Almost all PTLs are B-cell lymphomas which express the B-cell markers, CD20, CD79a, and Pax-5, whereas T-cell lymphomas are rare. Our cases were all non-Hodgkin’s lymphoma, and the proportion of female patients was relatively high, with an average age of 62 ± 11 years. The age of aggressive PTL was older when compared with indolent PTL, and most had elevated LDH levels which was consistent with previous reports[1, 15]. Therefore, when examining older patients at initial consultation for Hashimoto’s disease, clinicians must be aware of a high risk for PTL in these patients. DLBCL and MALT tumors were the most common PTL pathological types. In this study, the proportion of DLBCLs was the highest (51%), followed by MALT (33%). MALT-type lymphomas were mostly localized lesions, with low malignancy and a good prognosis, while DLBCLs were prone to metastasis and highly malignant. Burkitt lymphoma and follicular lymphoma are rare in PTL; their histological appearance and immunophenotypes are basically consistent with intra-lymph node lesion characteristics. DLBCL combined with MALT indicated a transformed lymphoma, which was more aggressive than DLBCL alone, suggesting MALT lymphoma could be transformed into higher-grade, more aggressive lymphomas. The mainstay treatment is combined modality therapy (CMT) for aggressive lymphoma and radiotherapy(RT) for localized indolent lymphoma. It was reported that CMT improved the prognosis of patients with aggressive lymphoma, while CMT for indolent lymphoma remains uncertain. Multi-modal ultrasound follow-up may be helpful for early differentiated aggressive PTL from indolent PTL among patients with Hashimoto’s disease.
PTL exhibits characteristic sonographic and doppler flow features which show central blood flow patterns highly suggestive of PTL rather than nodular goiter. However, some sonographic features, such as asymmetric goiter with marked hypoechogenicity, internal cord-like or grid-like hyperechoic, enhanced posterior echo, large size, absent calcification and hypervascularity, and aspect ratio is not misaligned, etc., are different from most solid malignant lesions[18, 19]. While PTL is rarely observed, my study had focused on multi-modal ultrasound. Cases in this study were divided into nodular, diffuse, and mixed types based on ultrasound image characteristics from previous reports. The mixed type was more prone to aggressive lymphoma, and was mainly based on lesion distribution and morphology, suggesting different PTL types may be manifested as different stages of lymphoma growth and development[17, 21]. A previous study reported that CEUS for PTL indicated a diffuse, non-uniform filling type, just like the snowflake enhancement observed in our study. Yang et al. reported that CEUS was an efficient diagnostic tool for the differential diagnosis of PTL and nodular Hashimoto’s thyroiditis for patients with diffuse HT. Previous reports have focused on nodular elastography for PTL. Wang et al. reported that along with several other parameters, a central blood flow pattern was highly suggestive of a PTL diagnosis rather than nodular goiter. Nodular blood flow signals in aggressive PTL exhibited higher grades (usually 2–3) than indolent PTL (generally 0–2) in our study.
Previous studies showed that for thyroid lymphoma, core needle biopsy (CNB) sensitivity and accuracy were higher than fine-needle aspiration(FNA) for both preoperative and postoperative patients, and that CNB reduced unnecessary diagnostic surgery[24, 25]. In our study, four patients underwent FNA, suggesting that malignant tumors and lymphomas were to be examined, and then CNB was diagnosed, suggesting that conventional thyroid FNA may be limited in the diagnosis of PTL due to the limited number of cells obtained and the limitation of immunohistochemical technology. In addition, multi-modal ultrasound provided more information on PTL lesions for puncture, therefore CNB guided by multi-modal ultrasound is more advantageous for diagnosing PTL when compared with FNA or surgery.
PTL combined with thyroid cancer is very rare[26, 27]. In this study, we observed five PTL cases with PTC, maximum age 62, and four cases are MALT lymphoma with HT and diffuse type of ultrasound pattern. Interestingly, the prognosis was not worsened by combined PTC and PTL, but was more likely affected by the more poorly staged tumor. Thus, for patients with concomitant PTC and PTL, treatments were conducted which prioritized the tumor with the worse prognosis and/or the worse stage at diagnosis. Graceffa et al.  expounded the frequent coexistence of PTC and HT. Similarly, the probability of PTL in HT populations was approximately 50 times higher than the general population[1, 9]. This situation highlights the importance of monitoring HT patients, particularly if they have long-lasting disease with nodules. Patients with coexisting PTC and PTL require a multidisciplinary approach for diagnostic work-up and optimal management.
PTL has a good prognosis, which is closely related to the pathological type and clinical stage, especially tumor size and extent of cancer invasion. MALT is an indolent lymphoma with a 5-year survival rate of 62–96%, while DLBCL is an aggressive lymphoma with a 5-year survival rate of 45–75%. Cha et al. reported that the 5-year OS and PFS rate of aggressive PTL was 75.6% and 73.9%, respectively. Watanabe et al. found that five-year overall survival and event-free survival for elderly patients with thyroid DLBCL were 87% (95% confidence interval [95% CI], 64–96%) and 74% (95% CI, 50–89%), respectively. In this study, the OS of indolent PTL patients was significantly better than aggressive PTL patients(P < 0.05). PTL patients with age > 70 years old, aggressive pathology, Ki67 > 30%, elastography scored > 3 are more likely to have poor prognosis. Multivariable cox regression analysis showed that age was an independent risk factor for PTL. Watanabe et al.  in another research reported that higher age and higher erythrocyte sedimentation rate (ESR) were significant risk factors for OS, which is almost similar to our research.
Our study had limitations. Firstly, PTL is rare and the single-center nature of our study meant our cohort was small. Secondly, to precisely identify histopathological PTL types over a long period, only patients with a pathologically proven diagnosis were included in this study. Also, some cases were lost to follow-up. However, PTL is relatively rare, therefore, it is difficult to perform prospective studies and identify large numbers for analysis.
In summary, the application of multiple ultrasound examination modes is beneficial for capturing disease information and PTL ultrasound patterns. Also, the approach comprehensively evaluates tumor boundaries, sizes, shapes, internal echo, hemodynamics, spatial structures, soft textures, and pathological tissues. In addition, PTL patients with age > 70 years old, aggressive pathology, Ki67 > 30%, elastography scored > 3 are more likely to have poor prognosis. It is recommended elderly patients with HT are closely followed-up by multi-mode ultrasound to improve PTL early detection and strategically target aggressive tumors.