Neoplasms
of the thyroid
Thyroid neoplasms are classified in Table
44.5.
Benign
tumours
Follicular adenomas present as clinically
solitary nodules and the distinction between a follicular carcinoma and an
adenoma can only be made by histological examination: in the
adenoma there is no invasion of the capsule or of pericapsular
blood vessels. Treatment is, therefore, by wide excision —
preferably a
lobectomy.
The remaining thyroid tissue
is normal so that
prolonged follow up is unnecessary. It is doubtful whether there is such an
entity as a papillary
adenoma and
all papillary tumours should
be considered as
malignant even if
encapsulated.
Malignant
tumours
The vast majority of primary growths is
carcinomas (Table 44.6).
Dunhill classified them histologically as differentiated and undifferentiated: and the
differentiated carcinomas are
Aetiology of malignant thyroid tumours
Differentiated thyroid carcinoma, particularly
papillary, frequently follows accidental irradiation of the thyroid in childhood7.
The incidence of follicular carcinoma is high in endemic goitrous areas,
possibly owing to TSH stimulation. Malignant lymphomas can present in a patient
known to have autoimmune thyroiditis, so that the lymphocytic infiltration in
the autoimmune process may be an aetiological factor. Indeed, it
is likely that
all lymphomas of the thyroid arise in glands affected by such thyroiditis.
Clinical
features of thyroid neoplasms
The annual incidence is about 3.7 per 100 000
of the population and the sex ratio is three females to one male. The
mortality should only be of the order of 2—3 per cent. The commonest presenting
symptom is a
thyroid swelling (Fig.
44.36) and a
5-year history is far from uncommon in
differentiated
growths. Enlarged cervical lymph nodes may be the presentation of papillary
carcinoma. Recurrent laryngeal nerve paralysis may be a presenting feature of
locally advanced disease.
Anaplastic
growths are usually hard, irregular and infiltrating. A differentiated carcinoma
may be suspiciously firm and irregular, but is often indistinguishable from a
benign swelling. Small
papillary tumours
may be impalpable (occult carcinoma) — even
when lymphatic metastases are
Diagnosis
of thyroid neoplasms
Diagnosis is obvious on clinical examination in
most cases of anaplastic carcinoma, although Riedel’s thyroiditis (see later)
is indistinguishable. The localised forms of granulomatous thyroiditis and
lymphadenoid goitre may simulate carcinoma. It is not always easy to exclude a
carcinoma in a multinodular goitre, and solitary nodules, particularly in the
young male, are always suspect. Failure to take up radio-iodine is
characteristic of almost all thyroid carcinomas [only very rarely will
differentiated carcinoma (primary or secondary) take up 1231
in the presence
of normal thyroid tissue], but occurs also in degenerating nodules and all forms
of thyroiditis. Thyroid antibody titres are often raised in carcinoma. The role
of FNAC in preoperative diagnosis has already been discussed. No diagnostic test
is absolutely certain, and exploration with excision in the form of lobectomy
is essential when in
doubt. Incisional
biopsy may cause
seeding of cells and
local recurrence, and
is most inadvisable in
a resectable
carcinoma. In an anaplastic and obviously irremovable carcinoma, however, incisional or needle biopsy is justified.
Papillary
carcinoma
Most papillary tumours contain a mixture of
papillary and colloid-filled
follicles, and in
some the follicular structure predominates. Nevertheless, if
any papillary structure
is present, the tumour will behave in a predictable fashion as a papillary
carcinoma. Histologically the tumour shows papillary projections and
characteristic pale, empty nuclei (Orphan Annie-eyed8 nuclei) (Fig.
44.37). Papillary carcinomas
are very seldom
encapsulated.
Occult
carcinoma
Papillary carcinoma may present as an enlarged
lymph node in the jugular chain with no palpable abnormality of the thyroid. The
primary tumour may be no more than a few millimetres in size and is termed
occult. Such primary foci of papillary carcinoma may also be discovered in
thyroid tissue resected for other reasons, e.g. Graves’ disease. The term
occult is now applied to all papillary carcinomas less than 1.5 cm in diameter.
These have an excellent prognosis and are regarded as of little clinical
significance.
Follicular
carcinoma
These appear to be macroscopically encapsulated
but microscopically there is invasion of the capsule and of the vascular spaces
in the capsular region (Fig. 44.38). Multiple foci are seldom seen and lymph
node involvement is much less common than in papillary carcinoma. Blood-borne
metastases are almost twice as common and the eventual mortality rate is twice
as high (Fig. 44.39). Hurthle cell tumours are a variant of follicular neo
plasm in which oxyphil (Hurthle, Askanazy) cells predominate histologically.
It is doubtful whether Hurthle cell neoplasms are ever benign and they may be
associated with a poorer prognosis.
Differences
between papillary and follicular carcinoma
The
major differences between papillary (including mixed papillary and follicular)
and follicular carcinoma have been set out by Cady on the basis of an analysis
of 40 years’ experience at the Lahey Clinic (Table
44.7).
