Differentiated Thyroid Cancer Presenting as DistantMetastasesAnjali Mishra1, Saroj Kanta Mishra1, Birendra Kishore Das2 and Prasanta Kumar Pradhan2

From the Departments of 1Endocrine Surgery and 2Nuclear Medicine, Sanjay Gandhi Post-Graduate Institute of MedicalSciences, Raebareli Road, Lucknow 226014, India

Eur J Surg 2002; 168: 305–309

Key words: occult carcinoma, thyroid scan, thyroidectomy, radioiodine.

INTRODUCTION

Differentiated thyroid cancer is a unique tumour that isusually associated with excellent long-term survival.The incidence of patients who present initially withdistant metastases of thyroid cancer is 1%–4% (13).Small clinically undetected thyroid carcinomas canproduce extensive lymphatic metastases, but, occultthyroid cancer rarely presents as distant metastaseswithout gross, clinically apparent, disease in thethyroid region (3, 4, 6, 8, 9, 11, 12). Occult thyroidcancers are often found at necropsy and commonlyregarded as being of no clinical relevance (10).However, these cases raise the question of whether itis prudent to consider all occult thyroid cancers asbenign, and if we can in some way differentiate thecancers that are likely to progress from the commonly-occurring innocuous occult thyroid cancer. The pur-pose of this paper is to describe four patients withdifferentiated thyroid cancer, who presented initiallywith distant metastases and no gross signs of thyroiddisease, and to emphasise that despite being small,some of these tumours may behave aggressively.

CASE REPORTS

Case 1

A 23-year-old woman was referred to us with history ofa swelling on the scalp that had been present for theprevious eight years. The swelling had recurred twiceafter excision at a peripheral hospital. The histopathol-ogy report of the excised tissue was not available. Shehad noticed swelling in her neck for the past twomonths. There was no other contributory history. Onexamination a solitary thyroid nodule was present inthe left thyroid lobe and a pulsatile 5 £ 5 cm bonyswelling was present in the right side of the occipitalregion. She was clinically and biochemically euthy-

roid. A thyroid scan showed a hypofunctioning nodulein the left lobe. Fine needle aspiration cytology(FNAC) of the thyroid showed follicular aspirate, andFNAC of the scalp swelling suggested metastaticfollicular carcinoma. A skull radiograph showed alytic expansile lesion in the occipital region. Chestradiograph and indirect laryngoscopy did not show anyabnormality.

We did a near total thyroidectomy and she made anuneventful postoperative recovery. The specimen con-sisted of two nodules, microscopic examination ofwhich showed microfollicles of different sizes fromboth nodules. Histopathological examination was con-sistent with a microinvasive follicular carcinoma.Whole body radioiodine scan done six weeks afteroperation showed minimal residual thyroid tissue in theneck and the metastatic lesion in the skull. She wastreated with 131I ablation (cumulative dose—16.1GBq). She was also given thyroxine suppressiontreatment. At her last follow up, nine months post-operatively, whole body radio iodine scan showedminimal uptake of radiotracer in the skull and no newmetastatic lesion.

Case 2

A 40-year-old woman presented with severe back painof two months duration. She had developed paraplegiathree weeks before admission. She also complained ofurinary incontinence and consulted a private practi-tioner who requested a radiograph of the thoracolumbarregion which showed erosion of T8 and narrowing ofthe disc space between T8 and T9. A myelogramshowed extradural compression. Laminectomy wasattempted at a peripheral hospital but was abandonedbecause of excessive bleeding. The histopathologicalexamination of the excised specimen was consistentwith metastatic follicular carcinoma. Subsequently the

Ó 2002 Taylor & Francis. ISSN 1102–4151 Eur J Surg 168

CASE REPORT

orthopaedic surgeon noticed a small thyroid nodule inthe right thyroid lobe and a nodule over the scapularregion. The excision biopsy of the scapular noduleshowed metastatic follicular carcinoma. She was thenreferred to our centre. We did FNAC of the thyroidnodule which suggested a follicular neoplasm. She wasclinically and biochemically euthyroid. Chest radio-graph and indirect laryngoscopy showed no abnorm-ality.

We did a total thyroidectomy and she made anuneventful postoperative recovery. The thyroidectomyspecimen consisted of two lobes measuring 4 £2.5 £ 2.0 cm and 4 £ 2.5 £ 2 cm. The right lobecontained a greyish white tumour in the lower polemeasuring 2 cm in diameter. Microscopic examinationshowed an encapsulated lesion consisting of variablesized follicles and small nests of cells separated bythin-walled vascular channels. The cells were cuboidalto columnar in shape and had pleomorphic nuclei. Afew mitotic �gures and capsular and vascular invasionwere present. There was a 0.5 cm colloid nodule in theupper pole of left lobe. The rest of the thyroidparenchyma was unremarkable. Postoperative wholebody radioiodine scan showed increased tracer con-centration in the region of the thoracic vertebra andsacrum. She was given single doses of 6.1 GBqradioiodine ablation. However, she declined further131I ablation and was discharged taking thyroxinesuppression. She died six months later at home.

