Thyroid metastasis from lung adenocarcinoma: diagnostic pitfalls and individualized management in a six-patient case series and literature review
Case Series

Thyroid metastasis from lung adenocarcinoma: diagnostic pitfalls and individualized management in a six-patient case series and literature review

Yan Liu1, Dongqiang Yang2, Yanzhao Wu1, Ping Shi1

1Department of Otolaryngology Head and Neck Surgery, The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, Shijiazhuang, China; 2Department of Radiological Intervention, The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, Shijiazhuang, China

Contributions: (I) Conception and design: P Shi, Y Wu; (II) Administrative support: Y Wu; (III) Provision of study materials or patients: P Shi, Y Wu; (IV) Collection and assembly of data: P Shi, D Yang; (V) Data analysis and interpretation: P Shi, Y Liu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Ping Shi, MD. Department of Otolaryngology Head and Neck Surgery, The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, No. 169 Tianshan Road, Shijiazhuang 050000, China. Email: shirping@hebmu.edu.cn.

Background: Clinically recognized thyroid metastasis from lung adenocarcinoma is rare and may mimic a primary thyroid malignancy because imaging, cytologic, and immunophenotypic findings overlap. We aimed to characterize the diagnostic pitfalls, management, and outcomes of 6 consecutive patients and to define the limited circumstances in which thyroid-directed treatment may be reasonable.

Case Description: Six patients with pathologically confirmed thyroid metastasis from lung adenocarcinoma were treated at an academic tertiary cancer hospital between September 2018 and September 2023. The cohort included 4 men and 2 women, with a mean age of 57 years. Of the 6 patients included in this case series, 2 underwent surgical resection after their primary lung lesions were identified. One of these 2 patients experienced postoperative recurrence with subsequent bone metastasis, and the other developed multiple intrapulmonary metastases and thyroid metastasis after surgery. The remaining 4 patients already had advanced-stage disease at initial detection and were not eligible for surgery, so they received systemic anti-tumor therapy. Thyroid metastasis was detected in all 6 cases during tumor staging or post-treatment follow-up. At the time of examination, 5 patients had no specific clinical symptoms, while 1 patient presented with a palpable neck mass. All patients underwent neck ultrasound and computed tomography (CT) scanning. The diagnosis was confirmed by ultrasound-guided fine-needle aspiration biopsy in 5 patients (Cases 1 and 3–6). In the remaining patient (Case 2), cytological findings were suggestive of primary medullary thyroid carcinoma, and the diagnosis of metastatic lung adenocarcinoma was established by postoperative histopathology following thyroidectomy, which was also performed to prevent local functional impairment. As of the data cutoff date, 1 patient was still alive with disease, 4 patients died from metastatic disease, and 1 patient was lost to follow-up.

Conclusions: A new thyroid lesion in a patient with current or previous lung adenocarcinoma should prompt consideration of metastatic disease and tissue confirmation with a focused immunohistochemical panel. Systemic therapy remains the main treatment for most patients. Thyroidectomy should not be routine and may be considered only after multidisciplinary assessment for truly isolated/oligometastatic disease amenable to complete local control or for imminent airway, swallowing, or laryngeal morbidity. No survival benefit from surgery can be inferred from this small series.

Keywords: Lung adenocarcinoma; thyroid metastasis; fine-needle aspiration; immunohistochemistry; case series

Submitted Apr 26, 2026. Accepted for publication Jun 30, 2026. Published online Jul 17, 2026.

doi: 10.21037/gs-2026-0256

Highlight box

Key findings

• In this six-patient series, thyroid metastasis from lung adenocarcinoma was usually clinically silent, frequently occurred with metastatic disease elsewhere, and could mimic primary thyroid malignancy on imaging and cytology.

• Five patients were managed principally with systemic therapy. Only one underwent thyroid-directed surgery because of threatening local anatomy; no survival benefit from surgery can be inferred from this series.

• Accurate diagnosis depended on integrating the oncologic history, imaging, tissue sampling, and a focused immunohistochemical panel.

What is known and what is new?

• Clinically recognized thyroid metastasis from lung adenocarcinoma is rare, may resemble primary thyroid cancer, and has no clearly established surgical treatment strategy.

