Hürthle cell carcinoma: diagnostic and therapeutic implications
© Hanief et al; licensee BioMed Central Ltd. 2004
Received: 02 May 2004
Accepted: 11 August 2004
Published: 11 August 2004
Hürthle cell carcinoma is a variant of follicular cell carcinoma of thyroid. It may present as a low-grade tumour or as a more aggressive type. Prognosis depends upon the age of the patient, tumour size, extent of invasion and initial nodal or distant metastasis.
Patient and methods
The case of Hürthle cell carcinoma is reported in a 79-year-old man who presented with a rapidly increasing lump on the left side of his neck, having had a right hemithyroidectomy for colloid goitre 24-years-ago. Fine needle aspiration cytology confirmed the presence of Hürthle cells, raising the possibility of a Hürthle cell neoplasm. The patient underwent staging and surgery. Histology showed Hürthle cell carcinoma and the patient underwent adjuvant therapy. The literature on Hürthle cell neoplasms is reviewed.
Fine needle aspiration cytology may recognise Hürthle cell lesion but final diagnosis of carcinoma depends upon histological confirmation of vascular or capsular invasion. Staging and surgery in Hürthle cell carcinoma are similar to follicular carcinoma of thyroid with favourable outcome despite the controversy regarding the histological classification and adjuvant therapy. Elderly patients with Hürthle cell carcinoma need to be made aware of their poorer prognosis and should be offered more radical treatment.
The natural history of Hürthle cell carcinoma (HCC) is not well understood. It accounts for <5% of all differentiated thyroid malignancies. Hürthle cells are characterised by eosinophilic cytoplasm with trabecular/follicular growth pattern. . Oncocytes are seen in follicular cell carcinoma but in HCC oncocytes represent more than 75% of cells, which exhibit a rather more trabecular growth pattern . There is much debate regarding its clinical behaviour and little is known about the long-term survival of patients with HCC. Some studies have reported a relatively benign course while others have found the tumour to behave aggressively [3–6]. Most studies show that advanced age (>45), male sex, size of primary tumour (>4 cm), degree of invasion and recurrence are poor prognostic indicators [6–8]. Fine needle aspiration cytology is a good predictor of Hürthle cell neoplasm but is of little diagnostic value in evaluating HCC, since for a tumour to be deemed malignant one has to show vascular or capsular invasion . Intraoperative frozen sections have a low predictive value. Udelsman et al found that in 96.4% cases with follicular neoplasm of thyroid, frozen section was neither informative nor cost-effective . Well-encapsulated HCC run a favourable course while locally advanced HCC are associated with higher mortality and should be treated aggressively [4, 11]. In a well-differentiated thyroid carcinoma death resulting from local disease is unusual and most die of distant metastases .
We report a case of a Hürthle cell carcinoma presenting in the left lobe of thyroid following a right hemithyroidectomy for a colloid goitre 24 years ago.
A 79-year-old male was referred in March 2003 with a lump on the left side of his neck. The patient had noted a sudden increase in the size of the lump over the preceding two months. He did not report any neck pressure symptoms, weight loss or anorexia. His past history included right partial thyroidectomy for a solitary nodule (colloid goitre) in 1978 and repair of abdominal aortic aneurysm in 1994. He had suffered myocardial infarction in 1995 and had an episode of acute coronary insufficiency in January 2003. His recent coronary angiograms showed an occluded left anterior descending artery and echocardiogram revealed good left ventricular function. He was a non-smoker and consumed alcohol in moderation. He had been taking warfarin, diltiazem MR, lisinopril, uniphyllin, glyceryl trinitrate tablets and buccal suscard.
The patient had adjuvant therapy with oral radioiodine 131 (3060 MBq Sodium Iodine). He was put on a daily dose of 100 mcg of thyroxine. This was to be followed by a second dose of 5911 MBq of radioactive iodine six months from the time of the first dose.
Hürthle cell carcinomas are heterogeneous neoplasms that display a wide range of biological behaviour and accounts for less than 5% of all differentiated thyroid malignancies. The term HCC should be restricted to tumours with more than 75% of oncocytic cells . Oncocytes are seen in follicular thyroid cell carcinoma and in papillary thyroid cell carcinoma [13, 14]. On one hand patients with HCC live for years with slow growing tumour and lymphatic metastases and on the other hand, patients die of highly aggressive tumour with haematogenous spread.
