Case report and literature review of synchronous follicular and papillary thyroid carcinoma with metastasis to femur

Abstract

Background

Thyroid carcinoma is common, but the synchronous occurrence of bilateral tumors with discordant histology—specifically follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC)—is extremely rare. It is even more uncommon for such cases to present initially with distant bone metastasis from an occult FTC, which poses a significant diagnostic challenge.

Case summary

We report a case of a 67-year-old male who presented to the orthopedic department with left hip pain. Imaging revealed bone destruction, and a biopsy confirmed metastatic thyroid carcinoma. Although the patient had no neck symptoms, a subsequent thyroid workup identified bilateral nodules. The patient underwent hip replacement followed by total thyroidectomy. Postoperative pathology confirmed a synchronous left-sided invasive FTC and a right-sided multifocal PTC. The bone metastasis was attributed to the FTC component. The patient was referred for radioactive iodine (I-131) therapy.

Conclusion

This case highlights that metastatic thyroid cancer should be considered in the differential diagnosis of lytic bone lesions, even in patients without palpable goiters. For rare synchronous bilateral carcinomas, the prognosis is often determined by the more aggressive subtype (FTC), necessitating a multidisciplinary approach involving surgery and systemic therapy.

Introduction

Thyroid cancer is the most common malignancy of the endocrine system, and its incidence has been rising continuously in recent years. According to GLOBOCAN 2022 statistics, thyroid cancer ranks seventh in incidence among all malignancies, accounting for 4.1% of total cases [1, 2]. Among these, papillary thyroid carcinoma (PTC) is the most prevalent subtype, accounting for approximately 84% of cases, followed by follicular thyroid carcinoma (FTC), which comprises about 4% [3–5] .Although thyroid carcinoma frequently presents as multifocal or bilateral disease, the histopathological subtypes of bilateral lesions are concordant in the majority of cases, typically manifesting as bilateral PTC. Synchronous bilateral thyroid carcinomas exhibiting discordant histological subtypes are clinically extremely rare. While Differentiated Thyroid Carcinoma (DTC), comprising Papillary Thyroid Carcinoma (PTC) and Follicular Thyroid Carcinoma (FTC), generally carries a favorable prognosis, distant metastasis remains a significant cause of thyroid cancer-related mortality. Unlike PTC, which predominantly spreads via the lymphatic system, FTC has a distinct predilection for hematogenous dissemination, frequently metastasizing to the bone and lungs [6].

In rare instances, distant metastasis—manifesting as bone pain or pathologic fracture—can be the initial presentation of an occult thyroid malignancy, misleading clinicians to suspect primary bone tumors. This diagnostic challenge is further compounded when the patient presents with synchronous bilateral thyroid carcinomas of discordant histology, a rare phenomenon where PTC and FTC coexist in separate lobes. The divergence in biological behaviors between these subtypes complicates preoperative assessment and therapeutic decision-making. Herein, we report a case of a 67-year-old male who initially presented to the orthopedic department with hip pain. A comprehensive workup revealed the pain was caused by metastatic bone disease originating from an occult left-sided FTC, coexisting with a synchronous right-sided PTC. We also review similar cases from the literature to discuss strategies for early recognition, diagnosis, and rational treatment, aiming to improve the prognosis of this rare condition.

Case presentation

A 67-year-old Asian male presented to our Department of Orthopedics on October 19, 2025, complaining of left hip pain and limited daily activity. Digital radiography (DR) of the left hip and femur, along with whole-body SPECT/CT imaging, revealed osteosclerosis at the edge of the left acetabulum and bone destruction in the proximal femur with slightly increased metabolic activity. Importantly, the whole-body SPECT/CT and subsequent chest CT scans confirmed that the left femur lesion was the sole site of distant metastasis, with no evidence of lung or other skeletal involvement. A primary bone disease was initially suspected. Two days later, a plain MRI scan of the left hip showed expansile bone destruction in the left femoral lesser trochanter. The lesion contained a mixed soft tissue density mass (approximately 3.7 cm × 5.2 cm × 5.2 cm, shown in Fig. 1A-1,2,3), primarily exhibiting isointense T1 and T2 signals. Inside the mass, nodular short T1 and long T2 signals were observed. T2 fat-suppressed images showed heterogeneous hyperintensity with rough margins. The surrounding soft tissue was slightly swollen, and increased long T2 signals were noted in the left hip joint. The joint space was slightly narrowed with osteohyperplasia.

