346

CARCINOMA OF THE THYROIDBy JOHN E. PIERCY, F.R.C.S., F.R.C.S.E.

Surgical Specialist i/c Thyroid Unit, New End Hospital, London

IntroductionGoitre is far more common in women than in

men and it follows that carcinoma of the thyroidis equally more common. The discrete nodule,although it is an unusual finding in men, is how-ever, more likely to be malignant than when foundin women. Cancer of the thyroid, unlike cancerelsewhere in the body, is more malignant in theaged than in the middle aged or young. The nodu-lar goitre in children, however, must be lookedupon with grave suspicion as it may well prove tobe malignant, or at any rate, is more likely to recurafter operation and again after re-operation, thefinal recurrence being frankly malignant.The incidence of thyroid cancer throughout the

general population is very low, whereas the hospitalincidence is a little over 2 per cent of all thosegoitres admitted. The goitre patients accepted byhospitals, however, are selective inasmuch asbeing suspect, have been referred, not necessarilybecause of the goitre, but because of an associatedtoxicity or because of its increase in size withaccompanying pressure symptoms, discomfort orchange in consistency. Any one of these lattersymptoms would bring its attention to the patientand general practitioner, perhaps giving rise to thesuspicion of malignancy.

Thyroid clinics throughout the world beingspecialized and often having radioiodine facilities,are bound to have difficult cases and cases ofthyroid cancer referred to them by general hospi-tals, resulting in a still greater selectivity and ahigher incidence of thyroid malignancy at suchunits. There is, however, a wide variation in thestatistics of thyroid cancer emanating from variouswell known thyroid clinics, ranging from six tothirty per cent. in the non-toxic goitre. This widestatistical variation can be partly explained by thewell known difficulty in differentiating the multi-nodular goitre, with its lower incidence of malig-nancy, from the discrete nodule with its muchhigher incidence. A further reason for the widevariation in statistics is the divergent views held bymany Pathologists on the criteria of malignancy,for there is no doubt that certain slow growingtypes of thyroid cancer can give rise to more diffi-

culty in pathological diagnosis than does carcinomaof any other organ of the body.

In a recent survey at our own clinic (Piercy,I955) we found that of the 2,000 thyroid opera-tions performed in the past six years, just overthree per cent. were for cancer of the thyroid.Analysing this figure further showed that eightper cent. of the non-toxic nodular goitres and20 per cent. of the discrete non-toxic adenomaswere malignant, and that only one per cent. of themalignant tumours were associated with thyro-toxicosis. The ages of the patients with cancer

ranged between eight and eighty years; only 20

per cent. being found in men.

Pathological ClassificationThe microscopic classification of differentiated

malignant thyroid tumours can be difficult as thereare often several cell types throughout the tumour.When the usual criteria of malignancy has beenfulfilled, such as irregular and abnormal cell pat-tern, invasion of capsule and blood vessels, anapla-sia and mitoses, the attempt is made to classify thetumour by the cellular structure that predominates,It follows, therefore, that frequently the more sec-tions of a tumour studied the greater the difficultyin its classification.The highly malignant and undifferentiated type

of carcinoma is also often difficult to classify, manydisplaying sarcomatous tendencies and othersbeing so undifferentiated that the type of malig-nancy cannot be determined.

Classification. Although all thyroid carcinomatacould come under the general term ' adenocarci-noma,' it is preferable to divide them into theirtwo main groups differentiated and undifferentiatedand sub-divide these two groups into the cellulartype predominating. This method of classificationboth describes the type and correlates to someextent its clinical course and prognosis. Themajority arise in pre-existing adenomata, theremainder arising' de novo ' in a lobe not the siteof an adenoma.

Classification of Carcinoma of Thyroid.A. Differentiated

(i) Papillary Carcinoma

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July 1957 PIERCY: Carcinoma of the Thyroid ,; , 347

(2) Follicular Carcinoma (alveolar adenocarci-noma)

(3) ' Hurthle cell' adenocarcinoma.B. Undifferentiated Carcinoma: which includes

Small cell (carcinoma simplex)Pleomorphic (giant celled)Carcinomata displaying sarcomatous tendencies.

