Thyroid Metastasis From Colorectal Adenocarcinoma: A Case Report and Literature Review

ABSTRACT

Colorectal adenocarcinoma is one of the most common malignancies worldwide. Although metastases typically affect the liver, lungs, and peritoneum, thyroid involvement is extremely rare, with fewer than 50 cases documented to date. We present the case of a 61‐year‐old woman with a history of sigmoid colon adenocarcinoma who subsequently developed a solitary pulmonary metastasis treated surgically. During follow‐up, a suspicious thyroid nodule with cervical lymphadenopathy was detected. The patient underwent total thyroidectomy with lymph node dissection, and histopathological evaluation revealed a moderately differentiated adenocarcinoma. Immunohistochemistry demonstrated negativity for CK7 and TTF‐1, with diffuse positivity for CDX2, CK20 and SATB2, confirming colorectal origin. Immunohistochemistry demonstrated negativity for CK7 and TTF‐1, with diffuse positivity for CDX2, CK20 and SATB2, confirming colorectal origin. Additionally, we performed a literature review (2014–2025) and present a table summarizing 24 reported cases of thyroid metastases from colorectal adenocarcinoma. This case underscores the importance of considering thyroid metastasis in patients with colorectal cancer who present with thyroid nodules. Awareness of this rare manifestation and the use of immunohistochemical markers are essential to achieve an accurate diagnosis and to guide appropriate clinical management.

Key Clinical Message

Colorectal adenocarcinoma rarely metastasizes to the thyroid. Awareness of this possibility and the use of immunohistochemical markers are crucial for differentiating metastases from primary thyroid neoplasms and guiding appropriate management.

Positron emission tomography‐computed tomography scan demonstrating thyroid metastasis from colorectal carcinoma in the context of metastatic disease.

1. Introduction

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy and the second leading cause of cancer‐related death worldwide [1]. Despite improvements in survival rates, metastatic CRC remains a lethal disease, with a 5‐year survival rate of approximately 14% [2]. The most common sites of metastasis include the liver, lungs, peritoneum, bones, brain, and distant lymph nodes [3].

The thyroid gland is an uncommon site for metastasis, accounting for only 1.4%–3% of all cases undergoing surgery for suspected thyroid cancer [4]. Metastatic spread of CRC to the thyroid is extremely rare, with around 50 cases reported in the literature to date [5].

The aim of this article is to present a case of metastatic colorectal cancer with pulmonary and thyroid involvement, diagnosed by immunohistochemistry after histopathological confirmation of the primary colonic lesion.

2. Case History

2.1. Patient Information and Physical Examination

We present the case of a 61‐year‐old female with a history of well‐controlled arterial hypertension, hysterectomy, laparoscopic cholecystectomy, and passive tobacco exposure due to a smoking spouse. She presented to the emergency department with a five‐day history of progressive abdominal pain and distension, absence of bowel movements, and unintentional weight loss during the preceding 6 months. On physical examination, she was tachycardic, with abdominal distension and diffuse tenderness to palpation; no hernial defects were detected. Digital rectal examination showed no fecal impaction or intraluminal masses.

2.2. Diagnosis, Treatment and Follow‐Up

Abdominal computed tomography (CT) demonstrated a tumoral lesion in the sigmoid colon with proximal small‐bowel dilation. Given these findings, an urgent laparotomy with sigmoidectomy and colorectal anastomosis was performed. The immediate postoperative course was uneventful, with satisfactory recovery of bowel function.

Histopathological examination confirmed a moderately differentiated adenocarcinoma of the colon with low microsatellite instability (MSI). Five of twelve lymph nodes were positive (5/12). Staging investigations, including contrast‐enhanced CT of the chest and abdomen, showed no distant metastatic disease, consistent with T3N2M0 (stage III). The patient received adjuvant chemotherapy with capecitabine and oxaliplatin (XELOX); follow‐up imaging showed no locoregional recurrence.

