1. Thyroid Malignancy

2. 36 y/o from Pampanga
Admitted with anterior neck mass

3. 39 y/o female from Bicol
C/C: anterior neck mass

4. HPI 7 yrs PTA Noted an enlarging left anterior neck mass 1 yr PTA
Experienced easy fatigability, palpitations and weight loss
Consulted with a physician and was prescribed with medications that relieved her symptoms
The mass continued to increase in size, prompting admission

5. HPI 10 yrs PTC History of slow growing nodular anterior neck mass
No other accompanying symptoms
2 yrs PTC
Rapid increase in size of mass
6 mo PTC
Hoarseness and difficulty swallowing

6. ROS No fever, weight loss and tremors
No chest pain and easy fatigability
No abdominal pain
Past medical and family history both unremarkable

7. Physical Examination PR = 100/min RR = 20/min Temperature = 37 °C
No exophthalmos
Neck:
12x10 cm multilobulated firm mass on the left neck, moves with deglutition

8. Clinical Impression:
Thyroid malignancy

9. What is your clinical impression? What are the differential diagnosis?

10. Differential Diagnoses
Patient
Thyroid Carcinoma
Toxic Multinodular Goiter
Rapid increase in size of the mass  
Hoarseness and difficulty in swallowing
Weight loss
Tremors
Exophthalmos
Easy Fatigability
Palpable cervical lymphadenopathy

12. Thyroid cancer Most common malignancy of the endocrine system
Accounts for less than 1% of all malignancies
Common among chinese males & filipino females

13. Risk factors for thyroid carcinoma in patients with thyroid nodule
History of head & neck irradiation
Age <20 or > 70 y/o
Increased nodule size (>4cm)
New or enlarging neck mass
Male gender

14. Family history of thyroid cancer or MEN 2
Vocal cord paralysis, hoarse voice
Nodule fixed to adjacent structures
Suspected lymph node involvement
Iodine deficiency (follicular)

15. Clinical features: Lump in the neck Gradually enlarging mass
Firm or hard
Rapidly growing: soft or fluctuant
May be painful
May present with hoarseness, dysphagia, dysphonia, dyspnea
Rare: hyperthyroidism

16. Papillary Carcinoma 80-85%
Predominant: children & individuals exposed to external radiation
2:1 F:M ratio
Mean age: y/o
S/Sx: slow growing painless mass
Dysphagia, dyspnea, dsyphonia
Lymph nodes metastases (common)
Distal mets uncommon (lungs, bone, liver, brain)

17. Characteristic cellular patterns: Orphan Annie nuclei
Psamomma bodies
Multifocality (85%)
Prognosis: excellent (95% 10 yr survival rate)

18. Diagnosis
discovered when a hard nodule is found in multinodular goiter
when enlarged cervical lymph nodes are detected
when there are unidentified metastatic lesions elsewhere in the body
Other clinical signs that could indicate papillary thyroid are:
fixation to the trachea, stony hardness, damage to recurrent laryngeal or cervical sympathetic nerves.

19. Follicular Carcinoma Second most common (10%) Iodine deficient areas
3:1 F:M ratio
Mean age: 50 y/o
Usually solitary (rapid size increase & goiter)
s/sx: pain & cervical lymphadenopathy uncommon initial presentation

20. 1%: hyperfunctioning - thyrotoxicosis
Solitary & encapsulated
Prognosis: mortality 15% at 10 yrs, 30% at 20 yrs

21. Hurthle Cell CA 3-5% Variant of follicular CA
Vascular or capsular invasion
Multifocal & bilateral
Metastasize to local & distant sites
Higher mortality rate

22. Medullary CA 5% From parafollicular or C cells 1.5:1 F:M ratio
Mean age: y/o
70-80% are sporadic
20-30% familial autosomal dominant syndromes

23. s/sx:neck mass w/ cervical lymphadenopathy
- local pain
- dysphagia, dyspnea or dysphonia
2-4%: Cushing’s syndrome
Unilateral (sporadic); multicentric (familial)
Presence of amyloid
Prognosis: related to disease stage

24. Anaplastic CA 1% F>M Mean age: 65 y/o
s/sx: rapidly enlarging, long standing neck mass, painful
- dysphonia, dysphagia, dyspnea
Tumor: large, hard, poorly circumscribed & fixed

25. Palpable lymph nodes
Metastatic spread
Prognosis: one of the most aggressive, few survive beyond 6 months

26. Lymphoma <1% Most: Non-Hodgkin’s B-cell type 2-3xF>M Age: 62 y/o
Patients with chronic lymphocytic thyroiditis
Prognosis: overall 5 yr survival rate: 50%

27. 2. What work ups are needed, if any?

