neoplasms of thyroid, thyroid tumors, including the surgical treatment of differentiated thyroid cancer

In conclusion, this presentation on Neoplasms of the Thyroid provides a comprehensive overview of various aspects related to thyroid tumors, including the surgical treatment of differentiated thyroid cancer, considerations for specific situations such as widespread nodal disease or suspicion of invasive disease, and the importance of accurate diagnosis in cases of rapidly growing thyroid masses. The document emphasizes the need for risk stratification, multidisciplinary discussions, and individualized approaches to treatment based on the specific characteristics of the tumor and the patient. Overall, it highlights the complexity of managing thyroid neoplasms and the critical role of healthcare professionals from different specialties in ensuring optimal patient outcomes.

1. NEOPLASMS OF THE THYROID
BY: MUHAMMAD KHOSHKANI
FACULTY OF MEDICINE
1

2. NEOPLASMS OF THE
THYROID
By: Muhammad Khoshkani
Faculty of medicine
2

3. Classifcation of thyroid neoplasms is presented
in Table 55.6 and the relative incidence of
malignancies in Table 55.7.
3

4. Classifcation of thyroid neoplasms is presented
in Table 55.6 and the relative incidence of
malignancies in Table 55.7.
4

5. Benign tumours
Follicular adenomas present as clinically solitary nodules (Figure 55.21) 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. For this reason, FNA, which provides cytological
detail but not tissue architecture, cannot diferentiate between benign and
malignant follicular lesions. Diagnosis and treatment is, therefore, by wide
excision,
i.e. total lobectomy. The remaining thyroid tissue is normal so
that prolonged follow-up is unnecessary.
5

6. Figure 55.21 Isolated swelling in the
upper pole of the right thyroid lobe.
6

7. Malignant tumours
The vast majority of primary malignancies are carcinomas derived from the
follicular cells (Table 55.6). Such tumours were thought of as differentiated
(papillary, follicular and Hürthle cell) and undifferentiated (anaplastic). However,
now an intermediate class of ‘poorly differentiated carcinoma’ is recognised,
which is likely to represent a state of dedifferentiated – between classic
differentiated and undifferentiated diseases. The parafollicular C cells can undergo malignant transformation into medullary carcinoma, and thyroid lymphoma is another primary thyroid malignancy. In addition, the thyroid can be involved by direct spread from surrounding structures (larynx and oesophagus ) or
metastases (most commonly from renal cell carcinoma). Lymph node and blood-
borne metastases of thyroid cancer occur primarily to bone and lung and may be
the mode of presentation (
Figure 55.22).
7

8. Figure 55.22 Metastasis in the humerus from
thyroid carcinoma
8

9. Aetiology of malignant thyroid tumours
The great majority of thyroid cancers have no known aetiological factor. The
most important identifable aetiological factor in diferentiated thyroid carcinoma
(particularly papillary) is irradiation of the thyroid under 5 years of age. In the
town of Gomel, Ukraine, the incidence of childhood thyroid cancer rose from <1
per million to 96 per million following the Chernobyl nuclear disaster.
Short latency aggressive PTC is associated with the
ret/PTC3 oncogene and later
developing, possibly less aggressive, cancers with
ret/PTC1. The incidence of
follicular carcinoma is high in endemic goitrous areas, possibly because of TSH
stimulation. Malignant lymphomas sometimes develop in autoimmune thyroiditis,
and the lymphocytic infltration in the autoimmune process may be an aetiological
factor.
9

10. Clinical features of thyroid cancers
The annual incidence is about 0.8 per million of the population and the sex ratio
is three females to one male. However, the incidence of PTC is increasing rapidly
across the world. This is mostly due to increased rates of imaging detecting
previously occult disease. For that reason, although the incidence is increasing,
the mortality rates remain static at over 80% 5-year survival for all groups. In
particular, anaplastic carcinoma predicts poor outcome with diferentiated
carcinomas generally having excellent outcomes. The most common presenting
symptom is a thyroid swelling (Figures 55.21 and 55.23). Enlarged cervical lymph
nodes may be the presentation of PTC. RLN paralysis is very suggestive of locally
advanced disease.
10