One year later, surveillance chest CT identified an 18‐mm pulmonary nodule in the right lower lobe, highly suspicious for metastasis. The lesion was resected by video‐assisted thoracoscopic surgery (VATS). Immunohistochemistry (IHC) reported a moderately differentiated metastatic adenocarcinoma, likely of distal gastrointestinal origin, with low MSI; consequently, a new adjuvant chemotherapy regimen with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRI) was initiated.

Two years thereafter, during follow‐up, the patient exhibited elevated carcinoembryonic antigen (CEA) levels. An 18‐fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) demonstrated diffusely increased metabolic activity in both thyroid lobes, greater on the left, with a maximum standardized uptake value (SUVmax) of 8.46 (Figure 1).

FIGURE 1.

Fused 18F‐FDG PET/CT images: (A, B) coronal views and (C) axial view. Diffusely increased uptake is observed in both thyroid lobes, greater in the left lobe (white arrows); SUVmax = 8.46. Source: Image provided by the authors.

Accordingly, a thyroid ultrasound was performed, which revealed a solid hypoechoic isthmic nodule extending into the left lobe, measuring 30 × 9 × 16 mm, with internal microcalcifications (highly suspicious). In addition, a right level VI cervical lymph node was identified, oval, measuring 8 × 5 mm, with loss of fatty hilum and internal calcifications. Thyroid function tests were within normal limits.

2.3. Conclusion and Results

Ultrasound‐guided fine‐needle aspiration (US‐FNA) of the suspicious thyroid lesion was performed. Cytologic smears were hypercellular and were reported as Bethesda V (suspicious for malignancy). In conjunction with the oncology service and given the isthmic nodule with extension into the left lobe, its considerable size, the presence of microcalcifications, the suspicious cervical adenopathy, and the Bethesda V cytology, total thyroidectomy with cervical lymph node dissection was considered the most appropriate management for oncologic control, staging, and definitive histopathologic confirmation. The postoperative course was favorable and the patient experienced a good clinical recovery. Histopathological examination of the thyroid specimen confirmed a moderately differentiated adenocarcinoma with positive lymphovascular invasion (Figure 2). Tumor involvement was present in four of six lymph nodes (4/6), with extranodal extension.

FIGURE 2.

Cytopathology of tumor cells in the thyroid gland. Hematoxylin and eosin staining. Thyroid parenchyma showing a malignant epithelial lineage tumor lesion, characterized by a proliferation of glandular structures with disorganized atypia, cystic dilatation containing mucinous material, and surrounded by fibrotic, sclerotic stroma with chronic inflammation. (A) Low‐power view of the thyroid gland (4×). Adenocarcinoma involvement is observed in the upper right corner (black arrow). (B) Thyroid parenchyma (10×). Moderately differentiated adenocarcinoma is evident (black arrow). (C, D) Thyroid parenchyma (40×). Adenocarcinoma with solid and glandular areas infiltrating thyroid follicles (black arrow). Source: Image provided by the authors.

IHC demonstrated negativity for cytokeratin 7 (CK7) and thyroid transcription factor‐1 (TTF‐1) in the thyroid tissue, and diffuse positivity for caudal type homeobox 2 (CDX2), cytokeratin 20 (CK20) and special AT‐rich sequence‐binding protein 2 (SATB2) in the neoplastic cells—findings compatible with thyroid metastasis from a primary colorectal adenocarcinoma (Figure 3). Genetic testing showed no mutations in exons 2, 3, or 4 of the KRAS, NRAS, and HRAS genes.

FIGURE 3.

Immunohistochemistry of tumor cells in the thyroid gland. (A) Low‐power view of the thyroid gland (4×). CK7 staining is positive in thyroid follicles and negative in the metastatic lesion (black arrow). (B) Thyroid parenchyma (40×). CK20 shows positive staining in metastatic glandular structures, consistent with gastrointestinal adenocarcinoma. (C) Thyroid parenchyma (40×). CDX2 is negative in native thyroid tissue and positive in metastatic lesions. Source: Image provided by the authors.

By consensus of the multidisciplinary team, systemic chemotherapy was resumed with the FOLFOX regimen (fluorouracil, leucovorin and oxaliplatin), with an adequate clinical response. The patient is currently alive, with 24 months of follow‐up since the diagnosis of thyroid metastasis of colorectal origin.

