Thyroid Neoplasms

Thyroid Neoplasms is a course designed to teach you about the clinical presentation, relevant history,  clinical skills assessment techniques, physical exam findings, referral recommendations, specialist procedures, surgical pathology and endocrinology  findings, indications for surgery and treatments, patient prognosis and followup for three different types of thyroid carcinomas.

We also hope to enhance your learning through the use of google cardboard that will allow you to perform an ultrasound guided fine needle aspiration(FNA) in virtual reality.

You will learn how to approach 3 different neoplasms

  OBJECTIVES                                                                                                               

 

Pretest

Papillary carcinomas are more common in:

  • Women or men aged 25-50
  • women aged 25-50
  • men aged 25-50

Papillary carcinomas account for about ___ % of thyroid cancers.

  • 85
  • 10-15
  • 70
  • <5

The first sample you would expect to receive for a patient presenting with suspicion of thyroid cancer on a PATHOLOGY elective would be:

  • you would not receive anything, any biopsy or thyroidectomy would go to endocrinology
  • contents from a subtotal thyroidectomy
  • contents from a fine needle aspiration

Papillary carcinomas are commonly associated with which risk factor?

  • exposure to toxins found in improperly stored foods
  • exposure to ionizing radiation
  • iodine deficiency

Follicular carcinomas account for __% of thyroid cancers.

  • 5-15
  • 85
  • <5

Thyroid cancers (are) usually:

  • painful
  • itchy
  • painless
  • cause constriction of the airway

Follicular carcinoma is most common among:

  • women age 25-55
  • children and young adult women
  • women aged 40-60 years

Follicular carcinomas differ from papillary carcinomas in that they only have:

  • lymphatic spread
  • hematogenous spread
  • orphan Annie eye nuclear inclusions

What are some other risk factors besides radiation exposure that are associated with an increased risk of thyroid cancer?

  • history of familial adenomatous polyposis (FAP)
  • Hashimoto's diagnosis
  • biologically female sex
  • All of the above

Diagnosis of follicular cancer can be made after FNA alone:

  • true
  • false
  • sometimes

Follicular carcinomas are commonly associated with which risk factor:

  • iodine deficiency
  • ionizing radiation
  • being biologically male

Medullary thyroid carcinoma  accounts for __ % of thyroid cancers.

  • 10
  • <2
  • <5
  • 10-15

What percent of papillary carcinoma's metastasize to the cervical lymph nodes?

  • 50
  • 20
  • 5
  • 85

Medullary thyroid carcinoma arises from what cells of the thyroid?

  • parafollicular cells
  • parathyroid cells
  • follicular cells
  • medullary cells

MEN-2a and 2b are associated with which type of thyroid carcinoma?

  • follicular
  • parafollicular
  • papillary
  • medullary

REVIEW (CLINICAL SKILLS/ANATOMY)

The physical exam

In this video, you can learn how to properly identify the thyroid gland and perform a physical exam. 

https://www.youtube.com/watch?v=lmEus_ZDipg

 

For thyroid neoplasms, it is important to assess the head and neck lymph nodes.

https://www.youtube.com/watch?v=SZkIq6P-0UQ

 

Can you label the diagram?

  • Isthmus
  • Thyroid lobe
  • cricothyroid ligament
  • cricoid cartilage

Continue to the Patient Cases

Now that you know your anatomy, continue to the patient cases.

 

CASE #1

JUDY BRIDGES

Meet Judy Bridges


Judy Bridges is a 35 year old female who has been referred to Dr. Angelo by Dr. Sunny Day. You can begin by reading her REFERRAL LETTER to see why she is here. 

REFERRAL LETTER

Dear Dr. Angelo,

I am referring Judy Bridges a 35 year old female dentist to you for further evaluation of a 2cm cold nodule in the right lobe of her thyroid. She presented to my office on January 1, 2018 with a painless enlargement of the right lobe of the thyroid gland. The history revealed thyroid malignancy risk factors including occupational radiation exposure. Upon physical exam, a palpable solid mass was located in the right lobe of the thyroid. A palpably enlarged cervical lymph node was also discovered on the right side during the physical exam. Upon further testing, she was found to be euthyroid and had a normal chest x-ray. Enclosed you will find the lab results, and copies of imaging.