11. Anaplastic cancers 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, even when lymphatic metastases are
present. Pain, often referred to the ear, is suggestive of nerve
involvement from infiltrating tumours.
11

12. Figure 55.23 Follicular neoplasm of the
thyroid presenting as an isolated swelling.
Figure 55.21 Isolated swelling in the
upper pole of the right thyroid lobe.
12

13. Diagnosis of thyroid neoplasms
Clinical history and examination continue to be the cornerstone of diagnosis of
thyroid neoplasms. As previously mentioned, radiation exposure and family
history should be discussed. Examination of the central neck and regional
lymphatics should be combined with assessment of vocal cord function.
Biochemical assessment of thyroid function should also be considered in this first
encounter, if not already performed. Following initial assessment, the next step is
ultrasonography. This non-invasive investigation is most accurate at assessing
thyroid swellings. Not only can a judgement be made on the presence, size and
number of thyroid nodules present, but an estimate of risk of malignancy can be
made depending on these findings. Following ultrasonography, lesions can be
categorised as benign, indeterminate or malignant. Benign lesions require no
further assessment unless surgery is considered for compressive symptoms.
Indeterminate or malignant lesions should be investigated with FNAC.
13

14. Occasionally, the surgeon will encounter a thyrotoxic patient. Such
cases are one of the few indications for a radio-iodine uptake scan.
This allows assessment of the function of a nodule. Hot nodules are
very rarely malignant. Cold nodules will require assessment as for all
other thyroid neoplasms.
Following clinical, ultrasonographic and cytological assessment, the
vast majority of lesions will be characterised as benign, malignant or
indeterminate. Further treatment will be planned accordingly.
14

15. Certain situations require specific consideration. For patients with
widespread nodal disease or suspicion of locally invasive disease
affecting the airway, contrast-enhanced imaging should be considered.
This should cover the neck and chest. This not only allows accurate
assessment of any visceral invasion, but is superior to ultrasonography
at defining disease in the mediastinum and thorax. Concerns over the
impact of iodine-containing contrast on delays to radioactive iodine
therapy have been overplayed, and it is more critical that the surgeon
has an accurate assessment of disease extent prior to surgery.
15

16. Patients with a rapidly growing thyroid mass, particularly if solid and
fixed, should be considered at risk of anaplastic carcinoma. However,
this diagnosis can be difficult to differentiate from thyroid lymphoma
or occasionally thyroiditis. Despite the difficulty, an accurate diagnosis
is critical as anaplastic carcinoma is rapidly fatal and palliative
measures are generally recommended, whereas confounding disease
processes may respond to therapy. In this setting, core or even open
biopsy may be required to make a confident diagnosis.
16

17. Papillary thyroid carcinoma
PTC is the most common thyroid malignancy. Interestingly, up to 30% of patients
who die of non-thyroid disease have deposits of PTC in autopsy studies,
suggesting that many patients live with this disease undetected. Nonetheless, when
PTC is diagnosed most patients will be offered treatment. The disease is known
for its propensity for lymph node metastases. These are more common in
younger patients, in whom they do not affect the otherwise excellent survival. This
finding is in contrast to most malignancies, where the finding of metastatic disease
confers a poor outcome. One contentious finding in patients with PTC is a high
rate of occult micrometastases (as high as 40% of N0 patients in the central neck).
Despite the presence of metastases, few patients progress to have clinically
meaningful disease and the role of elective nodal surgery is in question. Distant
metastases are uncommon in PTC.
17

18. Recently, increasing interest has focused on ‘papillary microcarcinoma’. This
term is used to describe PTC that is <10 mm in size. These lesions are common
(detected in about 10% of benign thyroid resections) and not associated with
adverse outcomes, including recurrence or non-survival. As such, management
and follow-up of patients with these lesions of doubtful clinical significance is
controversial. In Korea, for example, national screening has led to a significant
increase in these cases. In Japan groups are opting for an observational approach
without surgery. These studies have shown that at least two-thirds never progress.
In the USA some groups are attempting non-surgical management with ablation
techniques using ethanol or radiofrequency. In most of the world, however,
groups try to avoid diagnosing these small, insignificant lesions by limiting biopsies
to >10 mm lesions and being conservative in the management of lesions following
their diagnosis.
18

