Follicular Thyroid Carcinoma - Clinicals, Diagnosis, and Management

Endocrine

Clinicals - History

Fact Explanation
Newly discovered palpable thyroid nodule or increase in size of a pre-existing nodule. Malignant cells have a high proliferation rate therefore it appear as a new nodule or present as a rapidly enlarging mass. Newly discovered palpable thyroid nodule or increase in size of a pre-existing nodule.
Malignant cells have a high proliferation rate therefore it appear as a new nodule or present as a rapidly enlarging mass.
Sudden onset of pain in a thyroid lump. In malignancy, there is neo vascularisation with friable blood vessels.Therefore there can be sudden haemorrhage.The central part of the tumor can also get necrosed due to the rapid proliferation rate which exceeds it's blood supply. These reasons can cause pain. Sudden onset of pain in a thyroid lump.
In malignancy, there is neo vascularisation with friable blood vessels.Therefore there can be sudden haemorrhage.The central part of the tumor can also get necrosed due to the rapid proliferation rate which exceeds it's blood supply. These reasons can cause pain.
Unexplained hoarseness or voice changes associated with a goitre Malignancy can invade the recurrent laryngeal nerve or the external branch of the superior laryngeal nerve. Unexplained hoarseness or voice changes associated with a goitre
Malignancy can invade the recurrent laryngeal nerve or the external branch of the superior laryngeal nerve.
Positional and nocturnal dry cough, dyspnoea, dysphonia and stridor Narrowing of the the trachea by the compressive force caused by enlarged thyroid gland. Positional and nocturnal dry cough, dyspnoea, dysphonia and stridor
Narrowing of the the trachea by the compressive force caused by enlarged thyroid gland.
History of neck irradiation in childhood, family or personal history of thyroid adenoma  familial thyroid cancer These are risk factors of thyroid malignancy. History of neck irradiation in childhood, family or personal history of thyroid adenoma  familial thyroid cancer
These are risk factors of thyroid malignancy.
Dysphagia for solid foods and pills. Compression of the oesophagus by the enlarging gland cause this but this is rare as the muscular esophagus merely relocates itself when compressed. Dysphagia for solid foods and pills.
Compression of the oesophagus by the enlarging gland cause this but this is rare as the muscular esophagus merely relocates itself when compressed.

Clinicals - Examination

Fact Explanation
Butterfly shaped, midline neck mass which moves upwards with swallowing. Indicates it's a mass arising from the thyroid gland. Butterfly shaped, midline neck mass which moves upwards with swallowing.
Indicates it's a mass arising from the thyroid gland.
Irregular,hard and fixed nodules These features of a nodule highly suggest it's a malignancy. Irregular,hard and fixed nodules
These features of a nodule highly suggest it's a malignancy.
Hard, irregular and fixed cervical lymphadenopathy Indicates that it's more likely to be malignant. Hard, irregular and fixed cervical lymphadenopathy
Indicates that it's more likely to be malignant.
Displaced and/absent carotid pulses Indicates the goiter has compressed and displaced the carotid artery. Displaced and/absent carotid pulses
Indicates the goiter has compressed and displaced the carotid artery.
Tracheal deviation Indicates the goitre has compressed the trachea. Tracheal deviation
Indicates the goitre has compressed the trachea.
Pulsatile scalp lumps Since scalp is a site of metastasis hematogenous spread is the commonest mode of metastasis in follicular carcinoma. Pulsatile scalp lumps
Since scalp is a site of metastasis hematogenous spread is the commonest mode of metastasis in follicular carcinoma.
Foci of decreased breath sounds,foci of dull percussion note Lung metastasis can have these signs. Foci of decreased breath sounds,foci of dull percussion note
Lung metastasis can have these signs.
Bone tenderness, pathological fractures Bone metastasis can have these signs. Bone tenderness, pathological fractures
Bone metastasis can have these signs.
Jaundice Liver metastasis can have these signs. Jaundice
Liver metastasis can have these signs.