Fig. 1.

A Imaging and pathology of the bone tumor. B Imaging and pathology of the thyroid tumor

Subsequently, the patient underwent a core needle biopsy(CNB). Histology revealed atypical glands within fibrinous exudates. Immunohistochemical (IHC) analysis showed positive results for CKpan, TTF-1, Tg, CD56, TPO, Pax-8, and CK7, while Syn, CDX-2, CK20, EMA, NapsinA, P504s, P63, PAP, PSA, Vimentin, and CgA were negative. The Ki67 index was 1%. These findings supported a diagnosis of metastatic carcinoma, highly suggestive of a thyroid origin.

Although the standard treatment sequence for metastatic differentiated thyroid cancer typically involves thyroidectomy followed by systemic therapy (e.g., RAI), a multidisciplinary decision was made to prioritize orthopedic intervention in this patient. Because the large osteolytic metastasis was located in a critical weight-bearing joint (the hip), there was an exceptionally high risk of an impending pathological fracture. Consequently, prophylactic orthopedic surgery was performed first to immediately restore mechanical stability and preserve the patient’s mobility, ensuring a safe functional baseline prior to proceeding with the thyroidectomy. This MDT decision strictly aligns with the 2025 American Thyroid Association (ATA) Management Guidelines, which emphasize a multidisciplinary approach for advanced disease. For symptomatic or structurally unstable bone metastases posing a risk of impending fracture, directed local therapiesm, such as immediate orthopedic surgical stabilization, are highly recommended to relieve severe pain and preserve the patient’s quality of life prior to subsequent oncological treatments [18].

Following an orthopedic assessment, the patient underwent left hip replacement and tumor resection. Postoperative pathology revealed malignant infiltration into bone, bone marrow, and fibro-adipose tissue. The tumor measured approximately 4 cm × 3 cm × 2 cm. IHC staining was positive for CD56, CK19, CyclinD1, Pax-8, Tg, and TTF-1, with partial positivity for Mesothelial and TPO, and rare positivity for Galectin-3. The Ki67 index was approximately 5%. Vascular tumor emboli were observed. Based on the imaging and clinical history, the metastasis was attributed to follicular thyroid carcinoma (FTC) (Shown in Fig. 1A-4).

A multidisciplinary team (MDT) discussion was held. The thyroid surgeon recommended total thyroidectomy with central lymph node dissection, and the nuclear medicine physician suggested subsequent radioactive iodine (I-131) therapy.

On December 19, 2025, the patient was readmitted. Initial thyroid function tests were unremarkable. A superficial ultrasound of the thyroid and lymph nodes revealed a hypoechoic nodule in the right lobe (approx. 1.34 cm*1.54 cm*1.51 cm, TIRADS 4B, shown in Figs. 1B and 2) and an enlarged left lobe containing a hypoechoic mass (approx. 2.64 cm*2.66 cm*2.74 cm, TIRADS 4 A, shown in Fig. 1B-1). several cystic-solid nodules (TIRADS 3) were found bilaterally. No suspicious lymphadenopathy was detected. A neck CT scan performed two days later confirmed bilateral thyroid enlargement with multiple nodules; the dominant lesion was in the left lobe ( approx. 2.90 cm*2.70 cm*3.10 cm, shown in Fig. 1B-3) and showed heterogeneous enhancement.

Fig. 2.