C. LymphomasReticulum cell SarcomaLymphosarcomaHodgkin's disease.

i. PAPILLARY CARCINOMA (Fig. i)Approximately half of all malignant thyroid

tumours are predominantly papillary in type, yetcontaining follicles; the occasional tumour beinga pure papillary type.

Taking all differentiated carcinomas, the pres-ence and amount of papillary tissue determineprognosis, the more papillary tissue present, theslower growing and less malignant the tumour.The pure papillary tumour is a slowly growingneoplasm, often giving rise to a chain of large softsecondary nodes, perhaps as large as the thyroidlobe itself (Fig. I); whilst the primary carcinomain the lobe may be too small to be detected by the

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FIG. I.-Papillary carcinoma in the sectioned right lobeabove with a chain of invaded cervical lymphaticnodes.

naked eye. In the past, these large s'otgilandswere erroneously considered to be ' aberrantthyroid nodes,' and not associated with a primarytumour of the thyroid. The prognosis of thesepurely papillary tumours is in the main good.They occur most commonly under the age offifty years, the majority metastasising to the cervicaland innominate lymph nodes, whilst a small per-centage metastasise to the lungs, resembling pul-monary tuberculosis or giving a fine' snow storm'effect. Those growths which contain follicularstructures as well, may occasionally metastasise tothe bones. It must be recognized that in a smallpercentage of cases a mixed papillary carcinomawill not follow the accepted slow low grade malig-nant picture, but will prove to be invasive havinga rapidly fatal termination. >

2. FOLLICULAR CARCINOMA (alveolar adenocarci-noma) (Fig. '):9 ' ' '

Approximately one-third of all thyroid carci-nomas are predominantly follicular in type. -Theyhave a mixed cellular structure with,.as their nameimplies, tfollicre's'in different stager of activity.Papillary tissue' is almost always present but to a;lesser extent. It is possible for the tumour tissue

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FIG. 2.-Follicular adenocarcinoma, the growth havingbroken through the capsule of the adenoma,

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348 POSTGRADUATE MEDICAL JOURNAL July 1957

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FIG. 3.-Undifferentiated small cell carcinoma of theleft upper lobe with a blood-borne secondarydeposit in the lower right lobe.

to be so well differentiated as to resemble hyper-plastic thyroid. It is not uncommon for this typeof cancer to commence in a pre-existing adenomawhich has been present for many years. Thesuspicion of malignancy arises when the nodule,which has remained stationary and unchanged fora long period, begins to increase in size, changes inconsistency and causes pressure discomfort andreferred pains. The follicular carcinoma is moreinclined to metastasise early to lungs and bones byway of the blood stream and may lead to pathologi-cal fractures, whilst early invasion of the capsulecan occur with involvement of the cervical nodes.The prognosis in the follicular carcinoma is less

good than in the papillary type and, although thetumour is resistant to radiotherapy, fortunatelysomething like a quarter of them contain function-ing follicles, as shown by radioactive iodine uptake,and are therefore amenable to radioactive iodinetherapy.3. ' HURTHLE CELL' ADENOCARCINOMA

This comparatively rare tumour often formsfollicles and may be included with the follicularcancers, following much the same pattern inregard to progress, prognosis and therapy.Undifferentiated Carcinoma

Approximately 25 per cent. of thyroid carcinomaare undifferentiated in type, consisting of a regularcell pattern without follicles or papillary elements,These include mainly the small cell tumour orcarcinoma simplex, and the Pleomorphic or giantcell tumour. They are all highly malignant andare most commonly found in the upper age groups.

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FIG. 4.-Large pleomorphic giant cell carcinoma.

SMALL CELL TYPE (carcinoma simplex) (Fig. 3)This most frequent type of undifferentiated

carcinoma commonly arises in patients over fiftyyears of age. The unencapsulated growth usuallycommences in an apparently normal thyroid glandwithout previous evidence of goitre. It is highlyanaplastic and spreads rapidly by local invasionand metastasises extensively by way of the lympha-tics and blood stream. The prognosis is bad, asthe growth has usually spread before being recog-nized; it may temporarily respond, however, toirradiation.