Investigations - Diagnosis

Fact Explanation
TFT In malignancy usually thyroid function is normal.Therefore TSH and T4 will be within the normal range. TFT
In malignancy usually thyroid function is normal.Therefore TSH and T4 will be within the normal range.
Ultrasonography In the US markedly hypoechoic nature of the nodule, presence of microcalcifications, ill-defined margins, nodule with shape taller than wide,absent halo and intranodular hypervascularity at color doppler makes it malignant.
The main US features for malignant adenopathy include: rounded lymph node, loss of normal echogenic fatty hilum, and loss of normal hilar vascularization. Several patterns are highly suggestive of thyroid cancer metastasis: microcalcifications, cystic components, hyperechoic nodes, mimicking thyroid tissue.
High-resolution ultrasonography is sensitive and capable of detecting many small, nonpalpable thyroid nodules. Most of these lesions are benign. For most patients with nonpalpable nodules that are incidentally detected by thyroid imaging, simple follow-up neck palpation is sufficient.
Ultrasonography
In the US markedly hypoechoic nature of the nodule, presence of microcalcifications, ill-defined margins, nodule with shape taller than wide,absent halo and intranodular hypervascularity at color doppler makes it malignant.
The main US features for malignant adenopathy include: rounded lymph node, loss of normal echogenic fatty hilum, and loss of normal hilar vascularization. Several patterns are highly suggestive of thyroid cancer metastasis: microcalcifications, cystic components, hyperechoic nodes, mimicking thyroid tissue.
High-resolution ultrasonography is sensitive and capable of detecting many small, nonpalpable thyroid nodules. Most of these lesions are benign. For most patients with nonpalpable nodules that are incidentally detected by thyroid imaging, simple follow-up neck palpation is sufficient.
FNAC FNAC cannot at present distinguish follicular adenoma or benign hyperplastic nodules
from carcinoma.
Thy1:
Non-diagnostic (inadequate or where technical artefact precludes interpretation; adequate smears
usually contain six or more groups of over 10 thyroid follicular cells, but the balance between
cellularity and colloid is more important)

Thy2 :
Non-neoplastic (with the descriptive report documenting the features consistent with a colloid
nodule or thyroiditis). Cysts may be classified as Thy2 if benign epithelial cells are present.\

Thy3:
(i) Follicular lesion/suspected follicular neoplasm. While some of these will be tumours, many will
be shown to be hyperplastic nodules on surgical excision. The descriptive text will indicate the
level of suspicion of neoplasia
(ii) There may be a very small number of other cases where the cytological findings warrant inclusion
in this category rather than Thy2 or Thy4 (eg worrying features but cells too scanty to qualify for
Thy4, repeat FNAC advised). The text of the report should indicate the worrying findings

Thy4:
Suspicious of malignancy (suspicious, but not diagnostic, of papillary, medullary or anaplastic
carcinoma, or lymphoma).

Thy 5:
Diagnostic of malignancy (unequivocal features of papillary, medullary or anaplastic carcinoma,
lymphoma or metastatic tumour).
FNAC
FNAC cannot at present distinguish follicular adenoma or benign hyperplastic nodules
from carcinoma.
Thy1:
Non-diagnostic (inadequate or where technical artefact precludes interpretation; adequate smears
usually contain six or more groups of over 10 thyroid follicular cells, but the balance between
cellularity and colloid is more important)

Thy2 :
Non-neoplastic (with the descriptive report documenting the features consistent with a colloid
nodule or thyroiditis). Cysts may be classified as Thy2 if benign epithelial cells are present.\

Thy3:
(i) Follicular lesion/suspected follicular neoplasm. While some of these will be tumours, many will
be shown to be hyperplastic nodules on surgical excision. The descriptive text will indicate the
level of suspicion of neoplasia
(ii) There may be a very small number of other cases where the cytological findings warrant inclusion
in this category rather than Thy2 or Thy4 (eg worrying features but cells too scanty to qualify for
Thy4, repeat FNAC advised). The text of the report should indicate the worrying findings

Thy4:
Suspicious of malignancy (suspicious, but not diagnostic, of papillary, medullary or anaplastic
carcinoma, or lymphoma).