19. Follicular carcinoma
Follicular carcinoma can normally only be differentiated from follicular adenoma
by the architecture on histology. For this reason, follicular lesions on FNA are
unable to be diagnosed as malignant in the absence of clinical features such as
metastases (Figure 55.24). Multiple foci of follicular carcinoma are seldom seen
and lymph node involvement is much less common than in PTC. Blood-borne
metastases are more common and the eventual mortality rate, although still low, is
twice that of PTC (Figure 55.25).
Hürthle cell tumours are a rare variant of follicular neoplasm in which oxyphil
(Hürthle, Askanazy) cells predominate histologically. Hürthle cell cancers are
associated with a poor prognosis.
19

20. Figure 55.24 Histology of follicular thyroid
carcinoma showing vascular (red arrow) and
capsular (black arrow) invasion
Figure 55.25 Follicular carcinoma
of the thyroid with skull secondaries.
20

21. Prognosis in differentiated thyroid carcinoma
The prognosis in differentiated thyroid cancers is generally excellent. In terms of
survival, older patients, those with large tumours or those with extrathyroid
extension or distant metastases have worse outcomes. A system of risk
stratification can be used to predict the risk on an individual basis. In a young
patient with a low-risk tumour, the risk of death following appropriate treatment is
almost zero. In an older patient with a high-risk tumour (extrathyroid extension or
distant metastases), the risk is as high as 55% at 5 years. Older patients with low-
risk tumours and younger patients with high-risk tumours are an intermediate- risk
group. Nodal metastases deserve special mention. In younger patients they
predict for recurrence but not for death. This is because recurrent neck disease in
young patients can almost always be successfully salvaged.
21

22. In contrast, for older patients neck metastases (particularly in the
lateral neck) are a marker of distant metastases in some, and therefore
carry a negative prognostic implication for both recurrence and death.
The American Joint Committee on Cancer system stages all patients
<55 years as stage I unless they have distant metastases, when they are
stage II. Older T1N0M0 patients are stage I and T2N0M0 patients
are stage II. The presence of nodal disease upstages older patients to
stage II, as does T3 disease. All older patients with locally invasive
primary disease (T4) or distant metastases are stage IV.
22

23. Surgical treatment for differentiated thyroid cancer
This subject has many contentious aspects. For the vast majority of
patients, outcome is excellent irrespective of the extent of surgery.
The low number of recurrences and deaths has made prospective
trials difficult; as such, very few exist.
The aim of surgery is to rid the patient of macroscopic disease, reduce
the chance of recurrence and minimise surgical morbidity. Achieving
a balance between these aims is critical. In addition, the surgeon must
consider whether radioactive iodine is to be recommended. In low-
risk cases this is rarely indicated, whereas in high-risk patients it is
used almost universally. Risk stratification is therefore critical.
23

24. In high-risk patients with nodal or distant metastases, total
thyroidectomy will be performed to eradicate disease in the thyroid
and prepare the patient for radioactive iodine. For low-risk patients
with a single focus of disease limited to the thyroid, a thyroid
lobectomy can be offered. This has the significant advantage of
protecting the contralateral RLN and parathyroid glands. This
approach is now considered appropriate unless there are high-risk
features of disease. In terms of the neck, when metastatic disease is
present, a therapeutic compartment-orientated neck dissection should
be performed to remove disease from the central or lateral neck,
depending on the site of involvement.
24

25. The role of elective neck surgery when no disease in the nodes is
detected preoperatively is far more controversial. Lateral neck
dissection carries significant morbidity and, despite high rates of occult
metastases in PTC, has been abandoned. The reason for this is that,
even in patients who are thought to have occult metastases, very few
progress to clinically meaningful disease. In contrast, the morbidity of
central neck dissection is lower, and the compartment has to be
opened during a thyroidectomy. In addition, salvage surgery in the
central neck carries a high risk to the RLN and parathyroid glands.
For these reasons elective central neck dissection has been popular in
the last few decades.
25

