Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :3126
Small font sizeDefault font sizeIncrease font size
Navigate here
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (1,058 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

  In this article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    PDF Downloaded425    
    Comments [Add]    
    Cited by others 2    

Recommend this journal


  Table of Contents  
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 546-550

Evaluation of primary thyroid lymphoma by ultrasonography combined with contrast-enhanced ultrasonography: A pilot study

1 Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
2 The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
3 Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
4 Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

Date of Web Publication10-Mar-2016

Correspondence Address:
M Gao
Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.178419

Rights and Permissions

 » Abstract 

OBJECTIVE: To evaluate the features of primary thyroid lymphoma (PTL) by ultrasonography (US) combined with contrast-enhanced ultrasonography (CEUS). MATERIALS AND METHODS: In this retrospective study, 20 patients (8 male and 12 female) with PTL were evaluated by conventional US and among them, 10 patients underwent CEUS examination. The appearance of US features was classified into three types: Diffusive mass type, multiple nodular type and mixed type. The CEUS patterns included diffusive homogeneous enhancement and diffusive heterogeneous enhancement pattern. Parameters of CEUS time-intensive curve were analyzed in primary tumor and involved lymph nodes compared to ipsilateral common carotid artery. RESULTS: Of 20 patients with PTL, 18 presented an enlarging neck mass that grew rapidly with an average duration of 3.2 months, and 17 were associated with Hashimoto's thyroiditis. In conventional US, all patients had marked hypoechoic masses. Among them, 12 patients were diffusive mass type, 6 were multiple nodular type and 2 were mixed type. For CEUS patterns, 8 were diffusive homogeneous enhancement and 2 were diffusive heterogeneous enhancement. Necrosis areas were showed in diffuse heterogeneous pattern which were hardly seen in conventional US. In the quantitative analysis of CEUS parameters, the time to peak of time-intensive curve in the primary tumors or involved lymph nodes was longer than that of the ipsilateral common carotid artery (P = 0.004). CONCLUSION: PTL mainly demonstrated as a diffusive mass type with marked hypoechogenecity on conventional US and diffusive homogeneous enhancement pattern on CEUS. And the heterogeneous enhancement pattern is also helpful for detecting necrosis areas of PTL.

Keywords: Contrast-enhanced ultrasonography, primary thyroid lymphoma, ultrasonography

How to cite this article:
Wei X, Li Y, Zhang S, Li X, Gao M. Evaluation of primary thyroid lymphoma by ultrasonography combined with contrast-enhanced ultrasonography: A pilot study. Indian J Cancer 2015;52:546-50

How to cite this URL:
Wei X, Li Y, Zhang S, Li X, Gao M. Evaluation of primary thyroid lymphoma by ultrasonography combined with contrast-enhanced ultrasonography: A pilot study. Indian J Cancer [serial online] 2015 [cited 2020 Oct 25];52:546-50. Available from:

 » Introduction Top

Primary thyroid lymphoma (PTL) is a rare thyroid tumor, representing approximately 0.5-5% of thyroid malignancies.[1],[2] It is more common in elderly women who have chronic Hashimoto's thyroiditis.[3],[4],[5] Most patients represent a rapidly enlarging thyroid mass and have compression symptoms.[2],[6] Because pressure symptoms and airway obstruction are life threatening, early diagnosis and prompt therapies, such as surgery or chemo-radiation therapy, should be given during its early phase. However, in the previous studies, there are diagnostic dilemmas in the early diagnosis of PTL, because the features of radiologic imagings, such as ultrasonography (US), computerized tomography, magnetic resonance imaging (MRI) and positron emission tomography are not typical.[7],[8],[9],[10] In our study, we retrospectively reviewed 20 cases of thyroid lymphomas in conventional US findings and 10 of 20 in contrast-enhanced ultrasonography (CEUS) to determine the typical features of PTL. We also searched for the first line diagnostic method for early diagnosing thyroid lymphomas.

 » Materials and Methods Top

This retrospective study was approved by the ethics committee of our institution, and written informed consent was obtained. From July 2009 to February 2012, 20 patients with PTL confirmed histologically were included in this pilot study. Among 20 patients, 8 were male and 12 were female (Male:Female = 2:3). The mean age was 67 years with a range from 42 years to 85 years. We reviewed the clinical and laboratory informations, conventional US, CEUS images of all patients.