Sincerely,

Dr. Sunny Day

IMAGING AND LABS

Thyroid scan: radioactive iodine (I-123 or I-131) 

AP - CXR

Thyroid function test 

The thyroid nodule is usually ________ in thyroid cancer.

  • cold
  • hot
  • radioactive

High risk clinical and radiographic features indicates the need for Fine Needle Aspiration (FNA) when the examined nodule is greater than or equal to:

  • An FNA is not indicated for solid nodules
  • 2cm
  • 1cm

NEXT STEPS

After reading the referral letter, Dr. Angelo performs an ultrasound guided fine needle aspiration. The results come back from the pathology lab "inconclusive."

Based on the pathologists initial findings, what do you expect to be found submitted to the pathology lab next?

  • total thyroidectomy with post-operative pathology evaluation
  • subtotal thyroidectomy with intra-operative pathology evolution
  • total thyroidectomy with zones 6&7 neck dissections
  • cervical lymph node removal with intra-operative pathology evaluation

SURGICAL PATHOLOGY FINDINGS

The following images were viewed under the microscope in the pathology lab. Can you see anything that might help to in determine which thyroid carcinoma may be implicated?

Review the images for the features you learned were diagnostic for papillary cancer from Robin's. Try to name the architecture and cytology that help to define the diagnosis.

In this view of the thyroid, you can see the following: (click all that apply)

  • Orphan Annie Nuclei
  • normal thyroid follicles
  • papillary architecture

Labelled architecture

Dr. K asks you if a diagnosis of papillary carcinoma can now be made. You reply:

  • yes, papillary cancer can now be made on the basis of nuclear features
  • no, although this looks like papillary cancer, a final diagnosis cannot be made unless an endocrinologist provides confirmation

Dr. K challenges you again because he realizes how much you want to learn. He asks you: "By what means does this cancer spread?"

  • By extra thyroidal extension to the lymph nodes and hematogenous distant metastases.
  • By extra thyroidal extension to the cervical lymph nodes
  • By extra thyroidal extension to the cervical lymph nodes and although rare, by distant lymphatic metastases.
  • By extra thyroidal extension to the inguinal lymph nodes and although rare, by distant lymphatic metastases.

PROGNOSIS AND THE AMES CRITERIA

Diagnosis After the pathologist confirms the diagnosis of papillary thyroid cancer with the surgeon, the patient is sent to recovery. When she wakes up, she is told the surgery went well, and the confirmed diagnosis of papillary cancer that has been surgically resected. She looks worried. The AMES had been used to risk stratify the patients prognosis. 

 

Low Risk High Risk

Age - Men ≤40 & Women ≤ 50 or older only involving thyroid.
Metasteses - none
Extra thyroidal extension - none (note risk does not change with 1 lymph node involved) 
Size - ≤5cm

Survival - 99%

Age - Men>40 & Women>50
Metasteses - distant metastases
Extra thyroidal extension - extra thyroid papillary (more than 1 lymph node)
Size -≥ 5cm

Survival - 61%


 

Based on the AMES criteria, what is the patients overall prognosis

  • 99% survival up to 10 years
  • 95% survival up to 5 years
  • 95% survival up to 10 years
  • 61% survival up to 10 years

TAKE A BREAK

CASE #2

MARY THOMAS

Meet Mary Thomas

Mary Thomas is another patient of Dr. Sunny Day's.  She is a 49 year old female who has been referred to an ENT surgeon who you are shadowing. You can begin by reading her REFERRAL LETTER to see why she is here. 


REFERRAL LETTER

Hi Dr. Angelo, 

I am referring Mary Thomas a 49 year old female to you for further evaluation of a cold nodule in the left lobe of her thyroid. She presented to my office on December 3, 2017 with a painless nodule of the right lobe of the thyroid gland. Mrs. Thomas noticed the nodule "some months ago," and believes it has enlarged somewhat. 

Upon physical exam, a palpable solid mass was located in the left lobe of the thyroid. Upon further testing, she was found to be thyroid antibody negative and euthyroid. A thyroid scan was performed and it showed a “Cold” nodule. 

Of note, Mrs. Thomas lived in Balrus for many of her adult years, where there is a moderate risk for iodine deficiency. 

