Abstract
Anaplastic thyroid carcinomas are the most lethal tumours in humans. They are rare and usually occur in cases of long standing benign thyroid disease or other thyroid tumours. Prognosis is poor with a mean survival rate of about 6 months after diagnosis. However patients with small foci, in well-differentiated thyroid tumours, that are excised completely, are reported to have better survival rates. Death is usually due to local recurrence or distant metastasis to lungs, bone or brain. Paraneoplastic syndrome in a case of anaplastic carcinoma has probably not been reported till now.
We report an interesting case of anaplastic thyroid carcinoma, in a colloid goitre of long standing, in a 80 year old lady who went on to develop lung metastasis and a paraneoplastic syndrome in-spite of good regional control

Anaplastic thyroid carcinoma, one of the most aggressive tumours known in humans, is almost always lethal. It is known to have a dismal outcome, with a mean survival of about 6 months after diagnosis. However patients with small foci, in well-differentiated thyroid tumours, are reported to have better survival rates.
We report an interesting case of anaplastic thyroid carcinoma, in a colloid goitre of long standing, in a 80 year old lady who went on to develop lung metastasis and a paraneoplastic syndrome in-spite of good regional control.

Case report

An 80-year-old lady presented with a large midline swelling of the neck since 40 years. There was no pain, dysphagia, altered voice or breathlessness. There was no history of sudden increase in size or fever. She was not known to have any major illness or major surgery in the past. However at this visit her blood pressure was raised and she was treated for the same. Patient had been investigated for her neck swelling 5 years ago and was advised surgery, which she had ignored.

On examination : Patient had a midline neck swelling, 6 inches x 5 inches, moving freely upwards with deglutition. It was possible to get below the swelling and the carotids were well felt on both sides behind the swelling. On fibreoptic flexible laryngoscopy, both her cords were moving well. Larynx was found slightly shifted to the right
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As a part of the preoperative workup, an FNAC was done of the swelling, and was reported as: Abundant colloid, groups of thyroid follicular cells with degenerative changes and foamy macrophages consistent with nodular colloid goitre.

X-ray of the neck showed an ill-defined soft tissue mass in the pre-tracheal space with multiple foci of calcification suggestive of goitre. X-ray chest was normal. She was euthyroid and T3, T4; TSH levels done were 1.61 ng/ml, 10.7 mcg/dl, and 0.27U/dl respectively. USG done for the same was reported as multiple echogenic nodules, maximum size being 4.5 x 4.0 cm.

Incidentally an FNAC done in 1997 was reported as: cellular, thyroid follicular epithelial cells in sheets, pigmented histiocytes and colloid material with a few Hurthle’s cells consistent with MNG. Thyroid function tests were T3- 1.44 ng/ml, T4-7.66 mcg/dl, TSH-0.18 mcU/dl indicating an euthyroid status.

During her present visit a subtotal thyroidectomy was performed and specimen was sent for histopathology, which showed an encapsulated anaplastic carcinoma of thyroid arising in a multinodular goitre. Tumour showed divergent differentiation in the form of osteoid production and a myogenic trait (Figs. 1 and 2).

Fig. 1: Histopathology showing anaplastic thyroid carcinoma H&E 100X.	Fig. 2 : Histopathology showing anaplastic thyroid carcinoma H&E 400X.

Postoperative levels of T4 and TSH done on 21.03.03 were 10.4 mcg/dl and 3.53 U/dl respectively. Her serum calcium levels were also normal. Patient was explained about nature of disease and advised further therapy but she refused any further treatment. She was then kept on eltroxin suppression therapy and was advised regular follow up.

Patient was asymptomatic for 5 months, when she presented to our Casualty with complaints of severe left frontoparietal headache and vomiting since 3-4 days. Examination revealed a high B.P. and ptosis of the left eye. She also had bilateral basal crepts. Her neck was normal.

Pupils were normal and reacting to light. Fundus examination was also normal. An ophthalmic consultation revealed no local abnormality.

A CT scan done on the same day showed age-related prominence of CSF spaces without proportional dilatation of ventricular spaces.

Patient later underwent MRI Scan of the brain and orbit, which was reported as normal except for “ischaemic changes in the frontoparietal region”.