Twenty patients were performed by B-mode ultrasound examination with a 12M or 9M transducer (IU22, Phillip Medical Systems, USA). Each patient was supine with the neck hyperextended during the US examination, for detecting primary tumors, lymph nodes and surrounding structures, including the tracheal and larynx. Retrospective picture archiving and communication systems (PACS) review of static sonograms was performed by 2 radiologists (WX and ZS) with 4 and 15 years of experience in thyroid imaging, respectively.

Conventional ultrasonographic features of PTL were classified into three types: Diffusive mass type, multiple nodular one, and mixed type. The diffusive mass type indicates that goiter of both lobes or one lobe and the echoes of lesion were extremely hypoechoic and pseudocystic (mimics cyst) [Figure 1]a. The multiple nodular type shows multiple nodules in one or two lobes with well-defined border from peripheral normal tissues [Figure 1]b. The mixed type means mixed pattern with mentioned two types above, which resembles the echoes of adenomatous goiters [Figure 1]c. Lymph nodes with round shape, absence of fatty hilum and minimal axial diameter larger than 10 mm were considered to be involved [Figure 1]d.
Figure 1: (a) Diffusive mass type of PTL by ultrasonography (US) (b) Multiple nodular type of PTL by ultrasonography (US) (c) Mixed type of PTL by ultrasonography (US), T: Tracheal (d) Multiple lymph nodes, right thyroid tumor and common carotid artery at the same level by ultrasonography (US), LN: Lymph node, R-THY: Right thyroid, CCA: Common carotid artery

Click here to view

Ten patients were performed CEUS examination by the 9M transducer (IU22, Phillip Medical Systems, USA). The contrast agent was SonoVue (sulfur hexafluoride microbubbles, Braco company, Italy). 2.4 ml contrast agents were injected intravenously via a 20-gauge intravenous cannula in 1-2 s, followed by 5 ml saline solution. The real-time CEUS imaging process lasted for 180 s. The imaging parameters were as follows: Mechanical index, less than 0.1 gain, 100-120 dB; frame rate, 12-15 frames/s. The whole CEUS process was stored on the hard disk of the scanner for PACS review. After examination, the same radiologists (W.X. and Z.S.) studied PACS review of CEUS blinded for diagnosis, respectively. In cases of discrepancy between the two radiologists (W.X. and Z.S.), a consensus was reached.

The CEUS patterns of PTL were classified as diffusive homogeneous enhancement and diffusive heterogeneous enhancement. Diffusive homogeneous enhancement pattern shows hyper-perfusion of the lesion and surrounding tissue after contrast agent injection [Figure 2]a, while the diffusive heterogeneous enhancement pattern has some separate non-perfused areas in lesions, while other parts of lesions are hyper-perfused [Figure 2]b. Common carotid artery (CCA), primary tumor and lymph nodes involved were analyzed as time-intensity curves by QLAB software. The region of interest was drawn as the same size of 5 mm 2 in the remarkable perfusion area of a lesion or lymph node involved and in the ipsilateral CCA at the same level. The time-intensity curve was analyzed for the following parameters: Arrival time (AT) (in seconds), defined as the first point of the curve clearly above the baseline intensity followed by a further rise; time to peak (in seconds), defined as the time from the start of injection to the maximum intensity of the curve; peak intensity (PI) (in intensity/1000), defined as the intensity at the peak time; and area under the time-intensity curve (AUC): (intensity × s)/1000.
Figure 2: (a) Diffusive homogeneous enhancement pattern seen in both involved lymph nodes and right thyroid tumor by contrast-enhanced ultrasonography. LN: Lymph node, R-THY: Right thyroid, CCA: Common carotid artery; (b) Diffusive heterogeneous enhancement pattern (necrosis in the tumor, red arrow) detected in both involved lymph node and right thyroid tumor by contrast-enhanced ultrasonography; (c) Three contrast-enhanced ultrasonography time-intensity curves in carotid artery (red), primary tumor (green) and involved lymph node (yellow)

Click here to view

Paraffin-embedded sections of each sample were submitted to common histology, immunohistochemistry, and cytochemistry using a panel of monoclonal antibody (anti-CD3, anti-CD5, anti-CD10, anti-CD19, anti-CD20, anti-CD23, anti-CD30, anti-CD43, anti-CD45, anti-CD79a, surface Ig characterization, and Mib-1). The following categories were defined: Negative (<30% positively stained tumor cells) and positive (>30% positively stained tumor cells). The diagnosis of lymphoma was based on the lymphoma classification Revised European-American lymphoma classification (REAL).[11]

All statistical analyses were performed with software (SPSS, version 17.0). The values of CEUS time-intensity curve quantitative analysis parameters were presented as average ± standard deviation. The quantitative data were then analyzed by the Student t-test or Mann-Whitney U test. P <<i> 0.05 was considered indicative of a statistically significant difference.