28. Evaluation of a Thyroid Nodule
History
Risk factors for thyroid cancer
History of thyroid irradiation, especially in infancy or childhood
Age < 20 yr
Male sex
Family history of thyroid cancer or multiple endocrine neoplasia
A solitary nodule
Dysphagia
Dysphonia
Increasing size (particularly rapid growth or growth while receiving thyroid suppression treatment)
Physical Examination
Signs that suggest thyroid cancer
stony hard consistency or fixation to surrounding structures
cervical lymphadenopathy
hoarseness due to recurrent laryngeal nerve paralysis

29. Testing

30. Testing Fine-Needle Aspiration Biopsy (FNAB)
Cornerstone in the evaluation of solitary thyroid nodules and also dominant nodules within multinodular goiters
Currently considered to be the best first-line diagnostic procedure in the evaluation of the thyroid nodule

31. Fine-Needle Aspiration Biopsy
Advantages:
Safe
Cost-effective
Minimally invasive
Leads to better selection of patients for surgery than any other test (Rojeski, 1985)
Halved the number of patients requiring thyroidectomy (Mazzaferri, 1993)
Double the yield of cancer in those who do undergo thyroidectomy (Mazzaferri, 1993)

32. Fine-Needle Aspiration Biopsy
Four Categories of Cytologic Diagnosis
Benign (Negative) – 69%
Suspicious (Indeterminate) – 10%
Malignant (Positive) – 4%
Unsatisfactory (Nondiagnostic) – 17%
Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

33. Benign Cytology
Aspirates obtained from multinodular goiters, benign microfollicular adenoma, or normal thyroid are referred to as “colloid nodules” and show loosely cohesive sheaths of follicular epithelium, colloid, blood, and rare macrophages
Colloid nodules are the most common cytology and contain an abundance of colloid with sparse follicular cells
There is considerable variation in the number of cells as well as the type and amount of colloid present

34. Benign Cytology Hashimoto’s Thyroiditis
It has a fairly characteristic pattern on FNA smears, showing hypercellularity with lymphocytes, Hürthle cells, and minimal or no colloid
Subacute(granulomatous) Thyroiditis
Smear shows multinucleated giant cells, epithelioid histiocytes, and scattered inflammatory cells
Group of Hürthle cells, with large cytoplasm and prominent nuclei, surrounded by a teratogeneous population of lymphocytes
Hypercellular aspirate with lymphocytes and Hürthle cells
Large multinucleated giant cells in a mixed inflammatory background. Absence of colloid is noticeable.
Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

35. Malignant Cytology Papillary carcinoma Medullary thyroid carcinoma
the most common thyroid malignancy
readily diagnosed by FNAB
Typically, cytology shows a papillary configuration, large irregular nuclei, and nuclear grooves.
Psammoma bodies may or may not be present, but if present, they are highly suggestive of papillary thyroid carcinoma
Medullary thyroid carcinoma
accounts for 5% to 10% of thyroid cancers and may present as a thyroid nodule or neck mass
Typically, aspirates from a medullary thyroid carcinoma are hypercellular, composed of large, poorly cohesive cells, and are predominantly spindle‑shaped.
Amyloid is often, but not invariably, present, and there is no colloid
High-grade carcinoma
Can be diagnosed cytologically, but distinguishing between primary and metastatic cancer is not easy
Follicular cells with large irregular nuclei, nuclear grooving, and pale chromatin.
Histologic preparation showing typical papillary configurations.
Cellular specimen staining positively for calcitonin with immunoperoxidase
Loosely cohesive fragments of spindle-shaped cells. Amyloid is present as amorphous blue material intimately associated with neoplastic cells.
Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