Our patient had several indicators for poor prognosis such as his advanced age, male gender, large tumour size (8 cm), extra thyroid extension and nodal metastasis. Interestingly enough the patient had no pressure symptoms despite marked deviation of larynx, trachea and oesophagus, which may be due to previous right hemithyroidectomy. In elderly patients with sudden enlargement of neck mass and pre-existing thyroid conditions such as benign thyroid nodule, goitre (as in our case), Grave's disease or differentiated thyroid carcinoma, one has to bear in mind anaplastic thyroid carcinoma (ATC). In ATC local compression symptoms such as hoarseness, strider, dyspnoea and dysphagia occur as a rule [15–17]. In aggressive type of HCC haematogenous spread has been noted, but in ATC, at presentation patients are quite likely to have distant metastases involving lung, bone, brain and soft tissues [15, 16].
Our patient had undergone fine needle aspiration cytology, which revealed Hürthle cells. Since the lesion was rapidly growing with mediastinal extension and nodal involvement, the patient underwent staging and left hemithyroidectomy with modified neck dissection. Histology confirmed HCC based on vascular and capsular invasion. Intraoperative frozen sections have low predictive value and are particularly not a sensitive test for diagnosing HCC therefore this was not carried out . McIvor et al have clearly shown that FNAC can easily recognise the tumour as Hürthle cell lesion . Cases with suspicious histology and over 50 years of age carry a high risk of cancer .
In the management of HCC the primary mode of treatment is surgical, ranging from hemithyroidectomy to total thyroidectomy. Larger tumours (>T2) require total thyroidectomy and lymphadenectomy if lymph nodes are involved . Adjuvant radioiodine treatment or external beam radiotherapy is used for widely invasive carcinoma or locally advanced disease .
Several reports in literature have identified contra lateral foci of carcinoma in 40–70% of cases of HCC [11, 19]. HCC is less responsive to radioactive iodine therapy  and taking into account the aggressive behaviour, it has been suggested that every Hürthle cell tumour greater than 2 cm should be treated by total thyroidectomy . In 1990 they showed that recurrent disease was noted in 17% of patients treated with total thyroidectomy compared to 59% in cases where a more limited procedure was carried out [21, 22]. Other authors support the role of total thyroidectomy as there is 15 to 35% incidence of multiple foci in HCC .
There are several reasons favouring the use of 131I remnant ablation after near-total thyroidectomy . First, presence of thyroid remnant can obscure 131I uptake in cervical or lung metastases [25, 26]. Second, distant (lung) metastases may be seen only on the post treatment whole body scan after remnant ablation . Finally, remnant ablation may destroy residual normal follicular cells, which may become malignant  and any occult cancer that may recur years later.
Stojdinovic et al have treated 56 patients with HCC between the years 1940 and 2000 . Of these patients 23(41%) had minimally invasive disease with no evidence of extra thyroid invasion (T2 N0 M0) and 33(56%) had widely invasive HCC. Primary mode of treatment was surgery ranging from lobectomy and isthumusectomy to total thyroidectomy with cervical lymphadenectomy in presence of lymph node involvement. Some patients received adjuvant radioiodine or external beam radiotherapy for widely invasive carcinoma. Study end points were relapse free survival and disease specific survival. They reported 8 years survival rate of 100% and 58% for low and high-risk cancers respectively. In their entire study cohort age was not found to predict the outcome but the most significant factor was widely invasive carcinoma.
Khafif et al in their series (42 patients with HCC between 1957–1997) used radioiodine in patients with distant metastases; none had thyroid remnant ablation with radioactive iodine . They reported an overall survival rate of 90.5% and noted that age, size of tumour and extent of resection adversely affected the prognosis.
Hürthle cell lesion can be easily picked up on FNAC but to make a diagnosis of HCC one has to demonstrate vascular or capsular invasion. Intraoperative frozen sections have low predictive value and cases with advanced age (over 50), rapid enlargement of lump and palpable nodes should be regarded with high index of suspicion for presence of HCC. HCC or other differentiated carcinomas of thyroid in the elderly patients are generally more aggressive with less favourable prognosis compared to younger patients. They should be offered total thyroidectomy and selective lymph node dissection (when lymph nodes are involved) followed by ablative radioiodine therapy, provided they can withstand the above treatment. Coexisting medical disorders should be recognized and managed effectively prior to surgery . Further research is needed to clarify the role of adjuvant radioiodine therapy in the management of HCC.
Patients consent was obtained for publication of his case records.
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