26. However, increased recognition that performing such surgery in all
patients with PTC leads to high rates of morbidity and the lack of
evidence that outcomes improve as a result of more aggressive surgery
have led to a move away from this practice. At this point, patients who
are considered at highest risk of having occult metastases in the central
neck (those with extrathyroid extension, for example) are considered
most likely to beneft from elective surgery. It is not recommended
routinely in low-risk patients. Many patients will only be diagnosed
with their thyroid cancer following a diagnostic lobectomy. In this
setting, risk assessment is again critical. If the patient is considered low
risk, further surgery is unlikely to be benefcial and active surveillance
should be considered.
26

27. This approach, pioneered in Japan, has been adopted in a number of
centres for PTCs <1 cm as only 30% of patients develop tumour
growth that requires intervention. Larger tumours and younger
patients are at higher risk and radioactive iodine may be
recommended, in which case completion thyroidectomy may be
required.
Given the complexity of decision making in thyroid cancer and the
different groups involved (surgeons, endocrinologists, radiologists,
cytologists, pathologists and nuclear medicine physicians), all cases
should be discussed in a multidisciplinary setting.
27

28. Thyroxine
Following surgery, thyroid cells (both normal and malignant) can be suppressed
using high doses of thyroxine. This was once considered routine for all
differentiated thyroid cancers during follow-up. Again, risk stratification has
modified the approach to these patients. Following surgery, patients can be
considered high or low risk. For those patients at high risk from disease,
thyroxine will be prescribed at levels that suppress TSH without making the
patient biochemically hyperthyroid. In contrast, low-risk patients may be
considered for thyroxine replacement at physiological levels. In this patient group,
a balance of benefit (remember these patients have extremely low rates of
recurrence or death) versus risk must be made. In particular, long-term TSH
suppression can result in cardiac arrhythmia and osteoporosis. As such the
multidisciplinary team should consider all risks during follow-up to strike this
balance.
28

29. Radioiodine
131
I can be given to deliver tumoricidal doses of radioactivity directly to thyroid
tissue, both benign and malignant. In the setting of thyroid cancer, all normal
tissue should be removed (total thyroidectomy) along with any gross neck disease
(neck dissection) in order for any residual microscopic disease or distant
metastases to receive an optimal dose. Radioiodine treatment is not an alternative
to surgical resection for resectable disease.
In order to effectively drive the radioiodine into cells, high levels of TSH are
required. This can be achieved by rendering the patient hypothyroid (of
thyroxine) or by using recombinant TSH, which is injected prior to radioiodine
administration.
29

30. Following radioiodine administration, an uptake scan is performed. This
demonstrates areas of iodine uptake in the whole body and can be used to
identify any metastatic disease not recognised on initial imaging. This information
is useful for risk stratification following initial therapy.
Outside the setting of primary treatment, radioiodine treatment may be
considered in cases of recurrence. Multiple doses can be used to treat
unresectable disease or distant metastases.
Most differentiated thyroid cancers will concentrate iodine. However, with
advancing patient age and particularly if disease is multiply recurrent the tumour
will lose iodine avidity. This is called radioiodine refractory disease. Such cases
may be considered for external beam radiotherapy, although this is uncommon.
30

31. Thyroglobulin
Thyroglobulin is a tumour marker produced by normal thyroid cells and most
differentiated thyroid cancers and offers an extremely accurate method of
following patients postoperatively. If a lobectomy has been performed the level
will not be undetectable, but trends can be used to monitor for recurrence.
Following total thyroidectomy, the aim is to have an undetectable thyroglobulin.
Patients who achieve this point are at extremely low risk of recurrence. Serial
thyroglobulin measurement (6- to 12-monthly) combined with ultrasonographic
assessment of the neck can then be used to monitor patients during follow-up.
If an undetectable level is not achieved, the thyroglobulin can be followed. If it
increases, imaging should be performed to look for gross recurrent disease.
Resectable disease should be addressed surgically, and normally further
radioactive iodine would be indicated. The role of radioactive iodine in a rising
thyroglobulin without structural disease is controversial.
31