36. Suspicious Cytology
Cytologic features neither confirm nor rule out malignancy
Hypercellular specimens from follicular or Hürthle cell lesions may have features suggestive of, but not diagnostic for, malignancy
Histologic examination is necessary for definitive diagnosis
Hypercellularity may be seen with nonneoplastic lesions, and Hürthle cell changes may be seen in patients with lymphocytic thyroiditis.
The diagnosis of follicular neoplasm is indicative of an underlying malignancy in 14% of cases and Hürthle cell neoplasm in 15%.
Many pathologists maintain that benign and malignant follicular or Hürthle cell tumors cannot be distinguished on the basis of aspirated cells only and the lesion must be removed for histopathologic examination.
However, follicular adenomas and follicular carcinomas usually can be differentiated on the basis of nuclear size but Hürthle cell lesions are difficult to diagnose cytologically (Kini, 1993).
Cytology shows hypercellularity, dispersed microfollicular pattern, and absent colloid.
Thyroidectomy showed benign follicular adenoma
Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

37. Nondiagnostic Cytology
Factors that influence nondiagnostic rates for FNAB results:
skill of the operator
vascularity of the nodule
criteria used to judge adequacy of the specimen
cystic component of the nodule
Overall, a satisfactory smear contains at least 6 clusters of well‑preserved cells, with each group consisting of at least 10 to 15 cells.
Reaspiration yields satisfactory specimens in at least 50% of cases that are considered nondiagnostic on initial FNA

38. Fine-Needle Aspiration Biopsy
Limitations
Skill of the aspirator
Expertise of the cytologist
Difficulty in distinguishing some benign cellular adenomas from their malignant counterparts (follicular and Hurthle cell)
Sensitivity: 65 – 98% (avg. 83%)
Specificity: 72 – 100% (avg. 92%)
Positive Predictive Value: 50 – 96% (avg. 75%)
False-negative Rates: 1.5 – 11.5% (avg. < 5%)
False-positive Rates: 0 – 8% (avg. 3%)
Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

39. CT/MRI

40. AMES Low risk: High risk:
Younger patients (men =/< 40, women =/< 50) with no metastases
Older patients (intrathyroid papillary, minor capsular invasion for follicular lesions)
Primary cancers <5 cm
No distant metastases
High risk:
All patients with distant metastases
Extrathyroid papillary, major capsular invasion follicular
Primary cancers >/= 5 cm in older patients (men >40, women >50)
Survival by AMES risk-groups (20-yr):
   Low risk = 99%
   High risk = 61%

41. MAICS

42. AMES

43. Surgical Treatment: Papillary CA
High risk or bilateral tumors: Total or near - total thyroidectomy Minimal Papillary Thyroid Tumor Unilateral lobectomy and isthmusectomy

44. Total Thyroidectomy Unilateral Lobectomy Lower complication rate
Enables the use of RAI for detecting and treating residual thyroid tissue and metastatic disease.
Makes serum Tg level a more sensitive marker of recurrent or persistent disease
Eliminates contralateral occult cancer as sites of recurrence
Reduces risk of recurrence
Increases survival
Decreases 1% risk of progression to ATC
Reduces need for reoperative surgery
Lower complication rate
Recurrence is unusual (5%)
Excellent prognosis

45. Why Thyroidectomy?
Recurrence rates are lowered and survival is improved when a patient underwent thyroidectomy
Diminished survival was noted in patients with low-risk disease

46. Total Thyroidectomy
Enables the use of RAI for detecting and treating residual thyroid tissue and metastatic disease.
Makes serum Tg level a more sensitive marker of recurrent or persistent disease
Eliminates contralateral occult cancer as sites of recurrence
Reduces risk of recurrence
Increases survival
Decreases 1% risk of progression to ATC
Reduces need for reoperative surgery

47. Rationale for total thyroidectomy
1) 30%-87.5% of papillary carcinomas involve opposite lobe (Hirabayashi, 1961, Russell, 1983)
2) 7%-10% develop recurrence in the contralateral lobe (Soh, 1996)
3) Lower recurrence rates, some studies show increased survival (Mazzaferri, 1991)
4) Facilitates earlier detection and tx for recurrent or metastatic carcinoma with RAI (Soh, 1996)
5) Residual WDTC has the potential to dedifferentiate to ATC

48. Indications for total thyroidectomy
1) Patients older than 40 years with papillary or follicular carcinoma
2) Anyone with a thyroid nodule with a history of irradiation
3) Patients with bilateral disease

49. Rationale for subtotal thyroidectomy
1) Lower incidence of complications
Hypoparathyroidism (1%-29%) (Schroder, 1993)
Recurrent laryngeal nerve injury (1%-2%) (Schroder, 1993)
Superior laryngeal nerve injury
2) Long term prognosis is not improved by total thyroidectomy (Grant, 1988)