• This study combines six consecutive institutional cases with a targeted review of published patient-level cases and identifies practical diagnostic pitfalls. It also proposes a selective management framework in which thyroidectomy is reserved for truly isolated or oligometastatic disease suitable for complete local control, or for lesions threatening airway, swallowing, or laryngeal function.

What is the implication, and what should change now?

• A new thyroid lesion in a patient with current or previous lung adenocarcinoma should prompt consideration of metastasis and image-guided pathological confirmation. Systemic treatment should remain the main approach for most patients, while thyroid-directed intervention should be individualized through multidisciplinary assessment rather than performed routinely.

Introduction

Despite its rich vascular supply, the thyroid gland is an uncommon site of clinically recognized metastasis. In a recent single-center study, thyroid metastasis was identified in 9 of 9,714 patients with lung adenocarcinoma (approximately 0.1%), emphasizing the rarity of this presentation (1-7). Autopsy studies suggest that occult thyroid involvement is more common than clinically detected disease (2-6).

Thyroid metastasis from lung adenocarcinoma is diagnostically challenging. Lesions may present as focal hypoechoic nodules or diffuse gland enlargement, and cytomorphologic overlap with papillary thyroid carcinoma, high-grade follicular-derived thyroid carcinoma, anaplastic thyroid carcinoma, or medullary thyroid carcinoma can lead to error when morphology is interpreted without the oncologic history and immunophenotype (7-13).

The therapeutic importance of thyroidectomy is uncertain because most patients have disease outside the thyroid and require systemic treatment. Local treatment may nevertheless be considered for a truly isolated or oligometastatic deposit that can be completely controlled, or for a lesion threatening voice, swallowing, or airway function. We therefore reviewed six consecutive institutional cases and a targeted set of published patient-level reports to clarify diagnostic pitfalls, disease distribution, and individualized management rather than to advocate routine surgery. We present this article in accordance with the AME Case Series reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0256/rc).

Case presentation

Study design, registration, ethics, and case identification

This retrospective, single-center case series was conducted at The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, an academic tertiary cancer hospital in Shijiazhuang, Hebei, China. Six consecutive patients diagnosed between September 2018 and September 2023 were included. Eligibility required pathologic confirmation of thyroid metastasis by ultrasound-guided fine-needle aspiration and/or surgical histopathology together with a definitive diagnosis of primary lung adenocarcinoma. Cases without thyroid pathologic confirmation, metastasis from another lung histology, or direct extension from an adjacent cervical organ were excluded.

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital (No. 2024KS009). Written informed consent was obtained from all 6 patients and their legal representatives for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Clinical variables and missing data

The extracted variables included age, sex, TNM stage, smoking history, initial treatment of lung lesions, thyroid detection status, time interval from lung cancer diagnosis to thyroid metastasis, disease sites other than the thyroid, thyroid imaging results, pathological and immunohistochemical findings, treatment category, adverse events, follow-up duration, and survival status. These archived records were compiled for routine clinical diagnosis and treatment, rather than collected through standardized research protocols. As a result, the specific names, doses, and durations of systemic medications were not uniformly documented.

Imaging and literature-review methods

Thyroid ultrasonography and available computed tomography (CT) images were reviewed descriptively. None of the 6 patients underwent a comprehensive positron emission tomography (PET)/CT examination. Most patients underwent comprehensive bone imaging and chest and neck CT scans to assess their overall condition. Two patients underwent CT examinations at the local hospital, but the imaging results are currently unavailable. Enhanced CT was not used as a routine examination method for evaluating cervical masses. Neck ultrasound was used to assess the local condition of the thyroid gland. Ultrasound-guided thyroid biopsy results combined with pathological examination are considered the diagnostic gold standard.

A targeted literature search was performed in PubMed/Web of Science and Google Scholar from database inception through June 14, 2026, using combinations of “thyroid metastasis”, “metastasis to the thyroid”, “lung adenocarcinoma”, and “pulmonary adenocarcinoma”. Reference lists of eligible articles were screened manually. English-language reports were included when they described pathologically confirmed thyroid metastasis from lung adenocarcinoma and provided extractable patient-level clinical, imaging, diagnostic, treatment, or outcome data. Reports of non-adenocarcinoma lung primaries, direct cervical extension, duplicate cases, conference abstracts without sufficient detail, and aggregate series without extractable patient-level data were excluded. This was a targeted descriptive review, not a systematic review or meta-analysis; no formal risk-of-bias assessment was performed.

