Clinical and imaging manifestations of metastases from rare sites

Introduction

The most common metastatic organs of malignant tumors are the lungs, liver, brain, and bone, whereas metastases to rare organs or sites such as the eyes, paranasal sinus, pituitary gland, parotid gland, thyroid gland, breast, heart, gallbladder, gastric colon, prostate, kidney, pancreas, spleen, uterus, bladder, etc., are rare (1). Most cases of rare sites of metastasis in the literature have been reported as individual cases, but their etiology and genetics remain unclear. Some cases of metastases have an insidious onset, with the majority of patients in case series being asymptomatic. The discovery of these metastases may be due to palpation of a mass or by accidental findings on imaging, and there is a high rate of clinical underdiagnosis. The metastatic pathways of primary malignant tumors include direct invasion of adjacent organs, lymph node metastasis, hematogenous metastasis, and implantation metastasis, while most metastases to rare sites are caused by hematogenous metastasis (2). Since patients with metastases have a worse prognosis than do those without them (1), accurate diagnosis is essential for appropriate treatment. Imaging findings play an important role in accurately assessing the detection and characterization of metastases. Therefore, the number, location, and size of metastases need to be accurately determined.

Moreover, given the possibility of synchronous primary tumors, metachronous neoplasms, or occult primary tumors, precise recognition of the imaging signatures that distinguish primary carcinomas from metastases of varying origins is imperative. Laboratory tests and treatment strategies vary depending the type of cancer. For example, distinguishing between metastatic and primary thyroid cancer is important because it has implications for treatment and prognosis. When the thyroid gland is the only site of metastasis, partial surgical resection can affect the prognosis of a portion of patients and does not require cervical lymph node dissection; however, if primary thyroid cancer is diagnosed, some patients may require total removal of the thyroid gland and cervical lymph node dissection (2).

Laboratory test indicators may be useful in the monitoring for the recurrence or metastasis of tumors. When primary tumors recur or metastasize, the levels of certain tumor markers, such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), CA125, or prostate-specific antigen (PSA), may be elevated in patients (3). For example, patients with metastatic thyroid cancer do not have specific laboratory markers that are different from those of patients with primary thyroid cancer (4,5). Thyroid globulin staining is often positive in primary thyroid cancer but negative in thyroid metastasis (4). In thyroid radionuclide scanning, the metastatic cancer has no iodine uptake and appears as cold nodules, whereas primary thyroid cancer presents as warm or hot nodules.

The presence or absence of metastasis significantly affects tumor staging and consequently influences treatment decisions. Emerging evidence indicates that early identification and complete surgical resection of metastases confined to uncommon sites-particularly when the lesion represents the sole metastatic focus-may confer a survival benefit. Due to the rarity of such presentations, no standardized treatment algorithm exists; nevertheless, our data suggest that en bloc surgical excision followed by adjuvant radiotherapy or systemic chemotherapy, especially in cases with evidence of local invasion, can prolong overall survival (6). Further mechanistic studies and prospective trials on this issue are urgently needed to refine management guidelines. Building on our institutional series of 27 histologically proven thyroid metastases (6), we delineated their clinical phenotypes and imaging signatures. Ongoing work is aimed at correlating quantitative imaging variables—lesion size, morphology, and enhancement kinetics—with progression-free and overall survival to establish objective imaging biomarkers that can be integrated into individualized clinical decision-making.

This paper briefly discussed the anatomy of metastatic organs, the cellular origin of metastatic tumors, and the associated clinical, pathologic, and epidemiologic features of metastatic tumors. Additionally, a flowchart for the diagnosis of metastases in rare sites (Figure 1) is provided. The imaging features of each organ associated with uncommon metastases are described in greater depth.

Figure 1 Diagnosis flowchart for metastases in rare sites. CT, computed tomography; MDT, multidisciplinary team; MRI, magnetic resonance imaging; PET, positron emission tomography.

Head and neck

Pituitary

Pituitary metastasis (PM) is highly uncommon in clinical practice and is a rare complication of advanced malignancy, with autopsy studies indicating an incidence of 1–3.6% among patients with malignancy (7). PMs account for only 1% of all surgically removed pituitary masses and fewer than 1% of all intracranial metastatic lesions (8). PMs are derived mainly from breast, lung, kidney, prostate, thyroid, prostate, and colon cancers but have been reported being from almost every type of cancer. Brain metastases involve mainly the neurohypophysis, and most cases are asymptomatic. Clinical manifestations include uveitis, headache, hypopituitarism, visual disturbances, oculomotor palsy, and compression of adjacent structures by an aggressive tumor mass. If PM involves glandular eosinophils, endocrine and electrolyte disorders, along with sexual dysfunction, may occur (9). Diabetes insipidus is a common and characteristic clinical manifestation of PM. The majority of patients with PM are diagnosed between 45 to 74 years old.

Contrast-enhanced magnetic resonance imaging (MRI) is a pivotal imaging modality for the detection of PM. In a small series of T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) studies, metastatic lesions were found to be isointense to the brain parenchyma and invade the cavernous sinus and hypothalamus (10) (Figure 2). In one review of patients with PM (n=65), contrast enhancement was common (68%), and basal enhancement or thickening was also observed (23%) (11). Furthermore, in a series of studies, rapid tumor growth was associated with metastasis (9). As a result of lumbar contraction of the diaphragm, metastatic masses may have a dumbbell shape, whereas adenomas usually dilate the diaphragm (12). The presence of diaphragmatic bone erosion without diaphragmatic enlargement may support the diagnosis of PM. MRI offers excellent soft-tissue resolution, yet it is less sensitive than computed tomography (CT) in detecting destruction of the sellar floor, and CT can clearly delineate bony erosion or enlargement of the pituitary fossa. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT is of limited value in differentiating adenoma from metastasis, as pituitary adenoma can also appear as a hypermetabolic mass. Unlike pituitary adenomas, the PMs are likely to be aggressive and often cause painful ophthalmoplegia and vision loss due to involvement of the cavernous sinus and pedicle. Approximately half or more of the patients initially present with symptoms of pituitary dysfunction, which is the first manifestation of malignancy (7).

Figure 2 MRI scans of a 55-year-old female with PM and a history of breast cancer. (A-C) Sagittal T1WI, T2WI, and coronal T2WI. Pituitary enlargement with thickening of the pituitary stalk was observed, which exhibited isointensity to hypointensity on T1WI, along with isointensity on T2WI. (D,E) Heterogenous enhancement on T1+C. IM, image; MRI, magnetic resonance imaging; PM, pituitary metastasis; SE, series; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Orbit and eyeball

Orbital metastatic tumors account for 3% to 7% of orbital tumors and occur in approximately 8–10% of patients with advanced cancer. Orbital metastases reach intraocular structures via hematogenous dissemination, mostly involving the uveal tract, but rarely occur in the optic nerve, retina, or vitreous (13). Intraocular metastases are most commonly observed in primary cancers such as breast, lung, gastrointestinal, renal, pancreatic, prostate, thyroid, and skin cancers (14-17). For most patients, the mean age at diagnosis is 60 years, and intraocular metastasis is relatively common in women (14,15).

The most commonly reported sites of orbital metastases are the extraocular muscles and choroid, which may be due to hypervascularization of the extraocular muscles and choroid (18,19). Clinical manifestations may include symptoms such as decreased visual acuity and diplopia (18) and physical signs including exophthalmos and swelling (18).

The presentation of intraocular metastases varies depending on the location of the tumor and usually requires adjunctive imaging. B-mode ultrasonography scans typically reveal dense, dome-shaped, or lobulated lesions with moderate-to-high internal reflectivity. MRI is integral to oncologic diagnosis and therapeutic planning. Metastatic deposits typically appear moderately hypointense or isointense on T1WI and isointense or mildly hyperintense on T2WI. CT is valuable for diagnosing bone involvement with sinus or intracranial expansion (20) (Figures 3,4). CT, MRI, and ultrasound each offer distinct advantages in evaluating orbital and ocular disorders. MRI best delineates involvement of the orbital apex and cavernous sinus, CT excels at assessing skull-base foramina and sinonasal pathways, and ultrasound enables dynamic monitoring of intraocular lesions. These three modalities complement and reinforce one another.

Figure 3 MRI scans of a 52-year-old male with orbital metastatic tumors and a history of kidney cancer. (A,B) T1WI and T2WI: a mass in the left retro-orbital space with isointensity on T1WI and T2WI. (C,D) T1+C: heterogenous enhancement on T1+C, notably prominent at the periphery. IM, image; MRI, magnetic resonance imaging; SE, series; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Figure 4 MRI scans of a 23-year-old male with eyeball metastasis and history of kidney cancer. (A,B). Axial and coronal T2WI: a nodule with slightly hyperintensity on T2WI was visible within the eye. Additionally, an eye-internal “V” shaped lesion with hyperintensity on T2WI was noted. (C) T1+C: marked enhancement. MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Nasal sinuses

Nasal sinus metastases are very rare and account for fewer than 1% of all malignant tumors (21). The most common sites of nasal sinus metastasis are the maxillary sinuses, ethmoid sinuses, sphenoid sinuses, and, less frequently, the frontal sinuses and turbinates. In the literature, the most common primary tumor of sinus metastasis is renal cell carcinoma (RCC), followed by breast, thyroid, lung, prostate, and gastrointestinal tract tumors, along with hepatocellular carcinoma and pancreatic carcinoma (22,23). Primary tumors tend to metastasize through hematogenous metastasis via two possible mechanisms. One is the spreading of malignancy to the lungs via the inferior vena cava, which later reaches the head and neck via the carotid arterial system. The other, as proposed by Nahum and Baily in 1963, involves the tumor cells flowing to the head and neck via the Batson vertebral venous plexus; more specifically, the tumor cells circulate through the non-valved vertebral venous plexus and enter the pterygoid venous plexus and cavernous sinuses, as well as the nasal and paranasal sinuses, bypassing the lungs and eventually leading to nasal sinus metastasis (21,24).

