In the period from 1986 – 2011, a total of 433 malignant tumours of the thyroid gland were diagnosed in surgical biopsies at St. Olav’s Hospital. Of these, nine were metastases (2.1 %), of which three represented the spread of clear cell renal carcinoma. This is in good agreement with findings reported in several other clinical series (1, 8). A review of studies from the last ten years has shown that renal cell carcinomas account for 48 % of metastases, followed by colorectal carcinomas (10.4 %), lung carcinomas (8.3 %), carcinomas of the mammary glands (7.8 %) and sarcomas (4 %) (4).
Up to 30 – 40 % of those with renal cell carcinoma have metastases at the time of diagnosis, while most of the later metastases appear over the course of 3 – 5 years (9, 10). On average, metastases in the thyroid gland manifest themselves nine years after the nephrectomy (6, 11), but it can take up to 25 years, as two of our cases show. It has previously been reported that in one patient, 26 years passed before the metastasis was recognised (5). Metastases can also occur in other organs, as in two of our patients. Based on an analysis of archival material for a 40-year period, Heffes et al (6) reported that for 13 of their 36 patients with kidney cancer, metastasis in the thyroid gland was the first sign of malignant kidney disease. Eleven of these patients then underwent nephrectomy. Other reports likewise show that metastasis can be an early clinical manifestation of kidney cancer (1, 12).
Diagnoses were verified in our patients by review of histological and immunohistochemical examinations. Morphologically, it can be difficult to distinguish metastases with certainty from other tumours in the thyroid gland, which can also have a strong «clear cell» component and resemble hypernephroma (13), but immunohistochemical examination can be used to exclude this possibility (1). All of the patients had clear cell tumour tissue which tested negative for thyroglobulin and TTF-1.
Ki67 has been shown in some studies to be an independent prognostic marker of renal cell carcinoma (14) – (16), but it is difficult to use it in daily routine diagnostics since it often reveals only a very low proportion of tumour cells in the growth phase (17). This was also the case in three of the five kidney biopsies in this study. A combination of a low Fuhrman grade and a low Ki67-positive fraction in a primary tumour suggests that metastases in these cases will initially grow slowly. A higher Ki67-positive fraction and higher Fuhrman grade in the metastases is consistent with increased cellular proliferation when they show up clinically many years later.
It is still uncertain which factors might come into play and inhibit further tumour development in malignant cells originating from a primary tumour. Hadfield (18) introduced the concept of «the dormant cancer cell» and believed that inhibition of mitosis could be a consequence of anoxia. It has also been speculated that local hormonal factors and a high tissue iodine concentration may potentially affect metastatic cell growth in the thyroid gland (11). The development of metastasis probably involves a complex interplay between genetic factors in the tumour cells, the microenvironment of different tissue types, and genetic factors in the affected individual (19).
Patients tend to be elderly, between 60 and 80 years of age, with a slight excess of females (11, 20), as was also the case in our series. The metastasis was either a solitary nodule or it caused diffuse enlargement of the gland. There was no side preference.
There have been occasional reports of metastases occurring in a primary tumour of the thyroid («collision tumours») (21). Bohn & Gjørup (22) reported the first Scandinavian case of metastasis from renal carcinoma to the thyroid. The patient was a male who had been treated for ten years for hyperthyroidism. The authors argued that metastases in the thyroid gland preferentially occur where there are prior pathological changes. Of our patients, one of the females had had a multinodular goitre for many years, but the specimen did not allow us to determine whether any other pathological changes might have been present. A review of the literature from the last ten years (4) showed that 44.2 % of metastases actually occurred simultaneously with colloid nodular goitres, benign neoplasms or thyroiditis, and it was suggested that this could be explained by changes in the blood supply resulting in reduced oxygenation and iodine content.
The treatment for metastatic disease in the thyroid gland from kidney cancer consists of surgery, either partial resection or total thyroidectomy (8). Active surgical intervention is particularly relevant if there are no other signs that the tumour has spread (23), but palliative interventions to relieve specific symptoms, for example stridor, may also be appropriate (1, 24). Following surgery, the patients in our series had a median survival time of 14 months. A larger European series containing 45 patients showed 51 % five-year survival (25). Multivariate analysis revealed that the prognosis was poorest for patients over the age of 70 and for patients who had metastatic disease in the remaining kidney. In another data series with metastases from various malignant tumours, median survival was 26 months (8). With partial thyroidectomy, there is a not insignificant risk of recurrence (1) if the tumour is not completely isolated and the edges of the resection zone definitely free of tumour cells.
Even though metastases to the thyroid gland will often represent a terminal phenomenon and occur late in the course of cancer, it is important to consider the possibility that isolated tumours in the thyroid gland in patients with previous renal cancer may be metastases that can be treated surgically with good results.