Case 3

A 62-year-old woman was referred from the neurosur-gical department. She had had a swelling over the rightparietal bone for the past two years. A skull radiographshowed a lytic lesion, and a computed tomogram (CT)of head showed a hypodense lesion eroding the rightparietal bone. The swelling was excised together withthe underlying bone. The histopathologica l examina-tion was reported as: angiosarcoma or possibly meta-static papillary carcinoma. One month postoperativelyshe noticed a swelling in the right supraclavicularregion and on examination the thyroid was justpalpable. The right supraclavicular lymph nodes wereenlarged. She was clinically and biochemically euthyr-oid. Thyroid scan (131I) revealed a cold nodule in theleft lobe (Fig. 1). FNAC of the thyroid and lymphnodes showed papillary carcinoma. The chest radio-graph showed no metastases.

We did a near total thyroidectomy with lymph nodedissection (central compartment, right functional, andsuperior mediastinal), and she made an uneventfulpostoperative recovery. The thyroidectomy specimenweighed 18 g and consisted of the right lobe measuring4 £ 3.5 cm and the left lobe measuring 5 £ 3 cm. Theleft lobe contained a whitish nodule measuring 2.0 cm

in the largest diameter in the lower pole and one0.5 £ 0.5 cm nodule in the left lobe. The largest lymphnode nodule measured 4.5 cm in its largest diameter.Microscopic examination of the nodule showed thestructure of a poorly circumscribed noncapsulatedtumour composed of papillary, follicular, and alveolarstructures lined by cubocolumnar epithelium withprominent nuclear grooving. Patchy dense sclerosis,solid trabecular and insular areas, and foci that lookedlike columnar cells with cellular and nuclear strati�ca-tion and frequent mitotic �gures were present. Thetumour was in�ltrating the adjacent �brofatty tissue.There were similar small foci in the sections from theopposite lobe and the isthmus. The lymph nodes alsocontained metastases with large areas of haemorrhageand necrosis. Histopathological examination was con-sistent with multicentric papillary carcinoma withnodal metastases. Postoperatively the patient was given3.7 GBq of radioiodine, after which a whole bodyradioiodine scan showed uptake in the lateral neck butnot in the region of the skull or any site. In view of thelack of tracer uptake and visible metastases on CT shewas advised to have external radiotherapy to the skull,but abandoned it. She died three months later.

Case 4

A 55-year-old woman was referred to our centre with ahistory of swelling of the skull of 11 months’ duration,which had recurred within one month after excision bya private practitioner. Four months after her �rstoperation she developed back pain and weakness inthe both lower limbs followed by urinary incontinence.She consulted an orthopaedic surgeon. Skeletal radi-ography showed collapse of T12 and multiple osteo-lytic lesions in the skull. CT showed a heterodenselesion involving T12 and multiple hypodense skull

Fig. 1. Thyroid scan (131I) of case 3 showing a cold nodulein the lower pole of the left lobe of thyroid.

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lesions. FNAC of the skull swelling suggested meta-static follicular carcinoma. At the time of admissionshe was catheterised, and power in various lower limbmuscle groups ranged between grades 3/5 and 4/5. Shehad a 2 £ 2 cm stony hard nodule in the lower pole ofright thyroid lobe that was palpable only duringextension of her neck. We did a FNAC of the thyroidnodule, but it was inconclusive. However, FNAC fromthe skull swelling suggested metastatic follicularcarcinoma. The corresponding thyroid nodule showeda mixed echogenic pattern with calci�cation onultrasonography. She was clinically and biochemicallyeuthyroid. The chest radiograph showed a metastaticlesion in the right lung.

We did a total thyroidectomy, and the specimenweighed 27 g. The right lobe measured 6 £ 4 £ 1 cmand the left 4.5 £ 2.5 £ 1.0 cm. There was a hardcalci�ed nodule measuring 2 £ 2 cm in the lower poleof the right lobe, the cut surface of which was solidgreyish-white with a calci�ed capsule. Microscopicexamination showed acini and follicles of variable size

lined by �attened to cuboidal epithelium. The nucleishowed mild pleomorphism. The stroma showed focaloedema, hyalinisation, and mononuclear cell in�ltra-tion. Similar tumour emboli were present in vesselswithin the tumour capsule. The histopathologicalexamination was consistent with follicular carcinoma.Postoperative whole body scan showed multiple meta-static lesions in the region of shoulders, vertebrae,skull, and lungs. The patient has so far been given 9.1GBq of radioiodine and is alive with disease 12 monthspostoperatively. She has been given thyroxine suppres-sion and is due for her next follow up.

