Thyroid tuberculosis misdiagnosed as papillary thyroid carcinoma under ultrasound-guided fine-needle aspiration cytology: a case report and literature review

Introduction

Tuberculosis primarily affects the lungs, accounting for 90% of cases. However, in 15–20% of cases, it can also involve other sites. The most common affected areas include the lymph nodes, bones and joints, pleura, and central nervous system, particularly in immunocompromised individuals. Other sites include the peritoneum, gastrointestinal tract, urogenital tract, and pericardium (1). Organs such as the heart, thyroid, and pancreas are relatively resistant to tuberculosis infection (2,3).

Thyroid tuberculosis is a rare form of tuberculosis that affects the thyroid gland, causing granulomatous inflammation. It is usually asymptomatic or presents with nonspecific symptoms, making diagnosis challenging. Clinical manifestations may include palpable thyroid nodules, pain, and in some cases, systemic symptoms such as fever and weight loss. Due to its rarity, thyroid tuberculosis is often misdiagnosed as a more common disease, particularly thyroid cancer such as papillary thyroid carcinoma (PTC) (4). The clinical and radiological features of thyroid tuberculosis are nonspecific, and definitive diagnosis requires fine-needle aspiration cytology (FNAC) or postoperative histopathological examination (5).

Here, we report a patient without any underlying diseases who underwent surgery due to suspected thyroid carcinoma from FNAC, but it was subsequently diagnosed with thyroid tuberculosis. We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-19/rc).

Case presentation

Patient information

The patient was a 68-year-old female who experienced a subjective sensation of neck fullness without pain and underwent a neck ultrasound (US) examination at a local hospital ten days prior to her visit, which revealed a suspicious malignant nodule in the thyroid. She was a long-term resident of her birthplace, working as a farmer by occupation with relatively poor economic conditions. For further diagnosis and treatment, the patient was transferred to our hospital. Upon admission, the physical examination showed that the patient was well-developed and in good nutritional health. The neck skin was intact, with no redness, swelling, or ulcers, and the trachea was midline. The hard area was palpable in the right lobe of the thyroid. No enlarged lymph nodes were palpated in the neck, and the patient did not exhibit hoarseness. The patient had a history of coronary heart disease for over one year, managed with intermittent oral medications (specifics unknown). Notably, she denied any history of tuberculosis or hepatitis.

US examination

The thyroid US revealed an irregular hypoechoic area in the right lobe, extending into the isthmus. The boundaries of this area were unclear. It displayed uneven internal echoes and multiple strong linear echoes that created a grid-like pattern. The larger area measured approximately 2.5 cm × 1.0 cm. Color Doppler imaging revealed both punctate and linear blood flow signals (Figure 1A,1B). A hypoechoic area was also observed near the isthmus of the left lobe, measuring approximately 0.6 cm × 0.3 cm × 0.5 cm, with echo characteristics like those of the hypoechoic area in the right lobe. Based on the European Thyroid Imaging and Reporting Data System (EU-TIRADS), the patient’s thyroid nodule was classified as Category 4B, and ultrasound-guided fine-needle aspiration cytology (US-FNAC) was recommended for diagnosis (6).

Figure 1 Cervical US: (A) the scan shows an irregularly margins hypoechoic area in the right lobe of the thyroid, with multiple linear strong echoes within the hypoechoic area (larger area approximately 2.5 cm × 1.0 cm); (B) color Doppler flow imaging shows sparse blood flow signals. US, ultrasound.

Laboratory examination

The patient’s white blood cell count, neutrophil ratio, and lymphocyte ratio were normal. Thyroid-stimulating hormone levels were mildly elevated at 5.28 mIU/L (normal range, 0.38–4.94 mIU/L), while anti-thyroid peroxidase antibodies (TPOAb) were significantly elevated at 365.09 IU/L (normal range, 0–5.61 IU/L). Serum levels of thyroxine, triiodothyronine free thyroxine, free triiodothyronine, anti-thyroglobulin antibodies (TGAb), and thyroglobulin were all normal.

