Unusual metastasis of differentiated thyroid carcinoma

Distant metastases of differentiated thyroid cancer are usually localised in the lung and bone; less common sites of metastases are the brain, liver, and skin. To find it in other sites it is exceptional. This work shows the clinical, histological and therapeutical characteristic of primary tumour in three cases of non-typical distant metastases of differentiated thyroid cancer. Follicular thyroid carcinoma was displayed in two cases, the first presented one metastases in right adrenal gland and the second in left kidney. Both cases were initially treated only with hemithyroidectomy, without posterior radioiodine. In one case, elevated serum thyroglobulin did not receive radioiodine treatment because Whole-Body Scintigraphy was negative. The thirst case was a papillary thyroid carcinoma treated with total thyroidectomy, ablative radioiodine and suppressor therapy with levothyroxine. However, posterior evolution was unfavourable and tumour presented metastases in common and less common sites like choroid. Histological study showed tall cell variant of papillary thyroid carcinoma. In summary, when the initial treatment of well-differentiated thyroid carcinoma it is inaccurate, it is possible to find common and less common sites metastases. Some variants of papillary thyroid carcinoma, like tall cell, have a worse prognosis and they can present metastases in less common sites.     

An intrasellar pituitary tumour producing metastases in liver, bone and lymph glands and demonstration of ACTH in the metastatic deposits

We report the history, laboratory and histological findings in a man who presented with Cushing's disease. Despite removal of the primary pituitary tumour, his disease progressed and after bilateral adrenalectomy, he became pigmented and plasma ACTH levels remained elevated. He had further pituitary surgery and radiotherapy, to relieve compression of the optic chiasma. Plasma ACTH levels remained elevated. He developed liver, bone and lymph gland metastases and after an acute paraparesis due to spinal metastases he died. Immunoperoxidase staining techniques demonstrated ACTH in the pituitary recurrence and metastases. The combination of bone, liver and lymph node metastases has not previously been reported, nor has ACTH been reported before in metastases from a primary intrasellar tumour.     

Metastasis to the thyroid gland: a case report and review of the literature

Metastatic cancer to the thyroid is uncommon. Although the thyroid is richly supplied with blood, there are a few reports of metastatic cancer spreading to this gland. The overall incidence in autopsy series has been quite varied, with rates from 1.2 to 24% of malignant tumors. Most of this metastases are not detected in clinical practice. The majority of these patients had widespread metastases and, as a result, had very short survival times. Although detection of metastases to the thyroid gland often indicates poor prognosis, aggressive surgical and medical treatment may be effective, especially for renal carcinoma. In this report, we present a case of renal carcinoma with thyroid metastases and a review of the literature.     

Metastasis to the thyroid diagnosed by fine-needle aspiration biopsy

BACKGROUND: Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine-needle aspiration biopsy (FNAB) in any suspected case. DESIGN: A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre. PATIENTS: Twenty-two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years. RESULTS: Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru-cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work-up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis. CONCLUSIONS: Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general.     

A case of watery diarrhoea syndrome due to an adrenal phaeochromocytoma secreting vasoactive intestinal polypeptide with coincidental autoimmune thyroid disease

A 40 year old woman presented with a 10 year history of watery diarrhoea and an acute quadriparesis. On clinical examination there was severe muscle weakness and a nodule was palpable in the thyroid gland. Biochemical testing revealed a hypokalaemia at 1.6 mmol/l. Plasma levels of VIP were raised at 202 pmol/l. CT scanning demonstrated a mass in the area of the left adrenal gland, and isotope scanning of the thyroid gland showed a 'cold' nodule. The plasma catecholamines and calcitonin were elevated. The patient also presented with psychiatric symptoms, and the relevance of these to her condition has been discussed. At operation a left adrenal tumour was removed. Post-operatively the patient's symptoms disappeared and the plasma hormone levels returned to normal values. Histological examination of the tumour revealed a well differentiated phaeochromocytoma which contained VIP and calcitonin. The thyroid nodule was excised and showed histological features of autoimmune thyroid disease. It is suggested that in all cases of the WDHA syndrome where the tumour is in an extra-pancreatic site patients should be screened for phaeochromocytoma.     

