Introduction

The pathologic diagnosis of primary thyroid follicular epithelium-derived tumors is usually straightforward as they are predominantly well-differentiated neoplasms that recapitulate normal histology. On the other hand, histopathologic recognition, and clinical management of metastatic tumors to the thyroid neoplasms is less well-understood. This is partly because metastasis to the thyroid is uncommon - it is estimated that ~ 1–2% of clinically appreciable thyroid neoplasms are of metastatic origin [1, 2]. Several large-scale institutional series have examined the occurrence of metastatic disease to the thyroid [3,4,5,6,7,8,9,10,11]. However, the clinical presentation of metastatic disease to the thyroid with a concurrent primary thyroid malignancy is rarer and less described, with only case reports of such occurrences in the literature. The occurrence of an index case prompted us to examine our archives for cases of metastatic carcinoma to the thyroid. The purpose of our study was (a) to better characterize the phenomenon by summarizing the clinicopathologic features in this patient population and describe the unique histopathologic features of metastatic carcinoma to thyroid, especially when the metastasis involves an existing primary tumor in the thyroid, and (b) to review the literature to summarize the reported cases of tumor-to-tumor metastasis involving the thyroid.

Materials and Methods

This was a descriptive retrospective study. The conduct of this study was approved by the University of Iowa Hospitals and Clinics institutional review board (IRB). The files of the Department of Pathology at the University of Iowa Hospitals and Clinics were searched to identify patients over a twenty-two period (2000–2021) who had been diagnosed with metastatic tumors to the thyroid, either by pathologic examination of thyroid lobectomy, hemi- or total thyroidectomy specimens, or via needle biopsy samples. We employed keyword searches to query the files for matching patients. In order to not miss potential cases, all pathology reports with the words ‘thyroid,’ and ‘metastatic,’ or ‘metastasis’ were retrieved and manually reviewed. Those with direct tumor extension from adjacent sites (larynx, mediastinum) to the thyroid or cases where such a possibility couldn’t be definitively ruled out were excluded. After cases that satisfied inclusion criteria were identified, clinical, radiologic and information on histopathologic features were retrieved from the electronic health records and pathology reports, and collated as follows: age, sex, thyroid diagnosis, type of primary malignancy and most current clinical status. Routine hematoxylin and eosin (HE) stained slides, and immunostained sections, where applicable, were retrieved and reviewed by two members of the study team (EA, DAR) to re-confirm the original diagnosis. Immunohistochemical studies, where applicable, were performed on 4-µm sections of paraffin-embedded tissue, with appropriate positive and negative controls using standard techniques. Review of literature: We comprehensively reviewed the literature for cases of tumor-to-tumor metastasis to the thyroid by searching Pubmed and Dimensions (https://www.dimensions.ai/). We identified and included case reports or case series where a clear tumor-to-tumor spread could be established from available text in the English language. Cases of collision tumors and synchronous metastatic spread with a concurrent thyroid primary were excluded.

Results

Cases

From a total of 1836 cases with thyroidectomy performed in the specified 22-year period (2000–2021), 679 patients were identified by the initial keyword searches, with reports that included the words ‘thyroid,’ and ‘metastatic,’ or ‘metastasis.’ Following thorough review of the pathology reports, 14 patients were identified to have definitive involvement of the thyroid gland by histopathologically confirmed metastatic carcinoma. The majority of the patients were female (11/14, 78.5%). The age of the patients ranged from 30 to 73 years. The primary sites were commonly lung, breast, and the kidney, with the lung being the most common. The demographic and clinical features of these patients are presented in Table 1. Of the 14, 35% (n = 5) were tumors which were metastatic to a concurrent primary thyroid lesion whereas the rest exhibited metastasis to otherwise unremarkable thyroid parenchyma. Of the 5 cases, 4 had sufficient clinical data and available slides for re-review and confirmation of the original diagnosis (cases #1–4, Table 1) whereas one case could not be histologically re-confirmed (case #8, Table 1). We present a more detailed narrative discussion of these patients below, with follow-up information where available.