Clinical presentation and diagnosis

The cohort included four men and two women, with a mean age of 57 years (range, 45–72 years) (Table 1). Of the 6 patients included in this case series, 2 underwent surgical resection after their primary lung lesions were identified. One of these 2 patients experienced postoperative recurrence with subsequent bone metastasis, and the other developed multiple intrapulmonary metastases and thyroid metastasis after surgery. The remaining 4 patients already had advanced-stage disease at initial detection and were not eligible for surgery, so they received systemic anti-tumor therapy. Four patients had synchronous thyroid metastasis; two developed thyroid involvement 28 and 60 months after treatment of the primary lung cancer. Five lesions were detected incidentally during systemic work-up or surveillance, whereas Case 1 presented with a palpable anterior neck mass. None of the 6 patients had strictly isolated thyroid metastasis. Cases 1 and 3–6 had documented metastatic disease beyond the lung and thyroid; Case 2 had residual intrapulmonary lesions and no documented extrathoracic metastases, so it was not classified as isolated thyroid metastasis.

Table 1

Clinicopathologic features of the six institutional cases

Case Sex/age (years) Stage Smoking history Initial treatment method of the primary lung tumor Systemic treatment category Disease outside thyroid at diagnosis Thyroid presentation Time to detection of thyroid metastasis Thyroid imaging Diagnostic method Thyroid-directed treatment Outcome/follow-up
1 M/48 T1cN3M1c 20 years Surgery Chemotherapy Bone Palpable neck mass 28 mo Bilateral diffuse involvement; 3.5 cm FNA + IHC None LTFU, 13 mo
2 M/57 T1cN2M1c No Surgery None Residual intrapulmonary lesions; no documented extrathoracic metastases Incidental surveillance finding 60 mo Unilateral focal nodule; 1.5 cm Surgery after discordant FNA; IHC Total thyroidectomy + central dissection + radiotherapy AWD, 56 mo
3 F/58 T2bN3M1c No Antitumor drug therapy Targeted therapy Brain; bone Incidental systemic work-up Synchronous Unilateral focal nodule; 0.5 cm FNA + IHC None DOD, 6 mo
4 F/63 T3N3M1c No Antitumor drug therapy Targeted therapy Adrenal; brain; bone Incidental systemic work-up Synchronous Unilateral focal nodule; 1.6 cm FNA + IHC None DOD, 18 mo
5 M/45 T2aN3M1c 20 years Antitumor drug therapy Chemotherapy + immunotherapy Brain; liver Incidental systemic work-up Synchronous Bilateral diffuse involvement; 3.0 cm FNA + IHC None DOD, 16 mo
6 M/72 T3N3M1c 50 years Antitumor drug therapy Immunotherapy + targeted therapy Abdominal wall Incidental systemic work-up Synchronous Unilateral focal nodule; 5.4 cm FNA + IHC None DOD, 15 mo

None of the institutional cases had strictly isolated thyroid metastasis. Comprehensive molecular profiling and systematic patient-level PET/CT data were not available. Exact systemic agents, doses, and treatment durations were incompletely documented. AWD, alive with disease; DOD, dead of disease; F, female; FNA, fine-needle aspiration; IHC, immunohistochemistry; LTFU, lost to follow-up; M, male; mo, months; PET/CT, positron emission tomography/computed tomography.

Ultrasonography showed diffuse involvement in Cases 1 and 5 and focal hypoechoic nodules in Cases 2, 3, 4, and 6 (Figure 1). Available CT images showed low-attenuation thyroid lesions or asymmetric enlargement (Figure 2). Five patients were diagnosed by ultrasound-guided fine-needle aspiration. In Case 2, preoperative cytology suggested medullary thyroid carcinoma; definitive histology and immunohistochemistry after thyroidectomy supported pulmonary origin, with AE1/AE3, TTF-1, CK19, and Napsin A positivity and thyroglobulin, BRAF immunostain, and parathyroid hormone negativity (Figure 3). Comprehensive genomic profiling was not available for the institutional cohort. The negative BRAF result in Case 2 was an immunohistochemical finding and should not be interpreted as molecular genotyping.