Four patients with cutaneous metastases from medullary thyroid cancer

Cutaneous metastasis from thyroid cancer, especially medullary thyroid cancer (MTC) is rare. We report four patients with cutaneous metastases from sporadic MTC, three women and one man, aged 50 to 69 years. They presented different cutaneous lesions phenotypes. The first patient had a remote history of MTC and initial presentation of the recurrence was a rapidly progressing cutaneous lesion; on subsequent disease staging, widely metastatic disease was discovered. The other three patients developed cutaneous metastases in the presence of known distant metastases, indicating systemic spread of thyroid cancer. Definitive diagnosis of cutaneous metastases of MTC was made on biopsy of the lesions with cells that stained positive for neuroendocrine markers. Accurate diagnosis of cutaneous metastasis from MTC is important because it is a negative prognostic factor indicative of multisystemic disease. Thus, MTC metastases should be included in the differential diagnosis of erythematous maculopapular eruptions and nodular lesions of the skin, especially when these metastases occur in the upper part of the body and if the patient has a history of MTC. The appearing of cutaneous metastasis is a negative prognostic factor since all the patients here described died within one year from the diagnosis of cutaneous metastases.     

Severe intestinal bleeding caused by intestinal metastases of a primary angiosarcome of the thyroid gland

A 75 year old male presented with gastrointestinal bleeding after resection of both upper lobes of the lungs because of metastases. One year ago an angiosarcoma was the reason for a complete removal of the thyroid gland. In esophago-gastro-duodenoscopy we found multiple hemorrhagically stained polyploids lesions in the postbulbar duodenum and jejunum. Colonoscopy showed isolated polyploid lesions of the right flexura. Because of persistent gastrointestinal bleeding a diagnostic laparotomy was done. Intraoperative intestinoscopy demonstrated multiple bleeding metastasis. To remove many of the bleeding lesions two longer intestinal segments of the jejunum and ileum were resected. The histology of the metastases showed arrangements of polygonal cells with prominent nucleoli and atypical mitosis. Immunohistochemistry identified CD 31, vimentin and factor VIII associated antigen. There was an erosion of the superficial intestinal mucosal cells with resulting hemorrhage; same histology had been found in the thyroid gland and the right upper lobe of lung. Eight days after surgery the patient died because of respiratory and circulatory insufficiency.     

A graft-versus-colonic cancer effect of allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (ASCT) has proved to have an important immune-mediated anti-tumour effect in patients with haematologic malignancies. There is also evidence of such an effect in patients with malignant tumours. We studied this effect of ASCT in a patient with colorectal cancer. A 77-year-old man having a primarily resected colonic cancer with disseminated lymph node involvement received ASCT from his HLA-identical sibling as the only treatment. Mixed haematopoietic chimerism was monitored using PCR-amplification of variable number tandem repeats and tumour size, assessed by repeated CT scans. Recipient leucocytes were gradually replaced by donor cells for 1 month. Continuous resolution of lymph node metastases was seen together with clinical graft-versus-host disease (GVHD). The patient died of pneumonia and cardiac insufficiency 4 months after transplantation. At autopsy, most of the metastases were necrotic, with few remaining tumour cells. Clinical and histopathological postmortem results showed a graft-versus-colorectal cancer effect.     

Unusual cause for miliary lung mottling in a child

A 12-year-old boy presented to us with a diagnosis of disseminated tuberculosis which was made based on a history of prolonged fever, multiple neck swellings and radiological findings of bilateral multiple micronodular opacities. Examination showed a diffuse thyroid gland swelling. He was diagnosed to have papillary thyroid carcinoma with distant metastases to cervical lymphnode on histopathology and to lungs.     