DISCUSSION

Though some thyroid cancer can present with distantmetastases, it is rare (13). We know of no large seriesbut there are a few case reports (3, 4, 6, 8, 11, 12, 14).In a series of 568 cases of differentiated thyroid cancer,Lind et al. reported �ve (0.9%) of occult thyroid cancerthat presented as distant metastases (9). The de�nitionof occult and microcarcinoma may mean differentthings to different workers. The WHO classi�cation(1988) recommends that the term “occult” should bereplaced by “microcarcinoma”, referring to tumoursless than 1 cm in diameter (7). On the other hand, Alloet al. (1) reported that occult carcinomas need not beminimal, and in their discussion they included refer-ences that included tumours ranging from 0.3 to 4.5 cmin diameter that were referred to as “occult” becausethe patient �rst presented with distant metastases. Ourfour cases do not strictly ful�ll the criteria ofmicrocarcinoma but they were occult. However, therewas a considerable time interval between the presenta-tion of distant metastases and thyroid surgery. It is alsoimportant to note that all these patients had undergonesome sort of surgical intervention on distant metas-tases, and the primary physicians at the time could notfeel any thyroid nodules. It can therefore be presumedthat these were truly occult to begin with.

Over a period of 10 years (1989–1999) at our centrewe managed 156 cases of differentiated thyroid cancer.These included 107 cases of papillary carcinoma(69%), 39 cases of follicular carcinoma (25%) and 10cases of poorly differentiated thyroid cancer (6%). Thedistribution was: T0 14 (13%), T1 16 (15%), T2 32(30%), T3 15 (14%), T4 30 (28%) patients in papillarycarcinoma; T0 12 (31%), T1 4 (10%), T2 7 (18%), T314 (36%), T4 2 (5%) patients in follicular carcinoma;and T0 2 (20.0%), T1 (0%), T2 1 (10.0%), T3 1(10.0%), and T4 6 (60.0%) patients in the poorlydifferentiated group. The incidence of lymph nodeinvolvement was in 54 (51%), 2 (5%) and 5 (50%)patients, respectively. The incidence of distant metas-tases in these three groups was 11 (10%), 17 (44%) and

Fig. 2. Computed tomogram of the head of the same patientshowing a hypodense lesion eroding the right parietal bone.

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6 (60%) patients respectively. These �gures for distantmetastases are higher than those reported elsewhere,which varied from 2% to 23% (13). Whether thisoverall presentation re�ects the aggressive nature ofthyroid cancer in an iodine-de�cient region or poorsocioeconomic status is a matter of debate (2). Four ofour 156 patients (3%) presented initially with distantmetastases. The various sites implicated elsewherewere soft tissue (12), lungs (14), orbit (4), skin (8),endobronchus (3), bone (11), and clivus (6). Most ofthe patients reported were elderly (9, 11). In our studytwo patients were young (22 and 40 years) while twowere older (62 and 55 years). The metastases may besolitary or diffuse (10).

In cases of primary thyroid lesions that present withdistant metastases the commonest histological type isfollicular (13). However, in the event of distantmetastases with occult primary lesions papillary hasbeen reported with almost equal frequency(3, 9, 11, 14). Clinically silent papillary thyroid canceris often found at necropsy and the patient may havedied of an unrelated cause (6). This cannot be used asan argument in favour of conservative management ofall cases of microcarcinoma, as many of the reportedcases have died of their cancers despite having primarymicrocarcinomas (6, 12), as did two of our patients.

Most authorities have advocated aggressive manage-ment including total thyroidectomy followed by 131Iablation (3, 4, 8, 13). Despite the presence of meta-stases, the bene�t of total thyroidectomy cannot beoveremphasised. It facilitates radioactive iodine treat-ment, and there is no competition for radioactive iodineby a normal thyroid gland (13). Lind et al. comparedpatients with occult and non-occult thyroid cancers andfound no survival difference between them. Theyconcluded that most of the occult thyroid cancers hada relatively benign course, but distant metastases maykill the patient. These cases should therefore be treatedin a manner similar to non-occult thyroid cancers (9).

Differentiated follicular thyroid cancer is a curablemalignancy but the biological behaviour of a thyroidcancer is dif�cult to predict. There are importantdifferences in the occurrence of clinical and occultcancers. While the former are common in youngwomen, the latter are found in older people of bothsexes (10). It has been suggested that in countries suchas Finland, Japan, and Hawaii, despite the highprevalence, most of the occult cancers remain occult.The reason may be greater availability of carcinogensbut lower number of promoting factors (5, 10). Highconcentration of thyroid stimulating hormone inwomen may be a promoter resulting in a high incidenceof clinically-manifest thyroid cancer in women (5). Thereported mortality of occult carcinoma ranges from0.8%–1% and cannot be considered inconsiderable in a

disease that itself has a mortality ranging from 4%–6%(1). As most of our patients hail from an endemicallyiodine-de�cient area and have seemingly aggressivetumours, we think that regardless of risk group anoccult papillary thyroid cancer in older people andfollicular cancer occurring in all age groups should betreated aggressively. We advocate completion thyroid-ectomy for all such tumours found in the course ofprocedures that are less than total thyroidectomy. Theapproach may seem radical but until research inmolecular biology provides a de�nitive answer aboutthe biological behaviour of a particular case; this maybe justi�ed if it prevents a single cancer death.

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Submitted March 21, 2001; submitted after revision August29, 2001; accepted September 19, 2001

Address for correspondence:Professor S. K. MishraDepartment of Endocrine SurgerySanjay Gandhi Post-Graduate Institute of MedicalSciencesRaebareli RoadLucknow 226014IndiaFax: ‡91522 440999.E-mail: skmishra@sgpgi.ac.in

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