Beyond genetic and biological differences, cultural practices and socio-environmental determinants in Asia can greatly influence thyroid pathology outcomes. For instance, dietary iodine intake, prevalent in many Asian diets, can significantly affect thyroid physiology and pathology.

Diverse Asian nations, with their distinct historical trajectories, have developed unique healthcare infrastructures. The accessibility and quality of healthcare, including diagnostic facilities, can vary even within countries, let alone between them.

The juxtaposition of North American and Asian healthcare expenditure strategies underlines more profound socio-economic and policy-driven differences. These variations often dictate clinical decisions, with patient affordability playing a crucial role. Medical expenses vary significantly across countries, with North America typically experiencing higher costs. Immediate surgery is frequently chosen to reduce these expenses. However, in other parts of the world, the approach often leans towards risk stratification for surgery and long-term clinical monitoring, as these tend to be more cost-effective than surgical interventions compared to the United States.

Health insurance schemes’ dynamics, influenced by public policies and private market forces, can significantly sway diagnostic and treatment choices.

The density of pathologists across countries significantly shapes the landscape of medical practice [17]. The number of pathologists in a country is intrinsically linked to the efficiency and effectiveness of its medical system.

The medico-legal environment molds clinical practice considerably. In some countries, clinical practice guidelines are established with a defensive approach due to the potential for physicians to face malpractice lawsuits. While defensive medicine may seem prudent in litigious societies, it can inadvertently lead to overdiagnosis and overtreatment, escalating healthcare costs. Conversely, other nations resist such defensive medicine because it escalates societal costs and burdens patients financially [18-20].

The evolution of medical terminologies and classifications, often reflecting deeper understandings of diseases, underscores the importance of constant knowledge exchange and adaptation among global medical communities. The noninvasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) was once classified as a malignant tumor in American thyroid nodule practices. Its prevalence in the West is elevated due to a lower threshold for recognizing papillary thyroid carcinoma (PTC) nuclear features (Fig. 1) [21,22]. However, this classification was later changed to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) [2,23]. In many Asian practices, these are typically observed in benign follicular adenomas (FAs) due to a higher threshold for PTC-type nuclear features (Fig. 1), resulting in a lower prevalence of NIFTP in surgically removed nodules in Asia [2,8,11,12,14-16].

The decision-making algorithms in medicine are based on clinical evidence, patient preferences, physician experiences, and systemic constraints. In Asian clinical practice, a more conservative management approach is typically adopted, emphasizing clinical risk stratification for high-risk indeterminate thyroid nodules, specifically follicular neoplasm (FN) [9-11,13-16]. Conversely, in North America, diagnostic surgery becomes the preferred course when patients cannot afford molecular tests [1,4,9, 10,11,13-15]. Consequently, in the West, indeterminate nodules, categorized as Bethesda III (atypia of undetermined significance [AUS]) and IV (FN), have a high resection rate (RR) of over 50% but a lower risk of malignancy (ROM) of less than 30%. In contrast, most Asian practices show a lower RR of less than 40% for these nodules, with a ROM exceeding 40%, even in the absence of molecular testing [9-11,13-16].

Each country, influenced by its unique medical history, patient demographics, and healthcare policies, carves out its distinct approach to disease management. In Japan, a more conservative approach to management is prevalent [10,11,24-26]. Traditionally, lobectomy is the chosen procedure for low-risk small PTCs measuring 1–2 cm and for slightly larger low-risk PTCs, specifically, those sized less than 4 cm and categorized as T1–2, extrathyroidal extension (Ex) 0–1, N0–1, and M0 [24-26]. This conservative strategy offers notable benefits, most crucially the potential preservation of thyroid function. Such a conservative approach is particularly vital as patients who undergo total thyroidectomy and subsequently experience poorly managed hypothyroidism face severe risks, especially as they age and potentially struggle with proper hormone supplement management. Contrarily, in most other regions of Asia, as well as in North America and Europe, the predominant choice leans towards total thyroidectomy in the past [4,24-27].