FNAC

Fine-needle aspiration, smearing, and liquid-based cytology were performed on the hypoechoic area in the right lobe using US guidance (Figure 2). The results revealed a significant number of follicular epithelial cells arranged in sheets and dense clusters. These cells had pale-staining nuclei, prominent nuclear grooves, and irregular nuclear shapes. Additionally, multinucleated giant cells and concentrated colloid were present, while no intranuclear inclusions were observed (Figure 3). The morphological findings indicated a suspicion of PTC, classified as Bethesda category V (suspicious for malignancy) (7).

Figure 2 Ultrasound-guided fine needle aspiration image. A 22G puncture needle (arrow) is inserted into the hypoechoic area on the right side of the thyroid. The transducer was positioned in reversed orientation, with its marker positioned on the patient’s left side.

Figure 3 FNAC image of the thyroid gland (400×, hematoxylin-eosin staining): multinucleated giant cells were suspected by FNAC findings and papillary carcinoma could be considered. FNAC, fine-needle aspiration cytology.

Postoperative pathology

The cytological results suggested a suspicion of PTC, and further examinations indicated that there were no surgical contraindications. The patient underwent surgical treatment under general anesthesia. During the surgery, the right lobe and isthmus of the thyroid were slightly enlarged. They had a firm texture, an uneven surface, and a palpable hard area measuring about 2.0 cm × 1.5 cm, which was clearly separated from the surrounding normal muscle and tissue. No significantly enlarged lymph nodes were found around the thyroid. Based on the preoperative cytopathological findings, a right thyroid lobectomy and isthmusectomy were performed, with the resected specimen sent for intraoperative frozen section pathological examination. The intraoperative rapid frozen section diagnosis indicated that the right thyroid lesion was an epithelioid granuloma, with no tumor tissue observed. The surgery was immediately terminated, and the wound was cosmetically sutured. The paraffin section examination results showed: epithelioid granuloma with necrosis (Figure 4). An immunohistochemistry analysis revealed a positive finding for cluster of differentiation 68 (CD68⁺), and acid-fast bacilli staining was negative, with repeated tuberculosis staging also negative. Given the morphological findings suggesting tuberculosis, clinical testing for the disease was recommended.

Figure 4 Right thyroid lobe specimen (100×, hematoxylin-eosin staining): epithelioid granuloma with necrosis; no malignant tumor cells identified.

On the second postoperative day, tuberculosis infection T-cell testing showed a calculated TB-γ interferon concentration of 16.02 pg/mL (normal range, 0–14 pg/mL), with Specific T lymphocytes positive for tuberculosis infection.

Final diagnosis and treatment

Following a thorough examination that ruled out extrathyroidal tuberculosis, the patient was diagnosed with primary thyroid tuberculosis (granulomatous type) based on the surgical pathology results and serum tuberculosis markers. The patient recovered well after surgery and received anti-tuberculosis therapy in a tuberculosis hospital for 1 year. The US findings at one month postoperatively revealed a hypoechoic area measuring 0.6 cm × 0.4 cm × 0.5 cm in the upper pole of the residual left thyroid lobe, with heterogeneous internal echogenicity. Follow-up US at 5 months postoperatively showed that the hypoechoic area in the left lobe had decreased in size compared to the previous examination, indicating effective anti-tuberculosis therapy.

Ethics

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Primary thyroid tuberculosis is a rare disease. According to the 2024 World Health Organization (WHO) Global Tuberculosis Report, China reported 741,000 incident cases of tuberculosis in 2023, accounting for 6.8% of the global tuberculosis burden (8). The incidence of thyroid tuberculosis is low even in countries where prevalence of pulmonary tuberculosis is high (0.1–0.4%) (9). In China, the incidence of thyroid tuberculosis is slightly higher than in other countries, with literature report indicating that it accounts for 0.4–0.76% of thyroid surgery cases (10). Thyroid tuberculosis mostly has a slow onset and a long course. The clinical features are often vague and mild. The most common presentation includes a painless solitary nodule and diffuse mild to moderate enlargement of the thyroid gland, without systemic symptoms of tuberculosis. However, thyroid tuberculosis can be severe when abscesses or subacute thyroiditis are present, with main symptoms including fever, weight loss, and neck pain. Abscess rupture and sinus formation may also occur. The rare symptoms associated with this condition are hoarseness, dysphagia, and dyspnea (9,11). The patient experienced only a subjective sensation of neck fullness, with no tenderness, pain or fever, and had no underlying conditions or signs of extrapulmonary tuberculosis.