Recombinant human thyrotropin for the diagnosis and treatment of a highly functional metastatic struma ovarii

The optimal treatment of metastatic thyroid cancer that produces high amounts of thyroid hormone has not been well defined. A 46-yr-old woman presented with a follicular thyroid carcinoma arising from a struma ovarii with hepatic metastases. After the removal of both the struma and the thyroid gland, the liver metastases showed evidence of a high degree of hormonogenesis. Brain, chest, abdomen, and bone imaging was negative for additional metastases. Because iodine uptake by most thyroid carcinomas is quite low in the absence of high levels of ambient TSH, we used recombinant human TSH (rhTSH) (Thyrogen) to achieve a concentration of 131I activity in the tumor high enough for a significant cytotoxic effect. After rhTSH administration (0.9 mg im daily for 2 consecutive days), a 131I diagnostic whole body scan confirmed the existence of 17 discrete hepatic foci of 131I uptake. To calculate the amount of 131I that would deliver an absorbed radiation dose that would be optimally cytotoxic to the metastases (>8000 rad/lesion) and not to the normal liver, we performed lesion dosimetry. Analysis of dosimetric data showed that 15 of 17 lesions would receive an adequate radiation dose following the administration of 65 mCi of 131I. Additionally, we performed whole body dosimetry to assure that this dose would not cause bone marrow toxicity. The patient was reevaluated 6 months after therapy; the liver metastases showed significant, but partial, response. In conclusion, we used the combination of rhTSH with lesional and whole body dosimetry for the treatment of highly functional metastases from follicular thyroid carcinoma arising within a struma ovarii. This strategy can be applied to determine a safe and effective dose of 131I for the treatment of any thyroid cancer metastases that produce enough TH to preclude stimulation of endogenous pituitary TSH secretion.     

Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer

Total thyroidectomy and central neck dissection are the procedures of choice in patients affected with medullary thyroid cancer. It is known that a medullary thyroid cancer with node metastases can be rarely cured, and therefore the utility of a modified radical neck dissection in the absence of suspicious node metastases still needs further evidence. The study aims to verify whether other epidemiological and pathological parameters could affect the prognosis of medullary thyroid cancer patients. We prospectively studied 70 medullary thyroid cancer patients consecutively operated on (from 2000 to 2004) at the same institution and analysed by the same pathologists. All patients underwent total thyroidectomy and central lymphadenectomy. In 27 cases, the ipsilateral (n=19) or bilateral (n=8) modified radical neck dissection was performed in the presence of suspicious lateral neck node metastases. After surgical treatment, basal and stimulated serum calcitonins (Cts) were measured in all patients. Follow-up ranged between 1 and 4 years. Patients were considered 'cured' when stimulated Ct was undetectable. Age, sex, tumour size, tumour capsule, multicentricity, nodes in the central neck and mean number of positive nodes were analysed in 'cured' and 'not-cured' patients. The presence of node metastases in the central compartment was significantly correlated with the outcome of the patients, being present in 9 and 72% of cured and not-cured patients respectively (P<0.000001). Tumour size was also significantly correlated with the outcome of the disease (P<0.00006). The presence of the tumour capsule correlated with better prognosis (P=0.0005) and absence of node metastases (P=0.0080). By multivariate analysis, the presence of node metastasis remained the most significant variable affecting the outcome of the disease (P=0.000014). Our results show that the outcome of encapsulated cancer is significantly better regardless of tumour size and node metastases. Although the early diagnosis and the extensive surgical treatment may favour the good outcome of medullary thyroid cancer, they do not always guarantee the definitive cure of the disease, being the capsular infiltration an independent bad prognostic factor.     

Review of thyroid cancer cases among patients with previous benign thyroid disorders.