The balance between surgical intervention and observation hinges on the collective experiences of a medical community, patient trust, and the broader healthcare framework. In Japan, over half of the patients with low-risk, small PTCs (less than 10 mm) opt for active surveillance, undergoing clinical follow-ups without surgery once a fine needle aspiration (FNA) confirms the malignancy [4,28-31]. Conversely, in the majority of other nations, FNA is typically not recommended for thyroid nodules that are small and low-risk, especially those under 1 cm [4]. This distinction arises from the fact that once an FNA identifies a nodule as malignant, surgery becomes the frequent choice, leading to potential overtreatment for patients with low-risk, small PTCs [4,14-16].

As medicine advances, so does the need for precision. Nevertheless, precision must be juxtaposed against practicality in the light of resource optimization. Grossing techniques for encapsulated follicular pattern thyroid tumors vary globally. In Western countries, where pathologists often adopt defensive medical practices due to malpractice concerns, there is an emphasis on meticulously sampling the entire tumor capsules [2,15,16,32,33]. As recommended in Western textbooks, this practice has influenced the protocols in certain Asian laboratories, notably in China, Korea, Taiwan, and Thailand [32]. Conversely, Indian, Indonesian and Japanese labs generally select only representative sections, typically fewer than 10 per nodule, adhering to prior textbook guidelines [33,34]. This streamlined approach reduces the number of hematoxylin and eosin sections taken (from more than 20 sections to fewer than 10 per nodule) and conserves both pathologist time and societal resources.

The reasoning behind this more economical approach in India, Indonesia and Japan is multifaceted: (1) Lobectomy is deemed suitable for a range of nodules, from benign (e.g., FA) to borderline tumors (e.g., NIFTP, thyroid tumors of uncertain malignant potential), and even low-risk malignancies (like minimally invasive follicular thyroid carcinoma [FTC] or encapsulated conventional PTC) [4,24-26,33]. (2) Only pronounced, clear invasions carry significant implications for a patient’s prognosis. With this method focused on Sustainable Development Goals, there is virtually no risk of overlooking clinically consequential carcinomas, such as extensively angio-invasive or widely invasive carcinomas [2,3,33]. (3) Conducting exhaustive histological examinations to identify ambiguous invasions can result in the overtreatment of low-risk tumors, such as those termed minimally invasive FTCs or encapsulated FVPTCs (EFVPTCs). (4) Restricting the number of samples (to less than 10 sections) mirrors the clinical guideline of refraining from FNAs on low-risk thyroid nodules smaller than 1 cm. This approach encourages a clinical follow-up, subsequently reducing surgeries for small papillary carcinomas. Moreover, limiting samples can mitigate the unintended identification of questionable capsular invasions and, consequently, the diagnoses of minimally invasive FTCs and EFVPTCs. This, in turn, lessens the likelihood of excessive treatments, like completion thyroidectomy or radioactive iodine abrasion, particularly for very low-risk thyroid tumors with negligible prognostic impact [36-39].

How we classify and interpret diagnostic samples evolves with our understanding of disease processes and the nuances of clinical implications. In past cytological practices, including in the United States, cyst fluid only samples from thyroid FNA cytology were typically categorized as benign. However, current Western practices have moved these samples to the inadequate category due to the substantial risk they pose for false-negative diagnoses and the potential inability to completely exclude cystic PTC [1,14-16]. In contrast, some countries in Asia/Oceania still classify these samples as benign, while European countries might place them in a specific subcategory under the inadequate category. This reclassification in Europe is attributed to the extremely low malignancy risk associated with these samples, which is on par with or even lower than the risk associated with samples in the benign category [9,15,16].

In 2002, some members of the Asian Thyroid Working Group observed notable discrepancies between Japanese and American pathologists concerning the classification of encapsulated follicular pattern thyroid tumors [5,6]. The majority of noninvasive encapsulated follicular pattern thyroid nodules exhibiting subtle nuclear atypia consistent with RAS-like tumors (RAS-like dysplasia) were classified as malignant PTCs by American pathologists. In contrast, Japanese pathologists often categorized them as benign FAs or hyperplastic nodules (Fig. 1) [5,6,16,21,22]. This observation was further corroborated by multiple subsequent studies [7,15,21,22]. Following a comprehensive review of 109 cases, which exhibited neither recurrence nor metastasis over an average 14-year follow-up period, the international NIFTP working group reclassified these noninvasive encapsulated follicular pattern tumors in 2016. Previously deemed as malignant (FVPTC), they were redefined as borderline tumors (NIFTP) [23]. Despite this, considerable disparities persist between Asian and Western practices, notably in the prevalence of NIFTP— a statistic that remains higher in the West [2,8,11,12,14-16,22,40-43] compared to Asia [12,14,44-49].