Figure 1 Representative thyroid ultrasonography from the institutional series. (A,B) Case 2; (C) Case 3; (D,E) Case 5; (F) Case 4; (G) Case 6; (H,I) Case 1. Cases 1 and 5 show diffuse heterogeneous hypoechogenicity; Cases 2, 3, 4, and 6 show focal hypoechoic nodules. Doppler images demonstrate intralesional or peripheral vascularity.
Figure 2 Representative CT images from the institutional series. (A,B) Case 2; (C) Case 3; (D) Case 5; (E) Case 6. Arrows indicate low-attenuation thyroid lesions or asymmetric thyroid enlargement. CT acquisition protocols were heterogeneous, and contrast status was not uniformly retrievable. Diagnostic CT images were not available for Case 1 and Case 4. CT, computed tomography.
Figure 3 Pathologic findings in Case 2. (A) Preoperative fine-needle aspiration cytology showing malignant epithelial clusters (hematoxylin and eosin staining, 200×). (B) Postoperative histology confirming metastatic adenocarcinoma involving the thyroid (hematoxylin and eosin staining, 20×). (C-H) Immunohistochemical staining results (20×) are shown, with the following markers in order: TTF-1(+), CK19(+), Napsin A(+), TG(−), PTH(−), and BRAF(−).

Treatment and outcomes

Management was individualized according to systemic disease burden, performance status, available molecular information, and anticipated local risk. Systemic therapy was the principal treatment in 5 patients. Only Case 2 (1/6, 16.7%) received thyroid-directed surgery, consisting of total thyroidectomy with right central compartment dissection followed by radiotherapy and targeted therapy. The indication was not an isolated metastasis or an expectation of cure. Rather, the lesion was deep within the gland, adhered to the superficial esophageal wall, and encased a right non-recurrent laryngeal nerve at the laryngeal entry point, creating a substantial risk of future voice, swallowing, or airway morbidity. Meticulous dissection preserved the nerve (Figure 4).

Figure 4 Intraoperative findings in Case 2. (A) The lesion was located at the laryngeal entry point, encased the non-recurrent laryngeal nerve, and adhered to the superficial esophageal wall. (B) The non-recurrent laryngeal nerve was preserved after meticulous sharp dissection. These intraoperative images are published with patient consent.

Case 2 developed transient postoperative hoarseness without hypocalcemia or dysphagia. No other unexpected surgery-related adverse event was recorded. At the December 31, 2025 data cutoff, Case 2 was alive with disease after 56 months, 4 patients had died of disseminated cancer, and one was lost to follow-up after 13 months (16.7%) despite attempted contact. The median observed follow-up after diagnosis of thyroid metastasis was 15.5 months (range, 6–56 months) (Figure 5). The favorable duration observed in the operated patient cannot be attributed to surgery in the absence of a comparator and given the markedly different disease burden among patients.

Figure 5 Patient-level course of the six institutional cases. Bars show observed follow-up from diagnosis of thyroid metastasis to last contact or death (data cutoff December 31, 2025). mo, months; sync, synchronous.

Targeted literature-review findings

The search identified 21 published patient-level cases from 10 reports (4,7-11,14-17) (Table 2). The reports included clinically occult lesions, PET/CT-detected bilateral thyroid uptake, tumor-to-tumor metastasis within a thyroid neoplasm, and cases initially interpreted as primary thyroid carcinoma. Surgical procedures were common in published reports, but this pattern is strongly affected by referral and publication bias and cannot be used to estimate how often thyroid-directed treatment is required in routine practice or whether it improves survival.