 » Results Top

The clinical and pathological data were shown in [Table 1]. Eighteen of 20 patients presented an enlarging neck mass that grew rapidly with a short duration of 6 months (mean 3.2 months). Ten of 20 patients have positive autoantibodies (antithyroglobulin and antimicrosomal) and 7 patients have abnormal thyroid function. Pathological specimens were obtained by total thyroidectomy in 3, lobectomy in 5, and open biopsy in 12 with frozen examination, and none was performed by fine-needle aspiration or core biopsy. All patients had non-Hodgkin lymphoma with B cell origin. There were diffuse large B-cell lymphomas (DLBCL) in 8 cases and marginal zone B-cell lymphoma in 12 cases. 17 of 20 patients were also pathologically diagnosed as Hashimoto's thyroiditis. Primary lymphoma was staged as 1 E in 9 patients and 2 E in 11 patients.
Table 1: Clinical findings in 20 patients with primary thyroid lymphoma

Click here to view

Extreme hypoechoic solid masses had been detected in 20 patients. Both lobes of thyroid gland were involved in 12 and one lobe was involved in 8. Diffusive mass type of PTL was in 12 patients [Figure 1]a, 6 were multiple nodular type [Figure 1]b, and 2 were mixed type [Figure 1]c. Calcifications in the tumor were found in one case, and necrosis was seen in two. Lymph nodes involved were marked hypoechoic and confirmed histoligically in 17 of 20 patients and the other 3 patients had no lymph nodes involved. Tracheal compression was demonstrated in 7 patients, and 2 patients had esophagus compression detected by US.

[Table 2] summarized the CEUS enhancement patterns of PTL in 10 patients. Diffusive mass type was detected in 7 patients, multiple nodular type was in two and mixed type was in one. Regional lymph node [Figure 1]d were detected as multiple in 8 patients, single was in one, and none was in one. During the arterial phase of CEUS, the perfusion patterns of the lesions were classified as diffusive homogeneous enhancement and diffusive heterogeneous enhancement. During venous phase the intensity of contrast agents decreased, but the perfusion patterns did not change. Among 10 patients, 8 showed diffusive homogeneous enhancement [Figure 2]a, while 2 diffusive heterogeneous enhancement [Figure 2]b. Primary tumors with necrosis areas were confirmed pathologically. In addition, involved lymph nodes showed the same CEUS perfusion pattern like primary tumors in our study [Figure 2]a and [Figure 2]b.
Table 2: Contrast--enhanced ultrasonography enhancement patterns and ultrasonography features of primary thyroid lymphoma in 10 patients

Click here to view

Comparison of CEUS time-intensity curve [Figure 2]c parameters in CCA, primary tumor and involved lymph nodes in 10 patients were shown in [Table 3] The time to peak of contrast agent diffusion into primary tumor or involved lymph nodes was longer than that of CCA (P = 0.004). However, there were no statistically differences among the ipsilateral CCA, primary tumor and involved lymph nodes in other CEUS parameters (P > 0.05), such as AT, PI and AUC.{Figure 2}
Table 3: Comparison of contrast--enhanced ultrasonography time--intensity curve quantitative analysis parameters in common carotid artery, primary tumor and lymph nodes involvement in 10 patients

Click here to view

 » Discussion Top

PTL is a rare condition accounting for approximately 2% of all malignant extranodal lymphomas. [2,13] Previous studies [2],[5],[12] showed that middle-to-older-aged female patients with chronic lymphocytic thyroiditis had an estimated 70-80% risk of developing PTL. In our studies, 85% patients were pathological diagnosed as Hashimoto's thyroiditis and the thyroid autoantibodies are abnormal in 50% patients. It is possible that patients with thyroiditis are susceptible to have neoplastic transformation due to chronic antigenic stimulation.[14] In addition, reviewing 1408 cases of PTL, Graff-Baker et al.[11] found that 68% of PTL were DLBCL), 10% were mucosa-associated lymphoid tissue (MALT) and 56% patients were stage I, while in our study, 40% DLBCL, 60% MALT and 45% in stage I of this disease were found.

