Metastatic Thyroid Carcinoma to the Kidneys Presenting Initially as Bilateral Renal Masses: A Rare Case Report and Literature Review

Introduction

Thyroid cancer is the most rapidly increasing malignancy in the United States for both men and women. ¹ Differentiated thyroid carcinomas are the most common histologic subtype of all thyroid cancers with a prevalence of 90%. ¹ Well-differentiated thyroid cancers include papillary, follicular, and Hürthle cell histologies, with papillary carcinoma and follicular carcinoma being the most common. Papillary thyroid carcinoma is the most common type, with a mean age of diagnosis ranging from 31 to 49 years and has a female to male ratio between 2:1 and 3:1. The main pattern of spread of papillary thyroid carcinoma is through lymphatic system. ² Metastasis of follicular thyroid carcinoma is also usually to regional lymphatic system, but distant metastasis is also observed in 10% to 15% of patients, mostly in the lungs and bone.^3,4 Renal involvement from primary thyroid cancer is very unusual, with a prevalence of less than 6%.^3–5 Herein we present a unique case of a 90-year-old woman with bilateral renal metastasis of the follicular variant of papillary thyroid carcinoma, and her pathological and clinical manifestations.

Case Presentation

A 90-year-old female presented with right-sided abdominal discomfort. Her initial laboratory evaluation revealed elevated creatinine levels (1.05 mg/dL). Following her primary evaluation, she was referred to a nephrologist who recommended an assessment for chronic kidney disease. Her past medical history was significant for congestive heart failure, hypertension, and a thyroid goiter for which she underwent a partial thyroidectomy 71 years ago, with a subsequent levothyroxine supplementation for hypothyroidism. Three years before her current clinical presentation, her primary care physician performed a neck ultrasound that revealed multiple benign adenomatoid thyroid nodules and for which clinical follow up was recommended. Biannual neck ultrasound did not show any changes in the size of the nodules for 3 years. The patient has no prior history of radiation exposure to the head and neck region. Her family history is significant for hypothyroidism and goitrous thyroid nodules without malignancies.

The initial abdominal ultrasound examination revealed large masses at the level of the left adrenal and right kidney regions. Further abdominal and pelvic CT (computed tomography) scan demonstrated a right renal mass (11.1 cm × 11.2 cm) involving the mid and upper pole (Figure 1), and a left suprarenal/adrenal gland mass (11.5 cm × 9.4 cm). A CT-guided fine-needle aspiration biopsy of the right kidney mass was ordered. Microscopic examination was positive for carcinoma (Figure 2A), and an additional immunohistochemical staining panel was performed on the cell block. The neoplastic cells were positive for TTF1 (transcription termination factor 1) (Figure 2B), thyroglobulin (Figure 2C), PAX8 (paired box 8) (Figure 2D), keratin 7 (KRT7), and vimentin. They were negative for AMACR (Alpha-methyl acyl-CoA racemase), confirming a primary thyroid carcinoma metastatic to the kidney. The final histopathologic exam rendered as a metastatic low-grade papillary thyroid carcinoma, follicular variant.

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Figure 1.

Axial contrast-enhanced computed tomography image demonstrates a large, heterogeneously enhancing mass arising from the superior pole of the right kidney (arrowheads). Hypoattenuation in the center of the mass (*) is consistent with central necrosis. Ultrasound-guided biopsy of this mass yielded metastatic thyroid carcinoma. Note the normal appearing inferior pole of the right kidney (open arrow).

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Figure 2.

Low power magnification of metastatic thyroid cancer to the kidney (A- 20×; cell block, H&E), the tumor cells were positive for TTF1 (B- 20×; cell block, TTF1), thyroglobulin (C- 20×; cell block, thyroglobulin), and PAX8 (D- 20×; cell block, PAX8).

As a result of the incidental renal findings, the patient underwent a neck ultrasound that revealed multiple bilateral thyroid nodules. The right lobe showed a large ill-defined nodule (2.9 cm × 1.8 cm × 1.9 cm) with a definitive extra-thyroidal extension (Figure 3). The left lobe showed a heterogeneous hypoechoic solid nodule with punctate micro-calcifications. Normal vascularity without neck adenopathy was noted. A clinical decision to proceed with a total thyroidectomy was made.

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Figure 3.

Longitudinal ultrasound image (inferior on the left) of the right thyroid lobe demonstrates a bilobed, heterogeneously echogenic nodule in the mid-upper pole (*). This nodule demonstrates ill-defined borders along the inferior margin (arrowheads) and several microcalcifications (arrows). Ultrasound-guided biopsy and subsequent surgical excision of this nodule revealed papillary thyroid carcinoma, follicular variant.

The thyroidectomy specimen's gross examination revealed a dominant 3.5 cm mass that replaces most of the right lobe and infiltrates into adjacent benign-appearing parenchyma with marked fibrosis and dense central hyalinization. The left thyroid lobe showed a densely sclerotic, calcified 2.5 cm mass. Histopathologic examination was consistent with a follicular variant of papillary thyroid carcinoma. Additional microscopic nodules (1.0 cm, left lobe; 0.5 cm, right lobe; 0.4 cm, isthmus) of follicular variant of papillary thyroid carcinoma were also identified. Lymphovascular invasion was present; however, the surgical resection margins were negative for carcinoma.

Surgical consultation determined that the patient was not a good surgical candidate as her bilateral renal masses were not amenable to partial nephrectomies. A subsequent diagnostic radioiodine scan was performed to determine if the masses were iodine avid, with additional dosimetry to calculate the required dose of radioactive iodine. She completed external beam radiation therapy with a total dose of 3600 cGy in 20 fractions. Follow-up abdominal and pelvic imaging showed a slight interval decrease in the size of the bilateral renal masses. No additional metastatic lesions were identified. She also notably had a decrease in thyroglobulin to 7982, down from approximately 140,000 before treatment.

Discussion

Thyroid cancer exists in multiple forms with differentiated thyroid carcinomas being the most common histologic subtype. Differentiated thyroid carcinomas are characterized by a slowly progressive course with a 10-year survival rate as high as 80% to 95%. Papillary thyroid carcinoma is the most common form of differentiated thyroid carcinoma, representing 80% of cases, and is associated with lymphatic spread.^1,2 Classic papillary thyroid carcinoma is the most common subtype of papillary thyroid carcinoma, while a follicular variant of papillary thyroid cancer (FVPTC) is the second most common subtype. The follicular variant of papillary thyroid carcinoma is characterized by nuclear features consistent with classic papillary thyroid carcinoma but has a follicular architecture with a mixture of micro- and macro-follicles that lacks classic papillary morphology,^6,7 and it demonstrates more tendency to metastasize to lymph nodes than hematogenous metastasis. ⁸ The colloid in follicular variant of papillary thyroid carcinoma is usually thick and eosinophilic and demonstrates peripheral scalloping.

Morphologically, follicular variant of papillary thyroid carcinoma has 2 main subtypes: invasive (or non-capsulated) and noninvasive (encapsulated). A recently described entity known as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) that was previously classified as non-invasive (encapsulated) follicular variant of papillary thyroid carcinoma has an excellent prognosis. NIFTP is described as a follicular patterned lesion that is well-demarcated/encapsulated that displays similar nuclear features as papillary thyroid carcinoma and lacks capsular and vascular invasion in addition to absence of necrosis, papillae, psammatous calcifications and high mitotic activity. ⁹ The diagnosis of NIFTP can only be made histologically on the surgical specimen, which requires evaluation of the entire tumor nodule and its capsule or border. A main diagnostic pitfall still exists where follicular variant of papillary thyroid carcinoma can be misdiagnosed as follicular adenoma or as follicular thyroid carcinoma if a capsular or vascular invasion is present. ¹⁰

Before the reclassification of the NIFTP, all encapsulated follicular pattern tumors with nuclear features of papillary thyroid carcinoma, even without invasive growth, were categorized as malignant tumors (ie, noninvasive follicular variant of papillary thyroid carcinoma). ¹¹ Also, encapsulated follicular variant of papillary thyroid carcinoma imposed a diagnostic challenge where the diagnosis rests exclusively on the characteristic nuclei. The nuclear features include enlargement and overlapping, oval shape, irregularity of nuclear contours, dispersion of heterochromatin (ground-glass nuclei), nuclear grooves, and intra-nuclear cytoplasmic pseudo-inclusions. ¹² The primary goal of the new nomenclature was to reduce overtreatment of indolent tumors and avoid unnecessary surgeries and radioactive iodine therapy with its inherent complications and morbidities. The introduction of this new entity resulted in fewer surgeries and complications since NIFTP are sufficiently treated with lobectomy due to their indolent behavior.^11,13 Different molecular alterations are detected in different variants of papillary thyroid carcinoma. RET translocation and BRAFV600E mutations are associated with classic papillary thyroid carcinoma, while RAS and PAX8/PPARγ mutations are frequent in follicular-pattern tumors, including follicular adenoma, follicular carcinoma, and NIFTP.

The well-differentiated thyroid cancers infrequently metastasize beyond the thyrocervical region. ¹⁴ Distant metastases occur in a minority of patients: the reported rates of occurrence range from 4% to 15%, and commonly involve the lung, bone, and lymph nodes. ¹⁵ Most common sites for metastasis include bone, followed by lung and mediastinum. ¹⁶ Thyroid cancers rarely metastasize to the kidney and mostly remain clinically undetected,^6,17 with a prevalence of less than 6%. There are less than 30 cases reported in the literature so far. ² Metastasis to the kidneys often occurs in the setting of multifocal metastases and can develop several years following the excision of the primary tumor.^17,18 Renal metastasis of thyroid cancers usually presents as unilateral masses; however, our reported case here is the second case documented in the English literature of metastatic follicular variant of papillary thyroid carcinoma presenting as bilateral renal masses. ⁶

It has been difficult to detect renal metastasis, which may be attributed to the inability of the metastatic lesions to trap iodide on the iodine-131 scan. Ultrasound imaging and fine-needle aspiration biopsy are common tools necessary for investigating patients suspected of having thyroid cancer, although fine-needle aspiration biopsy has a low sensitivity for diagnosing FVPTC. ⁶ Various immunohistochemical and molecular markers can aid in the diagnosis of follicular variant of papillary thyroid carcinoma, including keratin 19 (KRT 19), HBME-1 (Hector Battifora mesothelial-1), galectin 3 (LGALS13), and RET-PTC. ¹⁹ TTF1 is found both in the lung and the thyroid gland but is negative in renal tumors. PAX8 is a sensitive marker for thyroid cancer and renal tumors.^20,21

Thyroid-like follicular renal cell carcinoma is a recently described new entity in renal tumors, which arise from epithelium of renal tubules.^22–24 These tumors consist of closely packed cysts that resemble thyroid follicles on histopathological examination, ²⁵ therefore metastatic thyroid cancer should be considered as a very important differential diagnosis when handling these patients. Both neoplasms are stained positive for PAX8. TTF1 and thyroglobulin immunohistochemistry staining can be helpful with differential diagnosis because metastasis from the thyroid often expresses TTF1 and thyroglobulin whereas thyroid-like follicular renal cell carcinomas do not express TTF1. ²⁶ In addition, thyroid-like follicular renal cell carcinomas do not have the common mutations that most of the follicular, papillary, and follicular variant thyroid carcinomas have, such as NRAS, HRAS, or BRAF mutations.^27–29 Recently, this subset of thyroid-like follicular renal cell carcinomas have been shown to have specific genetic alterations such as EWSR1::PATZ1 fusion, which can propose a pathologic and diagnostic importance. ²⁵

Management of metastatic well-differentiated thyroid cancer relies on the extent of metastasis and the radioiodine avidity of the disease. The optimal treatment approach is based upon surgical removal of the thyroid gland and the metastatic lesions followed by Iodine-131 ablation therapy and levothyroxine. The surgical treatment options (lobectomy vs total thyroidectomy) for well-differentiated thyroid cancer have been debated for several years. Lobectomy is still considered the surgical option of choice for small thyroid carcinomas (1.0-3.9 cm) with node negative disease (N0) according to the 2015 American Thyroid Association guidelines ³⁰ with no difference in survival when compared to total thyroidectomy. However, total thyroidectomy is still entertained as a viable option since papillary thyroid carcinoma is typically a multifocal disease and this reduces the chance of missing residual disease in the contralateral lobe. In addition, post-operative treatment with radioactive iodine and the use of serum thyroglobulin for detecting residual disease and recurrence are supplemental treatment strategies used in addition to surgery. ³¹ Whole-body scintigraphy should be performed in high-risk cases, especially in patients with elevated thyroglobulin levels. ⁶ External beam radiation therapy is utilized as a palliative treatment for patients with advanced or inoperable thyroid cancer. It is usually considered in patients aged >45 years who have a grossly visible extra-thyroidal extension with a high suspicion of residual disease during surgery. ³² Post-therapeutic 131I-WBS and 131I single-photon emission computed tomography/computed tomography (131I-SPECT/CT) fusion imaging techniques are utilized for the management of patients with differentiated thyroid carcinomas since it is highly sensitive and specific.

The follicular variant of papillary thyroid carcinoma carries a less favorable prognosis than the classic papillary thyroid carcinoma. A relatively desirable outcome relies in part on the patient's age.^31,33 Patients with classic papillary thyroid carcinoma treated with total thyroidectomy were younger than those treated with lobectomy. Management of thyroid cancer relies on the histologic subtype and the tumor stage at the time of diagnosis. For our patient, the surgical decision was to undergo total thyroidectomy with subsequent diagnostic radioiodine scan to determine if the abdominal masses were iodine avid. The patient was a poor surgical candidate for bilateral nephrectomy, and the masses were not amenable to surgical resection; hence radiotherapy was administered. She completed external beam radiation therapy with a total dose of 3600 cGy in 20 fractions to her bilateral renal masses. Our patient passed away 6 years after her initial diagnosis due to sepsis-related acute respiratory distress syndrome.

Conclusion

This is the second case in the literature to demonstrate bilateral metastasis of follicular variant of papillary thyroid carcinoma. Our experience suggests that, when a renal mass of unidentified origin suspicious for malignancy is revealed in patients with unspecific symptoms, the possibility of an occult undiagnosed thyroid carcinoma should be considered.