Thank you for your further investigation,

Dr. Sunny Day

What do euthyroid and Anti-thyroid antibodies (ATA) negative test results mean for the patient?

  • the patient has Hashimoto's thyroiditis
  • the patient has Graves disease
  • the patient does not have hypothyroidism, hyperthyroidism or Hashimoto's thyroiditis.
  • the patient does not have graves disease but does have Hashimoto's thyroiditis

What does a cold nodule mean?

  • The nodule is more likely benign
  • The nodule is more likely malignant
  • The nodule is radioactive
  • The nodule is cystic

What is your DIFFERENTIAL DIAGNOSIS

A hint for coming up with a differential diagnosis is to think about malignant and non-malignant causes of a thyroid mass. Think about the risk factors, age, and test results available for Mary, and order them according to the MOST likely cause. 

INVESTIGATIONS & DIAGNOSIS

After determining that Mary will need further investigations, Dr. Angelo performs a fine needle aspiration (FNA).  The cytopathologist reported: Numerous follicular cells in keeping with follicular neoplasms. 

DIANGOSIS

  • The patient is diagnosed with follicular carcinoma and surgical resection of the thyroid gland is completed

INTRA-OPERATIVE SURGICAL PATHOLOGY REPORT

The pathologist did a frozen section and reported “follicular neoplasm.” No further surgery was done. The final pathology report was follicular carcinoma. Note that follicular cells individually look the same as the follicular cells of a normal thyroid. However in these sections you can see they are infiltrating the capsule (capsular invasion). The pathology images can be reviewed below.

Click anywhere along the capsule

Follicular carcinoma (malignant) can be difficult to differentiate from an adenoma (benign). Click all of the true statements below:

  • Minimally invasive carcinomas are indistinguishable
  • Both have hurthle cell variants, and are located within the follicular epithelium
  • Adenomas do not have capsular or vascular invasion
  • A sample of the capsule is required to distinguish follicular carcinoma from an adenoma

Papillary and follicular carcinomas are quite different in their features. Compare the two by matching the following terms:

  • Frequency of follicular carcinoma
    less common
  • Follicular Carcinoma
    associated with iodine deficiency

RECOVERY

While you were learning about the relevant follicular carcinoma features, Mary was sent to recovery.  Upon waking up, she was informed that she had confirmed follicular carcinoma that was surgically resected. She was told that her prognosis was excellent. Dr. Angelo would like you to create a patient information sheet that explains some of the possible problems associated with the surgery. 

Click all of the items you would like to include on the list of possible problems arising from thyroid surgery.

  • airway compromise from bilateral nerve injuries
  • hypothyroidism
  • hypoparathyroidism
  • stridor
  • recurrent laryngeal nerve damage
  • hyperparathyroidism

Summary

Here is a chart that summarizes some key differences between follicular and papillary carcinoma

FEATURE  FOLLICULAR   PAPILLARY
FREQUENCY 

Less common
(5-15%)

Most common in women (age 40-60)

Most common (85%)

Most common in women (age 25-50)

PREDISPOSING RISK FACTORS iodine deficiency ionizing radiation

FEATURES

  • Solitary cold nodule
  • Capsular invasion
  • Uniform cells with small follicles 
  • Ground glass nuclei 

  • Pseudo-inclusions

  • Psammoma bodies 
USUAL ROUTE OF SPREAD

Haematogenous 

Local lymph nodes  & Lymphatics 
PROGNOSIS AND FACTORS WHICH INFLUENCE IT

10 year survival 95%

AMES classification of prognostic factors 

Staging is important for survival rates

  • I - 100% 
  • II - 100% 
  • III - 79%
  • IV - 47%

Overall 10 year survival 95% but worse prognosis with high risk AMES criteria:

  • Older than 40
  • Cancer that has spread to distant parts of the body
  • Cancer that has spread to soft tissue
  • Large tumor(> 5cm)

TAKE A BREAK

CASE #3

HASAN NISSAR

Meet Hassan Nissar

Hassan is a 53 year old male referred to Dr. Endono by Dr. Sunny Day. You can begin by reading his REFERRAL LETTER to see why he is here. 