Sonographic features of thyroid tuberculosis usually reveal: (I) an enlarged thyroid volume; (II) oval or irregular hypoechoic nodules; (III) uneven echo distribution; (IV) unclear boundaries; (V) sparse blood flow signals. As the disease progresses, various US features may appear, such as echo-free areas from liquefaction, low echoes, and high echoes due to calcification. These features may be associated with several factors, such as caseous necrosis in the lesions, the development of cold abscesses, the presence of a fibrotic wall formed by thyroid tissue around the abscess, tuberculous granulomas, and an increase in fibrous connective tissue. This study’s grayscale US finding revealed irregular low-echo areas in the thyroid with indistinct boundaries and strong linear echoes. In contrast, the bilateral cervical lymph nodes showed no enlargement, which should be distinguished from typical PTC (12). In this case, the US image revealed multiple strong linear echoes within a low echo area, consistent with Hashimoto’s thyroiditis (9). This could be caused by fibrous tissue hyperplasia, which may help differentiate thyroid tuberculosis from PTC in US imaging.

Due to the absence of specific signs and symptoms, thyroid tuberculosis is clinically difficult to diagnose. US-FNAC demonstrates technical simplicity, minimal invasiveness, favorable safety profile, and high diagnostic accuracy with low complication rates. Thyroid tuberculosis cytological smears often display epithelioid granulomas accompanied by necrosis. Additionally, the presence of caseous necrosis and acid-fast bacilli is a dependable diagnostic indicator (13). Nowadays, it is stated that acid-fast bacilli are not always found, therefore, multiple coalesced and caseated epithelioid cell granulomas along with giant cells are considered to be diagnostic of tuberculous affection of the gland (9). Despite its usefulness, US-FNAC has a notable false-negative rate, with no reported false positives. In fact, the indeterminate rate of fine-needle aspiration for thyroid lesions remains relatively high. Studies have demonstrated that automated image analysis and artificial intelligence applications in thyroid cytopathology can effectively screen fine-needle aspiration smears, thereby improving the diagnostic reliability of thyroid FNAC (14-17). Currently, its accuracy rate for diagnosing thyroid tuberculosis stands at approximately 70% (18). Most cases of thyroid tuberculosis are diagnosed postoperatively or at postmortem examination. The polymerase chain reaction (PCR) is an effective method for detecting mycobacterium tuberculosis deoxyribonucleic acid (DNA) in fine-needle aspirates from thyroid lesions, and it increases the sensitivity of cytological examinations (19). Regrettably, after excluding the possibility of extrathyroidal tuberculosis, a notable limitation of this case was the lack of further confirmatory test—such as mycobacterial tuberculosis culture, or PCR—due to the patient’s financial constraints.

Kinoshita et al. described a patient who had surgery for suspected thyroid cancer following FNAC but was later diagnosed with thyroid tuberculosis (20). The patient had chronic renal failure and was undergoing peritoneal dialysis, experiencing fever and neck pain. The FNAC images suggested the presence of nuclear inclusions in the altered residual follicular epithelial cells, leading them to consider papillary carcinoma.

In our case, FNAC incorrectly identified thyroid tuberculosis as PTC for several reasons: First, the fine-needle aspiration failed to collect epithelial granulomatous structures. Second, epithelial-like tissue cells were incorrectly identified as thyroid follicular epithelial cells. Third, multinucleated giant cells in the tissue were confused with those from the thyroid follicular epithelium. Fourth, thyroid tuberculosis is uncommon, and its cytological characteristics are not well understood, especially among younger cytopathologists with limited diagnostic experience.