PLEOMORPHIC GIANT CELLED CARCINOMA (Fig. 4)These highly malignant vascular anaplastic

tumours, at one time, were thought to be sarcoma-tous. They arise in large pre-existing goitres ofmany years duration, and spread locally with greatrapidity. They appear in the elderly and usuallycause death within a few months from rapid localinvasion of the tissues of the neck, often beforemetastases have had time to appear. The giantcell carcinoma, unlike other anaplastic tumours, isresistant to irradiation and the prognosis is usuallyhopeless from the onset.

LymphomasLYMPHOSARCOMARETICULUM CELL SARCOMA (Fig. 5)These two primary sarcomatous thyroid growths

run much the same clinical course and there is anabundance of reticulum cells and lymphocytes inthe thyroid for their origin (Winship, 1955). They

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July 1957 PIERCY: Carcinoma of the Thyroid 349

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FIG. 5.-Reticulosarcoma with invaded nodes.

occur most commonly in elderly females and havebeen found both with and without the history ofpre-existing goitre. The tumour increases rapidlyin size, the growth quickly involving all of thethyroid and metastasising to the cervical andmediastinal lymph nodes. At this unit we havefound several such growths presenting in pre-existing lymphadenoid goitres. Although theprognosis in lympho and reticulum sarcoma is notgood, they are radio sensitive and temporarilyrespond to irradiation which is also an importantfactor in their diagnosis. If the tumour is seenwhen still localized to the thyroid, surgery is indi-cated to be followed by X-ray therapy. (Fig. 5).

Prognosis in carcinoma of the thyroid is governedby several factors:-

(a) Age of the patient-unlike carcinoma else-where in the body, it is invariably more highlymalignant in the elderly than in the middle agedand young.

(b) The stage of the growth found on clinicalexamination-the prognosis is in inverse propor-tion to the certainty of diagnosis.

(c) The speed of onset-the more rapid anincrease in size, the less favourable the prognosis.

(d) The greater the cellular differentiation of thetumour, the more favourable the prognosis.

Clinical ClassificationClinically, carcinoma of the thyroid may be

conveniently classified into:-(I) Obvious carcinoma(2) Suspect carcinoma(3) Hidden carcinoma.

I. CLINICALLY OBVIOUS CARCINOMAThe patient, usually in the upper age groups,

complains of an increase in the size of her goitre,radiating pain, and hoarseness of the voice due totracheal pressure or involvement of a recurrentlaryngeal nerve. The mass is hard, fixed, nodularand tender. Firm lymph nodes are often presentin the neck. In this obvious example the malig-nancy is advanced, the growth having brokenthrough the true capsule of the thyroid and invadedthe cervical tissues. The prognosis is very bad,the patient usually dying within a year in spite ofthyroidectomy and irradiation.

2. CLINICALLY SUSPECT CARCINOMAMalignancy is suggested when a nodular goitre

or a discrete adenoma, which has been stationaryfor many years, gradually begins to increase insize. The patient complains of discomfort in thegoitre often with a sense of constriction in theneck. On examination the nodular mass is foundto be tender and firm.The prognosis is very much better in the sus-

pected case, as it is likely that the carcinoma is stillcontained within the capsule of the adenoma andcan be satisfactorily removed. The growth is mostoften differentiated in type and commonly seen inthe middle age group. It must not be confusedwith the sudden tenderness and increase in size ofan adenoma resulting from a haemorrhage withinit.

3. CLINICALLY HIDDEN CARCINOMA (see Fig. 2)First diagnosed either during a partial thyroidec-

tomy for a nodular goitre or after routine post-operation microscopy. It must be appreciated,however, that carcinoma of the thyroid, unlikecarcinoma of most other organs, can be notoriouslydifficult to recognize at the time of operation andmay easily be confused with degenerative, cysticand fibrous processes. The prognosis is excellentin these cases of obscure carcinoma, if the growthhas not already invaded the blood vessels and givenrise to secondary deposits.

In considering the all important question ofprognosis based on clinical classification, we findthat the prognosis in clinically obvious carcinomais bad, in clinically suspect carcinoma is good,whereas the prognosis in clinically hidden carci-noma is usually excellent.

