Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma.
Thyroid metastases are an uncommon occurrence. Reported incidence ranges from 0.5% to 24.2% in autopsy studies [
We present the case of a 63-year-old French national who was residing in Ireland. He was diagnosed with right ocular melanoma and underwent enucleation in a specialist institution in February 2011. Histopathology at this time revealed a superonasal posterior pole uveal melanoma measuring 17 × 12 × 10 millimeters. There was histopathological evidence of extrascleral extension, spindle B cell morphology, and considered stage pT4e. There were no mitoses in 40 high power fields. Tumour involved the overlying retina and 17% of cell revealed monosomy of chromosome 3 using fluorescence in situ hybridisation (FISH) analysis. FISH also indicated normal results for chromosome 8 and MYC abnormalities. At time of initial staging and workup our patient was found to have subcentimetre lung nodules on computed tomography (CT) scanning. These were biopsied and on histopathological assessment were identified as benign on both FNAC and core biopsy. Follow-up scanning with annual CT and positron emission tomography- (PET-) CT revealed stable cold lung nodules and no evidence of metastatic melanoma over a thirty-two-month period.
In October 2013, he underwent a routine surveillance CT neck, thorax, abdomen, and pelvis, which noted increased size of all lung nodules. For instance, a nodule in the right middle pulmonary lobe measured 8 mm from previous 3 mm. It also identified two new solid lesions in the thyroid, the largest of which was 8 mm in diameter (Figure
CT neck image of thyroid nodules (identified by white arrows).
Ultrasound guided biopsy of the largest lesion revealed metastatic melanoma (Figure
Ultrasound images of thyroid metastasis (identified by white arrows).
Pathological examination showed the presence of metastatic spindle and epithelioid malignant melanoma cells (positive staining for HMB45, MelanA, and S100 immunocytochemistry (ICC)) amongst residual thyroid follicles (positive staining for TTF-1 ICC). Some of the metastatic melanoma cells showed fine intracytoplasmic pigment and prominent nucleoli (Figure
(a) Spindle and epithelioid malignant melanoma cells (arrowheads) admixed with background residual thyroid follicular cells (arrows). Papanicolaou stain, original magnification ×400. (b) TTF-1 highlights residual thyroid follicular cells and is negative in the lesional cells (arrows). TTF-1 ICC, original magnification ×200. (c) HMB45 and (d) MelanA ICC show strong positivity in the lesional cells. Original magnifications ×200. (e) S100 ICC weakly highlights the fine intracytoplasmic pigment present in the lesional cells (arrows). Original magnification ×100.
The case patient was of protooncogene
CT neck image of thyroid nodule (identified by white arrows) over time.
Thyroid metastases are an uncommon occurrence in clinical practice. Autopsy reports vary considerably between 0.5% and 24% in incidence [
Uveal melanomas differ from cutaneous melanomas in a number of areas. Firstly, ocular melanomas have a predilection to metastasise to the liver along haematogenous drainage pathways although spread can occur to lung, bone, brain, skin, and potentially any site within the body [
Management of thyroid metastasis is varied and depends upon symptoms at presentation. Treatment strategies can include surgical resection or debulking by complete or partial thyroidectomy, radiotherapy, and/or systemic therapy. The aim of surgical intervention should be primarily for compressive symptom control such as dysphagia, dyspnea, and stridor [
In this case report, we describe a rare case of uveal melanoma with metastasis to the thyroid gland. To date, the literature only records one such case previously published in 1986 [
In conclusion, unusual metastasis, for instance, to the thyroid should always be considered in the setting of carcinoma, including uveal melanoma. The disease should be managed according to the primary malignancy with appropriate chemotherapy, biological therapy and radiotherapy, and multidisciplinary discussion. Surgical resection of thyroid metastasis can be considered on a case-by-case basis, keeping in mind the natural biology of the primary malignancy as well as available systemic treatment strategies. Although immunotherapies such as ipilimumab and pembrolizumab are frequently used in cutaneous melanoma, they can be efficacious on metastatic uveal melanoma also.
The authors declare that they have no competing interests.
The authors would like to acknowledge the patient and his family in permitting our publication of his disease history. They would also like to acknowledge Dr. Emily Harrold for her help in obtaining images.