Conclusions

In conclusion, this case underscores the need to enhance diagnostic strategies to avoid future misdiagnoses. Clinicians should remain highly suspicious of patients with unusual thyroid nodule presentations. FNAC struggles to distinguish between thyroid carcinoma and thyroid tuberculosis. Thus, raising awareness and employing comprehensive diagnostic methods—such as imaging, cytology, and molecular techniques—can ensure timely and accurate diagnoses.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-19/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-19/prf

Funding: This work was supported by the Shaanxi Province Key Research and Development Plan Project (No. 2023-YBSF-011).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-19/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Rodriguez-Takeuchi SY, Renjifo ME, Medina FJ. Extrapulmonary Tuberculosis: Pathophysiology and Imaging Findings. Radiographics 2019;39:2023-37. [Crossref] [PubMed]
2. McMullan GS, Lewis JH. Tuberculosis of the Liver, Biliary Tract, and Pancreas. Microbiol Spectr 2017; [Crossref]
3. Das KM, Mansoori TA, Alattar YH, et al. Tuberculosis of the Heart: A Diagnostic Challenge. Tomography 2022;8:1649-65. [Crossref] [PubMed]
4. Majumder A, Sen D. Uncommon affliction of a common disease - primary tuberculosis of thyroid gland. Indian J Pathol Microbiol 2020;63:83-5. [Crossref] [PubMed]
5. Singh AP, Pramanik B, Tandon A, et al. Coexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid: a case report. J Med Case Rep 2024;18:535. [Crossref] [PubMed]
6. Russ G, Bonnema SJ, Erdogan MF, et al. European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS. Eur Thyroid J 2017;6:225-37. [Crossref] [PubMed]
7. Ali SZ, Baloch ZW, Cochand-Priollet B, et al. The 2023 Bethesda System for Reporting Thyroid Cytopathology. Thyroid 2023;33:1039-44. [Crossref] [PubMed]
8. Goletti D, Meintjes G, Andrade BB, et al. Insights from the 2024 WHO Global Tuberculosis Report - More Comprehensive Action, Innovation, and Investments required for achieving WHO End TB goals. Int J Infect Dis 2025;150:107325. [Crossref] [PubMed]
9. Bansal LK, Gupta S, Gupta AK, et al. Thyroid tuberculosis. Indian J Tuberc 2021;68:272-8. [Crossref] [PubMed]
10. Sun LL, Dong S, Xu JL, et al. Clinical diagnosis and treatment of primary thyroid tuberculosis: a retrospective study. Sao Paulo Med J 2022;140:547-52. [Crossref] [PubMed]
11. Chacko A, Ajaykumar K, Geetha CG. 'Primary Thyroid Tuberculosis'-The Masquerader: A Case Report. Indian J Otolaryngol Head Neck Surg 2022;74:5436-9. [Crossref] [PubMed]
12. Banmala S. Primary thyroid tuberculosis mimicking papillary carcinoma of thyroid: a rare case report. Ann Med Surg (Lond) 2023;85:2155-8. [Crossref] [PubMed]
13. Pachipala MS, Aiyappan SK. Two Interesting Cases of Thyroid Gland Tuberculosis. Cureus 2024;16:e68733. [Crossref] [PubMed]
14. Marletta S, Salatiello M, Pantanowitz L, et al. Delphi expert consensus for whole slide imaging in thyroid cytopathology. Cytopathology 2023;34:581-9. [Crossref] [PubMed]
15. Dov D, Kovalsky SZ, Feng Q, et al. Use of Machine Learning-Based Software for the Screening of Thyroid Cytopathology Whole Slide Images. Arch Pathol Lab Med 2022;146:872-8. [Crossref] [PubMed]
16. Girolami I, Marletta S, Pantanowitz L, et al. Impact of image analysis and artificial intelligence in thyroid pathology, with particular reference to cytological aspects. Cytopathology 2020;31:432-44. [Crossref] [PubMed]
17. Eccher A, Girolami I. Current state of whole slide imaging use in cytopathology: Pros and pitfalls. Cytopathology 2020;31:372-8. [Crossref] [PubMed]
18. Chaudhary P, Bhadana U, Anand A, et al. Diagnostic and Management Guidelines of Thyroid Tuberculosis: Our Experience and Systematic Review. Indian J Otolaryngol Head Neck Surg 2023;75:1302-10. [Crossref] [PubMed]
19. Darre T, Amana B, Pegbessou E, et al. Tuberculosis of the thyroid in Togo: a clinicopathologic study of 11 presumed cases. Trop Doct 2018;48:313-6. [Crossref] [PubMed]
20. Kinoshita I, Higashino M, Omura S, et al. Thyroid tuberculosis diagnosed as papillary thyroid carcinoma with fever of unknown origin. Auris Nasus Larynx 2022;49:1093-7. [Crossref] [PubMed]