Thy 5:
Diagnostic of malignancy (unequivocal features of papillary, medullary or anaplastic carcinoma,
lymphoma or metastatic tumour).
Isotope scanning Radioactive iodine, trapped and organified in the gland and can be used to determine functionality of a nodule. Benign nodules appear as hot owing to their hyperfunctionality and have a high uptake of radionuclide. Malignant nodules, because they are not functioning usually appear as cold nodules . Isotope scanning
Radioactive iodine, trapped and organified in the gland and can be used to determine functionality of a nodule. Benign nodules appear as hot owing to their hyperfunctionality and have a high uptake of radionuclide. Malignant nodules, because they are not functioning usually appear as cold nodules .
Thyroid autoantibodies This may be measured if there is a suspicion of concurrent
autoimmune thyroid disease (lymphoma of the thyroid occurs almost exclusively on a
background of Hashimoto’s thyroiditis)
Thyroid autoantibodies
This may be measured if there is a suspicion of concurrent
autoimmune thyroid disease (lymphoma of the thyroid occurs almost exclusively on a
background of Hashimoto’s thyroiditis)
MRI and CT These are indicated when the limits of the goitre cannot be determined clinically or for fixed tumours or in patients with haemoptysis Gadolinium enhanced MRI may provide useful
information without compromising subsequent radioiodine uptake by any remaining
thyroid tissue.
MRI and CT
These are indicated when the limits of the goitre cannot be determined clinically or for fixed tumours or in patients with haemoptysis Gadolinium enhanced MRI may provide useful
information without compromising subsequent radioiodine uptake by any remaining
thyroid tissue.
Calcitonin level Basal plasma calcitonin levels may be useful if medullary thyroid carcinoma is suspected. Calcitonin level
Basal plasma calcitonin levels may be useful if medullary thyroid carcinoma is suspected.

Investigations - Management

Fact Explanation
Serum thyroglobulin(Tg) level. Detectable serum Tg is
highly suggestive of thyroid remnant, residual or recurrent tumour.
A serum Tg rising with time while on suppressive thyroxine therapy is highly suggestive of
tumour recurrence or progression.
There is normally no need to measure serum Tg more frequently than 3-monthly during
routine follow-up; for patients in remission, an annual check of serum Tg should be
measured while on suppressive levothyroxine treatment.
Serum thyroglobulin(Tg) level.
Detectable serum Tg is
highly suggestive of thyroid remnant, residual or recurrent tumour.
A serum Tg rising with time while on suppressive thyroxine therapy is highly suggestive of
tumour recurrence or progression.
There is normally no need to measure serum Tg more frequently than 3-monthly during
routine follow-up; for patients in remission, an annual check of serum Tg should be
measured while on suppressive levothyroxine treatment.
Ultrasonography Ultrasonography is a sensitive method for detection of residual disease in the thyroid bed and
metastatic disease in lymph nodes
Ultrasonography
Ultrasonography is a sensitive method for detection of residual disease in the thyroid bed and
metastatic disease in lymph nodes
whole-body 131I scanning(WBS A single diagnostic WBS performed 6–8 months after 131I ablation is generally indicated except in those with low-risk disease
If this is negative, further WBS is not usually required, depending on
results of monitoring by measurement of serum Tg.
whole-body 131I scanning(WBS
A single diagnostic WBS performed 6–8 months after 131I ablation is generally indicated except in those with low-risk disease
If this is negative, further WBS is not usually required, depending on
results of monitoring by measurement of serum Tg.
renal function Radio iodine is excreted in urine therefore before this therapy renal function is assessed. renal function
Radio iodine is excreted in urine therefore before this therapy renal function is assessed.
Indirect laryngoscopy If thyroidectomy is performed as a treatment option this could damage the recurrent laryngeal nerve and result in dysfunction of the vocal cords.Therefore to assess the baseline vocal cord function indirect laryngoscopy is done. Indirect laryngoscopy
If thyroidectomy is performed as a treatment option this could damage the recurrent laryngeal nerve and result in dysfunction of the vocal cords.Therefore to assess the baseline vocal cord function indirect laryngoscopy is done.
Serum Ca2+ level If thyroidectomy is performed as a treatment option this could cause a transient hypoparathyroidism or a permanent hypoparathyroidism if the parathyroid gland gets damaged.Therefore to get an idea about the baseline Ca2+ level is done. Serum Ca2+ level
If thyroidectomy is performed as a treatment option this could cause a transient hypoparathyroidism or a permanent hypoparathyroidism if the parathyroid gland gets damaged.Therefore to get an idea about the baseline Ca2+ level is done.
Direct laryngoscopy This is done to ascertain the difficulty of intubation and to calculate the Malampati/ Cormack Lehane score. Direct laryngoscopy
This is done to ascertain the difficulty of intubation and to calculate the Malampati/ Cormack Lehane score.
Chest X-Ray To detect any lung metastases. Chest X-Ray
To detect any lung metastases.
USS To detect the size of the tumor.
pT1: Intrathyroidal tumour, ≤1 cm in greatest dimension