A previous register linkage study showed an increased risk of thyroid cancer among patients previously discharged from a hospital with a diagnosis of a benign thyroid disorder. In this study, we have reviewed all available medical records, first to validate the earlier result and second to describe the symptomatology of patients with a history of benign thyroid disorder prior to the cancer diagnosis. The previous study identified 189 patients with a benign and subsequent malignant thyroid disorder. Medical records were obtainable for 156 of these patients and were reviewed. For 104 patients, benign and malignant thyroid diseases were metachronous (a clearly separated disease history of the benign and malignant diseases), and for 48 patients synchronous. In 4 cases, thyroid cancer could not be confirmed. Among patients with metachronous thyroid disorders, all major benign thyroid disorders were represented including hot nodules, diffuse and multinodular toxic and nontoxic goiter. Symptoms preceding diagnosis of thyroid cancer included growth of goiter/nodules, globulus, stridor, hoarseness, and metastasis. No major differences were found among patients with metachronous and synchronous benign and malignant thyroid disorder, apart from the fact that all metastases were found among metachronous cases. This study confirmed the conclusion that patients with a previous history of goiter or nodules have an increased risk of thyroid cancer. However, thyroid cancer still occurs too infrequently to warrant screening in all patients with a previous history of goiter or nodules.     

Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer.

We studied the feasibility of employing the measurement of thyroglobulin (Tg) in the washout of the needle used to perform the fine needle aspiration cytology (FNA-Tg) for the differential diagnosis of nonthyroidal neck masses of unknown etiology. We studied 35 patients presenting for 1 or more neck lumps outside the thyroid gland. A previous history of treated differentiated thyroid cancer (DTC) was given by 23 patients and of nonthyroidal malignancy by 3 patients. FNA-Tg was measured in the Tg-free serum used to wash out the needle employed for the cytology. Finally, all patients were treated by surgery. FNA-Tg was always detectable in 14 patients with thyroid cancer metastases demonstrated by histology, with a mean (+/- SD) of 27,087 +/- 37,622 ng/FNA (P less than 0.002) compared to patients without thyroid cancer metastases (mean +/- SD, 12.1 +/- 4.8 ng/FNA in 7 cases; undetectable in 14 cases). Assuming 21.7 ng/FNA (the mean +/- 2 SD of the negative patients) as the cut-off value, all patients with metastases from DTC were detected by FNA-Tg. FNA-Tg had better negative predictive value than cytology, since this last technique gave 10 inconclusive results, comprising 2 false negative results in patients with metastases from DTC. Our results indicate that elevated concentrations of FNA-Tg in nonthyroidal neck nodes strongly suggest the diagnosis of metastases from DTC.     

Unusual bony colorectal metastases in post-hepatometastasectomy patients

Colorectal cancer metastases occur predominantly in the liver, with extrahepatic sites being far less common and equally distributed in the lung, brain, skin, and bone. We report two cases of unusual bony metastases of colorectal cancer. A 55‐year‐old man underwent an abdominoperineal resection for a Dukes B carcinoma of the rectum, followed 17 months later by a right hemihepatectomy for metachronous liver metastases. He subsequently presented 11 months later with a solitary metastatic deposit in the mandible. Seven months after resection and reconstruction, he remained well and disease‐free. A 67‐year‐old man underwent a right hemicolectomy and right hemihepatectomy for carcinoma of the cecum and synchronous liver metastases. He presented 16 months later with a lesion suspicious of metastases in his clavicle. He subsequently died 18 months after his original operation. The prolongation of survival after hepatic metastasectomy results in the presentation of metastases at sites not commonly seen in colorectal malignancy. Postoperative surveillance after apparently curative hepatectomy should be directed to the evaluation of any unusual new symptoms.     

A special case of bilateral ovarian metastases in a woman with papillary carcinoma of the thyroid.

Papillary thyroid carcinoma is a slow growing tumor with low metastatic potential. The most frequent sites of distant metastases are lung and bone; less frequent sites are brain, liver, kidney, and skin. Ovarian metastases from papillary thyroid carcinoma are exceptional. We describe a case of bilateral ovarian metastases from a papillary thyroid carcinoma associated with autoimmune thyroiditis in a 38-year-old woman who underwent thyroidectomy and cervical lymph-node dissection 7 years before, followed by 948 mCi of 131I. A primary ovarian cancer could be excluded by the typical pathological aspects of a papillary thyroid carcinoma in a context of an aggressive form of thyroid cancer. On the other hand, the clinical history and the absence of normal thyroid epithelium and teratomatous components could exclude a papillary thyroid carcinoma arising in struma ovarii. This is a singular case of papillary thyroid carcinoma metastasizing to the ovary, combined with an autoimmune thyroiditis.     