Diagnosis and treatment process diagram

On December 22, following further MDT discussion, the patient underwent a total thyroidectomy and a central lymph node dissection. The definitive postoperative paraffin-embedded pathology confirmed the diagnosis of a follicular thyroid tumor (FTC) with active epithelial proliferation, partial capsular invasion, and extrathyroidal nodular growth. Multiple vascular invasions were noted, consistent with invasive FTC (Shown in Fig. 1B-4), though no definitive nerve invasion was seen. IHC analysis showed positivity for CKpan, CK8/18, CK19, CyclinD1, and Mesothelial, with partial positivity for CD56 and TPO. P53 was wild-type, and Vimentin was negative. The Ki67 index was 5–10%. The right lobe revealed papillary thyroid carcinoma (PTC) with multifocal lesions (0.6 cm × 0.4 cm × 0.2 cm and 0.4 cm × 0.4 cm × 0.4 cm) alongside nodular goiter (Fig. 1B). Additionally, a central lymph node dissection (CLND) was performed. The final histopathological evaluation of the harvested lymph nodes, including 5 prelaryngeal and 1 central compartment node, revealed no evidence of metastasis (0/6). The complete diagnostic and treatment timeline is illustrated in Fig. 2.

Discussion and conclusions

While thyroid cancer is common, the simultaneous occurrence of FTC and PTC in different lobes is extremely rare. A unique feature of this case is the initial presentation of bone metastasis originating from the occult FTC, masking the primary thyroid pathology. The coexistence of PTC and FTC was first described by Plauche et al. [7] in 2013, who characterized the lesion as a collision tumor. Since that initial report, only 15 cases [7–11] of synchronous PTC and FTC—including the case presented herein—have been documented in the English literature. However, it is important to acknowledge that the reported number of cases likely underestimates the true incidence of this condition. Because this synchronous presentation is a known, albeit rare, clinical entity, it is highly probable that many similar cases encountered in clinical practice remain unreported by various medical centers. This underreporting or publication bias inevitably masks the actual count and prevalence of this disease in the real-world setting. The clinicopathological characteristics of previously published similar cases are summarized in Table 1.

Table 1.

Summary of the reported case series of co-existence of PTC and FTC

Case no	Author	Year of publication	Age	type	Gender	Size location of PTC	Size location of FTC	Distant metastasis
1	Plauche, et al. [7]	2013	62	Collision	F	Multifocal, largest 1 cm, left lobe	4.1 cm, left lobe and 0.3 cm right lobe	None
2	Daunia Verdi, et al. [8]	2013	64	Collision	M	Multifocal/bilateral, maximum 0.1 cm	4.0 cm, right lobe	None
3	Haggi Mazeh, et al. [9]	2015	72	Not mentioned	M	0.3 cm, right lobe	2.5 cm, left lobe	None
4	Vincent Cracolici, et al. [10]	2018	63	Synchronous thyroid carcinoma	F	1.7 cm, left lobe	1.1 cm, right lobe	Metastatic of PTC to lymph node, metastasis of FTC to bone
5	Abdelrahman Abdelaal, et al. [11]	2020	31	Collision	F	5 cm, left lobe	1.3 cm, left lobe	None
6	Abdelrahman Abdelaal, et al. [11]	2020	61	Collision	M	0.3 mm, right lobe	6.0 cm, right lobe	None
7	Abdelrahman Abdelaal, et al. [11]	2020	59	Collision	M	1.5 cm, left lobe and isthmus	5 cm, left lobe and isthmus	None
8	Abdelrahman Abdelaal, et al. [11]	2020	56	Collision	F	Multifocal, both lobes, largest 1 cm	4.5 cm, left lobe	None
9	Abdelrahman Abdelaal, et al. [11]	2020	35	Collision	F	Two foci, largest 0.8 cm, right lobe	1.3 cm, right lobe	None
10	Abdelrahman Abdelaal, et al. [11]	2020	52	Collision	F	0.8 cm right lobe	2.7 cm, right lobe	None
11	Adam Stenman, et al. [12]	2022	43	Collision	F	Multifocal, largest 3 cm, right lobe	1.2 cm, right lobe	Metastasis of PTC to lymph node
12	Kanako Kawasaki, et al. [13]	2023	69	Collision	F	5.2 cm, right lobe	4.0 cm, right lobe and isthmus	Metastasis of PTC to central and lateral lymph node
13	Sana Ahuja, et al. [14]	2024	35	Collision	F	1.5 × 1 × 1 cm, Left lobe	6.7 × 4.5 × 3.5 cm Left, right lobe and isthmus;	Metastasis of PTC to lymph node, Metastasis of the FTC to scalp
14	Gerald Sng Gui Ren, et al. [15]	2024	67	Synchronous thyroid carcinoma	F	1.7 × 1.6 × 1.4 cm, isthmus	2.0 × 2.0 × 1.8 cm, right lobe	Metastasis of FTC to lymph node and bone
15	Present case	2025	67	Synchronous thyroid carcinoma	M	0.6 × 0.4 × 0.2 cm/0.4 × 0.4 × 0.4 cm, right lobe	3.0 × 2.5 × 2.4 cm, left lobe and isthmus	Metastasis of FTC to bone