Prognosis
in differentiated
thyroid carcinoma
The prognosis of differentiated thyroid
carcinoma , although influenced by
histological type,
is much more dependent on
Patients
in the low-risk group account for 90 per cent of cases of differentiated thyroid
carcinoma.
Surgical
treatment
There is continuing disagreement on the most
appropriate operation for differentiated thyroid carcinoma. The conservative
approach advocates lobectomy with isthmusectomy in most patients with total
thyroidectomy reserved for
The
case for a policy of total thyroidectomy is theoretically based on the
prevalence of multifocality in papillary carcinoma and on the feasibility
thereafter of using radioiodine scanning to detect metastases, the thyroid
having been ablated (Fig. 44.40). However, the clinical significance of
multifocality
is low as local recurrence is infrequent after unilateral resection. In
addition, in those selected patients in whom scanning may be indicated, the
remaining thyroid tissue may be ablated safely with a preliminary dose of
radioiodine. Most importantly there is no evidence that the long-term results of
routine total thyroidectomy as a policy are better than those of more
conservative operations, and there is a substantial risk of permanent
hypoparathyroidism. Clearly the risk of parathyroid damage varies according to
expertise and the frequency with which the operation is done but, even at the
Mayo Clinic, where thyroid surgery is frequently and expertly done, the rate of
hypoparathyroidism is significant (Hay).
The
large majority of patients with differentiated carcinoma, particularly since
90 per cent fall into a group with a 2 per cent mortality rate, is appropriately
treated by lobectomy with isthmusectomy on the affected side. At the same time
clinically obvious nodes, which may be pretracheal, paratracheal or in the
jugular chain, are removed. If the jugular nodes are extensively involved, a
modified neck dissection with preservation of the accessory nerve and
sternomastoid muscle may be carried out through extension of the thyroidectomy
incision. Very occasionally it may be necessary to sacrifice the recurrent
laryngeal nerve if it is completely encircled and, on even more rare occasions,
extrathyroidal spread may require resection of part of the trachea.
When
there is clinically obvious bilateral disease at operation, bilateral resection
is clearly indicated and bilateral resection may also be indicated in the few
patients classified as high risk, although the evidence at present for improved
prognosis is rather weak. Retrospective analysis of outcome in 860 patients with
papillary carcinoma treated at the Mayo Clinic between 1946 and 1970 showed
improved survival in high-risk patients undergoing bilateral resection, compared
with lobectomy alone, although the difference was not statistically significant
(Hay). There was no advantage for total compared with near-total thyroidectomy
in which 1—2 g of thyroid tissue is preserved on the contralateral side to
protect the blood supply to one or more parathyroid glands.
Surgical
operations
Isthmusectomy. Swellings confined to the
thyroid isthmus, including small differentiated carcinomas, may be appropriately
removed by resection of the isthmus alone. Isthmusectomy is also an effective
method of relieving tracheal obstruction and obtaining tissue for diagnosis in
anaplastic carcinoma and lymphoma.
Thyroid
lobectomy. Total lobectomy on the- affected side together with isthmusectomy is
the appropriate operation for removal of a discrete thyroid swelling and for
most patients with differentiated carcinoma. The procedure, if performed
meticulously by an experienced surgeon, is associated with very little risk of
postoperative complications such as recurrent laryngeal nerve injury. The
parathyroid glands should be seen and preserved in
situ if possible; although the intact glands on the contralateral side will
ensure normal function, removal of the contralateral lobe may occasionally be
necessary in the future. It is unnecessary to ligate the main trunks of the
inferior thyroid arteries. Instead, the individual arterial branches supplying
the thyroid gland should be ligated close to the thyroid, preserving the
parathyroid blood supply. The recurrent laryngeal nerve is carefully exposed
throughout the dissection. It is particularly vulnerable close to where it
angulates posteriorly to enter the larynx, at which site it is intimately
related to the lateral thyroid ligament (ligament of Berry).
Near-total
thyroidectomy. This consists of total thyroid lobectomy on the affected side,
with conservation of 1—2 g of thyroid tissue on the contralateral side, which
preserves the blood supply to one or both parathyroids.
Total
thyroidectomy. The technique is essentially that of bilateral lobectomy and, if
meticulous, the risk of complications is very low except for permanent
hypoparathyroidism. The risk of hypoparathyroidism is variable but may be
appreciable even in experienced hands.
Additional
measures
Thyroxine. It is standard practice to
prescribe thyroxine in a dose of 0.1—0.2 mg daily, to suppress endogenous TSH
production, for all patients after operation for differentiated thyroid
carcinoma on the basis that some tumours are TSH dependent. Suppression of the
TSH level should be confirmed by measurement. Failure of suppression to a
level of <0.1 i.t/litre may indicate an inadequate dose of thyroxine or more
usually that the patient is noncompliant. However, suppressive thyroxine is
probably not of value in follicular carcinoma, and is unlikely to be of benefit
in low-risk patients treated by lobectomy.