Table 2

Published patient-level cases identified by the targeted literature review (21 cases from 10 reports)

Report/case Age (years)/sex Thyroid presentation or imaging Timing Other metastatic disease Initial diagnostic issue Thyroid procedure Outcome/follow-up Molecular information
Ghossein et al. 2021 (4)
   Case 1 83/F 1.4-cm unilateral nodule 36.8 mo Bone; spine NA Resection AWD, 21.2 mo NA
   Case 2 44/F 2.5-cm bilateral lesion 1.1 mo Bone; liver No Resection DOD, 16.4 mo NA
   Case 3 63/M 3.0-cm unilateral lesion adjacent to papillary microcarcinoma NA Brain; intrapulmonary lesion; cervical nodes Initially ATC Resection AWD, 14 mo NA
   Case 4 28/M 6.2-cm unilateral lesion NA Bone; gastrointestinal tract; peritoneum NA Resection DOD, 6.3 mo NA
Rossini et al. 2015 (14) 72/M 4.0-cm thyroid lesion Synchronous None reported NA Resection AWD, 6 mo NA
Tu and Lin 2021 (15) 69/F Bilateral hypoechoic lesion with irregular borders and microcalcifications NA None reported Mimicked papillary thyroid carcinoma Resection NA NA
Elouarith et al. 2022 (8) 62/F 1.6-cm solid hypoechoic EU-TIRADS 5 nodule Synchronous Pleural and pulmonary lesions Initial thyroid-primary concern Resection NA NA
Yadav et al. 2023 (9) 57/F Multiple thyroid nodules; 1.5-cm dominant nodule Synchronous None reported Intratumoral metastasis to NIFTP Resection LTFU NA
Momin et al. 2024 (10) 35/F Diffuse thyroid enlargement Synchronous Extensive nodal disease No Excisional biopsy LTFU NA
Gao et al. 2025 (7)
   Case 1 NA Bilateral multiple lesions; 4.0 cm 0.2 mo Nodal, brain, pleural, intra-abdominal disease NA Surgery/biopsy DOD, 5 mo NA
   Case 2 NA Bilateral multiple lesions; 3.9 cm 5.1 mo Nodal, bilateral lung, bone disease NA Surgery AWD, 35 mo NA
   Case 3 NA Bilateral multiple lesions; 1.8 cm 0.3 mo Hilar/mediastinal nodes; pleura; bone; brain NA FNA AWD, 7 mo NA
   Case 4 NA Unilateral unifocal lesion; 1.9 cm 3.7 mo Bone; spleen; bilateral lungs; pleural effusion NA FNA DOD, 56 mo NA
   Case 5 NA Bilateral multiple lesions; 0.7 cm 0.1 mo Cervical/mediastinal nodes; bone; pleural/pericardial effusion NA FNA AWD, 28 mo NA
   Case 6 NA Bilateral multiple lesions; 4.7 cm 12 mo Brain; bilateral lungs; hilar/mediastinal nodes; pleural effusion NA FNA AWD, 33 mo NA
   Case 7 NA Bilateral multiple lesions; 0.8 cm 8.4 mo Bilateral lungs; nodal, bone, pleural/pericardial disease NA FNA AWD, 84 mo NA
   Case 8 NA Bilateral multiple lesions; 1.0 cm 12.3 mo Nodal, bone, pleural, subcutaneous disease NA Surgery/biopsy DOD, 19 mo NA
   Case 9 NA Bilateral multiple lesions; 3.2 cm 0.7 mo Nodal, adrenal, kidney, breast, liver, pleural, subcutaneous disease NA Autopsy DOD, 1 mo NA
Liu et al. 2025 (11) 72/M 2.3-cm unilateral hypoechoic nodule Synchronous None reported Initially HGFCTC Resection AWD, 16 mo BRAF V600E
Özdemir Bek et al. 2025 (16) 61/M Bilateral thyroid enlargement with FDG uptake on PET/CT Synchronous None reported No Thyroid biopsy NA NA
Wang et al. 2026 (17) 46/F 6.0-cm left thyroid mass with contralateral PTC Synchronous; thyroid first No disease outside lung/thyroid reported Complex tumor-to-tumor metastasis Total thyroidectomy DOD, 16 mo EGFR L858R

“None reported” does not prove complete absence of disease outside the thyroid because staging and reporting varied across publications. ATC, anaplastic thyroid carcinoma; AWD, alive with disease; DOD, dead of disease; EU-TIRADS, European Thyroid Imaging Reporting and Data System; F, female; FDG, fluorodeoxyglucose; FNA, fine-needle aspiration; HGFCTC, high-grade follicular-derived thyroid carcinoma; LTFU, lost to follow-up; M, male; mo, months; NA, not available; NIFTP, non-invasive follicular thyroid neoplasm with papillary-like nuclear features; PET/CT, positron emission tomography/computed tomography; PTC, papillary thyroid carcinoma.