The Asian Thyroid Working Group was inaugurated in 2017 during the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea [49,50]. The group’s initial endeavors explored the distinctions between Asian and Western approaches to thyroid nodule management. In the West, FVPTC (often synonymous with RAS-like PTC) represents a significant portion of PTC diagnoses [1-4,12,22,23,37,51]. Consequently, the frequency of the BRAF V600E mutation is somewhat diminished in Western PTC cases, given that EFVPTCs are typically non-BRAF (RAS-like) tumors [40]. Conversely, Asian PTC samples manifest a higher prevalence of the BRAF V600E mutation, largely because EFVPTCs are scarcely identified in Asian thyroid evaluations. A majority of encapsulated follicular pattern tumors with mild RAS-like dysplastic nuclear alterations are designated as benign FA in prevalent Asian practices [6-8,11,14-16,40,41].

This manuscript chronicles the endeavors and discoveries of the Asian Thyroid Working Group from 2017 to 2023, underscoring the nuanced distinctions in thyroid nodule practices between Asia and the West. A comprehensive exploration of these global thyroid nodule practice variances will be the centerpiece of an upcoming textbook titled “Thyroid FNA Cytology, Differential Diagnoses, and Pitfalls: 3rd Edition” [52].

Since 2016, multiple Asian Thyroid Working Group members have curated special issues in various journals. These special issues include:

The inaugural Asian Thyroid Working Group Companion Meeting was convened at the 18th AOTA Congress in Busan, Korea, on March 16, 2017. Subsequent Companion Meetings have been held annually, as detailed in Tables 4–8. However, the meetings scheduled for 2020 and 2021 were canceled due to the COVID-19 pandemic.

Kennichi Kakudo served as the esteemed president of the Asian Thyroid Working Group from 2017 to 2023, concluding his tenure in July 2023. During this period, the core members who played a pivotal role alongside Dr. Kakudo were Chan Kwon Jung from Korea, Zhiyan Liu from China, Mitsuyoshi Hirokawa from Japan, and Andrey Bychkov, who had affiliations with Russia, Thailand, and Japan. In a significant transition, Chiung-Ru Lai (Taiwan) was nominated as the president in July 2023. This nomination was subsequently ratified during a web meeting held by the core members. As of August 2023, the core team under Dr. Lai’s leadership includes Chan Kwon Jung (Korea), Zhiyan Liu (China), Andrey Bychkov (Japan), Radhika Srinivasan (India), Mitsuyoshi Hirokawa (Japan), Somboon Keelawat (Thailand), with Kennichi Kakudo (Japan) serving as a consultant, and Jen-Fan Hang (Taiwan) fulfilling the role of secretary.

There are numerous group studies that are presently under-way, with their findings expected to be published in the near future. The Asian Thyroid Working Group remains committed to offering a collaborative platform for all its members, which is composed of 58 members from 14 countries in September 2023. A notable contribution to the academic community will be the 3rd edition of “Thyroid FNA Cytology, Differential Diagnosis, and Pitfalls,” slated for release in 2023. This edition will encompass an in-depth discussion of all topics presented in the article as mentioned above [52]. The volume will feature more than 60 chapters penned by esteemed Asian authors. Within these chapters, we present a reporting system tailored to the Asian medical context, given that high-cost gene panel tests are not a commonplace practice (as detailed in Table 9).

The core team, along with the project leader, is enthusiastic about creating more avenues for budding Asian pathologists and cytopathologists to engage with the broader international pathology community. We ardently hope that the activities under the aegis of the Asian Thyroid Working Group will act as a springboard for the younger generation, integrating them with the global community and bolstering their careers in pathology and cytopathology. A list of publications by the Asian Thyroid Working members from 2017 to 2023 is available in Supplementary Table S1.