3. Discussion

Thyroid metastases originating from CRC are extremely rare, with around 50 cases reported in the literature to date [6, 7]. Despite its rich vascular supply, the thyroid gland is an uncommon site for metastatic disease. This has been attributed to factors such as high iodine content, turbulent blood flow, and elevated oxygen pressure, which are thought to hinder tumor implantation and proliferation [8, 9].

In the present case, we describe a patient with a history of stage III sigmoid colon adenocarcinoma who developed pulmonary and thyroid metastases during clinical follow‐up. Pulmonary involvement preceded the thyroid finding, consistent with patterns described in the literature, in which thyroid metastases typically occur as late or synchronous events in patients with existing pulmonary or hepatic dissemination [5, 6]. A rare case of tumoral thrombosis involving the tricuspid valve and the superior vena cava following hepatic and pulmonary spread has also been documented [10].

A 2013 literature review identified 34 reported cases of colon carcinoma metastasis to the thyroid dating back to 1931 [11]. We performed a literature search from 2014 to the present to identify articles describing colorectal cancer metastases to the thyroid gland across multiple databases, including PubMed, the Cochrane Library, and MEDLINE. Since the 2013 review, at least 24 cases of thyroid metastases of colorectal origin have been reported and are summarized in Table 1.

TABLE 1.

Reported cases of thyroid metastases from colorectal adenocarcinoma (2014–2025). Summary of 24 cases.