Discussion

Key findings and clinical context

This series confirms that thyroid metastasis from lung adenocarcinoma is usually clinically silent, commonly accompanies disease outside the thyroid, and can imitate several primary thyroid malignancies. Only 1 of 6 institutional patients required thyroid-directed treatment. The remaining patients were managed principally with systemic therapy, supporting the view that the thyroid lesion usually reflects systemic cancer biology rather than an independent surgical disease.

Diagnostic work-up and the role of imaging

A practical diagnostic sequence begins with review of the oncologic history and whole-body disease distribution, followed by thyroid ultrasound and image-guided tissue sampling. PET/CT may draw attention to an FDG-avid thyroid lesion during lung-cancer staging or follow-up, as illustrated by a recent report of bilateral FDG-avid thyroid enlargement (16), but uptake is not specific for metastasis. Tissue confirmation remains necessary when the result would change management. On cytology or histology, a pattern of Napsin A and/or TTF-1 positivity together with thyroglobulin and usually PAX8 negativity supports pulmonary origin; calcitonin is useful when medullary thyroid carcinoma is considered. TTF-1 should not be interpreted alone because it may be expressed in thyroid tumors. The diagnostic and management sequence is summarized in Figure 6, and the main differential diagnostic features are presented in Table 3.

Figure 6 Diagnostic and management workflow for suspected thyroid metastasis from lung adenocarcinoma. CT, computed tomography; FNA, fine-needle aspiration; IHC, immunohistochemistry; PET, positron emission tomography.

Table 3

Differential diagnosis of thyroid metastasis from lung adenocarcinoma and selected primary thyroid malignancies

Entity Clinical clue Imaging clue Cytology clue Typical IHC profile Common pitfall Most useful confirmatory step
Metastatic lung adenocarcinoma to thyroid History of lung adenocarcinoma; the thyroid lesion may be incidental or present with local or compressive symptoms Focal hypoechoic nodule or diffuse thyroid enlargement; low-attenuation lesion on CT Malignant epithelial clusters; may mimic papillary, high-grade, or medullary thyroid carcinoma TTF-1 positive and/or Napsin A positive; thyroglobulin negative; usually PAX8 negative; calcitonin negative in most cases Assuming that a new thyroid lesion is primary thyroid cancer without integrating the oncologic history Correlate FNA with chest imaging and use a focused pulmonary-versus-thyroid IHC panel
Papillary thyroid carcinoma Often a primary thyroid lesion without a prior lung adenocarcinoma history Hypoechoic nodule with irregular margins, microcalcifications, or a taller-than-wide shape Papillary nuclear features, grooves, inclusions, and chromatin clearing Thyroglobulin positive and/or PAX8 positive; TTF-1 may overlap, so thyroid-lineage markers are important Overcalling metastatic papillary-pattern lung adenocarcinoma as papillary thyroid carcinoma on morphology alone Confirm with thyroglobulin/PAX8 and the overall clinicopathologic context
Medullary thyroid carcinoma May present with a thyroid mass, cervical lymph nodes, or elevated serum calcitonin or CEA Solid hypoechoic thyroid nodule; imaging findings are not specific Plasmacytoid, spindled, or discohesive cells; may overlap with metastatic adenocarcinoma Calcitonin positive, CEA positive, and neuroendocrine-marker positive; thyroglobulin negative Misclassifying metastatic lung adenocarcinoma as medullary thyroid carcinoma when calcitonin has not been checked Measure serum calcitonin and include calcitonin in the IHC panel
Poorly differentiated/high-grade follicular-derived thyroid carcinoma Aggressive thyroid primary, usually accompanied by destructive local thyroid disease Large infiltrative thyroid lesion; imaging may overlap with metastasis High-grade malignant cells with limited specific differentiation Usually supported by thyroid-lineage markers; pulmonary markers are not dominant Relying on high-grade morphology alone when pulmonary metastasis is the true source Use combined morphology, IHC, and prior cancer history before labeling the lesion as primary thyroid cancer

CEA, carcinoembryonic antigen; CT, computed tomography; FNA, fine-needle aspiration; IHC, immunohistochemistry.