The clinical and imaging manifestations of metastatic tumors in the nasal cavity and sinuses are highly similar to those of primary tumors in the nasal sinuses. Nasal obstruction, epistaxis, and facial swelling are the most frequent symptoms. Imaging has no obvious specificity for the diagnosis of nasal sinus malignant tumors. They often present as ill-defined soft tissue masses with irregular shapes, uneven density, and invasion adjacent tissues. Contrast-enhanced CT scans mostly reveal moderately or markedly uneven enhancement. On MRI, the lesion typically manifests as subtle hypointensity on T1WI and mild hyperintensity on T2WI. After enhancement, uneven and significant enhancement can be observed (Figures 5,6). CT may indicate the nature of the lesion, bone erosion and remodeling, enhancement, hypervascularization, or dilatation of the sphenopalatine foramen. The metastatic mass exhibits expansive growth and is typically accompanied by infiltrative bone destruction in the surrounding area. MRI can indicate invasion of the skull base and leptomeningeal region. Metastatic tumors may also be hypervascular, and angiography and embolization may be considered. Because of the deep location and shielding by bony plates, ultrasound beams cannot penetrate adequately, resulting in markedly reduced detection rates. Ultrasound is not necessary incapable of diagnosing nasal or paranasal sinus tumors, but its value is limited to certain scenarios; for instance, it offers high sensitivity and specificity for superficial, early-stage lesions. For deeper lesions or those involving bony structures, CT and MRI remain the primary imaging modalities. ¹⁸F-FDG PET/CT clearly demonstrates intense tracer uptake in both primary tumors and metastatic foci, aiding in initial staging and posttreatment surveillance (25); it is also useful for detecting asymptomatic tumor recurrence in patients with no endoscopic abnormalities after therapy (25).

Figure 5 MRI scans of a 45-year-old female with frontal sinus metastasis and a history of kidney cancer. (A,B) T1WI and T2WI: there was a mass in the right frontal sinus, with isointensity on T1WI and mild hyperintensity on T2WI (C,D). T1+C: marked enhancement. MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Figure 6 MRI scans of a 52-year-old female with ethmoidal sinus metastasis and a history of rectal cancer. (A,B) T1WI and T2WI: there was a mass within the left ethmoid sinus, which exhibited hypointensity on T1WI and hyperintensity on T2WI. (C) Contrast-enhanced MRI showed mild enhancement. MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Nasopharynx

Metastasis to the nasopharynx is a rare clinical phenomenon. Among nasopharynx metastases, lung, breast, thyroid, renal cell, hepatocellular, and colorectal cancers have been reported (26-28). The clinical presentation of nasopharyngeal metastases depends on their location and extension to adjacent structures. The typical clinical manifestations are unilateral nasal congestion, oronasal masses, a runny nose, hearing loss, and recurrent epistaxis. Other associated symptoms related to a spread to the skull base and cranial nerves include headache, diplopia, abducens nerve palsy, facial pain, or dysphonia.

CT is the preferred imaging modality for assessing bone destruction in patients with nasopharyngeal metastases (28), while MRI is better suited to visualizing perineural invasion and intracranial extension (28) (Figure 7). ¹⁸F-FDG PET/CT scanning is also widely used for the staging and treatment of nasopharyngeal metastases, especially for the detection of distant metastases, small lymph nodes in the neck, and local residual and recurrent disease (28). Ultimately, nasopharyngeal lesions require nasopharyngoscopy, which clearly displays the mass, permits direct visualization of the mucosal architecture and functional status assessment, and provides precise guidance for biopsy.

Figure 7 MRI scans of a 75-year-old male with nasopharyngeal metastases and a history of malignant melanoma. (A,B) T1WI and T2WI: a nodular protrusion was observed on the posterior left wall of the nasopharynx, which exhibited mixed hyperintensity on T1WI and hypointensity on T2WI signals. (C,D) Contrast-enhanced MRI showed marked enhancement, but no thickening of the adjacent mucosa was noted. MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Parotid gland

Metastasis to the parotid gland is exceedingly rare, but patients in whom this occurs have a particularly poor prognosis, with a 5-year survival rate of only 10% (29). Metastases account for approximately 6–25% of all parotid malignancies (30), but the process of this metastasis has not been elucidated. There are three routes of spread for parotid metastases: local extension of the original tumor, hematogenous spread of distant tumors, and lymphovascular spread. Malignant tumors such as melanoma, squamous cell carcinoma, nasopharyngeal carcinoma, lung cancer, breast cancer, and renal cancer can all metastasize to the parotid gland (29-31). Swelling and masses in the parotid gland are typical clinical manifestations of parotid metastases.

Fine needle aspiration cytology (FNAC) is the basic preoperative test for the diagnosis of parotid masses, and ultrasonography is the most common imaging modality. CT and MRI can differentiate between malignant and benign tumors and help to determine the local extent and involved lymph nodes (29) (Figure 8). ¹⁸F-FDG PET/CT improves staging and is recommended for local evaluation in the case of parotid metastases (31). However, radiological examination cannot distinguish between primary malignant adenomas and metastases.

Figure 8 MRI scans of a 60-year-old male with parotid metastases and a history of lung cancer. (A,B) T1WI and T2WI: in the left parotid region, the T1WI showed hypointensity, while the T2WI displayed hyperintensity. (C) Contrast-enhanced MRI: the enhancement was markedly heterogeneous, with more pronounced peripheral enhancement around the lesion. No enhancement was observed in the central area of liquefactive necrosis. MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Thyroid gland

Despite its extensive blood supply, the thyroid gland is an uncommon location of metastasis for primary tumors arising from other sites, accounting for approximately 1.4% to 3% of all thyroid tumors. Many large autopsy series on thyroid malignancies report incidence rates ranging from 1.9% to 24% (32). Thyroid metastases are most common in primary cancers such as lung, kidney, head and neck, breast, esophageal, colorectal, neuroendocrine, and cervical cancers (32). The disease has an insidious onset and is mostly asymptomatic (33). Therefore, it is easily missed and misdiagnosed.

Fine-needle aspiration biopsy and postoperative pathological analysis have emerged as valuable methods for diagnosing thyroid metastases. The majority of thyroid metastases are discovered incidentally during surveillance imaging or follow-up palpation after resection of the primary tumor (34). Consequently, early imaging surveillance is essential for the timely detection of thyroid metastasis. Thyroid metastases may present as “cold nodules” on radioiodine uptake studies and as heterogeneous hypoechoic masses on ultrasound; thus, both ultrasound and PET/CT lack specificity for diagnosing this entity. Our previous work (6) showed that thyroid metastases on ultrasound and CT manifested as solitary or multiple masses or diffuse infiltration, lacked distinctive features, and were thus difficult to distinguish from primary thyroid neoplasms. Ultrasound remains the first-line modality for lesion detection and differentiation from entities such as thyroid adenoma, characterized by a solitary, regular shape, well-defined border, with peripheral hypoechoic halo or capsule, and color Doppler flow imaging (CDFI) showing more blood flow in the perilesion than the intranodule area; nodular goiter, characterized by multiple solid or mixed solid-cystic nodules of variable echogenicity with coarse calcifications or colloid artifacts, and CDFI revealing either hyper- or hypovascularity; and Hashimoto thyroiditis, characterized by diffuse symmetric enlargement with a reticular or “pseudonodular” pattern. Definitive diagnosis requires correlation with serial imaging changes and FNAC. However, ultrasound-guided fine-needle aspiration biopsy plays an important role in the diagnosis of metastatic thyroid cancer. CT and MRI can reveal the size, extent, number, and degree of cervical lymph node metastasis of metastatic thyroid cancer, and it is important to assess the progression and invasion of adjacent tissues (Figure 9).

Figure 9 A 59-year-old male with thyroid metastases and a history of lung cancer. (A,B) Ultrasound: the thyroid gland was enlarged with several ill-defined, irregularly shaped diffuse hypoechoic foci. On CDFI, blood flow signals could be seen within some of the foci. It was classified as TI-RADS category 5. (C,D) Plain and contrast-enhanced CT: multiple nodular masses were observed in both lobes of the thyroid gland. There was a slightly hypodense lesion, the enhancement degree of which was less than that of normal thyroid tissue. CDFI, color Doppler flow imaging; CT, computed tomography; TI-RADS, Thyroid Imaging Reporting and Data System.

Masseter muscle

Data from the literature indicate that skeletomuscular metastases most frequently affect the lower limbs (37.2%), followed by the upper limbs (25.6%), trunk (20.9%), and the head-and-neck musculature (16.3%) (35). In contrast, muscle metastasis is more common in the head and neck and less so in the trunk and neck. In an autopsy series of patients with cancer, the incidence of masseter-muscle involvement was less than 1% (36). The rarity of submandibular muscle metastases is due to the skeletal structure, which limits the development of metastatic lesions. In addition, the high resistance of maxillofacial muscles to cancer is another reason for their rarity. Rapid blood flow, high tissue pressure, the antitumor activity of lymphocytes and natural killer cells, the production of lactic acid, skeletal muscle-derived digestive factors, and inhibition by protective inhibitors could explain this resistance (37). In addition, the specific location and surrounding structures of the intermaxillary muscle dictate a specific metastatic pathway. Nevertheless, in all the reports on intermaxillary muscle metastasis, the condition occurs only in males, and muscle metastasis occurs mainly in the older adult individuals. The majority of clinical manifestations are swelling of the masseter muscle.