Author, year	Age/sex	Presentation	Diagnostic method	FNA	Thyroid treatment	Other metastases	IHC/markers	Outcome (follow‐up, months)
Ozawa et al. [12], 2015	72/F	Found on follow‐up	US, PET/CT.	Metastasis from CCR	ST	Lung, adrenal	CK20+	Unknown
Payandeh et al. [13], 2016	54/M	Enlarging neck mass	US, CT, scintigraphy	Interpreted as ATC	TT	Lung	CK7+; CDX2−; CK20−; TTF‐1−	6 months, alive
Roloff et al. [14], 2016	42/F	Dysphagia	US	Metastasis from CCR	TT	Liver, lung	CDX2+, CK20+	Unknown
Mennet et al. [15], 2016	68/M	Found on follow‐up	PET/CT.	Unrealized	Two‐stage TT + CND	Iliac‐parietal nodules	CK20+; CK7−	Unknown
Minami et al. [16], 2016	61/F	Cervical mass and hoarseness	PET/CT, US	Interpreted as PTC	TT + BND	Lung, liver	CK20+; CK7−; TTF‐1−	24 months, alive
Nicosia et al. [17], 2016	75/M	Found on follow‐up	PET/CT, US.	Metastasis from CCR	Right LT	Lung	CDX2+; TTF‐1−	Unknown
Coelho et al. [18], 2017	64/F	Enlarging neck mass	PET/CT, US	Metastasis from CCR	LT + right CND	Lung, liver, pleura, pericardium, peritoneum	CDX2+, CK20+; CK7−; TTF‐1−	15 months, alive
Amante et al. [19], 2018	46/M	Cervical mass and hoarseness	CT, US	Suspected PTC	TT + tumor debulking (tracheostomy)	Larynx, trachea, esophagus, lung, bone	Not reported	2 months, died
Kim et al. [20], 2018	50/M	Enlarging neck mass	PET/CT, CT	Unrealized	Right LT + right SND	Para‐aortic/cervical lymph nodes	CDX2+; Tg−; TTF‐1−	12 months, alive
Scepanovic et al. [21], 2020	71/M	Found on follow‐up	CT, FNA	Metastasis from CCR	TT	Lung	CDX2+; Tg+; Calcitonin−; HBME1−; TTF‐1−	11 months, died
Zafar et al. [22], 2020	57/F	Enlarging neck mass; dysphagia	PET/CT, US, FNA	Interpreted as PTC	TT + right CND	Lung	CK20+, CDX2+; CK7−; TTF‐1−; PAX8−	Unknown
Mori et al. [23], 2020	45/F	Found on follow‐up	CT, PET/CT, US	Non‐diagnostic	Right LT + lymph node dissection	Lung	CK20+, CDX2+; CK7−; TTF‐1−	24 months, alive
Rojo et al. [24], 2020	85/F	Dysphonia; dysphagia	PET/CT, US	Malignancy	Right LT	Lung	CK20+, CDX2+; CK7−	Unknown
Ciriano et al. [25], 2020	50/F	Enlarging neck mass; dysphonia	PET/CT, US, CT	Suspected malignancy	TT + right CND + right LND	Lung	CDX2+, CK20+, TTF‐1−; CK7−	5 months, alive
Luo et al. [26], 2020	34/F	Enlarging neck mass; dysphonia	US, PET/CT	Interpreted as PTC	TT + BND	Lung	CDX2+, CK20+; TTF‐1−; PAX8−	12 months, alive
Kim H et al. [7], 2021	53/F	Found on follow‐up	CT, PET, US	Not reported	TT	None reported	Not reported	42 months, alive
Momin et al. [27], 2022	62/F	Found on follow‐up	US, MRI, PET/CT	Poorly differentiated thyroid carcinoma or metastasis	Right LT + right LND	Lung, liver	CDX2+, CK20+	Unknown
Mardani et al. [28], 2022	55/F	Found on follow‐up	PET/CT	Interpreted as PTC	TT + CND	Lung	CK7+; CK20+; CDX2+; TTF‐1−	Unknown
Li H et al. [6], 2023	54/F	Found on follow‐up	US	Interpreted as primary thyroid carcinoma.	TT	Lung	CDX2+, CK20+; TTF‐1−; Tg−; CK7−	60 months, alive
Hussain et al. [5], 2023	64/F	Enlarging neck mass; dysphagia	US	Malignancy	No surgery (palliative CT)	Lung, liver	CDX2+, CK20+; WT1−; CK7−; P63−; PAX8−; TTF‐1−	Unknown
Le [29], 2023	61/F	Vocal cord paralysis and laryngeal stridor; enlarging neck mass	CT, US	Atypical cells	Not reported (palliative RT + CT)	Lung	CDX2+, CK20+; CK7−; TTF‐1−	Unknown
Chen Yet al. [8], 2023	54/F	Enlarging neck mass	US	Suspected malignancy	LT + CND	Lung, left neck	CDX2+, CEA+; CK7−; Tg−; Calcitonin−; Synaptophysin−; HBME1−	48 months, alive
Lampropoulou et al. [9], 2023	45/F	Enlarging neck mass	US	Malignancy	TT + partial resection of thyroid cartilage	Lung	CDX2+, CK20+; CK7−; TTF‐1−	Unknown
Wang et al. [30], 2024	46/F	Enlarging neck mass	US	Interpreted as PTC	ST	Peritoneum	CDX2+, CK20+; TTF‐1−; Tg−	35 months, died

Abbreviations: ATC, anaplastic thyroid carcinoma; BND, bilateral neck dissection; CDX2, caudal‐type homeobox transcription factor 2; CEA, carcinoembryonic antigen; CK20, cytokeratin 20; CK7, cytokeratin 7; CND, central neck dissection (central compartment dissection); CT, chemotherapy; CT, computed tomography; F, female; FNA, fine‐needle aspiration; HBME1, Hector Battifora mesothelial‐1 or Mesothelial cell antibody; IHC, immunohistochemistry; LND, lateral neck dissection; LT, lobectomy; M, male; MRI, magnetic resonance imaging; P63, protein P63; PAX8, paired box gene 8; PET/CT, PET with computed tomography; PTC, papillary thyroid carcinoma; RT, radiotherapy; SND, selective neck dissection; ST, subtotal thyroidectomy; Tg, thyroglobulin; TT, total thyroidectomy; TTF‐1, thyroid transcription factor‐1; US, ultrasound.

