid papillary cancer and papillary like adenocarcinoma. Due to the adequate blood supply of CLT, the peninsular enhancement can be found on CT features.
The CT finding on CLT without nodule was symmetrical and diffused enhancement on the two lobes of the thyroid or more severe enhancement was presented on one lobe. The enhancement was midsize, homogeneous with significant decrease and the density is closed to soft tissue. No nodule image or calcification image was found in the thyroid. The enhanced scan showed a homogeneous enhancement. The secondary manifest of the CLT is chronic nodule lymphocytes thyroiditis, local lymphatic goiter or nodules formed by pseudo carcinoma. The combination of the CLT can be adenocarcinoma, nodular goiter, thyroid cancer and lymphatic carcinoma. No significant difference was found on the value of plain scan, net value of artery phase or venous phase in the CTL with benign or malignant nodules. We excluded 21 complete cystic change benign nodules and the nodules with parenchyma were included. Furthermore, 3 nodules with complete calcification were also excluded due to the inaccuracy of the measurement on this kind of nodules and error on the CT value. The increasing number of blood vessel and increased speed of blood flow in thyroid parenchyma of CLT patients are caused by autoimmune process. And the microvessel density (MVD) and vascular endothelial growth factor (VEGF) were involved in this process. (16) Since the lymphocytes infiltration is present in the benign and malignant nodules and CLT with malignant tumor is derived from CLT hyperplasia, there is a transition between CLT and papillary cancer. Therefore, there is overlap on plain and enhance scan on the CLT with benign and malignant nodules.
In conclusion, the MSCT features in CLT with benign and malignant nodules are similar to simple benign and malignant nodules in thyroid. Due to the pathological feature of the CLT, there is some minor difference. In the CLT with parenchyma nodule, most of the malignant nodules are presented with solid, ill-defined margin, unclear or no capsule. The calcification is also usually seen, especially the micro grain calcification and most of the lesions are located in the center. The benign nodules are presented with cystic constitute, well-defined multiple margin, intact capsule and rare happened calcification (Located in the periphery region if presence). The enhancement degree of the parenchyma has no obvious value in differentiating the benign and malignant nodules.