Owing to its ready availability and capacity for real-time assessment of intralesional vascularity, ultrasonography is usually selected as the first-line imaging modality. Ultrasonography reveals lesions that are regular in shape, well-defined, hypoechoic, heterogeneous, and in line with the long axis of the muscle, which can be corroborated by fine needle aspiration. The soft-tissue resolution of MRI is high, and it can better identify this type of tumor (Figure 10). Masseter muscle metastases often lack typical malignant features (36) and can easily be mistaken for benign lesions. CT findings of masseter-muscle metastases are nonspecific, yet the modality precisely delineates tumor extent, adjacent-tissue invasion, and lesion vascularity. Both CT and PET/CT facilitate tumor staging and posttreatment surveillance for assessing the therapeutic response.

Figure 10 MRI scanning of a 52-year-old male with masseter metastasis and a history of eccrine ductal carcinoma. (A) T2WI: a nodule with hyperintensity on T2WI was observed in the left masseter muscle. (B,C) T1+C showed marked ring-like enhancement. MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Heart

The heart is a special organ, and the incidence of primary cardiac tumors is particularly low, ranging from 0.3% to 0.7% in surgery and autopsy findings, with 25% of these tumors being malignant (38). In contrast, the incidence of cardiac metastases is 30 times greater than that of primary malignant tumors of the heart (39). Tumors that tend to cardiac metastases include pleural mesothelioma, lung cancer, melanoma, breast cancer, pancreatic cancer, renal cancer, and gastric cancer (39-41). Malignant tumors metastasize to the heart through the following four pathways. The first is direct infiltration, with direct invasion of mediastinal and thoracic cavity tumors often leading to pericardial metastasis. The second is hematogenous metastasis, which often causes myocardial and endocardial metastasis. The third is lymphatic dissemination, which often causes pericardial and epicardial metastasis. The fourth is venous spread, most commonly observed in renal cancer and hepatocellular carcinoma, with the route of spread being to the right atrium via the inferior vena cava (41).

The clinical manifestations of cardiac metastases are atypical and closely related to the site and scope of metastasis. The first of such signs is the presence of abnormalities on electrocardiography. Cardiac arrhythmia, including conduction block, ventricular premature beats, low voltage, sinus tachycardia, and myocardial infarction-like electrocardiogram changes, is often observed. The second type of arrhythmia involves cardiac ultrasound abnormalities, such as a substantial cardiac mass and decreased cardiac ejection fraction. The third type of arrhythmia involves pericardial effusion and a cardiac mass incidentally found via chest and abdominal CT examination. Imaging examination can also reveal myocardial, pericardial, and mediastinal invasion (Figure 11). The fourth is cardiac MRI abnormalities. Cardiac metastases usually show low signal in T1WI and high signal relative to the myocardium in T2WI, whereas melanoma and hemorrhagic metastases can manifest as a high signal in T1WI. Most metastases show enhancement during enhanced scanning (41,42). The fifth type corresponds to clinical symptoms: when cardiac metastasis occurs, the disease generally progresses rapidly, and heart failure symptoms such as chest tightness, precordial pain, palpitation, and dyspnea can appear in a short period of time. Most patients with cardiac metastasis are already at an advanced stage and have a variety of other symptoms. The symptoms caused by cardiac metastasis are often obscured and neglected. Therefore, cardiac metastasis should be considered when the abovementioned symptoms and examination results are present.

Figure 11 A 60-year-old male with cardiac metastases and a history of thigh synovial sarcoma. (A-C). Contrast-enhanced axial and sagittal CT revealed a moderately enhanced solid mass in the right atrium. Multiple metastatic masses were observed in both lungs. Bilateral pleural effusions were present. (D-G) PET/CT imaging showed a mass in the right ventricle with increased metabolic activity. CT, computed tomography; PET, positron emission tomography.

Cardiac lesions can be evaluated with multiple imaging modalities. Echocardiography is the first-line technique for detecting cardiac tumors. It assesses the morphology and function of all cardiac chambers and precisely depicts the tumor’s location, size, shape, mobility, and hemodynamic consequences (43). Cardiac MRI offers superior soft-tissue resolution. It distinguishes the cardiac chambers, great vessels, myocardium, pericardium, and endocardium. Moreover, it provides detailed information on tumor site, morphology, size, internal characteristics, and extent of involvement. Cardiac MRI can also clarify the relationship with adjacent vascular structures and supply functional and flow data to guide surgical planning. Contrast-enhanced CT typically reveals a hypo- or isoattenuating mass. Central necrosis may communicate with the cardiac chambers. CT clearly demonstrates myocardial infiltration, chamber compression, and involvement of the pericardium and great vessels, with postcontrast imaging further delineating necrotic and hemorrhagic areas. PET/CT, by fusing anatomic CT with functional PET data, can reflect the tumor metabolism to differentiate benign from malignant disease, define local invasion, and stage systemic metastases with high sensitivity, specificity, and whole-body coverage. ¹⁸F-FDG PET/CT is routinely employed to detect metastatic disease, with cardiac metastases exhibiting increased ¹⁸F-FDG uptake (43).

Trachea and bronchus

There definitions of tracheal/bronchial metastases (TBMs) are various. Some define it as tumor metastasizing to the tracheal or bronchus, whereas others include invasive tumors, such as esophageal cancer, directly invading the trachea and bronchus. Thus, the reported incidence of TBM ranges from 2% to 28% (44,45). Numerous types of malignant tumor can metastasize to the trachea or bronchus, with breast cancer, colon cancer, renal cancer, and esophageal cancer being the most common (44). The clinical manifestations vary according to the site of metastasis, but the most common symptoms are cough, hemoptysis, fever, and dyspnea.

It is necessary to perform chest CT examination to improve the detection rate of TBM and patient prognosis. The CT imaging manifestations of TBMs vary and include masses in the trachea/bronchus or lung hilum, localized thickening of the bronchial wall, obstructive pneumonia, emphysema, and atelectasis (45) (Figure 12). Patients with suspected TBM should undergo bronchoscopic examination and pathological analysis. CT is the optimal imaging modality for evaluating airway tumors. CT virtual endoscopy accurately delineates the sites and extent of luminal narrowing or obstruction. Meanwhile, PET/CT can identify intraluminal lesions associated with obstructive atelectasis or pneumonia. ¹⁸F-FDG PET/CT is particularly valuable for detecting small-volume disease; however, it cannot distinguish primary from metastatic lesions.

Figure 12 A 54-year-old male with TBM and a history of left lower lung squamous cell carcinoma. (A-C) Plain and contrast-enhanced CT: postoperative follow-up of squamous cell carcinoma in the lower left lung; in December 2021, multiple nodular thickening of the tracheal wall was observed. Following antitumor therapy, tracheal metastasis had regressed compared with that indicated in prior imaging. (D) Contrast-enhanced CT: in the follow-up examination on August 2023, the nodule on the posterior left wall of the tracheal was found to be continuously enlarging. (E) Electronic bronchoscopy revealed a globular mass on the left posterior wall of the tracheal with a rough mucosal surface. CT, computed tomography; TBM, tracheal/bronchial metastasis.

Breasts

Breast metastases (BMs) from non-breast malignant tumors are very rare, accounting for only 0.3% to 2.7% of all breast malignancies. The average survival time after the diagnosis of breast cancer metastasis is only 10 months (46,47). The majority of BMs are derived from malignant melanoma, followed by lymphoma, lung cancer, ovarian tumors, sarcoma, genitourinary and gastrointestinal tract cancers, and thyroid tumors (46-48). The bulk of BMs are asymptomatic, diagnosed incidentally during staging examination, and reported only as fast-growing masses without pain or unilateral axillary lymphadenopathy. Skin or nipple retraction is usually not present.

Doppler ultrasonography and mammography are integral tests for the evaluation of all palpable breast masses, regardless of whether they are primary or secondary. Breast masses are usually round masses. Carcinoid metastases appear as round or oval, noncalcified masses on mammograms (48-50). Less commonly, they can appear as spiculated masses (48-50). BM with primary ovarian cancer is often associated with microcalcifications. Ultrasonic features are not characteristic and can present as benign or malignant masses. The common ultrasonic features of BM are irregular, indistinct, hypoechoic, and uncalcified masses (48-50). BMs on MRI may mimic benign breast masses or primary breast cancer (49). Recognizing this entity is important for preventing unnecessary treatment of primary breast cancer (Figure 13). No systematic studies have analyzed the imaging features of BMs. The related literature consists almost entirely of case reports. Our team retrospectively collected the imaging data from 38 patients with pathologically proven BMs and summarized their imaging characteristics. Metastatic involvement was most often unilateral, while bilateral disease was uncommon. Imaging typically revealed a solitary nodule, although multiple nodules or diffuse disease could also be present, while calcification was rare. On contrast-enhanced imaging, lesions most frequently showed marked or moderate enhancement. Overall, the imaging findings lacked specific distinguishing features.

Figure 13 A 54-year-old female with BM and a history of liver cancer. (A,B) Plain and contrast-enhanced CT: a slightly high-density nodule was observed in the left breast, with a ring-like enhancement pattern after contrast administration. (C,D) Ultrasound: a hypoechoic mass was present in the left breast with uneven internal echoes, indistinct borders, and small bright echo points. Color Doppler ultrasonography showed perilesional vascularity. The dashed lines indicate the measured diameter, and the box represents the ultrasound sampling frame used to assess blood flow within the lesion. (E-K) MRI scanning: the mass exhibited hypointensity on T1WI and mild hyperintensity on T2WI. At the tumor margin, DWI showed hyperintensity, and ADC showed hypointensity, indicating restricted diffusion. With the tumor core, DWI demonstrated slight hypointensity, and ADC showed hypointensity. Contrast-enhanced imaging demonstrated marked enhancement. The dynamic curve shows an inflow pattern. ADC, apparent diffusion coefficient; BM, breast metastasis; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Digestive tract

Tumor metastasis to the digestive tract is less common than that to other organs but may occur more often among patients with malignant melanoma, lung cancer, or breast cancer. Gastric metastases occur in 1.7–5.4% of all cancers (51). A review from the Mayo Clinic reported that the incidence of esophageal metastasis reported in the literature is less than 0.4% (52). Only 73 of the 12,001 metastatic breast cancers are reported to be gastrointestinal metastases, with metastasis rates ranging from 8% to 35%. The proportion of metastases in different components of the digestive tract is as follows: 45% in the colorectum, 28% in the stomach, 19% in the small intestine, and 8% in the esophagus (53). The incidence of colorectal metastases is relatively high. The clinical presentation of metastatic disease in the gastrointestinal tract varies widely (51). Most signs and symptoms are nonspecific. Abdominal pain is the most common symptom, followed by abdominal distension, blood in the stool, nausea and vomiting, dysphagia, weight loss, gastrointestinal bleeding, intestinal obstruction, early satiety, anemia or fatigue, and a palpable mass.