Previous studies have demonstrated that patients with co-existence of PTC and FTC exhibit considerable heterogeneity in the tissue origins. The average age of the patients was 51.2 years (range: 31 to 72) and female predominance (10 of 15 cases) was noted. Six cases of metastases were found, only two of which were bone metastases. Specifically, the majority of reported cases were collision tumors involving both PTC and FTC in the same lobe [7–9, 12–14], whereas only two cases, including ours, represented synchronous bilateral thyroid carcinomas located in separate lobes [10, 15]. Consequently, synchronous bilateral thyroid carcinomas with different histological subtypes are extremely rare. The presence of distant metastasis further complicates the diagnosis and treatment, presenting significant clinical challenges. It is imperative to obtain pathological confirmation and to thoroughly evaluate the potential benefits of therapeutic interventions.

Furthermore, a highly deceptive differential diagnosis pertinent to this case warrants careful discussion. According to the 2022 World Health Organization (WHO) classification of thyroid neoplasms, both PTC and FTC are grouped under the broad spectrum of differentiated thyroid carcinomas (DTC). A legitimate differential diagnosis in our case would be a “multifocal follicular-predominant papillary carcinoma”or the follicular variant of papillary thyroid carcinoma (FVPTC), considering that PTC can present with multifocality and follicular growth patterns. However, our case was definitively diagnosed as synchronous PTC and FTC. This distinction was based on the fact that the two malignancies presented as anatomically separate and distinct nodules. Histopathologically, the two geographically distinct nodules exhibited entirely divergent morphologies. The left-sided large nodule (Fig. 1-B4) demonstrated an exclusive microfollicular growth pattern consistent with FTC, lacking any papillary architecture or PTC-type nuclear features, which definitively rules out FVPTC. Conversely, the contralateral right-sided nodule showed classical features of PTC (e.g., papillary architecture, nuclear grooves, and pseudoinclusions) without an invasive follicular component. Crucially, the absence of any mixed or transitional zones within a single tumor mass strongly supports the diagnosis of synchronous independent primary tumors, rather than a single multifocal entity.

The pathogenesis of such synchronous tumors is debated. Most literature suggests a polyclonal origin (independent clones) [10]. This is supported by the distinct metastatic patterns observed in our patient: the right PTC remained localized, while the left FTC showed aggressive hematogenous spread to the hip.