50. Complications Injury to RLN, Superior Laryngeal Nerve
Transient hypocalcemia (50%)
Permanent hypoparathyroidism (<2%)
Postoperative hematoma
Bilateral vocal cord dysfunction

51. Postoperative Management of Differentiated Thyroid Cancer
Thyroid Hormone
After thyroidectomy, should placed on thyroxine to ensure that the patient remains euthyroid
serves as a replacement therapy and also suppresses TSH
reduces growth stimulus to possible residual cancer cells
reduces recurrence rates (papillary ca)
risk of tumor recurrence must be balanced with the side effects associated with prolonged TSH suppression, including osteopenia and cardiac problems, particularly in older patients
After thyroidectomy, should placed on thyroxine to ensure that the patient remains euthyroid
serves as a replacement therapy and also suppresses TSH
reduces growth stimulus to possible residual cancer cells
reduces recurrence rates (papillary ca)
risk of tumor recurrence must be balanced with the side effects associated with prolonged TSH suppression, including osteopenia and cardiac problems, particularly in older patients

52. Postoperative Management of Differentiated Thyroid Cancer
Thyroglobulin Measurement
levels in patients who have undergone total thyroidectomy should be below 2 ng/mL when the patient is taking T4, and below 5 ng/mL when the patient is hypothyroid
level above 5ng/mL is highly suggestive of metastatic disease or persistent normal thyroid tissue. In this situation, radioiodine scan should be performed.
Measure serum levels every 6 months, and then annually if the patient is clinically disease free
Level >30 ng/ml is abnormal
High-risk patients should also have an ultrasound of the neck and CT or MRI scan of the neck and mediastinum for early detection of any persistent or recurrent disease.
Thyroglobulin levels in patients who have undergone total thyroidectomy should be below 2 ng/mL when the patient is taking thyroxine, and below 5ng/ml when the patient is not taking thyroxine. A thyroglobulin level above 5ng/mL is highly suggestive of metastatic disease or persistent normal thyroid tissue, especially if it increases when TSH levels increase when thyroid hormone treatment is discontinued in preparation for radioiodine scanning. In this situation, radioiodine scan should be performed.
Postoperative therapy/follow-up
Thyroglobulin (TG) (Gluckman)
measure serum levels every 6 months
Level >30 ng/ml are abnormal
Thyroid hormone suppression (control TSH dependent cancer) (Goldman, 1996)
should be done in - 1) all total thyroidectomy patients
2) all patients who have had radioactive ablation of any remaining thyroid tissue

53. Postoperative Management of Differentiated Thyroid Cancer
Radioiodine Therapy
I-131 whole body scan to detect residual normal thyroid tissue &/or metastatic disease
Metastatic differentiated thyroid carcinoma can be detected and treated by radioactive iodine in about 75 % of patients.
Administration
Scan at 4-6 weeks postoperatively
repeat scan at 6-12 months after ablation
repeat scan at 1 year then...
every 2 years thereafter
External Beam Radiotherapy and Chemotherapy
External beam radiotherapy is required occasionally to control unresectable locally invasive or recurrent disease
It also is of value for the treatment and control of pain from bony metastases when there is no appreciable radioiodine uptake.
I-131 whole body scan to detect residual normal thyroid tissue &/or metastatic disease
I-131 for ablation of residual normal thyroid tissue &/or metastasis