PTL diagnosis was difficult, because the radiologic imagings, such as cross-sectional imaging (CT/MRI) or PET do not have typical features.[7],[8],[9],[10] However, in our study, all patients have the symptoms of obstruction with an rapidly enlarging neck within 6 months before diagnosis. This may be clinical symptoms to help us to make diagnosis. And on the US imaging, all of PTL were detected as marked hypoechoic or pseudocystic masses and three types of US features were classified, including diffusive mass, multiple nodular and mixed type, which are similar to Ota H's group research.[14] Diffusive mass type was the main one in our study with enhanced posterior echoes in all types. However, it is not easy to distinguish diffuse type PTL from thyroiditis, which mimicked PTL.[15] While Nam et al.[16] indicated that diffuse hypoechoic parenchyma with intervening echogenic septa on sonography was correlated with pathologic features of PTL. Other researches.[8],[17] considered that thyroiditis showed ill-defined margins, while PTLs demonstrated well-defined margins. The margin characteristics on conventional US may be a clue for the differentiation of these two diseases.

In our series, we wanted to find some patterns of PTL in CEUS, a helpful tool on distinguishing benign from malignant thyroid nodules.[18],[19],[20] According to our results, CEUS patterns were classified as diffusive homogeneous enhancement and diffusive heterogeneous enhancement pattern. We found that 80% patients demonstrated diffusive homogeneous enhancement by CEUS, while 2 patients with necrosis areas in the tumors appeared diffusive heterogeneous enhancement. However, PTL appears as homogeneous markedly hypoechoic masses rarely associated with necrosis.[21] It is speculated that conventional US is not sensitive to find necrosis from abnormal parenchyma, due to similar echogenecity between necrosis and extremely hypoechoic parenchyma of PTL.[21] However, in CEUS imaging, the necrosis of PTL showed separate no-enhanced areas, while other parts of lesions are hyper-perfused. Therefore, CEUS imaging may be more useful than conventional US, to identify necrosis in PTL on the background of thyroiditis. Furthermore, multiple nodular type on US which often resembles follicular tumor or adenomatous nodules, showed diffusive homogeneous enhancement by CEUS. Moreover, involved lymph nodes has the same CEUS pattern like the primary tumors. This indicates that the lymph nodes displaying the same perfusion pattern like primary tumors on CEUS imaging can be taken as a feature for identifying involved lymph nodes of PTL in early stage.

In addition, we attempted to analyze the CEUS parameters to find features of quantitative analysis between thyroid lymphoma, involved lymph nodes and CCA. In our study, the time to peak of contrast agent distribution in PTL or involved lymph node was longer than that of CCA at the same level. However, for other parameters, such as AT, PI and area under the curve, no statistical significance existed between CCA, primary tumors and involved lymph nodes. The reason could be that a large number of micro-vessels in tumors or lymph nodes squeezed narrowly and tortuously, which cause micro-bubbles diffuse slowly in them. Further study should focus on large amounts of cases to find more features in US and CEUS patterns and identify PTL by other tools, such as real-time elastography and CEUS 3-D ultrasound imaging.[20],[22]

In conclusion, PTL is presented as marked hypoechoic and diffusive mass type in the conventional US imaging. And diffusive homogeneous enhancement pattern is considered as the main feature in CEUS patterns. And heterogeneous enhancement CEUS pattern is also helpful for detecting necrosis areas of PTL.