Molecular profiling

Our institutional series does not support conclusions about molecular alterations because comprehensive sequencing was unavailable. We therefore restrict molecular discussion to its potential adjunctive role in selected published cases. Paired or tumor-specific molecular findings can support the site of origin when morphology and immunohistochemistry remain equivocal; published examples include BRAF V600E-mutated lung adenocarcinoma (11) and an EGFR L858R-positive lung adenocarcinoma metastatic to a thyroid neoplasm (17). Molecular results should complement, not replace, clinicopathologic correlation.

When is local treatment reasonable?

The prognosis of patients with thyroid metastasis from lung adenocarcinoma is generally determined by total metastatic burden, tumor biology, response to systemic therapy, and performance status. No survival advantage from thyroidectomy can be inferred from our single operated case, and routine thyroidectomy is not justified. However, in selected patients, resection of the metastatic lesion followed by radiotherapy and targeted therapy may achieve better control of the disease (18-22). In clinical practice, local treatment may be considered in two distinct settings: (I) a strictly isolated or oligometastatic thyroid lesion after comprehensive staging, when the primary tumor and other sites are controlled and complete local treatment is feasible; or (II) impending local morbidity, including progressive hoarseness, dysphagia, airway compromise, bleeding, or invasion of the trachea, esophagus, or laryngeal nerve. Diagnostic surgery may rarely be necessary when minimally invasive sampling remains inconclusive and the result will change treatment.

None of our institutional patients met a strict isolated-metastasis criterion. Case 2 had residual intrapulmonary disease and was selected for local treatment because of threatening anatomy and relatively limited systemic burden, not because the thyroid was the only disease site. For patients with widespread or rapidly progressive disease and no compressive symptoms, systemic therapy and observation of the thyroid lesion are generally more appropriate. Decisions should be individualized in a multidisciplinary setting and should explicitly balance expected functional benefit against operative risk. These selection principles are incorporated into the multidisciplinary pathway in Figure 6.

Strengths and limitations

Strengths include consecutive case identification, pathologic confirmation, imaging-pathology correlation, and detailed description of a function-preserving operation. Limitations include the retrospective single-center design, six-patient sample, heterogeneous systemic treatment, absence of standardized comorbidity, PET/CT, contrast-CT, and genomic data, and one patient lost to follow-up. The literature review was targeted and descriptive and is vulnerable to publication bias and incomplete reporting. These limitations preclude estimates of treatment frequency, comparative effectiveness, or causal survival benefit.

Conclusions

Thyroid metastasis from lung adenocarcinoma is rare but should be considered when a new thyroid lesion develops in a patient with current or previous lung adenocarcinoma. Accurate diagnosis requires integration of disease history, imaging, fine-needle aspiration or histology, and a focused immunohistochemical panel. For most patients, treatment is driven by systemic disease. Thyroidectomy should not be routine; it may be considered after multidisciplinary assessment for a truly isolated or oligometastatic lesion amenable to complete local control or for a lesion that threatens airway, swallowing, or laryngeal function. Multicenter registries with standardized imaging, staging, molecular, treatment, and patient-reported functional data are needed.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0256/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0256/prf

Funding: This work was supported by the Natural Science Foundation of Hebei Province (No. H2020206273) and the Department of Health of Hebei Province (No. 20240378).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0256/coif). P.S. reports receiving research funding from the Natural Science Foundation of Hebei Province (No. H2020206273) and the Department of Health of Hebei Province (No. 20240378). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work and for 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 Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital (No. 2024KS009). Written informed consent was obtained from all six patients and their legal representatives for the publication of this case series 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/.

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Cite this article as: Liu Y, Yang D, Wu Y, Shi P. Thyroid metastasis from lung adenocarcinoma: diagnostic pitfalls and individualized management in a six-patient case series and literature review. Gland Surg 2026;15(8):239. doi: 10.21037/gs-2026-0256

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