Radioiodine.
If metastases take up radioiodine they may be detected by scanning and may be
treated with large doses of radioiodine. For effective scanning, all thyroid
tissue must have been ablated by either surgery or preliminary radioiodine and
the patient must be hypothyroid to improve uptake. The indications for scanning
after operations for differentiated carcinoma are disputed, but it is probably
only indicated in patients with unresectable local recurrence or metastatic
disease, high-risk patients, and in those with a rising serum thyroglobulin
level. In addition, if metastases take up radioiodine they are likely to be
suppressed as effectively by treatment with thyroxine as by radioiodine. Cases
in which suppression has failed and radioiodine has given permanent control
appear to be uncommon.
If
metastases have been treated, the scan should be repeated at annual intervals
and further therapeutic doses of radioiodine given as necessary. Solitary
distant metastases may be treated by external radiotherapy.
Thyroglobulin.
The measurement of serum thyroglobulin is of value in the follow-up and in the
detection of metastatic disease in patients who have undergone surgery for
differentiated thyroid cancer. This measurement may obviate the need for serial
radioactive iodine scanning but when a rise occurs, a scan will be indicated to
confirm and locate the metastatic disease. Thyroglobulin levels are, however,
only an adjunct to careful clinical palpation of the neck because local
recurrence detectable clinically may be present with a low thyroglobulin.
Undifferentiated
(ana plastic) carcinoma
This occurs mainly in elderly women and is
much less often diagnosed now than in the past when many thyroid lymphomas
were mistakenly classified histologically as anaplastic carcinomas. Local
infiltration is an early feature of these tumours with spread by lymphatics and
by the bloodstream. They are extremely lethal tumours and survival for more than
1—2 years after presentation is most unusual. In most cases death occurs
within months rather than within years. An attempt at curative resection is only
justified if there is no infiltration through the thyroid capsule and no
evidence of metastases. Many of these aggressive lesions present in an advanced
stage with tracheal obstruction and require urgent
Medullary
carcinoma
These are tumours of the parafollicular
(C)-cells derived from the neural crest and not from the cells of the thyroid
follicle as are other primary thyroid carcinomas. The cells are not unlike those
of a carcinoid tumour and there is a characteristic amyloid stroma (Fig.
44.41).
High levels of serum calcitonin (>0.08 ng/ml) are produced by many medullarv tumours. These levels fall after resection of a tumour and will rise again if
the tumour recurs. This is a valuable tumour marker in the follow-up of patients
with this
Some
tumours are familial and may account for 10—20 per cent of all cases.
Medullary carcinoma may occur in combination with adrenal phaeochromocytoma and
hyperparathyroidism (usually due to hyperplasia) in the syndrome known as
multiple endocrine neoplasia type ha (MEN IIa). The familial form of the disease
frequently affects children and young adults whereas the sporadic cases occur at
any age with no sex predominance. When the familial form is associated with
prominent mucosal neuromas involving the lips, tongue (Fig.
44.42) and inner
aspect of the eyelids, with occasionally a Marfanoid hahitus, the syndrome is
referred to as MEN type IIb.
Involvement
of lymph nodes occurs in 50—60 per cent of cases of medullary carcinoma and
blood-borne metastases are common. As would be expected, tumours are not hormone
dependent and do not take up radioactive iodine. The course of the tumour is
unpredictable; in general, life expectancy
Treatment
is by total thyroidectomy and resection of involved lymph nodes with either a
radical or modified radical neck dissection. Familial cases are now detected by
genetic screening for the RET oncogene mutations which identifies individuals
who will develop medullary cancer later in life (Fig.
44.43). The genetic tests
are supplemented by estimating serum calcitonin levels in the basal state and
after stimulation by either calcium or pentagastrin. A rise in calcitonin levels
under these circumstances should lead to a prophylactic thyroidectomy but even
then the disease may be beyond the preinvasive C-cell hyperplasia stage (Fig.
44.44).
Phaeochromocytoma
must be excluded by measurement of urinary catecholamine levels (Chapter 45)
in all cases before embarking upon thyroid surgery to avoid the potential
hazards associated with this condition.
Malignant
lymphoma
In the past, many malignant lymphomas were
diagnosed as small round-cell anaplastic carcinomas. Response to irradiation
is good (Fig. 44.45) and radical surgery is unnecessary once the diagnosis is
established by biopsy. Although the diagnosis may be made or suspected on FNAC,
sufficient material is seldom available for immunocytochemical classification,
and large-needle (Trucut) or open biopsy is usually necessary. In patients with
tracheal compression, isthmusectomy is the most appropriate form of biopsy. The
prognosis is good if there is no involvement of cervical lymph nodes. Rarely the
tumour is part of widespread malignant lymphoma disease, and the prognosis in
these cases is worse.