54. Surgery for Papillary Thyroid Carcinoma: Is Lobectomy Enough?
Mendelsohn AH, Elashoff DA, Abemayor E, St John MA.
Division of Head and Neck Surgery, Department of Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Le Conte Ave, Center for Health Sciences, Los Angeles, CA
OBJECTIVE: To further understanding of treatment of papillary thyroid carcinoma (PTC).
DESIGN: The Surveillance, Epidemiology, and End Results Program database was searched for patients who had undergone surgery for PTC.
SETTING: Areas covered by Surveillance, Epidemiology, and End Results population-based registries.
PATIENTS: Patients who had undergone PTC surgery between January 1, 1988, and December 31, 2001, were included in the study.
MAIN OUTCOME MEASURES: Disease-specific survival (DSS) and overall survival (OS).
Surgery for Papillary Thyroid Carcinoma: Is Lobectomy Enough?
Mendelsohn AH, Elashoff DA, Abemayor E, St John MA.
Division of Head and Neck Surgery, Department of Surgery, David Geffen School of
Medicine at the University of California, Los Angeles, Le Conte Ave,
Center for Health Sciences, Los Angeles, CA
OBJECTIVE: To further understanding of treatment of papillary thyroid carcinoma (PTC).
DESIGN: The Surveillance, Epidemiology, and End Results Program database was searched for patients who had undergone surgery for PTC.
SETTING: Areas covered by Surveillance, Epidemiology, and End Results population-based registries.
PATIENTS: Patients who had undergone PTC surgery between January 1, 1988, and December 31, 2001, were included in the study. MAIN OUTCOME
MEASURES: Disease-specific survival (DSS) and overall survival (OS). RESULTS: Of the total
22,724 patients with PTC, 5964 patients underwent lobectomy. There were 2138
total and 471 disease-specific deaths. Controlling for tumor size, multivariate
analysis revealed no survival difference between patients who had undergone total
thyroidectomy and those who had undergone lobectomy. Increased tumor size,
extrathyroidal extent, positive nodal status, and increased age displayed
significantly worse DSS and OS (P < .001). Histologically, follicular PTC subtype
did not affect DSS or OS. Patients who had received radioactive iodine had poorer
DSS but improved OS. Patients undergoing external beam radiation therapy had poor
DSS (hazard ratio, 4.48; 95% confidence interval, ; P < .001) and OS
(1.71; ; P < .001). CONCLUSIONS: The results of this study compel us to
reinvestigate the current PTC surgical recommendations of total thyroidectomy
based on tumor size because this may not affect survival across all populations.
In addition, the current use of external beam radiation therapy for the treatment
of PTC should be reexamined.

55. Surgery for Papillary Thyroid Carcinoma: Is Lobectomy Enough?
RESULTS:
Of the total 22 724 patients with PTC, 5964 patients underwent lobectomy. There were 2138 total and 471 disease-specific deaths.
Controlling for tumor size, multivariate analysis revealed no survival difference between patients who had undergone total thyroidectomy and those who had undergone lobectomy. Increased tumor size, extrathyroidal extent, positive nodal status, and increased age displayed significantly worse DSS and OS (P < .001).
Histologically, follicular PTC subtype did not affect DSS or OS.
Patients who had received radioactive iodine had poorer DSS but improved OS.
Patients undergoing external beam radiation therapy had poor DSS (hazard ratio, 4.48; 95% confidence interval, ; P < .001) and OS (1.71; ; P < .001).
CONCLUSIONS:
The results of this study compel us to reinvestigate the current PTC surgical recommendations of total thyroidectomy based on tumor size because this may not affect survival across all populations. In addition, the current use of external beam radiation therapy for the treatment of PTC should be reexamined.
Surgery for Papillary Thyroid Carcinoma: Is Lobectomy Enough?
Mendelsohn AH, Elashoff DA, Abemayor E, St John MA.
Division of Head and Neck Surgery, Department of Surgery, David Geffen School of
Medicine at the University of California, Los Angeles, Le Conte Ave,
Center for Health Sciences, Los Angeles, CA
OBJECTIVE: To further understanding of treatment of papillary thyroid carcinoma (PTC).
DESIGN: The Surveillance, Epidemiology, and End Results Program database was searched for patients who had undergone surgery for PTC.
SETTING: Areas covered by Surveillance, Epidemiology, and End Results population-based registries.
PATIENTS: Patients who had undergone PTC surgery between January 1, 1988, and December 31, 2001, were included in the study. MAIN OUTCOME
MEASURES: Disease-specific survival (DSS) and overall survival (OS). RESULTS: Of the total
22,724 patients with PTC, 5964 patients underwent lobectomy. There were 2138
total and 471 disease-specific deaths. Controlling for tumor size, multivariate
analysis revealed no survival difference between patients who had undergone total
thyroidectomy and those who had undergone lobectomy. Increased tumor size,
extrathyroidal extent, positive nodal status, and increased age displayed
significantly worse DSS and OS (P < .001). Histologically, follicular PTC subtype
did not affect DSS or OS. Patients who had received radioactive iodine had poorer
DSS but improved OS. Patients undergoing external beam radiation therapy had poor
DSS (hazard ratio, 4.48; 95% confidence interval, ; P < .001) and OS
(1.71; ; P < .001). CONCLUSIONS: The results of this study compel us to
reinvestigate the current PTC surgical recommendations of total thyroidectomy
based on tumor size because this may not affect survival across all populations.
In addition, the current use of external beam radiation therapy for the treatment
of PTC should be reexamined.