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POSTGRADUATE MEDICAL JOURNAL yuly I957

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FIG. 6.-Rapidly growing reticulosarcoma showing diagnostic needle puncture.

Considerations in regard to Partial Thyroid-ectomy for Nodular Goitre as a Precautionagainst CarcinomaThe ideal procedure would be the removal of all

non-toxic nodular goitres referred to hospital, bothas a precaution against clinically hidden cancerbeing present, and as an insurance for the future.The indication for operation being still. greaterwhen such a goitre is present in men and inchildren.

Operation should always be undertaken for anynodular goitre at the first suspicion of malignancy,such as an unusually firm nodule, its gradual in-crease in size, or evidence of tenderness or pressure.

Every discrete non-toxic adenoma should bewidely removed, as it has been shown at this clinicthat, of those proven by radioactive iodine to becold nodules at least 20 per cent. were malignant(Greene, 1956).

It has been suggested after animal experiment,that following partial thyroidectomy, small dosesof thyroxine or thyroid should be given to preventexcessive secretion of the pituitary hormone T.S.H.in order to lower the incidence of adenoma andcarcinoma production (Doniach, 1955). It has

been our practice to give thyroid medicationfollowing operation for cancer, both to maintainthe thyroid balance and with the above theory inview.

TreatmentT.:hyroidectomy is the treatment of choice.

* (a) Clinically obvious carcinomaThe involved lobe is completely removed in-

cluding invaded lymph nodes and muscle; a totalor near total lobectomy being undertaken on theopposite side to allow, if necessary, for radioactiveiodine to concentrate in local remnants or in localor distant metastases. The choice of the post-operative therapy would depend on whether thecancer was of a type sensitive to irradiation or hadan uptake of radioiodine, thereby making this formof treatment applicable.

(b) Carcinoma found initially at operation.When carcinoma is first recognized during an

operation (see Fig. 2) for an adenoma or a nodulargoitre, a total or near total thyroidectomy is under-taken, the complete removal of the invaded lobebeing considered essential. Post-operative treat-

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JYuly 195 PEiRCY: Carcinoma of the Thyroid 351

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FIG. 7.-The same after X-ray therapy.

ment by means of radioiodine or irradiation to beconsidered along the lines indicated in (a).

(c) When unsuspected malignancy is diagnosedinitially by post-operation microscopy.

If the operation was adequate inasmuch as allpathological tissue, innocent and malignant hadbeen removed, keeping the patient under observa-tion would be sufficient unless the carcinoma wasundifferentiated and anaplastic in type, or hadinvaded beyond the capsule of the adenoma. Inthe latter circumstances a total thyroidectomywould be indicated, or alternatively, the remainingtissue, destroyed by an ablation dose of radio-iodine.--

(d) Rapidly growing undifferentiated carcinoma.Operation is,often undertaken in the late stages

to relieve pressure, 'o institute a tracheotomy, andto resect tissue for microscopic pathological diag-nosis of the growth.:'-

In the early stages total thyroidectomy, if pos-sible, is undertakieniincluding removal of invaded

nodes or muscle, to be followed by irradiation, oroccasionally radioactive iodine, if an uptake of theIsotope is present or can be induced.

Needle puncture biopsy is occasionally indicatedin a rapidly advancing growth (Fig. 6), for if provento be sarcomatous it will temporarily respond toirradiation as will any invaded mediastinal nodes(Fig. 7).

It is to be reiterated that if for various reasonsit is impracticable to remove all non-toxic nodulargoitres when the prognosis of an unsuspectedmalignancy would still be excellent, at any rateoperation must be undertaken at the first suspicionof malignancy when results are still good, and notleft until the condition is obvious when theprognosis is bad.

BIBLIOGRAPHYDONIACH, I. (i955), Proc. roy. Soc. Med., 49, I73.GREENE, R. (November, 1956), Hunterian Lecture, R.C.S.PIERCY, J. E. (I955), Proc. roy. Soc. Med., 49, 173.WINSHIP, T., and GREENE, R. (I955), Brit. J. Cancer, 9, 401.

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