In the present series of 24 cases collected between 2014 and 2025, thyroid metastases of colorectal origin exhibited a clinical pattern consistent with previous reports: predominance in female patients (18/24; 75%), a variable presentation that included incidental findings on imaging studies (9/24; 37.5%) and symptomatic cervical mass (6/24; 25%), and a strong association with concomitant metastatic disease, particularly pulmonary involvement (20/24; 83.3%). These findings confirm historical observations of the condition and extend prior series that reported the metachronous appearance of thyroid metastases and their frequent association with systemic disease [11].

From a diagnostic standpoint, suspecting a colorectal metastatic origin in a thyroid lesion is a clinical challenge. Several reports have described persistent or unexplained elevations of CEA associated with thyroid neoplasms—particularly medullary thyroid carcinoma [31, 32, 33]; however, this finding is neither specific nor consistently present in thyroid metastases from colorectal cancer and should therefore be interpreted with caution [6]. In our case, the patient had elevated CEA levels, and PET/CT revealed increased metabolic activity in the thyroid gland.

In the series compiled for the present study, FNA showed initial utility but important limitations: only in 5/24 cases (20.8%) was the FNA interpreted directly as “metastasis from colorectal carcinoma,” in 6/24 cases (25.0%) it was reported as a primary thyroid carcinoma (papillary or anaplastic), and in 15/24 cases (62.5%) the cytology indicated “malignancy” or a nonspecific process. These findings corroborate studies and reviews documenting discrepancies between cytology and the definitive diagnosis, and they highlight the risk of misinterpreting FNA as a primary thyroid carcinoma in patients with a history of colorectal cancer [11]. Therefore, confirmation by IHC—using panels that include CDX2, CK20, and, when available, SATB2—and demonstration of negativity for thyroid markers such as TTF‐1 and CK7 are essential to establish metastatic origin and to avoid inappropriate treatment [7, 8, 9].

In terms of management, the large majority of patients in the series underwent surgical intervention (22/24; 91.7%) when systemic conditions and performance status permitted, reflecting a tendency to incorporate locoregional control—total thyroidectomy or lobectomy with lymph node dissection as indicated—within a multidisciplinary strategy combined with systemic therapy. Nevertheless, oncologic outcomes and survival were heterogeneous: reported mortality in the series was 3/24 (12.5%) during the follow‐up period. Some patients achieved prolonged survival after resection and adjuvant chemotherapy, whereas others experienced adverse outcomes related to extensive metastatic disease. These findings are consistent with the series by Froylich et al. [11], which suggests that thyroid resection may benefit carefully selected patients with controllable metastatic burden, although any potential benefit must be assessed on a case‐by‐case basis by a multidisciplinary team. In our case, the patient underwent total thyroidectomy with cervical lymph node dissection because of diffuse thyroid uptake on PET/CT, an FNA suspicious for malignancy, and sonographic evidence of nodal involvement.

In practical terms, the accumulated evidence supports several recommendations: (1) maintain a high index of suspicion for a new thyroid lesion in patients with a history of colorectal cancer; (2) use FNA as the initial diagnostic approach, but do not base definitive management solely on cytology when clinical or imaging findings are discordant; (3) request early IHC panels (including CDX2, CK20, and SATB2, with TTF‐1 and CK7 to assess thyroid‐origin negativity); and (4) discuss each case in a multidisciplinary tumor board to decide between surgical intervention and systemic therapies according to disease extent and the patient's functional status.

4. Conclusion

Thyroid metastases from colorectal cancer are exceedingly rare. The use of diagnostic tools such as immunohistochemistry is essential to distinguish primary from secondary lesions. Although there are no clear treatment guidelines, surgical resection may be valuable for establishing a definitive diagnosis and achieving local disease control. Reporting rare metastatic patterns remains essential to improve recognition and management strategies in oncologic surgery.

Author Contributions

Urías Hernandez Lopez: conceptualization, project administration, writing – review and editing. Pastor Thomas Olivares: writing – original draft. Liney Mendoza Suarez: project administration, writing – review and editing. Alejandro Tejada Giraldo: conceptualization, supervision. Astrid Del Valle Pestana: supervision, writing – review and editing. Vianeis Caicedo Mora: project administration. Audrey Vargas Buelvas: conceptualization, supervision.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient for medical treatment and for the use of anonymized clinical data in scientific reporting.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.