For differentiated thyroid cancer (DTC) which accounts for over 90% and has a favorable prognosis, bone metastasis is not only a major factor threatening the quality of life of patients, but also a problem that urgently needs to be addressed in the current clinical diagnosis and treatment field. Early identification of DTC bone metastasis is crucial for improving patient prognosis. The treatment for DTC bone metastasis involves various approaches, such as surgical procedures, interventional radiation therapy, and external beam radiotherapy to treat local lesions, or the use of radiopharmaceuticals, tyrosine kinase inhibitors (such as lenvatinib, sorafenib, etc.) or bone-targeted drugs (including zoledronic acid, denosumab, and 99TC-methylene diphosphonate) to control the development of systemic bone metastases [16]. Surgical procedures are a common treatment method for DTC bone metastasis. The updated 2025 guidelines of the American Thyroid Association (ATA) consistently recommend that isolated and symptomatic bone metastases can be considered for complete surgical resection or stabilization [17, 18]. The main surgical indications include unstable bone structure, fractures, and refractory bone pain. Studies have shown that complete resection of oligometastatic lesions can significantly improve the survival rate of patients with DTC bone metastasis. Diagnosing FTC is notoriously difficult. As seen in our patient, the thyroid primary was clinically silent, which means “occult”. This highlights a critical lesson for orthopedists: while missing a primary thyroid tumor is rare once the histopathological diagnosis (e.g., TTF-1 + and Tg+) of bone metastasis is established, the true clinical pitfall lies earlier in the diagnostic timeline. Therefore, a vital word of caution for orthopedists is to avoid omitting a routine thyroid evaluation (including careful cervical palpation and ultrasonography) when initially assessing an unexplained lytic bone lesion or pathological fracture, even before a definitive biopsy result is available. Immunohistochemistry markers, specifically TTF-1(+) and Tg (+), were pivotal in our diagnosis.

An additional diagnostic challenge in this case was that the thyroid nodule was missed in the initial clinical evaluation. Although the left thyroid nodule measured 2.6 cm on ultrasonography, it remained clinically occult during the initial physical examination. This highlights the inherent limitations of conventional palpation and emphasizes the pivotal role of routine imaging modalities, particularly ultrasonography, in identifying occult primary tumors. Furthermore, integrating routine imaging evaluations like ultrasonography for patients presenting with suspicious symptoms—such as unexplained bone metastasis—can significantly improve the early detection of thyroid malignancies.

Management requires a multidisciplinary team (MDT). We prioritized hip replacement to restore mobility, followed by total thyroidectomy. Total resection was mandatory not just for the bilateral tumors, but to facilitate postoperative radioactive iodine (RAI) therapy for the bone metastasis. According to ATA guidelines, this comprehensive approach offers the best survival outcome.

In conclusion, this case underscores the prognostic importance of the more aggressive component (FTC with metastasis) in synchronous bilateral thyroid carcinomas. More importantly, it highlights a critical diagnostic pitfall: clinicians must not overlook routine thyroid examinations when evaluating unexplained pathological fractures. Early recognition, facilitated by a comprehensive initial workup, along with aggressive multidisciplinary multimodal treatment, are key to improving patient outcomes in such rare and complex cases.

Author contributions

Cai Zhenying and Liu Mengsong : Analyzed the date, was responsible for collecting the relevant literature, and wrote the original the manuscript. Zhang Jianyong and Peng Yunsong: Contributed to funding acquisition, project administration, designed the study and revised this manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Guizhou Provincial People’s Hospital Talent Fund (Hospital Talent Project [2022]-5; PI: Peng Yunsong) and the Youth Science and Technology Talent Support Program of Guizhou Provincial Association for Science and Technology (PY) and the National Natural Science Foundation of China under Grand 82502837 (ZJ), QiankeheLC-2026-001 (JZ) and the health research project of Guizhou Province gzwkj2025-302 (JZ).

Data availability

The raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation.

Declarations

Ethics approval and consent to participate

The studies involving humans were approved by Ethics Committee of Guizhou Provincial People’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements.Written informed consent was obtained from the patient for participation in this clinical case report.We confirm that informed consent was obtained from the participant.

Consent for publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images or clinical details. A copy of the written consent is available for review by the Editor of this journal.

Competing interests

The authors declare no competing interests.