pT2: Intrathyroidal tumour, >1–4 cm in greatest dimension

PT3: Intrathyroidal tumour, >4 cm in greatest dimension

pT4: Tumour of any size, extending beyond thyroid capsule

pTX: Primary tumour cannot be assessed

To detect any regional lymph node involvement. (cervical or upper mediastinal)

N0: No nodes involved

N1 :Regional nodes involved
If possible, subdivide
N1a- Ipsilateral cervical nodes
N1b-Bilateral, midline or contralateral cervical nodes or mediastinal nodes

NX :Nodes cannot be assessed
USS
To detect the size of the tumor.
pT1: Intrathyroidal tumour, ≤1 cm in greatest dimension

pT2: Intrathyroidal tumour, >1–4 cm in greatest dimension

PT3: Intrathyroidal tumour, >4 cm in greatest dimension

pT4: Tumour of any size, extending beyond thyroid capsule

pTX: Primary tumour cannot be assessed

To detect any regional lymph node involvement. (cervical or upper mediastinal)

N0: No nodes involved

N1 :Regional nodes involved
If possible, subdivide
N1a- Ipsilateral cervical nodes
N1b-Bilateral, midline or contralateral cervical nodes or mediastinal nodes

NX :Nodes cannot be assessed
Chest CT, DEXA bone scan, Brain CT Distant metastases.

M0: No distant metastases

M1: Distant metastases

MX :Distant metastases cannot be assessed
Chest CT, DEXA bone scan, Brain CT
Distant metastases.

M0: No distant metastases

M1: Distant metastases

MX :Distant metastases cannot be assessed
By combining the above investigations TNM staging

Under 45 years
Stage I:Any T, any N, M0

Stage II:Any T, any N,M1


45 years and older
Stage I:pT1, N0, M0

Stage II:pT2, N0, M0
pT3, N0, M0

Stage iii:pT4, N0, M0
Any pT, N1, M0

Stage iv:Any pT,any N, M1
By combining the above investigations
TNM staging

Under 45 years
Stage I:Any T, any N, M0

Stage II:Any T, any N,M1


45 years and older
Stage I:pT1, N0, M0

Stage II:pT2, N0, M0
pT3, N0, M0

Stage iii:pT4, N0, M0
Any pT, N1, M0

Stage iv:Any pT,any N, M1

Management - Supportive

Fact Explanation
Palliative course of radiation therapy This is useful to relieve pain from bone metastases. Palliative course of radiation therapy
This is useful to relieve pain from bone metastases.