32. Undifferentiated (anaplastic) carcinoma
This is one of the most aggressive malignancies in humans. Thankfully it is rare. It
may develop
de novo or present as dedifferentiation of a papillary or poorly
differentiated carcinoma. The disease is characterised by rapid growth, visceral
invasion and distant metastases. The surgeon’s role in this disease is crucial.
Thyroid lymphoma can be incorrectly diagnosed as anaplastic cancer and so
biopsy is critical. This can be done using a core or open technique.
Management is controversial because of the extremely poor prognosis.
Occasional patients may present with disease limited to the neck, which appears
resectable on imaging. Such patients seem to have a slightly better outcome if
treated with aggressive surgery and postoperative adjuvant therapy (radiotherapy
with/without chemotherapy). However, in the majority, treatment is palliative.
Those who develop airway symptoms are generally better managed without
tracheostomy, despite the potentially distressing mode of death.
32

33. Medullary carcinoma
These are tumours of the parafollicular (C cells) derived from the neural crest
that are not unlike those of a carcinoid tumour (Figure 55.26). High levels of
serum calcitonin and carcinoembryonic antigen are produced. Calcitonin levels
fall after resection and rise again with recurrence, making it a valuable tumour
marker in the follow-up of patients with this disease. Diarrhoea is a feature in 30%
of cases and this may be due to 5-hydroxytryptamine or prostaglandins produced
by the tumour cells.
Medullary carcinoma may occur in combination with adrenal
phaeochromocytoma and hyperparathyroidism (usually due to hyperplasia) in the
syndrome known as multiple endocrine neoplasia type 2A (MEN-2A). The
familial form of the disease frequently affects children and young adults, whereas
the sporadic cases occur at any age with no sex predominance.
33

34. When the familial form is associated with prominent mucosal
neuromas involving the lips, tongue and inner aspect of the eyelids,
with a Marfanoid habitus, the syndrome is referred to as MEN type
2B .
Involvement of lymph nodes occurs in 55–60% of cases and blood-
borne metastases are common. Tumours are not TSH dependent and
do not take up radioactive iodine. The prognosis is variable and
depends on the stage at diagnosis. Any nodal involvement virtually
eliminates the prospect of cure and, unfortunately, even small
tumours confned to the thyroid gland may have spread by the time of
diagnosis, particularly in familial cancers.
34

35. In common with many endocrine tumours the progression of disease
may be very slow, with a characteristically indolent course and long
survival, even in the absence of cure.
In familial cases of medullary thyroid cancer, genetic screening of
relatives should be recommended and the information used to make
recommendations concerning prophylactic thyroidectomy. Some
relatives may be monitored into adulthood with serial calcitonin
monitoring. In contrast, the highest risk mutations are associated with
early-onset disease and total thyroidectomy is recommended during
infancy.
35

36. Figure 55.26 Histology of medullary carcinoma showing
characteristic ‘cell balls’ and amyloid
36

37. Treatment
When medullary carcinoma is diagnosed, staging of the neck and
chest should be performed. For patients with disease confined to the
thyroid, total thyroidectomy is recommended to remove all C cells
with elective dissection of the central neck nodes. If there is evidence
of nodal metastases, gross disease should be excised but the surgeon
should be mindful of morbidity. Such patients are highly likely to
develop recurrent disease, hence a pragmatic approach should be
adopted.
37

38. Malignant lymphoma
In the past, many malignant lymphomas were diagnosed as small round-cell
anaplastic carcinomas. Response to irradiation is dramatic (Figure 55.27) and
radical surgery is unnecessary once the diagnosis is established by biopsy. In
patients with tracheal compression, isthmusectomy is the most appropriate form
of biopsy, although the response to therapy is so rapid that this should rarely be
necessary unless there has been difficulty in making a histological diagnosis. The
prognosis is good, particularly 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. Most lymphomas occur against a background of
lymphocytic thyroiditis.
38

39. Figure 55.27 Magnetic resonance imaging scans of extensive malignant
lymphoma (a) before and (b) after 7 days of external beam radiotherapy
(a) (b)
39

40. Thank you
40