A case of papillary carcinoma of the thyroid with more than 30 years long-term asymptomatic pulmonary metastases

This is a case report of a patient with thyroid cancer with asymptomatic pulmonary metastases, and without obvious progression over 34 years. The patient, a 47-year-old male, was shown to have miliary shadows on chest radiographs from the age of 13; indeed, he was temporarily treated for pulmonary tuberculosis without success. A tumour appeared in the right neck in December 1988 (at age 47). A diagnosis of lymph node metastasis of papillary carcinoma of the thyroid was made by biopsy; he then underwent total thyroidectomy with radical dissection of the neck (April 1989). However, the bilateral metastatic lymph nodes in the neck had invaded the vasculature, preventing complete dissection. Post-operative whole body ¹³¹I scintigraphy revealed diffuse intensive uptake in the bilateral lung fields, demonstrating for the first time that the pulmonary lesions were metastases of the thyroid cancer. He remains under periodic effective treatment with ¹³¹I.     

Renal cell carcinoma metastases to the thyroid gland-8 cases reported.

OBJECTIVE: Clinically important, isolated metastases to the thyroid gland is a rare occurrence. Renal cell carcinoma (RCC) is the most common primary tumor site. We report on 8 cases of late onset metachronous thyroid metastases of RCC. DESIGN: Eight patients presented with metachronous thyroid metastases at a median of 12 years (range 9-18 years) after nephrectomy for RCC. Two patients had simultaneous lung and lymph node metastases, respectively. Four patients had been previously operated for other metastases 1 to 5 years earlier, three of them due to pancreatic metastases. The leading symptom was neck enlargement in all but one case. MAIN OUTCOME: Four total thyroidectomies, 3 subtotal resections, and 1 lobectomy were performed. Complete removal of metastases were achieved in all but one case. There was no postoperative morbidity. Six metastases were bilateral, two unilateral. The 4 year overall survival rate following metastasectomy was 53%, median survival from the date of nephrectomy was 21 years. CONCLUSION: Long-term survival can be achieved after resection of isolated metachronous RCC metastases to the thyroid gland. Total thyroidectomy is not required, unless it is necessary for complete metastasectomy.     

HYPERTHYROIDISM AND THYROID CANCER

Ten of 502 patients presenting with thyroid cancer were hyperthyroid due to Graves' disease (4 patients), multinodular goitre (3), an autonomous functioning nodule (1) and a large functioning tumour (2). In addition eight patients had a past history of Graves' disease and four of hyperthyroidism associated with multinodular goitre. Mortality in patients with Graves' disease and with multinodular goitre appeared similar to that of other patients of comparable age. Both patients with large functioning tumours died from progressive disease. Concentration 131I by tumour metastases was present in one patient with active Graves' disease who had a high serum concentration of TSH-receptor binding antibodies, indicating that these antibodies may chronically stimulate tumour function. The potential for 131I concentration by tumour when TSH secretion is suppressed should therefore be determined in patients with Graves' disease and if demonstrable tumour function is present, reflecting stimulation by Graves' immunoglobulins, then elimination of tumour remnants is particularly important.     

DNA ploidy, tumour site, and prognosis in colorectal cancer. A flow cytometric study of paraffin-embedded tissue

DNA ploidy patterns were studied by flow cytometry in nuclear suspensions from 149 paraffin-embedded colorectal adenocarcinomas. The DNA ploidy of rectal tumours was not significantly different from that of colonic tumours. Patients with DNA diploid tumours had a significant survival advantage compared with patients with non-diploid tumours, but DNA ploidy did not confer any significant additional prognostic information when tumour site, Dukes's stage, the invasiveness of the tumour, and the number of lymph node metastases were adjusted for in a proportional hazards regression analysis (Cox). It is concluded that DNA ploidy does not contribute significantly to the explanation of why patients with rectal cancer have a poorer prognosis than those with colonic cancer.