Management - Specific

Fact Explanation
Surgery FNAC cannot at present distinguish follicular adenoma or benign hyperplastic nodules
from carcinoma.Thy3 cytology usually mandates lobectomy as the least
surgical procedure
If definitive histology reveals a follicular adenoma or a hyperplastic nodule, no further
treatment is required
A follicular carcinoma under 1 cm in diameter with minimal capsular invasion should
be treated by lobectomy Patients with follicular cancer showing evidence of vascular invasion should be treated
with total thyroidectomy Patients with follicular carcinoma more than 4 cm in diameter should be treated with
near-total or total thyroidectomy
Palpable/suspicious cervical lymph nodes are dealt with in a similar manner to papillary
carcinoma
If the diagnosis of thyroid cancer has been made after thyroid lobectomy and
completion, (contralateral) thyroid lobectomy is required; the latter should be offered within 8 weeks of histological diagnosis of cancer.
Surgery
FNAC cannot at present distinguish follicular adenoma or benign hyperplastic nodules
from carcinoma.Thy3 cytology usually mandates lobectomy as the least
surgical procedure
If definitive histology reveals a follicular adenoma or a hyperplastic nodule, no further
treatment is required
A follicular carcinoma under 1 cm in diameter with minimal capsular invasion should
be treated by lobectomy Patients with follicular cancer showing evidence of vascular invasion should be treated
with total thyroidectomy Patients with follicular carcinoma more than 4 cm in diameter should be treated with
near-total or total thyroidectomy
Palpable/suspicious cervical lymph nodes are dealt with in a similar manner to papillary
carcinoma
If the diagnosis of thyroid cancer has been made after thyroid lobectomy and
completion, (contralateral) thyroid lobectomy is required; the latter should be offered within 8 weeks of histological diagnosis of cancer.
131I ablation or therapy Always exclude pregnancy and breast feeding before administering radioiodine therapy.

Patients should adopt a low iodine diet for 2 weeks prior to 131I and other sources of
excess iodine should be eliminated.Amiodarone may have to be
withdrawn for several months to ensure optimal conditions for 131I ablation or therapy

131I can be administered within 3–4 weeks of thyroidectomy, no thyroid hormone
replacement is required in the interim period. This would usually allow TSH to rise to
>30 mIU/L at the time of ablation.
For most centres, however, the interval between
thyroidectomy and 131I ablation will be longer. In these circumstances, patients should
start T3 20 mg tds following surgery; this should be stopped 2 weeks before planned
ablation to allow the serum TSH to rise to >30 mIU/L

a pre-ablation scan can be performed to assess remnant size. In such cases 123I
or 99mTc-pertechnetate is preferable.

Adequate hydration at the time of
treatment and for several days afterwards, regular emptying of the bladder and
avoidance of constipation helps to prevent a decrease in sperm count.

A post-ablation scan should be performed 3–10 days after the 131I dose

Patients should be reviewed after 2–3 months for
assessment, adjustment of TSH suppressive dose of levothyroxine, and to make
arrangements for follow-up Tg measurement and scanning.
131I ablation or therapy
Always exclude pregnancy and breast feeding before administering radioiodine therapy.

Patients should adopt a low iodine diet for 2 weeks prior to 131I and other sources of
excess iodine should be eliminated.Amiodarone may have to be
withdrawn for several months to ensure optimal conditions for 131I ablation or therapy

131I can be administered within 3–4 weeks of thyroidectomy, no thyroid hormone
replacement is required in the interim period. This would usually allow TSH to rise to
>30 mIU/L at the time of ablation.
For most centres, however, the interval between
thyroidectomy and 131I ablation will be longer. In these circumstances, patients should
start T3 20 mg tds following surgery; this should be stopped 2 weeks before planned
ablation to allow the serum TSH to rise to >30 mIU/L

a pre-ablation scan can be performed to assess remnant size. In such cases 123I
or 99mTc-pertechnetate is preferable.