X-ray chest showed bilateral cannon-ball shadows suggesting evidence of lung metastases. Thyroid function tests were normal.

A lumbar puncture was done, which showed proteins of 55 mg/dl and sugar of 53 mg%. There were no malignant cells.

A neurological opinion was sought and she was diagnosed as having Myasthenia Gravis Syndrome as a non-metastatic manifestation of Ca Thyroid. She was advised EMG nerve studies with decrement studies, anti-Ach receptor antibody level estimation and ANF tests to confirm the diagnosis.

Sadly, our patient deteriorated rapidly with ptosis of both eyes and restricted EOM and left pupil dilated and fixed. She had weakness of all limbs and succumbed to her illness before these tests could be done.

Discussion

Anaplastic thyroid carcinomas (ATC) are rare, accounting from 2 to 5% of all thyroid cancers.1,2 It is more common in the elderly with mean age at presentation reported variously as 66.5 years³ and 72 years.²

Like other thyroid disorders this too is commoner in females with female to male ratio of about 2:1.² Our patient did not present typically with a sudden increase in size, pain or signs and symptoms of compression of airway or oesophagus. Her only presentation was a large goitre of long standing (> 40 years) in which an anaplastic carcinoma seemed to have developed. Most cases of ATC grow out of pre-existing goitre or differentiated thyroid cancer though the exact aetiology is unclear.¹ P 53-gene mutation⁴ or accumulation of altered genes related with cell proliferation and differentiation⁵ are possible contributing factors whereby normal thyrocytes are transformed to differentiated thyroid cancer and progress to poorly differentiated thyroid cancer and ultimately anaplastic thyroid cancer. In this case FNAC also showed features of multinodular goitre and the diagnosis was missed pre-operatively. Yet complete excision of the tumour was achieved and this has been reported to result in much improved survival rates as compared with more extensive ATC.³ The most important prognostic factor seems to be the amount of disease at the time of diagnosis.⁶ Our patient had good local control of disease, which is also a significant predictor of survival.⁷ Most patients have local recurrence and distant metastasis is seen in 20- 50% cases. Lung and bone are the commonest site of metastasis.⁸

In spite of good prognostic factors, complete resection of tumour and good local and regional control the patient reported with distant metastasis in the lungs and a paraneoplastic syndrome (PNS). Paraneoplastic syndromes are effects of cancer that occur at sites remote from the primary tumour and its metastasis. They are supposed to have an autoimmune aetiology.⁹ Our patient presented with symptoms suggestive of Lembert Eaton myasthenic syndrome which is the commonest PNS affecting 1-2% of patients with small cell carcinoma of lung. They are extremely rare with thyroid malignancy.

Diagnosis of these conditions is often difficult with the currently available methodology. Conventional immunotherapy is rarely helpful and prognosis is poor.⁹

Patient having localized disease amenable to complete surgical resection are reported to have a longer survival rate of upto 5 years (5% of ATC cases).³ Current trends are to treat ATC aggressively using multiple modalities that include surgery, radiotherapy and chemotherapy. Despite this the survival rate remains poor.²

Redifferentiation therapy by either redifferentiation agents or gene transfer of dedifferentiation related genes might retard tumour growth and make these tumours more amenable to conventional therapy.¹⁰

These modalities are currently being researched.

Conclusion

ATC is an extremely lethal tumour. Though prognostic indices have been stated the outcome is usually poor. Multimodality treatment including surgery, fractionated radiotherapy and concurrent chemotherapy is at present considered the best modality of treatment option for patients having better prognosis. Besides distant metastasis, these tumours may also manifest as paraneoplastic syndromes. Considering recent reports of a genetic aetiology it would be useful if we could identify genetic markers in differentiated carcinoma that will enable us to predict the possibility of anaplastic dedifferentiation. Redifferentiation agents and gene therapy using thyroid specific genes are also being currently researched and investigated. While we wait for a novel, effective therapy for this type of cancer, it is important to provide these unfortunate patients with appropriate comfort measures and emotional support.

References

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Consultant ENT Surgeon and Head of Dept; **Resident Medical Officer, E.N.T Dept, B.A.R.C Hospital, Anushakti Nagar, Mumbai-400094. India.