Table 1 Demographic and clinical features of patients with metastasis to the thyroid in the present study. Cases 1–4 are further expanded upon in the Results section and in Table 2
Full size table
Table 2 Clinicopathologic profile of patients with tumor-to-tumor metastasis involving the thyroid, including patient age, type of primary tumor, type of thyroid neoplasm, and other sites of metastases identified during patient’s clinical course
Full size table

Case # 1

A 56-year-old woman was diagnosed with lung adenocarcinoma which was negative for EGFR mutations and showed a c.34G > T activating mutation in KRAS On molecular genetic analysis. She was found to have an incidental lesion of the right thyroid during a positron emission tomography (PET) scan to characterize her lung malignancy. Fine needle aspiration of the thyroid showed papillary thyroid carcinoma; however, since systemic chemotherapy treatment of her lung adenocarcinoma had already been scheduled, the patient did not undergo thyroidectomy. Three years after initial diagnosis, in order to be eligible for a clinical trial for treatment of lung adenocarcinoma, the patient underwent right thyroid lobectomy. Gross examination showed a well-circumscribed tumor that measured 2.2 cm. Careful histopathologic examination showed a second neoplastic component diffusely intermingled within the papillary thyroid carcinoma, with large polygonal pleomorphic epithelial cells with clear to eosinophilic cytoplasm that infiltrated papillary cores and follicular structures and, at places, colonized and replaced thyroid follicular epithelial cells within the PTC (Fig. 1, panels A). Immunohistochemistry demonstrated the two subsets of cells more distinctly (Fig. 1, panels B – F). The papillary thyroid carcinoma exhibited typical papillary architecture and the tumor cells were positive for PAX8, TTF-1, thyroglobulin, and BRAF V600E (panels B, D, E and F, respectively), and negative for Napsin-A (panel C) and p40. The admixed larger pleomorphic tumor cells were also positive for TTF-1 (panel D), but of slightly higher immunointensity. However, they were positive for Napsin-A (panel C), and negative for PAX8, thyroglobulin, BRAF V600E (panels B, E, and F, respectively), and p40. Given the differences in cytomorphologic appearance and immunohistochemical findings, combined with the findings in the original cytopathology, a diagnosis of metastatic lung adenocarcinoma to a pre-existing papillary thyroid carcinoma was made. Following thyroid surgery, the patient continued to be clinically asymptomatic with respect to thyroid disease. Through her clinical course, the patient had lung adenocarcinoma metastases to the brain, liver, and spine; however, there were no evidence of recurrence of her disease in the thyroid. The patient survived to present day, five and a half years since her initial diagnosis.

Fig. 1
figure 1

Case #1. A: Routine HE-stained section of papillary thyroid carcinoma composed of follicular-patterned areas with scattered papillae (arrow) with typical nuclei exhibiting enlargement, chromatin clearing, irregularity and overlapping (inset, 40x), along with coexistent metastatic carcinoma, highlighted by asterisks, composed of large polygonal tumor cells with marked nuclear pleomorphism. B: Immunohistochemistry for PAX8 shows strong nuclear immunoreactivity in PTC areas, C: Napsin A shows granular cytoplasmic positivity in admixed areas of metastatic lung adenocarcinoma, D: TTF-1 is positive in both components, though slightly stronger reactivity is noted in metastatic lung carcinoma, E: Thyroglobulin expression is confined to PTC, F: BRAF V600E immunohistochemistry shows faint-to-moderate but definite positivity in PTC and is distinctly negative in metastatic lung adenocarcinoma (arrows) (all panels 10x magnification)

Full size image

Case # 2

A 76-year-old female was diagnosed initially with lobular carcinoma of the right breast for which she underwent lumpectomy. Seven years later, the patient was found to have an invasive cancer in the contralateral breast with mixed lobular and ductal features. She underwent systemic chemotherapy along with radiation treatment followed by left mastectomy. She presented twelve years later (present day) with a sensation of a neck mass, along with dysphagia to solids and liquids. A thyroid ultrasound showed bilateral nodules and fine needle aspiration showed a follicular patterned neoplasm concerning for papillary thyroid carcinoma. A thyroidectomy was performed. Histopathologic examination showed the right lobe with multiple small foci of papillary thyroid microcarcinoma, ranging from 0.4 to 0.9 cm, along with a dominant follicular patterned 3.3 cm tumor that contained features of both papillary thyroid carcinoma and multifocal metastatic involvement by lobular breast carcinoma. The metastatic breast carcinoma was arranged in nests and in a single file pattern around compressed-appearing cords and follicles of papillary thyroid carcinoma (Fig. 2, A), infiltrating interstitial spaces between the native thyroid carcinoma and the underlying stroma. On immunohistochemistry, the lobular carcinoma component was positive for GATA-3, estrogen receptor (ER), and progesterone receptor (PR), and negative for chromogranin, synaptophysin, calcitonin, and PAX8 and thyroglobulin, the last two being both positive in thyroid carcinoma (Fig. 2, panels B – F). The left lobe of the thyroid contained only papillary thyroid carcinoma. The patient did not develop new symptoms concerning for continued thyroid disease; however, a recent PET scan showed foci of metastatic disease in the posterior right and caudate lobes of the liver.