Adequate hydration at the time of
treatment and for several days afterwards, regular emptying of the bladder and
avoidance of constipation helps to prevent a decrease in sperm count.

A post-ablation scan should be performed 3–10 days after the 131I dose

Patients should be reviewed after 2–3 months for
assessment, adjustment of TSH suppressive dose of levothyroxine, and to make
arrangements for follow-up Tg measurement and scanning.
External beam radiotherapy The main indications for adjuvant radiotherapy are:
1. gross evidence of local tumour invasion at surgery, presumed to have significant macro or microscopic residual disease, particularly if the residual tumour fails to concentrate
sufficient amounts of radioiodine
2.extensive pT4 disease in patients over 60 years of age with extensive extranodal spread
after optimal surgery, even in the absence of evident residual disease.
External beam radiotherapy
The main indications for adjuvant radiotherapy are:
1. gross evidence of local tumour invasion at surgery, presumed to have significant macro or microscopic residual disease, particularly if the residual tumour fails to concentrate
sufficient amounts of radioiodine
2.extensive pT4 disease in patients over 60 years of age with extensive extranodal spread
after optimal surgery, even in the absence of evident residual disease.
Long-term suppression of serum thyrotrophin Levothyroxine should be used in preference to T3 for long-term suppression.
The dose of levothyroxine should be adjusted by 25 μg (every 6 weeks) until the serum TSH is <0.1 mIU/L)
To achieve this, most patients will require 175 or 200 μg
daily.
Long-term suppression of serum thyrotrophin
Levothyroxine should be used in preference to T3 for long-term suppression.
The dose of levothyroxine should be adjusted by 25 μg (every 6 weeks) until the serum TSH is <0.1 mIU/L)
To achieve this, most patients will require 175 or 200 μg
daily.
Management of metastasis. Surgical re-exploration is the preferred method of management, usually followed by 131I
therapy. Recurrent neck disease uncontrolled by surgery and 131I therapy is best
treated by high-dose palliative external beam radiotherapy.

Lung and other soft tissue areas
metastases are usually not amenable to surgery and should be treated with 131I
therapy.
If the tumour takes up radioiodine, long-term survival is
possible in such cases. The preferred treatment is repeated doses of 131I; activities ranging from
3.7–10.1 GBq at 3–9 month intervals have been employed, the usualbeing 5.5 GBq given every
4–6 months until 131I uptake is no longer evident

Extensive bony metastases are generally not curable by 131I therapy alone. For solitary or
limited number of bony metastases that are not cured by 131I therapy, external beam
radiotherapy with/without resection and/or embolisation should be considered in selected cases.
External beam radiotherapy also has a very important role in the management of
spinal cord compression for vertebral metastases in addition to surgery.
External beam radiotherapy has an important palliative role in the management of cerebral
metastases along with surgery if appropriate.
Management of metastasis.
Surgical re-exploration is the preferred method of management, usually followed by 131I
therapy. Recurrent neck disease uncontrolled by surgery and 131I therapy is best
treated by high-dose palliative external beam radiotherapy.

Lung and other soft tissue areas
metastases are usually not amenable to surgery and should be treated with 131I
therapy.
If the tumour takes up radioiodine, long-term survival is
possible in such cases. The preferred treatment is repeated doses of 131I; activities ranging from
3.7–10.1 GBq at 3–9 month intervals have been employed, the usualbeing 5.5 GBq given every
4–6 months until 131I uptake is no longer evident

Extensive bony metastases are generally not curable by 131I therapy alone. For solitary or
limited number of bony metastases that are not cured by 131I therapy, external beam
radiotherapy with/without resection and/or embolisation should be considered in selected cases.
External beam radiotherapy also has a very important role in the management of
spinal cord compression for vertebral metastases in addition to surgery.
External beam radiotherapy has an important palliative role in the management of cerebral
metastases along with surgery if appropriate.

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