Barium meal and endoscopy are the imaging methods of choice for the examination of gastrointestinal diseases (52,53). Barium meal is associated with dilatation, delayed emptying, and thinning of the esophagus or gastrointestinal tract. Endoscopy reveals stenosis of the esophagus or gastrointestinal tract and a normal or abnormal esophageal mucosa (Figures 14-16). Microprobe endoscopic ultrasonography demonstrates loss of the normal structure of the esophagus and gastrointestinal tract at the stricture, which is replaced by a hypoechoic, circumferentially thickened lesion. The serosa layer is incomplete (54,55). In hollow organs, MRI can be limited by variable luminal distension, peristalsis, and differences in bowel emptying. In contrast, CT allows multiplanar three-dimensional reconstruction for precise lesion localization. CT virtual endoscopy further delineates sites of luminal narrowing or obstruction. PET/CT provides whole-body functional-metabolic mapping in a single acquisition, enabling the accurate detection of primary and even subtle lesions. Physiologic gastric-wall uptake and gastritis, however, are common sources of false-positive findings on PET/CT.

Figure 14 A 61-year-old female with esophageal metastasis and a history of cervical cancer. (A-D). Plain and contrast-enhanced CT (axial, coronal, and sagittal planes): postoperative follow-up CT for cervical cancer revealed uneven thickening of the esophageal wall (starting from the level of the aortic arch) with luminal narrowing. There was an irregular mass at the vaginal stump invading the bladder and thickening of the bladder wall. Multiple lymph node metastases were observed in the retroperitoneum. (E) Esophagoscopy: multiple submucosal elevations in the esophagus, with local mucosal roughness. The diagnosis of this case should also be integrated with the clinical history. Follow-up after cervical cancer surgery revealed a marked elevation of the tumor marker, SCC antigen. Esophagoscopy biopsy pathology suggested this increase was due to metastatic disease in the esophagus and not tumor at the vaginal stump and bladder. CT, computed tomography; SCC, squamous cell carcinoma.

Figure 15 A 72-year-old female with gastric metastases and a history of lung adenocarcinoma. (A-C) Plain and contrast-enhanced CT (axial and coronal): the gastric wall on the greater curvature side of the gastric body was thickened, showing marked enhancement after contrast administration. (D-J) MRI scanning. T2WI, fat-suppressed T2WI, T1+C (three-phase), DWI, and ADC: the lesion exhibited slight hyperintensity on T2WI, persistent enhancement during the three-phase contrast study, hyperintensity on DWI, and mild hypointensity on the ADC map. (K) Endoscopy: in the lower part of the gastric body on the greater curvature, there was an ulcerative infiltrative mass measuring approximately 2.5 cm × 4.0 cm in size. The edge featured a dam-like elevation, with coarse folds around the periphery showing club-like interruptions and fusion. The center was depressed, the mucosa was rough, and there was dark-red blood crust attached. The mass bled easily upon touch, and the gastric motility was suboptimal. (L-O) Plain and contrast-enhanced CT: upon 6-month follow-up, the tumor in the gastric body had significantly increased in size. Multiple metastatic tumors were observed in the liver. ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Figure 16 A 45-year-old male with colorectal metastases and a history of liver cancer. (A-C) Contrast-enhanced CT (axial and coronal) and MRI: the wall of the ileocecal region was thickened, with multiple enlarged lymph nodes in the surrounding mesentery. (D) Colonoscopy: near the cecum of the ascending colon, an ulcerated, elevated neoplasm was observed, with a necrotic and rigid surface causing distortion and twisting of the intestinal lumen. CT, computed tomography; MRI, magnetic resonance imaging.

Gallbladder

Gallbladder metastases are exceedingly rare. In two autopsy studies, gallbladder metastases were found in only 2.2% to 5.8% of patients with metastatic cancer (56,57). The most common primary tumor that metastasizes to the gallbladder is gastric cancer, followed by RCC, hepatocellular carcinoma, breast cancer, pancreatic cancer, and colorectal cancer.

Ultrasonography is the first-line modality for evaluating gallbladder lesions, typically showing a single or multiple moderately hyperechoic foci or focal thickening of the gallbladder wall; nevertheless, differentiation from polyps remains challenging. The CT manifestations of gallbladder metastases are an infiltrative or polypoid type and cannot be distinguished from those of primary gallbladder cancer (57,58). CT findings of gallbladder metastases vary significantly across primary tumors of different histologies. Adenocarcinomas that metastasize to the gallbladder show infiltrative wall thickening with persistent enhancement, whereas cases of metastatic melanoma, RCC, or hepatocellular carcinoma that metastasize to the gallbladder show polypoid lesions with early wash-in or wash-out enhancement (57,58) (Figure 17). The MRI features of gallbladder metastases mirror those apparent on CT and are similarly nonspecific.

Figure 17 A 47-year-old female with gallbladder metastases and a history of renal clear cell carcinoma. (A-G) MRI T1WI, T2WI, fat-suppressed T2WI, T1+C (two-phase), DWI, and ADC: a mass was present within the gallbladder lumen, and there was isointensity on T1WI, slight hyperintensity on T2WI, marked enhancement, hyperintensity on DWI, and hypointensity on ADC map. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Renal

The kidney is the fifth most common site of metastasis, with the majority of renal metastases originating from hematogenous metastases of the primary tumor. In the literature, the clinical incidence rate of renal metastases is approximately 7–13%, and the incidence of autopsy can reach 20% (59-61).

Renal metastases do not have specific laboratory tests or tumor markers distinct from those of primary renal tumors, and all indicators of renal function may be normal or elevated to different degrees and lack specificity. Renal metastases are most commonly identified incidentally during postoperative surveillance imaging or follow-up physical examination after resection of the primary tumor. Therefore, early detection of renal metastasis by imaging is crucial.

Ultrasonography is the most commonly used screening method for determining renal metastases and can provide observations of the location, size, morphology, elasticity, and blood flow status. The ultrasound manifestation is a low or equal or hyperechoic nodule or mass. Larger lesions can exhibit cystic necrosis, and blood flow signal can be observed in most of the lesions. CT and MRI findings of renal metastases are as follows (61-63): the center of the lesion is located mostly at the junction of the cortex and medulla, and most of the lesions appear as solid nodules or masses (Figure 18). The tumor is small and uniform, while larger tumors may cause cystic necrosis. The T1WI sequence of plain MRI shows a low signal, whereas the T2WI sequence shows a slightly high signal. The enhanced scan is consistent with the enhancement characteristics of the primary tumor. On PET/CT, most renal metastases present as foci of intense or mildly increased ¹⁸F-FDG uptake, while the remainder are iso- or hypometabolic, occasionally yielding false-negative results. In such cases, integration with the morphologic findings on CT is essential. Because ¹⁸F-FDG is predominantly excreted via the urinary tract, pronounced tracer accumulation in the renal pelvis and calyces can further complicate the detection and characterization of renal tumors.

Figure 18 A 41-year-old male with renal metastases and a history of nasal squamous cell carcinoma (A-C) and a 67-year-old male with renal metastases and a history of lung cancer (D-F). Plain and contrast-enhanced CT: the margins were indistinct, with mild-to-moderate enhancement. In both cases, the clinical and imaging presentations were atypical. The detection of renal metastases was incidental upon follow-up, and both were associated with multiple metastases in other regions. After antitumor treatment, the lesions showed reduction in size. CT, computed tomography.

Pancreas

Pancreatic metastasis is rare, with an incidence of only 2–5% in clinic, whereas it accounts for 3–12% of pancreatic malignancies at autopsy (64,65). The time interval between detection of pancreatic metastasis and primary tumors is between 1 and 3 years in most cases, but a period of 3–7.5 years has also been reported in the literature (64). The time of metastasis varies across different tumors. Pancreatic metastasis is an advanced manifestation of tumors that is prevalent in middle-aged and older adult individuals, with a slightly higher incidence in men than in women. Pancreatic cancer metastasis primarily occurs in lung cancer, breast cancer, renal cancer, gastric cancer, melanoma, colorectal cancer, etc. Lung cancer accounts for 0.63–1% of all pancreatic metastases (64-69). Pancreatic metastasis has a relatively insidious onset, and the majority of patients have no special clinical manifestations, which are only detected via imaging during regular follow-up. A portion of patients present with abdominal pain, jaundice, and similar symptoms. When the pancreatic duct is involved, manifestations similar to those of pancreatic cancer or acute pancreatitis may occur. Acute pancreatitis related to pancreas metastasis is uncommon, with an incidence of 3.3–7.5% (64-66).

Pancreatic metastases do not have specific laboratory tests or tumor markers that distinguish them from primary pancreatic cancer. CA19-9, CA125, and CEA may be normal or elevated to varying degrees and lack specificity. Pancreatic metastases are usually discovered incidentally during postoperative surveillance imaging; therefore, early radiological assessment is essential for timely detection.

The enhancement characteristics of CT and MRI of pancreatic metastasis are similar to those of primary tumors (Figure 19). According to the literature (65-69) and our own experience, the imaging characteristics of pancreatic metastasis are as follows: (I) unclear boundaries; (II) uneven reinforcement, often appearing as a ring or edge reinforcement; and (III) a varying degree of enhancement varies, with most metastases showing mild enhancement, which is related mainly to the type and blood supply of the primary tumor. Pancreatic metastasis can also invade the pancreatic duct, causing dilation of bile ducts and pancreatic ducts, and may be accompanied by atrophy of the pancreatic tail. Due to its retroperitoneal location and the overlying gas within the stomach or bowel, ultrasonography has inherent limitations in pancreatic assessment. In our previous study (70), pancreatic metastases appeared on imaging as solitary or multiple masses that were usually irregular in shape and lacked a capsule. Its enhancement depends on primary tumors.

Figure 19 A 57-year-old male with pancreas and adrenal gland metastases, along with a history of renal clear-cell carcinoma. (A-E) CT (plain and contrast-enhanced) and MRI (T2WI and T1+C): multiple nodules were observed in the pancreas, exhibiting marked ring-like enhancement; irregular masses were present in both adrenal glands, showing heterogeneous enhancement. The imaging manifestations were similar to those of clear cell RCC, both showing marked enhancement in the arterial phase. CT, computed tomography; MRI, magnetic resonance imaging; RCC, renal cell carcinoma; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Spleen

Splenic metastasis is rare, with the incidence rate ranging from 3.1% to 7.0%, and the autopsy rate ranging from 0.3% to 13%. Most splenic metastases are accompanied by extrasplenic metastases (71). Common primary tumors that easily metastasize to the spleen include lung cancer, breast cancer, malignant melanoma, prostate cancer, colon cancer, ovarian cancer, cervical cancer, and pancreatic cancer. The pathways of spleen metastasis mainly include direct invasion, lymphatic metastasis, and hematogenous metastasis, among which hematogenous metastasis is the most common (71,72). The clinical manifestations of splenic metastasis are not specific; thus, imaging examination is crucial.

Ultrasonography is limited by the device used and the experience of the examiner, which can affect the display of small and diffuse lesions. The diagnostic value of contrast-enhanced ultrasound for splenic metastasis is still in the exploratory stage. Plain CT scan can reveal lesions (single or multiple low-density nodules or masses) and changes in spleen morphology and size, but some metastases are isodense and can easily be missed (73,74). Owing to different primary tumors, splenic metastases can have various manifestations. Metastases originating from the pancreas, digestive tract, and ovaries usually contain mucus components and present as thick-wall, cystic lesions; that is, bull’s-eye sign-like manifestations. Splenic metastases from malignant melanoma often show hemorrhage within the lesion, which presents as a patchy, slightly hyperdense shadow. MRI has a high resolution of soft tissues. The imaging presentation of metastatic lesions is different from that of normal spleens in multistage MRI enhancement scans, thus aiding in the detection of lesions, especially small lesions. PET/CT is superior to CT and MRI in identifying benign and malignant splenic lesions, with the former presenting as a concentration of FDG. Therefore, ultrasound can be used as the preferred screening method, and the combined use of CT and MRI enhanced scanning along with PET/CT can improve the detection and identification of splenic lesions (73,74) (Figure 20).

Figure 20 A 52-year-old female with splenic metastasis and a history of ovarian cancer. (A-C) Plain and contrast-enhanced CT: a low-density mass with clear boundary was observed within the spleen. A small portion of solid component at the periphery showed enhancement on contrast scans. (D) PET/CT: an abnormal focus of radioactivity accumulation was seen within the spleen, with a maximum SUV of 8.06. Subsequent follow-up examinations revealed an increase in size and number of lesions in the spleen. CT, computed tomography; PET, positron emission tomography; SUV, standardized uptake value.

Bladder

Bladder metastasis is rare and often occurs in the bladder neck and deltoid region. Most secondary bladder tumors are caused by direct invasion from neighboring organ tumors, such as prostate, colorectal, cervical, or vaginal cancer, whereas a small percentage are distant metastases, most commonly from gastric cancer, followed by melanoma, colon cancer, breast cancer, and prostate cancer (75,76). Upper urinary tract transitional cell carcinoma can also seed the bladder through implantation metastasis, which may produce no symptoms or manifest as hematuria.

The presentation of bladder metastases on cystoscopy varies. It includes solid tumors, nonspecific inflammatory plaques, abnormal thickening of the bladder wall, and mucosal nodules or plaques with capillary dilatation (75,76). There is no literature summarizing the imaging presentation of bladder metastases. From cystoscopy results and cases in our center, we determined the imaging findings to be as follows: ultrasonography, CT, CT urography (CTU), MRI, and MR urography (MRU) reveal focal or diffuse thickening of the bladder wall, which could be single or multiple. It is difficult to distinguish these tumors from bladder cancer (Figures 21,22). Because of the interference from radioactive urine, false-negative findings can occasionally occur in urinary system lesions. However, dual-phase PET/CT imaging effectively addresses this limitation by providing accurate standardized uptake value (SUV) measurements for both the lesion and the urine in two distinct timepoints (77). Furthermore, during the delayed phase, the urinary tract remains well distended, allowing CT to depict the anatomic details of the ureteral or bladder, such as “cauliflower-like” or “papillary” tumors, and focal wall thickening. PET exploits the markedly higher metabolic activity of tumors compared with the low activity of urine to differentiate benign from malignant disease. The SUV is typically higher on delayed images than on standard images. Diagnostic accuracy is approximately 70% for conventional imaging and 95% for delayed imaging (77). Dual-timepoint PET/CT therefore offers high diagnostic precision for urinary tract lesions, with the delayed scan achieving superior accuracy by virtue of measures that minimize urinary radioactivity.

Figure 21 A 73-year-old female with bladder metastasis and a history of gastric cancer. (A-D) Plain and contrast-enhanced CT (coronal, sagittal, and axial): the posterior superior wall of the bladder was thickened, with visible enhancement after contrast administration; enhancing nodules could be seen in the uterus and cervix, and there were multiple metastatic lymph nodes in the retroperitoneum and mesentery. CT, computed tomography.

Figure 22 A 67-year-old female with bladder metastasis and a history of cervical carcinoma. (A-D) Plain and contrast-enhanced CT (axial and sagittal): the bladder wall showed uneven thickening with persistent enhancement; the vaginal wall and the posterior wall of the rectum exhibited areas of marked enhancement. (E-H) MRI, T2WI, and T1+C (axial, coronal, and sagittal): bladder wall thickening, which was slightly hyperintense on T2WI and demonstrated marked enhancement. CT, computed tomography; MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Renal pelvis and ureter

Secondary urinary tract tumors are uncommon and evolve mainly from direct invasion of neighboring organs or seeding via blood vessels or lymphatic vessels. Among tumors that directly invade, cervical carcinoma is the leading etiology, followed by colorectal cancer and retroperitoneal malignancies such as lymphoma and liposarcoma (78,79). It is widely accepted that renal pelvis urothelial carcinoma can seed the distal urinary tract via “drop” metastasis, and sporadic cases of drop metastasis from RCC to the distal genitourinary system have also been documented. In a report of a typical case (78), the ureteral tumor produced obstruction, giving rise to hydroureter and hydronephrosis. We postulate that retrograde reflux facilitates tumor-cell dislodgement and subsequent implantation. Previous experimental work has also demonstrated that a traumatized urothelium is particularly susceptible to drop metastasis (78). The most common primary tumors that metastasize to the urinary tract are lung cancer, breast cancer, prostate cancer, and colorectal cancer (78,79). Urinary tract metastases are usually asymptomatic clinically. Hematuria, low back pain, dysuria, and dyspareunia are rarely observed. Unilateral or bilateral hydronephrosis is a common complication.

Ureteroscopy is the test of choice, but the examination of masses located outside the lumen of the ureter, such as submucosal metastases or periureteral infiltrates, is dependent on imaging examination (Figure 23). Contrast-enhanced CT, particularly CTU, is the preferred modality. It clearly delineates intraluminal masses or mural thickening and shows filling defects on the excretory phase. Due to long acquisition times, MRI is not routinely used as the first-line modality unless the patient is allergic to iodinated contrast. MRU yields findings comparable to those of CTU. PET/CT findings for the renal pelvis and ureter metastases mirror those for bladder lesions.

Figure 23 A 64-year-old male with renal pelvis metastasis and a history of lung cancer. (A-D) Plain and contrast-enhanced CT (axial, coronal, and sagittal): the right renal parenchyma was atrophic, and there was a heterogeneously enhanced mass in the right renal pelvis and severe hydronephrosis of the right kidney. CT, computed tomography.

Prostate and seminal vesicles

Metastatic involvement of the prostate is extremely rare, accounting for only 0.2% of all prostate surgical cases and only 0.4–2.0% of autopsy cases (80-82). Metastatic prostate malignant tumors are most commonly caused by direct invasion of adjacent organs (bladder or rectum) or infiltration by hematologic malignancies (e.g., leukemia and lymphoma) (83). In a retrospective analysis of 6,000 prostate autopsies, 328 (5.6%) were detected as secondary prostate involvement, of which 143 were from invasion of neighboring organs, and 127 were associated with leukemia or lymphoma; of the remaining 58 cases, only three originated from the stomach (84). The most common primary tumors metastasizing to the prostate are gastrointestinal tract cancer, lung cancer, melanoma, pancreatic cancer, and renal cancer (81,82). Patients with secondary prostate tumors are usually symptomatic. The most common manifestations of prostate metastases are dysuria, pelvic pain, and hematuria. These symptoms are sometimes similar to those of primary prostate cancer (83). The tumor marker PSA can be negative, but it is not particularly specific.

In the presence of persistent urinary symptoms and a history of neoplasia, an accurate physical examination is recommended, along with comprehensive imaging such as CT, ultrasound, and MRI (81). The clinical symptoms and imaging findings of secondary prostate tumors may be nonspecific (Figures 24,25). Limitations persist in differential diagnosis, precise lesion localization, treatment-response monitoring, and detection of recurrent disease. Different PET radiotracers each offer distinct advantages in the management of patients with prostate cancer. In patients with high prostate-specific membrane antigen (PSMA) expression or those with nodal and osseous metastases, ⁶⁸Ga-PSMA PET/CT demonstrates clear superiority in diagnostic performance, whereas when PSMA expression is low or absent, ⁶⁸Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT is more effective (85). Consequently, the combined use of ⁶⁸Ga-PSMA PET/CT and ⁶⁸Ga-FAPI-04 PET/CT can enhance diagnostic accuracy, enable more precise staging, and provide comprehensive guidance for individualized clinical treatment (85).

Figure 24 A 59-year-old female with seminal vesicle metastasis and a history of colon cancer. (A-F) CT and MRI (T2WI, T1+C, DWI, and ADC): a markedly enhanced mass was observed in the right seminal vesicle, with irregular shape, uniform density, and slight hyperintensity on T2WI. It showed hyperintensity on DWI and hypointensity on the ADC map. ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Figure 25 A 59-year-old male with metastatic prostate tumors and a history of lung cancer. (A,B) Heterogenous enhancement of the prostate on CT. (C,D) For MRI, T2WI showed hyperintensity, (E,F) DWI showed hyperintensity, and ADC map showed hypointensity. (G,H) T1+C: markedly heterogenous enhancement. ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; T1+C, T1WI with contrast; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Histopathologic evaluation is required in the vast majority of cases. Therefore, transrectal ultrasound-guided prostate biopsy remains the most important method for diagnosing primary or metastatic prostate tumors (86,87).

Penis, testicles, and scrota

Secondary tumors of the male reproductive system are highly uncommon. It has been reported that secondary tumors account for 0.02% to 2.5% of all testicular tumors (88). Testis metastasis most commonly originates from prostate cancer (35%), lung cancer (18%), melanoma (18%), renal cancer (9%), and colorectal cancer (less than 8%) (89). The scrotum and penile skin are organs that rarely metastasize.

Imaging is essential for identifying secondary tumors of the male reproductive system, with ultrasound being the preferred modality. Typically, imaging reveals hypoechoic or heterogeneous masses. CDFI shows a blood signal, while contrast-enhanced CT can show homogeneously enhancing masses. MRI produces high soft-tissue resolution and can effectively detect tumors, but it is difficult to distinguish them from primary tumors (Figure 26). FDG PET/CT may reveal differences in physiological uptake in the testes, and novel imaging techniques, such as PSMA-targeted PET/CT, have advantages in detecting painless testicular metastases with very low physiological uptake (88). The diagnosis is based on patient history and a palpable mass on examination and ancillary investigations, but a definitive diagnosis and the determination of the nature and origin of the mass still require puncture and postoperative pathology.

Figure 26 A 57-year-old male with penis metastasis and a history of bladder cancer. (A,B) Axial plain and contrast-enhanced CT demonstrated an enhancing nodule within the penis. (C,D) Coronal and sagittal contrast-enhanced CT clearly depicted the penile lesion. (E) Non-contrast T2-weighted fat-suppressed MRI showed a hyperintense nodule within the penis. (F,G) DWI and ADC maps revealed diffusion restriction in the penile lesion. (H) Postcontrast T1-weighted MRI showed marked enhancement of the penile lesion. ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging.

Uterus, cervix, vagina, and perineum

Although metastatic tumors of the female genital tract are uncommon, they may occur at various anatomical sites. These metastatic lesions may be insidious, masquerading as primary disease at the site of metastases. In a review of 149 metastatic tumors reported in the female genital tract, the ovary (75.8%) and vagina (13.4%) were the most common sites of metastasis. They were followed by the cervix, uterine corpus, and fallopian tubes, while the uterus accounted for only 8.1% (with the endometrium and cervix accounting for 4.7% and 3.4%, respectively) (90). Primary tumors mostly originate from ovarian, breast, gastric, colorectal, melanoma, and lung cancers. In approximately two-thirds of patients, uterine involvement is due to retrograde lymphatic spread of the tumor from the ovary (90). The clinical presentation is atypical, with vaginal bleeding being the main symptom.

Ultrasonography is the first-line and most convenient modality, typically showing a heterogeneous hypoechoic mass with rich internal vascularity. However, ultrasound lacks specificity and can be degraded by overlying bowel gas. PET/CT is hampered by the false-positive uptake of FDG in benign pelvic tumors and inflammatory lesions such as abscesses. Nevertheless, PET/CT metabolic parameters, including SUV, total lesion glycolysis, and metabolic tumor volume, can quantify the tumor metabolism. The latter two volumetric indices also reflect tumor burden and are valuable for assessing treatment response and prognosis. By exploiting the elevated metabolic activity of neoplastic cells, PET/CT enables the early detection of recurrent disease. Studies have shown that the staging accuracy of cervical nodal metastasis by CT or MRI scanning is greater than that of clinical examination (Figures 27,28), but it is difficult to differentiate cervical nodal metastasis from the primary tumor. The diagnosis of this disease requires a combination of clinical, imaging, and pathological examinations (91).

Figure 27 A 59-year-old female with uterine, cervical, and vaginal metastases, along with a history of rectal cancer. (A,B) Plain and contrast-enhanced CT: the uterus was enlarged with heterogenous attenuation. After contrast administration, there was marked, heterogenous enhancement of the uterine, cervical, and vaginal lesions. (C-G) MRI: the uterus, cervix, and vagina showed hyperintensity on T2WI, hyperintensity on DWI, and hypointensity on ADC map. The lesion demonstrated marked heterogenous enhancement on T1WI with contrast. ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

Figure 28 A 65-year-old female with perineum metastasis and a history of renal cancer. (A,B) Plain and contrast-enhanced CT: a slightly hypodense mass was present in the perineal region, with enhanced peripheral rim after contrast administration. CT, computed tomography.

Conclusions

The variable imaging manifestations of metastatic tumors pose a formidable challenge to accurate diagnosis. With the integration of clinical history with the radiologic features of each lesion, imaging represents a critical tool for the timely detection and precise characterization of metastases, thereby guiding appropriate therapeutic decisions.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2953/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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of Hubei Cancer Hospital (approval No. LLHBCH2025YN-077). As this was a retrospective study, informed consent was waived.

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. Di Micco R, Santurro L, Gasparri ML, Zuber V, Fiacco E, Gazzetta G, Smart CE, Valentini A, Gentilini OD. Rare sites of breast cancer metastasis: a review. Transl Cancer Res 2019;8:S518-52. [Crossref] [PubMed]
2. Ozaki K, Higuchi S, Kimura H, Gabata T. Liver Metastases: Correlation between Imaging Features and Pathomolecular Environments. Radiographics 2022;42:1994-2013. [Crossref] [PubMed]
3. Filella X, Rodríguez-Garcia M, Fernández-Galán E. Clinical usefulness of circulating tumor markers. Clin Chem Lab Med 2023;61:895-905. [Crossref] [PubMed]
4. Eloy JA, Mortensen M, Gupta S, Lewis MS, Brett EM, Genden EM. Metastasis of uterine leiomyosarcoma to the thyroid gland: case report and review of the literature. Thyroid 2007;17:1295-7. [Crossref] [PubMed]
5. Dibelius G, Mehra S, Clain JB, Urken ML, Wenig BM. Noninvasive anaplastic thyroid carcinoma: report of a case and literature review. Thyroid 2014;24:1319-24. [Crossref] [PubMed]
6. Yang Q, Yao YH, Zhang SX, Liu YL. Clinical characteristics and imaging manifestations of thyroid metastatic carcinoma. Chin J Gen Surg 2023;38:843-5.
7. Bhatoe HS, Badwal S, Dutta V, Kannan N. Pituitary metastasis from medullary carcinoma of thyroid: case report and review of literature. J Neurooncol 2008;89:63-7. [Crossref] [PubMed]
8. Shimon I. Metastatic Spread to the Pituitary. Neuroendocrinology 2020;110:805-8. [Crossref] [PubMed]
9. Castle-Kirszbaum M, Goldschlager T, Ho B, Wang YY, King J. Twelve cases of pituitary metastasis: a case series and review of the literature. Pituitary 2018;21:463-73. [Crossref] [PubMed]
10. Mayr NA, Yuh WT, Muhonen MG, Koci TM, Tali ET, Nguyen HD, Bergman RA, Jinkins JR. Pituitary metastases: MR findings. J Comput Assist Tomogr 1993;17:432-7. [Crossref] [PubMed]
11. Komninos J, Vlassopoulou V, Protopapa D, Korfias S, Kontogeorgos G, Sakas DE, Thalassinos NC. Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 2004;89:574-80. [Crossref] [PubMed]
12. Schubiger O, Haller D. Metastases to the pituitary--hypothalamic axis. An MR study of 7 symptomatic patients. Neuroradiology 1992;34:131-4. [Crossref] [PubMed]
13. Williams BK Jr, Di Nicola M. Ocular Oncology-Primary and Metastatic Malignancies. Med Clin North Am 2021;105:531-50. [Crossref] [PubMed]
14. Welch RJ, Malik K, Mayro EL, Newman JH, Honig SE, Ang SM, Selzer EB, Acaba-Berrocal LA, McGarrey MP, Graf AE, Considine SP, Shields JA, Shields CL. Uveal metastasis in 1111 patients: Interval to metastasis and overall survival based on timing of primary cancer diagnosis. Saudi J Ophthalmol 2019;33:229-37. [Crossref] [PubMed]
15. Konstantinidis L, Rospond-Kubiak I, Zeolite I, Heimann H, Groenewald C, Coupland SE, Damato B. Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre. Br J Ophthalmol 2014;98:92-8. [Crossref] [PubMed]
16. La Salvia A, Persano I, Trevisi E, Parlagreco E, Muratori L, Scagliotti GV, Brizzi MP. Ocular metastases from neuroendocrine tumors: A literature review. Semin Oncol 2020;47:144-7. [Crossref] [PubMed]
17. Günalp I, Gündüz K. Metastatic orbital tumors. Jpn J Ophthalmol 1995;39:65-70.
18. Kamieniarz L, Armeni E, O'Mahony LF, Leigh C, Miah L, Narayan A, Bhatt A, Cox N, Mandair D, Navalkissoor S, Caplin M, Toumpanakis C. Orbital metastases from neuroendocrine neoplasms: clinical implications and outcomes. Endocrine 2020;67:485-93. [Crossref] [PubMed]
19. Font RL, Ferry AP. Carcinoma metastatic to the eye and orbit. III. A clinicopathologic study of 28 cases metastatic to the orbit. Cancer 1976;38:1326-35. [Crossref] [PubMed]
20. Ryan TG, Juniat V, Stewart C, Malhotra R, Hardy TG, McNab AA, Davis G, Selva D. Clinico-radiological findings of neuroendocrine tumour metastases to the orbit. Orbit 2022;41:44-52. [Crossref] [PubMed]
21. Mahajan R, Mayappa N, Prashanth V. Metastatic Renal Cell Carcinoma Presenting as Nasal Mass: Case Report and Review of Literature. Indian J Otolaryngol Head Neck Surg 2016;68:374-6. [Crossref] [PubMed]
22. Chang MH, Kuo YJ, Ho CY, Kuan EC, Lan MY. Metastatic Tumors of the Sinonasal Cavity: A 15-Year Review of 17 Cases. J Clin Med 2019;8:539. [Crossref] [PubMed]
23. López F, Devaney KO, Hanna EY, Rinaldo A, Ferlito A. Metastases to nasal cavity and paranasal sinuses. Head Neck 2016;38:1847-54. [Crossref] [PubMed]
24. Remenschneider AK, Sadow PM, Lin DT, Gray ST. Metastatic renal cell carcinoma to the sinonasal cavity: a case series. J Neurol Surg Rep 2013;74:67-72. [Crossref] [PubMed]
25. Ozturk K, Gencturk M, Caicedo-Granados E, Li F, Cayci Z. Performance of whole-body (18)F-FDG PET/CT as a posttreatment surveillance tool for sinonasal malignancies. Eur Arch Otorhinolaryngol 2019;276:847-55. [Crossref] [PubMed]
26. Guo S, Wang Y. A case of hepatocellular carcinoma in an elder man with metastasis to the nasopharynx. Int J Clin Exp Pathol 2015;8:5919-23.
27. Kattepur AK, Patil DB, Krishnamoorthy N, Srinivas KG, Swamy S, Amarendra S, Gopinath KS. Isolated nasopharyngeal metastasis from hepatocellular carcinoma. Int J Surg Case Rep 2014;5:115-7. [Crossref] [PubMed]
28. Sellami M, Kallel S, Ben Ayed M, Mellouli M, Boudawara TS, Mnejja M, Hammami B, Achour I, Charfeddine I. Nasopharyngeal Metastasis from Breast Carcinoma: A Case Report and a Review of the Literature. Ear Nose Throat J 2025;104:80S-4S. [Crossref] [PubMed]
29. Dhia SB, Belaid I, Stita W, Hochlaf M, Ezzairi F, Ahmed SB. Bilateral parotid gland metastasis from a breast invasive ductal carcinoma. J Cancer Res Ther 2020;16:672-4. [Crossref] [PubMed]
30. Sarangi J, Kakkar A, Roy D, Mishra D, Thakar A, Deo SVS, Sharma A, Bhasker S. Metastases to the Parotid Gland: Study from a Tertiary Care Centre. Head Neck Pathol 2022;16:1034-42. [Crossref] [PubMed]
31. Alath P, Kapila K, Hussein S, Amanguno H, Hebbar HG, George SS, Francis IM. Parotid gland metastasis of breast cancer diagnosed on fine needle aspiration cytology: case report and review of literature. Cytopathology 2014;25:346-8. [Crossref] [PubMed]
32. Celik SU, Besli D, Sak SD, Genc V. Thyroid Gland Metastasis from Cancer of the Uterine Cervix: An Extremely Rare Case Report. Acta Medica (Hradec Kralove) 2016;59:97-9. [Crossref] [PubMed]
33. McCabe DP, Farrar WB, Petkov TM, Finkelmeier W, O'Dwyer P, James A. Clinical and pathologic correlations in disease metastatic to the thyroid gland. Am J Surg 1985;150:519-23. [Crossref] [PubMed]
34. Chen H, Nicol TL, Udelsman R. Clinically significant, isolated metastatic disease to the thyroid gland. World J Surg 1999;23:177-80; discussion 181. [Crossref] [PubMed]
35. Haygood TM, Sayyouh M, Wong J, Lin JC, Matamoros A, Sandler C, Madewell JE. Skeletal Muscle Metastasis from Renal Cell Carcinoma: 21 cases and review of the literature. Sultan Qaboos Univ Med J 2015;15:e327-37. [Crossref] [PubMed]
36. Ahuja AT, King AD, Bradley MJ, Yeo WW, Mok TS, Metreweli C. Sonographic findings in masseter-muscle metastases. J Clin Ultrasound 2000;28:299-302. [Crossref] [PubMed]
37. Qin F, Zhang X, Zhang J, Liu S, Wang Z, Xie F, Zhang M, Zhang T, Wang S, Jiao W. Masseter Muscle Metastasis of Renal Cell Carcinoma: A Case Report and Literature Review. Front Oncol 2022;12:830195. [Crossref] [PubMed]
38. Maraj S, Pressman GS, Figueredo VM. Primary cardiac tumors. Int J Cardiol 2009;133:152-6. [Crossref] [PubMed]
39. Nova-Camacho LM, Gomez-Dorronsoro M, Guarch R, Cordoba A, Cevallos MI, Panizo-Santos A. Cardiac Metastasis From Solid Cancers: A 35-Year Single-Center Autopsy Study. Arch Pathol Lab Med 2023;147:177-84. [Crossref] [PubMed]
40. Uetani T, Inaba S, Nishiyama H, Yamaguchi O. Metastatic Cardiac Tumor-Induced Acute Coronary Syndrome. JACC Cardiovasc Interv 2020;13:e179-80. [Crossref] [PubMed]
41. Chiles C, Woodard PK, Gutierrez FR, Link KM. Metastatic involvement of the heart and pericardium: CT and MR imaging. Radiographics 2001;21:439-49. [Crossref] [PubMed]
42. Mousavi N, Cheezum MK, Aghayev A, Padera R, Vita T, Steigner M, Hulten E, Bittencourt MS, Dorbala S, Di Carli MF, Kwong RY, Dunne R, Blankstein R. Assessment of Cardiac Masses by Cardiac Magnetic Resonance Imaging: Histological Correlation and Clinical Outcomes. J Am Heart Assoc 2019;8:e007829. [Crossref] [PubMed]
43. Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, Westwood M, Ghosh AK, Guha A. Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC CardioOncol 2020;2:293-311. [Crossref] [PubMed]
44. Kiryu T, Hoshi H, Matsui E, Iwata H, Kokubo M, Shimokawa K, Kawaguchi S. Endotracheal/endobronchial metastases : clinicopathologic study with special reference to developmental modes. Chest 2001;119:768-75. [Crossref] [PubMed]
45. Marchioni A, Lasagni A, Busca A, Cavazza A, Agostini L, Migaldi M, Corradini P, Rossi G. Endobronchial metastasis: an epidemiologic and clinicopathologic study of 174 consecutive cases. Lung Cancer 2014;84:222-8. [Crossref] [PubMed]
46. Picasso R, Pistoia F, Zaottini F, Sanguinetti S, Calabrese M, Martinoli C, Derchi L. Breast Metastases: Updates on Epidemiology and Radiologic Findings. Cureus 2020;12:e12258. [Crossref] [PubMed]