Fig. 2
figure 2

Case #2. A: Panoramic view of subcapsular nodular focus of papillary thyroid microcarcinoma (PTMC) along with adjacent thyroid parenchyma and a second thinly encapsulated thyroid nodule (2x), B: Higher-power view of the area indicated by grey rectangle in Panel A shows microfollicular areas of PTC with adjacent admixed paler nests and cords of metastatic lobular breast carcinoma indicated by asterisks (12.6x), C: PTMC showing microfollicles of thyroid carcinoma with admixed lobular carcinoma arranged in cords and nests barely distinguishable from one another; inset (40x) showing PTMC with nuclear features of enlargement, overlapping, with chromatin margination and clearing, D: Immunohistochemistry for estrogen receptor (ER) shows nuclear expression in metastatic carcinoma and is negative in PTMC, E: Pankeratin is positive in both components but shows stronger expression in metastatic carcinoma, F: PAX8 is positive in thyroid carcinoma in an inverse pattern compared to panel D, G: GATA 3 shows strong nuclear immunoreactivity in breast carcinoma cells, H: thyroglobulin expression is preserved in the native thyroid carcinoma component (all panels except A and B, 20x magnification)

Full size image

Case # 3

A 54-year-old female presented with a history of left-sided oropharyngeal squamous cell carcinoma (SCC), with a PET scan showing a focus of increased uptake in the left lingual tonsillar region as well as an area of increased uptake in a large left level 2 lymph node. Fine needle aspiration of the neck mass showed findings consistent with metastatic SCC. The patient underwent chemoradiation therapy as primary treatment. A repeat PET scan 1 year later showed no evidence of residual disease. At this time, she noticed a nodule on the left side of her neck in the thyroid region. She underwent ultrasonographic examination, which showed an unremarkable right thyroid lobe and a single, hypoechoic solid 0.6 cm nodule in the mid-inferior left lobe. A fine needle aspiration of the left thyroid mass was performed, and it showed tumor composed of large polygonal cells with enlarged hyperchromatic nuclei with coarse chromatin, consistent with metastatic squamous cell carcinoma (Fig. 3, A). One year later, the patient reported a sensation of neck fullness; she denied any hoarseness, dysphagia, or goiter. The patient underwent total thyroidectomy. On histopathologic examination, a 0.7 cm mass with features of papillary thyroid carcinoma with intratumoral associated squamous cell carcinoma was identified in the left lobe of the thyroid. The papillary thyroid microcarcinoma exhibited classical features with well-formed papillae lined by thyroid follicular epithelial tumor cells with enlarged, overlapping cleared nuclei (Fig. 3, B). The squamous cell carcinoma was confined to the PTC and though within the same mass lesion, these two areas were distinct from each other. The metastatic SCC was composed of islands of markedly atypical squamous cells embedded in fibrotic stroma, admixed with hemorrhage and scant reactive fibroblastic proliferation (Fig. 3, C).

Fig. 3
figure 3

Case #3. A: Squamous cell carcinoma fragments with squamous pearl formation (arrow), left thyroid lobe fine needle aspiration, Giemsa stain, top panel and Papanicolaou stain, bottom panel (both 40x). B: areas of papillary thyroid carcinoma on subsequent thyroid lobectomy with classic morphology, HE stain, (14.2x). C, both panels: Foci of metastatic squamous cell carcinoma (arrows) in area adjacent to tumor depicted in panel B within the same mass (24.6x and 10x)(numbers in parenthesis indicate magnification level)

Full size image

Case # 4

The patient is a 75-year-old female who was identified to have a neuroendocrine carcinoma of the sigmoid colon treated with local resection. Approximately 10 years later, a follow-up computed tomography (CT) scan showed increased contrast uptake in the right thyroid gland. Ultrasonography showed a solid 2 cm nodule in the right thyroid lobe. She was subsequently identified to have widespread metastatic neuroendocrine cancer and underwent radiofrequency ablation of a kidney lesion, low anterior resection, as well as en bloc resection of tumor nodules on the left iliac vein. She underwent a right hemithyroidectomy later that year at an outside hospital due to the continued presence of a thyroid nodule with concern now growing for the thyroid focus representing metastatic disease. Referred material from the thyroidectomy was reviewed and histopathologic examination demonstrated metastatic well differentiated neuroendocrine tumor (NET) involving the thyroid, along with two adjacent foci of papillary thyroid microcarcinoma. The metastatic tumor exhibited distinct morphologic features of NET, including tumor cells arranged in cords and trabeculae with oval hyperchromatic nuclei with coarse heterochromatin. It was embedded in thyroid parenchyma amidst a focus of papillary thyroid microcarcinoma, which was composed to solid tumor nests with typical papillary nuclear features (Fig. 4 A, B). On immunohistochemistry, the metastatic tumor was positive for SSTR2A. Repeat PET scans showed continued spread of her neuroendocrine primary cancer, showing lesions in the liver, multiple osseus lesions in the axial and appendicular skeleton, and bilateral pulmonary nodules. There was no evidence of new or continued metastatic disease in the thyroid. The patient was treated with octreotide infusions along with palliative radiation therapy targeted to selected lesions. The patient is now deceased, dying approximately 21 years after initial diagnosis and 4 years after thyroid metastasis detection.

Fig. 4
figure 4

Case #4. A: Metastatic neuroendocrine tumor composed hyperchromatic tumor cells in solid sheets and nests (asterisk) involving papillary thyroid microcarcinoma with prominent sclerosis, exhibiting typical nuclear features of chromatin margination and clearing, nuclear enlargement and nuclear grooves (arrows), arranged in ill-defined nests (arrowheads). B: Another area showing neuroendocrine tumor (asterisk) embedded in papillary thyroid carcinoma. The arrowheads point to adjacent nonneoplastic thyroid follicles, which in contrast to the thyroid carcinoma show round, regular, darker nuclei with smooth nuclear contours (both panels 40x magnification)

Full size image

Review Of Literature Of Tumor-to-Tumor Metastasis to the Thyroid

We found 53 cases in 46 reports from 1962 to 2022. One of the reports was published in Japanese but the details of the case were able to be ascertained from the abstract in English. We excluded cases with incomplete descriptions of the pathologic findings such that collision tumors and synchronous metastatic spread with a concurrent thyroid primary could not be ruled out [12,13,14,15]. Of the 53 cases, the patient’s sex could be ascertained in 50, and 68% were female (34/50) with a female:male ratio of 2.12:1. The donor sites (i.e., primary extrathyroidal malignant neoplasms) were variable but the three most common were lung adenocarcinoma (14/53, 26%), renal cell carcinoma (12/53, ~ 22.5%) and colorectal adenocarcinoma (9/53, 17%) which collectively formed 67.5% of the reported cases. In the thyroid, these metastasized most commonly to follicular adenoma (20/53, ~ 38%) with papillary thyroid carcinoma (14/53, ~ 26.5%) and follicular variant papillary thyroid carcinoma (10/53, 18%) forming the other two common primary tumors. These together form 82.5% of the total reported cases. The reported cases are summarized in Table 3.

Table 3 Summary of tumor-to-tumor metastasis to neoplasms of the thyroid as reported in clinical case reports and case series (published 1962–2022). Tumors listed in column labeled ‘Donor’ are primary extrathyroidal neoplasms whereas ‘recipient’ refers to the thyroid neoplasm involved by metastatic spread from the primary
Full size table

Discussion

Metastatic disease to the thyroid gland is an uncommon event, with metastasis seeding a tumor within the thyroid being rarer. A recent systematic review of the literature shows that the incidence in all malignant thyroid resections is 0.3–1.15% and 0.07–0.3% in all thyroid fine needle aspiration [61]. However, it may be the case – given that the thyroid commonly shows benign nodules and thyroid masses are typically not resected all the time – that metastatic disease is clinically underrecognized and not histopathologically confirmed for concurrent metastatic involvement in every instance. This is suggested by autopsy studies where the incidence of metastasis to the thyroid is estimated to range from 0.4% to as high as 26.4% [62]. The higher estimates in these series of studies are particularly interesting as they come from studies that purposely oversampled thyroid tissue in patients with metastatic disease elsewhere in addition to the thyroid [63]. This suggests that the true incidence of thyroid metastasis is likely higher than is reported.

The occurrence of tumor-to-tumor metastasis has long held the interest of clinicians and researchers. In analyzing the presence of both a primary thyroid cancer and metastatic disease from extrathyroidal carcinoma, the possibilities are collision tumors, direct extension from an adjacent organ, intravascular spread of metastatic tumor without parenchymal growth, and synchronous involvement by primary and metastasis. These were formally stated as part of criteria for establishing tumor-to-tumor metastasis in 1968 [64]. Most of these are determined histopathologically. Collision tumors are recognized by two tumor present in distinct adjacent foci next to each other. Contiguous spread into the thyroid is determined from the clinical and imaging findings and careful gross examination. A synchronous metastatic focus (or foci) occurs at a different locations within the thyroid, away from an existing primary thyroid carcinoma. In the present case series, these factors were all considered, and it was determined that in all four cases, the most likely outcome was the development of a primary thyroid malignancy that served as a recipient site for a second metastatic malignancy.

The profile of ‘donor’ tumors in tumor-to-tumor metastasis in the literature is similar to those that commonly metastasize to the thyroid, namely, lung, breast, and the kidney. Follicular adenoma (FA) appears to be the most common recipient tumor. The most common malignant recipient tumor type is papillary thyroid carcinoma which forms close to half of all recipient tumors reported (24/53, 45%, classic and follicular PTC together).

In addition to careful morphologic assessment, ancillary techniques including immunohistochemistry to identify expression of tumor-specific markers and lines of differentiation play an important role in the diagnosis of tumor-to-tumor metastasis. Differentiation of highly pleomorphic, poorly differentiated metastatic carcinoma from primary anaplastic thyroid carcinoma (ATC) arising in a differentiated thyroid neoplasm may prove challenging. This is particularly true when the metastatic tumor is from a lung primary as both are (variably) TTF-1 positive. ATC largely retain nuclear PAX8 expression and lung adenocarcinoma are usually PAX8-negative, though not always if polyclonal PAX8 is used [65]. Lung adenocarcinomas typically retain strong TTF-1 expression when compared to ATC, as was seen in case #1 (Fig. 1, B). The distinction may not be a trivial exercise: Mizukami et al. [17] describe the case of a 75-year-old man with a follicular carcinoma of the thyroid associated with a poor differentiated carcinoma component with widespread lung and extrapulmonary metastases. This was initially thought to be primary thyroid carcinoma with dedifferentiation and systemic metastases before being diagnosed correctly as a lung primary adenocarcinoma with widespread metastases, including spread to a tumor in the thyroid. Typically, however, the distinction of a metastasis to the thyroid should be straightforward with the use of a panel of markers including but not limited to CDX2, SATB2, GATA-3, GCDFP15, mammaglobin, Napsin-A, TTF-1 and thyroglobulin. When tumors exhibit neuroendocrine differentiation, the use of calcitonin and monoclonal carcinoembryonic antigen (mCEA) may be particularly useful in the distinction between metastatic disease and primary medullary thyroid carcinoma – the latter being positive for both. In difficult cases, molecular testing may prove useful as tumor-specific gene mutations and rearrangements (BRAF V600E, EGFR, ALK, ROS, and others) provide a clue to the site of origin.

In cases of metastatic squamous cell carcinoma to papillary thyroid carcinoma (or to the thyroid), the primary differential diagnosis is diffuse sclerosing variant of papillary thyroid carcinoma, as was considered in relation to case #3. The diffuse sclerosing variant of PTC is a rare tumor that typically forms an ill-demarcated, large, infiltrative mass that spreads throughout the thyroid, with numerous psammoma bodies, prominent lymphovascular invasion, and dense tumor-associated chronic inflammation [66]. Uncommonly, squamous metaplasia and fibroblastic proliferation can follow fine needle aspiration in the thyroid [67, 68], and areas in the present tumor undoubtedly showed features that were reminiscent of such changes (Fig. 3, C). Other considerations include mucoepidermoid carcinoma, primary squamous cell carcinoma of the thyroid (as anaplastic thyroid carcinoma variant) and local spread from a thymic squamous cell carcinoma. The localized, non-diffuse nature of the metastatic tumor, with distinct PTC and squamous cell carcinoma areas within the same lesion, and the presence of definitive squamous cell carcinoma in the pre-resection diagnostic FNA material in the absence of prior thyroid aspiration, supported the diagnosis of a tumor-to-tumor metastasis. We were unable, however, to perform p16 immunohistochemistry on the metastatic tumor and the primary tumor was not subjected to p16 testing, having been treated by chemoradiation. The inability to obtain additional definitive confirmation constitutes a limitation in our diagnosis of the case.