 » References Top

Green LD, Mack L, Pasieka JL. Anaplastic thyroid cancer and primary thyroid lymphoma: A review of these rare thyroid malignancies. J Surg Oncol 2006;94:725-36.  Back to cited text no. 1
Wang SA, Rahemtullah A, Faquin WC, Roepke J, Harris NL, Hasserjian RP. Hodgkin's lymphoma of the thyroid: A clinicopathologic study of five cases and review of the literature. Mod Pathol 2005;18:1577-84.  Back to cited text no. 2
Yamauchi A, Tomita Y, Takakuwa T, Hoshida Y, Nakatsuka S, Sakamoto H, et al. Polymerase chain reaction-based clonality analysis in thyroid lymphoma. Int J Mol Med 2002;10:113-7.  Back to cited text no. 3
Alzouebi M, Goepel JR, Horsman JM, Hancock BW. Primary thyroid lymphoma: The 40 year experience of a UK lymphoma treatment centre. Int J Oncol 2012;40:2075-80.  Back to cited text no. 4
Watanabe N, Noh JY, Narimatsu H, Takeuchi K, Yamaguchi T, Kameyama K, et al. Clinicopathological features of 171 cases of primary thyroid lymphoma: A long-term study involving 24553 patients with Hashimoto's disease. Br J Haematol 2011;153:236-43.  Back to cited text no. 5
Beasley MJ. Lymphoma of the thyroid and head and neck. Clin Oncol (R Coll Radiol) 2012;24:345-51.  Back to cited text no. 6
Kim HC, Han MH, Kim KH, Jae HJ, Lee SH, Kim SS, et al. Primary thyroid lymphoma: CT findings. Eur J Radiol 2003;46:233-9.  Back to cited text no. 7
Takashima S, Nomura N, Noguchi Y, Matsuzuka F, Inoue T. Primary thyroid lymphoma: Evaluation with US, CT, and MRI. J Comput Assist Tomogr 1995;19:282-8.  Back to cited text no. 8
Shibata T, Noma S, Nakano Y, Konishi J. Primary thyroid lymphoma: MR appearance. J Comput Assist Tomogr 1991;15:629-33.  Back to cited text no. 9
Aiken AH, Glastonbury C. Imaging Hodgkin and non-Hodgkin lymphoma in the head and neck. Radiol Clin North Am 2008;46:363-78.  Back to cited text no. 10
Graff-Baker A, Roman SA, Thomas DC, Udelsman R, Sosa JA. Prognosis of primary thyroid lymphoma: Demographic, clinical, and pathologic predictors of survival in 1,408 cases. Surgery 2009;146:1105-15.  Back to cited text no. 11
Cheng V, Brainard J, Nasr C. Co-occurrence of papillary thyroid carcinoma and primary lymphoma of the thyroid in a patient with long-standing Hashimoto's thyroiditis. Thyroid 2012;22:647-50.  Back to cited text no. 12
Widder S, Pasieka JL. Primary thyroid lymphomas. Curr Treat Options Oncol 2004;5:307-13.  Back to cited text no. 13
Ota H, Ito Y, Matsuzuka F, Kuma S, Fukata S, Morita S, et al. Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid. Thyroid 2006;16:983-7.  Back to cited text no. 14
Takashima S, Sone S, Horii A, Honjho Y, Yoshida J. Subacute thyroiditis in Hashimoto's thyroiditis which mimicked primary thyroid lymphoma. J Clin Ultrasound 1997;25:279-81.  Back to cited text no. 15
Nam M, Shin JH, Han BK, Ko EY, Ko ES, Hahn SY, et al. Thyroid lymphoma: Correlation of radiologic and pathologic features. J Ultrasound Med 2012;31:589-94.  Back to cited text no. 16
Takashima S, Matsuzuka F, Nagareda T, Tomiyama N, Kozuka T. Thyroid nodules associated with Hashimoto thyroiditis: Assessment with US. Radiology 1992;185:125-30.  Back to cited text no. 17
Bartolotta TV, Midiri M, Galia M, Runza G, Attard M, Savoia G, et al. Qualitative and quantitative evaluation of solitary thyroid nodules with contrast-enhanced ultrasound: Initial results. Eur Radiol 2006;16:2234-41.  Back to cited text no. 18
Zhang B, Jiang YX, Liu JB, Yang M, Dai Q, Zhu QL, et al. Utility of contrast-enhanced ultrasound for evaluation of thyroid nodules. Thyroid 2010;20:51-7.  Back to cited text no. 19
Friedrich-Rust M, Sperber A, Holzer K, Diener J, Grünwald F, Badenhoop K, et al. Real-time elastography and contrast-enhanced ultrasound for the assessment of thyroid nodules. ExpClinEndocrinol Diabetes 2010;118:602-9.  Back to cited text no. 20
Sakorafas GH, Kokkoris P, Farley DR. Primary thyroid lymphoma (correction of lympoma): Diagnostic and therapeutic dilemmas. SurgOncol 2010;19:e124-9.  Back to cited text no. 21
Molinari F, Mantovani A, Deandrea M, Limone P, Garberoglio R, Suri JS. Characterization of single thyroid nodules by contrast-enhanced 3-D ultrasound. Ultrasound Med Biol 2010;36:1616-25.  Back to cited text no. 22


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Hashimoto Thyroiditis in Primary Thyroid Non-Hodgkin Lymphoma
Antonio Travaglino,Mirella Pace,Silvia Varricchio,Luigi Insabato,Claudia Giordano,Marco Picardi,Fabrizio Pane,Stefania Staibano,Massimo Mascolo
American Journal of Clinical Pathology. 2019;
[Pubmed] | [DOI]
2 A Review of Primary Thyroid Lymphoma: Molecular Factors, Diagnosis and Management
Efstathios T. Pavlidis,Theodoros E. Pavlidis
Journal of Investigative Surgery. 2019; 32(2): 137
[Pubmed] | [DOI]


Print this article  Email this article


  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow