Renal cell carcinoma metastasis to the thyroid gland: a case report

Abstract

Background

In this article, we report a case of renal cell carcinoma metastasis to the thyroid gland. Occult lesions of the thyroid were treated with a thyroidectomy. The case history presented below describes the patient’s pathway and subsequent results.

Case presentation

A routine medical examination of a 58-year-old Ukrainian woman revealed lesions in her thyroid gland. In total, two nodules 3.5 cm and 1.5 cm wide were found in the gland using ultrasound. Features of thyroid nodules were classified as Thyroid Imaging Reporting and Data System 3. A fine-needle aspiration biopsy showed Bethesda category IV thyroid nodules. Before this, the patient had a right-sided nephrectomy. The histopathology report confirmed renal cell carcinoma. The patient underwent a total thyroidectomy 13 years ago with confirmed metastatic renal cell carcinoma to the thyroid gland. Subsequent surgeries aimed at removing the local recurrences and distant metastases of the primary site. The patient got six cycles of Sunitinib (Sutent™, Pfizer) chemotherapy for renal cell carcinoma. Today, she lives in another country as a refugee and visits home occasionally. The patient takes thyroxine and waits for a suitable treatment option to cure advanced renal cell carcinoma.

Conclusion

A comprehensive investigation of the patient’s case history is crucial for determining a correct diagnosis. In our case, metastases to the thyroid were found 13 years after the initial renal cell carcinoma diagnosis. Moreover, foci of renal cancer cells in other organs indicates advanced disease with subsequent recurrence and distant metastases. Renal cell carcinoma may cause thyroid nodules.

Introduction

Renal cell carcinoma (RCC) is a common cause of kidney cancer. However, few cases of RCC metastases to the thyroid gland have been reported. Up to 0.15% of all malignant lesions in the gland originate from other organs [1]. Surgeons should be aware of a patient’s disease history and spot any mention of cancer to ensure correct decision-making. A comprehensive literature review shows that 48.1% of common nonthyroid malignancies are characterized by renal cell metastases. There are some difficulties in determining the type of lesion during the preoperative period. Fine-needle aspiration (FNA) can define pathology accurately in 70% of cases [2]. Ultrasound (US) helps detect suspicious signs of a nodule that mandate a FNA procedure. This case report describes a patient with RCC. A suspicious thyroid lesion was found 13 years after the primary cancer. In most cases, metastases are detected after kidney surgery, but sometimes they occur before.

Case presentation

Thyroid lesions in a 58-year-old Ukrainian woman were diagnosed using a neck US. A 35-mm-wide nodule was located on the left side, and a 15-mm-wide nodule was in the right lobe. The patient also had comorbidities and prior surgeries (Fig. 1). The underlying pathology was renal cell carcinoma of the right kidney, discovered 13 years earlier. The patient underwent resection of the ureter pelvic segment of the left kidney. Resection of the lower pole of the right kidney with a cancerous tumor took place within 12 months. A radical right-sided nephrectomy was performed after 6 years. RCC metastases to the lungs were also detected, and the patient underwent a subsequent atypical resection of the S3 segment of the left lung.

Fig. 1.

Detailed timeline of the patient’s case

Clinical findings

As mentioned above, 13 years have passed after an accurate diagnosis of RCC. At a routine medical examination, the patient complained of a lump on her neck, discomfort during swallowing, and an intermittent cough. The patient was also treated by a nephrologist, as she had a single functioning kidney, but refused hemodialysis. No chemotherapy or immunotherapy was prescribed. The patient had annual computed tomography (CT) and US of the kidneys and abdomen.

The thyroid US revealed two lesions in each lobe. The suspicious features of the nodules were as follows: hypoechoic with irregular, sharp margins, and microcalcification. The right lobe contained a 15-mm-wide nodule, and the left lobe consisted entirely of a 35-mm-wide nodule. The US did not detect other structural changes except tracheal deviation. A radiologist did not find any suspicious lymph nodes in the neck. The patient underwent a FNA that revealed Bethesda category IV thyroid nodules (follicular neoplasm).

The patient was scheduled for surgery after the diagnosis. She underwent the following laboratory tests: thyroid stimulating hormone (TSH), 4.08 mU/L (ref. 0.5–4.0); free thyroxine (T4), 1.1 ng/dL (ref. 0.8–1.8); thyroid peroxidase antibodies (TPO Ab), 19.1 IU/ml (ref. 0–34); and ionized calcium, 1.15 mmol/L (ref. 1.13–1.32). Biochemical testing detected grade III chronic kidney disease. The results were as follows: potassium, 4.15 mmol/L (ref. 3.5–5.0); creatinine, 273 µmol/L (ref. 59–104); and blood urea nitrogen, 17.3 mmol/L (ref. 1.8–7.1). The patient underwent a total thyroidectomy (TT) without lymph node dissection. The surgery was difficult due to the mild inflammation of the connective tissue. Surgeons used their own method of thyroid vessel ligation. Biological tissue welding was applied to avoid clips and threads placed on the vessels. Recurrent laryngeal nerves were preserved and detected. Parathyroid glands were found and were not damaged. The patient was discharged without any complications the next day after the surgery. Hemodialysis was not needed in the early postoperative period.

The first histology result did not confirm the diagnosis. Pathologists considered RCC metastasis and a light-cell variant of follicular cell thyroid carcinoma. Subsequently, immunohistochemical staining was carried out to define RCC metastases to the thyroid. The smaller metastasis in the right lobe invaded the capsule and thyroid tissue. Venous metastatic embolus was also detected in the tumor capsule’s vessel (Figs. 2 , 3). The metastatic nodule of the left lobe, which filled up the entire tissue, was encircled by the capsule. A total of two thyroid-specific transcription factors, PAX-8 and carbonic anhydrase IX protein (Th22), showed positive immunohistochemical reactions (Figs. 4 , 5). The latter marker plays a key role in RCC pathogenesis.

Fig. 2.

Renal cell carcinoma cells with wide, optically empty cytoplasm with clear borders (red arrows). It created solid, trabecular, and solitary follicular structures. The nuclei of the cells had slight pleomorphism and expressed anisokaryosis (yellow arrowheads) and are hyperchromic and enlightened

Fig. 3.

Renal cell carcinoma tumor (black asterisks) delineated by its capsule and invaded by cancerous cells in several spots. Tumor’s emboli were found in the lumen of the capsule’s vein (yellow arrowhead)

Fig. 4.

Box-like staining of the membrane (yellow arrowheads) of the renal cell carcinoma cells made by carbonic anhydrase IX protein

Fig. 5.

Diffuse nuclear staining (red arrows) with PAX-8 marker

In 2021, and before the war in 2022, the patient underwent six cycles of sunitinib chemotherapy. In May 2022, the patient had a surgery: excision of a recurrence in the renal bed and abdominal wall through a right-sided adrenalectomy. Histologically, the tumor was defined as a grade 2 RCC metastasis. The patient moved abroad shortly after the surgery. Currently, she lives in Czechia and occasionally comes to Ukraine for follow-up visits. The patient takes thyroxine tablets to maintain TSH levels within 0.5–2.5 mU/L.

In this report, we utilized the CARE guidelines.

Discussion

Renal cell carcinoma (RCC) accounts for up to 3% of all malignancies, and is the most frequent renal cancer [3]. There are no known causes for these cells to metastasize to the thyroid. Some investigators suggest that metastases get into the thyroid gland owing to sufficient blood supply, metabolic changes in the case of thyroiditis, insufficient iodine, and oxygen storage [4]. Men have RCC more often than women, but Green et al. noticed that RCC metastases to the thyroid occur more in women [5].

The patient was 58 years old at the time of the first diagnosis of thyroid lesion. The age is not typical for this diagnosis. An article by Heffess et al. [4] reports that female patients’ mean age is 67 years. However, our patient was 45 years old at the primary RCC presentation, which falls within the indicated reference range of 44–80 years for women [4].

Metastases to the thyroid of our patient were discovered 13 years after the primary RCC, as opposed to a study by Hegerova et al. [6] at the Mayo Clinic, which reported a mean time of 113 months [6]. We assume that this period was so long because the examinations were not detailed, and focused only on kidney disease. In fact, the patient did not have a thyroid US until 2018.

Today, the patient does not have any signs of recurrence in the thyroid bed. The nodules were 1.5 cm and 3.5 cm wide on both sides. No macroscopic spread of the tumors beyond the thyroid tissue was detected during the surgery. A study by Iesalnieks et al. revealed a 28% chance of having a local recurrence on the neck after thyroidectomy caused by RCC metastases over 3.5 cm-wide[7]. Recently, the patient had a neck US and no suspicious lesions were found. Moreover, using a method of biological tissue welding, we could perform extrafascial TT without leaving residual tissue at the recurrent laryngeal nerves.

A FNA revealed Bethesda IV thyroid nodules, defined as follicular neoplasm/suspicious for follicular neoplasm. The RCC metastases were correctly confirmed after histological examination following the thyroidectomy. As we know from a study by Khaddour et al. [8], only 29.4% of FNA specimens are confirmed as metastatic cells. Moreover, in 47.1% of cases, thyroid metastases to the thyroid parenchyma were unconfirmed [8]. The patient underwent a TT because of a trachea deviation and multiple nodular diseases indicative of follicular neoplasm.

Due to the RCC progression (multiple metastases to the thyroid and lungs), the patient was prescribed targeted therapy. She took a multitarget tyrosine kinase inhibitor (MTKIs) called sunitinib (Sutent^™, Pfizer). They interact with an adenosine triphosphate binding site in tyrosine kinase domains. This agent prevents autophosphorylation. A 31% response rate and a median progression-free survival of 11 months were observed with MTKIs [9]. Our patient had cancer progression 1 year after taking sunitinib. During the war, she underwent excision of the tumor recurrence of the abdominal wall and kidney bed. The patient had been postponing her last surgery for several months owing to the active hostilities in the north of Ukraine.

Conclusion

Surgeons should be aware of the previous RCC history of thyroid lesion patients. RCC metastases in the thyroid can be detected a decade or more after the primary cancer finding. FNA is not a reliable method for detecting a secondary tumor. RCC metastases are a potential cause of thyroid nodules. Total thyroidectomy has a good prognosis for local recurrence in the neck in the absence of tumor invasion in the adjacent tissue. Only one-third of patients respond to MTKIs used to treat multiple RCC metastases.

Abbreviations

RCC

Renal cell carcinoma

FNA

Fine-needle aspiration

PAX-8

Paired box gene 8

CARE guidelines

CAse REport guidelines

MTKI

Multitarget tyrosine kinase inhibitor

TSH

Thyroid-stimulating hormone

fT4

Free thyroxine

TI-RADS

Thyroid Imaging Reporting and Data System

TPOAb

Thyroid peroxidase antibodies

Author contributions

Hryshchyshyn A. contributed an idea for the manuscript. Bahrii A. performed surgery on this patient and contributed to collecting all data on the presented patient. Prof. Khimich S. contributed to the entire concept and revision of the presentation. Bohush H. wrote the introduction section and searched and reviewed references. Botsun P. and Chuba V. performed the histological investigation and collected and presented figures in this case report.

Funding

The authors confirmed that they do not have any source of additional funding.

Availability of data and materials

Not applicable.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare no competing interests.