47. DeLair DF, Corben AD, Catalano JP, Vallejo CE, Brogi E, Tan LK. Non-mammary metastases to the breast and axilla: a study of 85 cases. Mod Pathol 2013;26:343-9. [Crossref] [PubMed]
48. Wang B, Jiang Y, Li SY, Niu RL, Blasberg JD, Kaifi JT, Liu G, Wang ZL. Breast metastases from primary lung cancer: a retrospective case series on clinical, ultrasonographic, and immunohistochemical features. Transl Lung Cancer Res 2021;10:3226-35. [Crossref] [PubMed]
49. Glazebrook KN, Jones KN, Dilaveri CA, Perry K, Reynolds C. Imaging features of carcinoid tumors metastatic to the breast. Cancer Imaging 2011;11:109-15. [Crossref] [PubMed]
50. Surov A, Fiedler E, Holzhausen HJ, Ruschke K, Schmoll HJ, Spielmann RP. Metastases to the breast from non-mammary malignancies: primary tumors, prevalence, clinical signs, and radiological features. Acad Radiol 2011;18:565-74. [Crossref] [PubMed]
51. Cabezas-Camarero S, Puente J, Manzano A, Corona JA, González-Larriba JL, Bernal-Becerra I, Sotelo M, Díaz-Rubio E. Renal cell cancer metastases to esophagus and stomach successfully treated with radiotherapy and pazopanib. Anticancer Drugs 2015;26:112-6. [Crossref] [PubMed]
52. Harada JI, Matsutani T, Hagiwara N, Kawano Y, Matsuda A, Taniai N, Nomura T, Uchida E. Metastasis of Hepatocellular Carcinoma to the Esophagus: Case Report and Review. Case Rep Surg 2018;2018:8685371. [Crossref] [PubMed]
53. McLemore EC, Pockaj BA, Reynolds C, Gray RJ, Hernandez JL, Grant CS, Donohue JH. Breast cancer: presentation and intervention in women with gastrointestinal metastasis and carcinomatosis. Ann Surg Oncol 2005;12:886-94. [Crossref] [PubMed]
54. Huang J, Xu L, Cheng G, Wu W, Tang W, Xu L, Hu D. An unusual case: Pseudoachalasia caused by metastatic ovarian cancer. Endosc Ultrasound 2021;10:479-80. [Crossref] [PubMed]
55. Carbó-Bagué A, Cerón-Nasarre L, Valls-Masot L, Melendez-Munoz C, Bujons-Buscarons E, Liñan-Planas R, Barretina-Ginesta MP. Esophageal Infiltration by High-Grade Serous Ovarian Carcinoma: A Very Rare Case Report. Case Rep Oncol 2023;16:1436-42. [Crossref] [PubMed]
56. Hisa T, Takamatsu M, Shimizu T, Gibo N. Chronological changes in the ultrasonic findings of gallbladder metastasis from renal cell carcinoma: a case report and review. J Med Ultrason (2001) 2014;41:371-5. [Crossref] [PubMed]
57. de Bitter TJJ, Trapman DM, Simmer F, Hugen N, de Savornin Lohman EAJ, de Reuver PR, Verheij J, Nagtegaal ID, van der Post RS. Metastasis in the gallbladder: does literature reflect reality? Virchows Arch 2022;480:1201-9. [Crossref] [PubMed]
58. Choi WS, Kim SH, Lee ES, Lee KB, Yoon WJ, Shin CI, Han JK. CT findings of gallbladder metastases: emphasis on differences according to primary tumors. Korean J Radiol 2014;15:334-45. [Crossref] [PubMed]
59. Saeed F, Osunkoya AO. Secondary Tumors of the Kidney: A Comprehensive Clinicopathologic Analysis. Adv Anat Pathol 2022;29:241-51. [Crossref] [PubMed]
60. Huang H, Tamboli P, Karam JA, Vikram R, Zhang M. Secondary malignancies diagnosed using kidney needle core biopsies: a clinical and pathological study of 75 cases. Hum Pathol 2016;52:55-60. [Crossref] [PubMed]
61. Patel U, Ramachandran N, Halls J, Parthipun A, Slide C. Synchronous renal masses in patients with a nonrenal malignancy: incidence of metastasis to the kidney versus primary renal neoplasia and differentiating features on CT. AJR Am J Roentgenol 2011;197:W680-6. [Crossref] [PubMed]
62. Hietala SO, Wahlqvist L. Metastatic tumors to the kidney. A postmortem, radiologic and clinical investigation. Acta Radiol Diagn (Stockh) 1982;23:585-91. [Crossref] [PubMed]
63. Marcuzzi A, Haider EA, Salmi ISA. Hepatic epithelioid angiomyolipoma with renal metastasis: radiologic-pathologic correlation. Radiol Case Rep 2018;13:829-33. [Crossref] [PubMed]
64. Geramizadeh B, Kashkooe A, Nikeghbalian S, Malek-Hosseini SA. Metastatic Tumors to the Pancreas, a Single Center Study. Arch Iran Med 2019;22:50-2.
65. Nakajima Y, Iwasaki E, Kayashima A, Machida Y, Kawasaki S, Horibe M, Kawaida M, Masugi Y, Iwata T, Kanai T. Successful radiotherapy for recurrent obstructive pancreatitis secondary to pancreatic metastasis from cervical squamous-cell carcinoma. Clin J Gastroenterol 2023;16:755-60. [Crossref] [PubMed]
66. Datta D, Aggarwal D, Balakrishnan S, Varshney VK, Kumar R. Metastasis from Cervical Cancer Presenting as a Pancreatic Head Mass - an Unexpected Diagnosis! J Gastrointest Cancer 2023;54:300-3. [Crossref] [PubMed]
67. Kawaguchi S, Ohtsu T, Terada S, Endo S. Obstructive pancreatitis secondary to a pancreatic metastasis from lung cancer treated with nasopancreatic drainage. Clin J Gastroenterol 2019;12:382-6. [Crossref] [PubMed]
68. Lu T, Li X, Zhou Y. Pancreatic metastasis from squamous cell lung cancer: computed tomography and magnetic resonance imaging findings. J Int Med Res 2021;49:300060521996188. [Crossref] [PubMed]
69. Dong J, Cong L, Zhang TP, Zhao YP. Pancreatic metastasis of renal cell carcinoma. Hepatobiliary Pancreat Dis Int 2016;15:30-8. [Crossref] [PubMed]
70. Yang Q, Zhang SX, Liu YL. Imaging Findings and Clinical Features of Pancreatic Metastases. Journal of Clinical Radiology 2025;44:315-9.
71. Klein B, Stein M, Kuten A, Steiner M, Barshalom D, Robinson E, Gal D. Splenomegaly and solitary spleen metastasis in solid tumors. Cancer 1987;60:100-2. [Crossref] [PubMed]
72. Lam KY, Tang V. Metastatic tumors to the spleen: a 25-year clinicopathologic study. Arch Pathol Lab Med 2000;124:526-30. [Crossref] [PubMed]
73. Wu CW, Yang TL. Spleen metastasis of recurrent malignant thymoma. J Surg Case Rep 2022;2022:rjac375. [Crossref] [PubMed]
74. Vancauwenberghe T, Snoeckx A, Vanbeckevoort D, Dymarkowski S, Vanhoenacker FM. Imaging of the spleen: what the clinician needs to know. Singapore Med J 2015;56:133-44. [Crossref] [PubMed]
75. Machuca-Aguado J, Rodríguez-Zarco E, Carrero-García B, Vázquez-Ramírez FJ. Metastasis of Uveal Melanoma in Bladder: Presentation of Two Cases and Review of the Literature. Arch Esp Urol 2022;75:873-7. [Crossref] [PubMed]
76. Feldman A, Borak S, Rais-Bahrami S, Gordetsky J. Secondary Malignancies of the Bladder: Avoiding the Diagnostic Pitfall. Int J Surg Pathol 2018;26:120-5. [Crossref] [PubMed]
77. Harkirat S, Anand S, Jacob M. Forced diuresis and dual-phase F-fluorodeoxyglucose-PET/CT scan for restaging of urinary bladder cancers. Indian J Radiol Imaging 2010;20:13-9. [Crossref] [PubMed]
78. Fejes Z, Király IE, Fehér ÁM, Kovács PG, Gyuris Z, Sükösd F, Torday L, Kuthi L. Multifocal Urinary Tract Metastasis of Colorectal Carcinoma. Pathobiology 2022;89:56-62. [Crossref] [PubMed]
79. Karaosmanoglu AD, Onur MR, Karcaaltincaba M, Akata D, Ozmen MN. Secondary Tumors of the Urinary System: An Imaging Conundrum. Korean J Radiol 2018;19:742-51. [Crossref] [PubMed]
80. Bates AW, Baithun SI. Secondary solid neoplasms of the prostate: a clinico-pathological series of 51 cases. Virchows Arch 2002;440:392-6. [Crossref] [PubMed]
81. Fusco N, Sciarra A, Guerini-Rocco E, Marchiò C, Vignani F, Colombo P, Ferrero S. Rediscovering Secondary Tumors of the Prostate in the Molecular Era. Adv Anat Pathol 2016;23:170-9. [Crossref] [PubMed]
82. Goto K, Kambara T, Kagiyama Y, Takemoto K, Kobatake K, Ikeda K, Inoue S, Hayashi T, Takeshima Y, Teishima J. The secondary tumor of the prostate derived from upper tract urothelial carcinoma: An autopsy case. IJU Case Rep 2021;4:397-402. [Crossref] [PubMed]
83. Roshni S, Anoop T, Preethi T, Shubanshu G, Lijeesh A. Gastric adenocarcinoma with prostatic metastasis. J Gastric Cancer 2014;14:135-7. [Crossref] [PubMed]
84. Zein TA, Huben R, Lane W, Pontes JE, Englander LS. Secondary tumors of the prostate. J Urol 1985;133:615-6. [Crossref] [PubMed]
85. Pabst KM, Mei R, Lückerath K, Hadaschik BA, Kesch C, Rawitzer J, Kessler L, Bodensieck LS, Hamacher R, Pomykala KL, Fanti S, Herrmann K, Fendler WP. Detection of tumour heterogeneity in patients with advanced, metastatic castration-resistant prostate cancer on [68Ga]Ga-/[18F]F-PSMA-11/-1007, [68Ga]Ga-FAPI-46 and 2-[18F]FDG PET/CT: a pilot study. Eur J Nucl Med Mol Imaging 2024;52:342-53.
86. Sehgal R, Virata AR, Bansal P, Hart M. Metastatic Carcinoma of Prostate as a Mimicker of SAPHO Syndrome. Clin Med Res 2021;19:141-7. [Crossref] [PubMed]
87. Zhang P, Zheng Y, Ran H, Leng Z, Wang Z. Case report: gastric adenocarcinoma metastatic to the prostate gland. J Radiol Case Rep 2010;4:35-8. [Crossref] [PubMed]
88. Mamaliga T, Obando JA, Liu Y. Testicular Metastasis From Prostate Cancer Demonstrated on PSMA PET/CT. Clin Nucl Med 2023;48:645-6. [Crossref] [PubMed]
89. Omar HA, Mohiuddin M, Sharif A. Colon cancer presenting as a testicular metastasis. Transl Gastroenterol Hepatol 2016;1:89. [Crossref] [PubMed]
90. Mazur MT, Hsueh S, Gersell DJ. Metastases to the female genital tract. Analysis of 325 cases. Cancer 1984;53:1978-84. [Crossref] [PubMed]
91. Lydiatt DD, Markin RS, Williams SM, Davis LF, Yonkers AJ. Computed tomography and magnetic resonance imaging of cervical metastasis. Otolaryngol Head Neck Surg 1989;101:422-5. [Crossref] [PubMed]