Striking patterns of histologic involvement of the primary tumor by the metastasis were noted in our series. In case #1, a prominent intrafollicular pattern of tumor growth (Fig. 5, panels A, B) was identified. Follicular structures in the primary tumor showed colloid replaced by metastatic carcinoma, with a residual rim of thyroid follicular epithelium. Case #2 was notable for presence of an interstitial pattern of infiltration of papillary thyroid carcinoma by lobular breast carcinoma with follicles being encircled and enveloped by metastatic tumor (Fig. 5, panels C, D). Interestingly, both of these patterns were described by Matias-Guiu and colleagues in neuroendocrine tumor metastatic to the thyroid gland [69] and Mistelou et al. in their series of cases of secondary malignancies involving the thyroid [62]. A further pattern of cancerization of thyroid follicles has been described in a case of endometrial carcinoma metastatic to papillary thyroid carcinoma [46]. These findings imply that common biologic mechanisms likely underlie the dissemination of extrathyroidal carcinomas through thyroid tumors.

Fig. 5
figure 5

Architectural features from Cases #1 and #2. A, B: Areas of tumor from Case #1, HE stain, A and TTF-1 immunostain, B (both 20x). Arrows points to intrafollicular involvement by metastatic lung adenocarcinoma. C, D: Areas of tumor from Case #2, HE stain, C, and GATA-3 immunostain, D (both 40x). Nests of metastatic lobular carcinoma (arrows) are festooned on the outside of compressed cords of papillary thyroid carcinoma that exhibit small follicles (arrowheads) (numbers in parenthesis indicate magnification level)

Full size image

Given its high vascularity, the thyroid should act as a suitable recipient for metastatic disease. It has been long postulated that this does not typically occur due to tumor owing to the high arterial flow rate in the organ [70]. Close to half of all metastases to the thyroid occur to a gland that exhibit a form of concurrent pathology, benign or malignant [71]. A primary thyroid carcinoma or even microcarcinoma may be a permissive tumor microenvironment and constitute a mechanism that facilitates metastasis to the thyroid. The mechanistic picture is still poorly characterized and is likely due to a combination of many factors, such as disruption of the normal vascular barrier and altered immune surveillance in recipient thyroid lesions. In light of the rarity of thyroid involvement in metastatic disease, the relative high rate of metastasis to a thyroid primary carcinoma in our case series is more striking. Metastatic thyroid involvement is typically a late event in cancer progression with coexisting multiorgan involvement [72]. There is emerging evidence that patients with isolated metastatic disease to the thyroid have better survival outcomes [73].

From our review of cases and the literature, we believe the main ‘stumbling block’ is the consideration of the possibility at the time of diagnosis of tumor-to-thyroid or tumor-to-tumor metastasis. Sometimes, pertinent clinical information is not fully available to the pathologist (or even the clinician) at the time of diagnosis, particularly at the juncture when the patient undergoes thyroid FNA [32, 44]. Careful clinical examination and review of the clinical history of prior malignancies are critical and can often but not always obviate a long panel of immunostains.

Conclusion

Metastatic disease to the thyroid is an uncommon but significant clinical event. We hereby describe a case series of tumor-to-tumor metastasis involving neoplasms in the thyroid, with the ‘donor’ primary site being the lung and the breast in two cases. While metastatic disease to the thyroid gland is a rare event, the phenomenon may be altered in frequency when there is a separate primary thyroid malignancy present. In these scenarios, the clinical management and implications of the patient’s other malignancy is not well characterized. We highlight the unique histopathologic patterns of involvement in tumor-to-tumor metastasis in the thyroid and the associated diagnostic challenges in its recognition.