REFERRAL LETTER

Dear Dr. Endono,

I am referring Hassan Nissar a 53 year old retired male  to you for further evaluation of a painless mass of the right side of his neck. He was euthyroid and thyroid scan showed a cold nodule. When the neck was explored an infiltrated firm pale mass occupied the right lobe of the thyroid with extension into the left lobe

Sincerely,

Dr. Sunny Day

DIANGOSIS and TREATMENT

After ordering and reviewing of a number of lab tests, Mr. Nissar was diagnosed with sporadic medullary thyroid carcinoma. A total thyroidectomy was performed and followed with thyroid hormone therapy. He is now being followed by Dr. Endono. 

So what exactly is Medullary Thyroid Carcinoma?

Normal Thyroid Histology (above)

Medullary thyroid carcinoma (MTC) is a neuroendocrine neoplasm that arises from the C-cells of the thyroid and secretes calcitonin.  The tumor cells may secrete somatostatin, serotonin, and vasoactive intestinal peptide (VIP).

70% of MTC cases are sporadic and 30% are familial (caused by MEN2A/B mutations). RET proto-oncogene mutations are seen in approximately 50% of sporadic and close to 100% of familial cases). 

Histopathological differences can be seen in familial cases. Multi-centric C-cell hyperplasia in the surrounding thyroid parenchyma is seen in MEN2A/B associated MTC

Below is a list of defining features for each sporadic and MEN associated MTC:

  Sporadic MEN associated
Multi-focality and precursor lesions

70%

RET mutations

Foci of C cells

30% 

RET mutations

Foci of C-cells

Multicentricity

multi centric c-cell hyperplasia

age of presentation 50-60 years old younger including children
Setting of presentations Sporadic  Coexists in people with Parathyroid and adrenal (phenochromocytosis = medulla) cancer comorbidities + mucous membrane involvement

 

 

The following images will be displayed during the thyroid tutorial (Small group session).

The slides referenced below can be found here:  http://www.med.mun.ca/pathimgdb/imagedatabase/endocrinepath/index.html

K E 21 Gross picture of cut surfaces of papillary carcinoma of thyroid, Cystic areas are present and small projection can be discerned projecting into the cystic cavity.

 

K E 22 Microscopic features of papillary carcinoma. Slide X shows Psammoma bodies

K E 23 Calcospherites. They can also be seen in other tumours such as serous cysts

 

K E 24 adenoma and carcinoma of ovary, renal cell carcinoma and in meningiomas – Slide Y shows metatstatic papillary carcinoma of thyroid in a lymph node. Note the pale nucleus of the tumour similar to “Orphan Annie’s EYE”

K E 25 – both slides show follicular carcinomas of thyoid gland. Follicular pattern is well illustrated in other slides and another slide shows capsular invasion.

 

K E 27 Medullary carcinoma of thyroid. Note fibrous tissue

K E 28 Dividing the tumor tissue into small compartments. Tumour cells are fairly uniform.

 

K E 29 No follicles amorphous pale pink masses of amyloid in the stroma. Amyloid can be stained by Congo Red, Thioflavin or identified by EM. Medullary carcinomas arise from para-follicular C-cells which originate from neural crest. Medullary carcinoma does not take up iodine. Another special stain shown that demonstrates the calcitonin in medullary carcinoma by munoperoxidase method

 

What lab tests would have been helped Dr. Endono to make the diagnosis?

  • Calcitonin
  • 5-HT
  • VIP
  • Genetic Testing for RET or MEN2 mutations

PATHOLOGY: Here are the labelled images obtained from the pathology lab. Review the imaging and take note of the pathologic features that are characteristic of meduallary carcinoma.

Dr. Endono asks you what you would NOT be concerned about if a biologically female patient presented at age 25 with confirmed MTC. You answer:

  • MEN-2 mutations are more common in younger patients
  • The patient is of childbearing age, she could pass this mutation on
  • The patient has a 50% chance of developing or having co-exisiting pheochromocytoma
  • The patient is at risk of developing a pituitary adenoma

What is the prognosis of this tumour?

  • 5-year survival 70-80%
  • 10-year survival 70-80%
  • 10-year survival 30-50%

You have completed the module!

Congratulations you have completed the module. This should have helped to prepare you for the upcoming tutorial session.