Board Review Questions
Last revised 1 October 2018
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Question 1
Histological features of nodular goiter include all of the following except:

  1. Cysts, hemorrhage, granulomatous response, fibrosis, calcification or osseous metaplasia
  2. Nodules with distinct thick capsule
  3. Papillary projections of the epithelium
  4. Variable sized follicles with flattened hyperplastic epithelium
Answer 1
B. Nodules may or may not be present in nodular goiter but generally lack a thick capsule. Prominent features are variable sized dilated follicles with flattened hyperplastic epithelium. Secondary changes include foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia. Some of the cystically dilated follicles may show papillary projections (Sanderson polsters). Cytologic atypia in the form of highly atypical nuclei occurs in patients exposed to radioactive substances.
Question 2
Which statement is False for metastatic clear cell renal cell carcinoma to the thyroid?

  1. Metastasis from renal cell carcinoma is generally a solitary mass.
  2. Metastatic clear cell renal cell carcinoma can have a very long latency after nephrectomy.
  3. Metastatic clear cell renal cell carcinoma can have a spurious thyroglobulin stain.
  4. TTF1 and PAX8 can be used to differentiate tumors of renal and thyroid origins.
  5. Metastatic tumor to the thyroid gland is the initial manifestation of renal cell carcinoma in 1/3 of cases.
Answer 2
D. TTF1 and PAX8 can be used to differentiate renal and thyroid origins.

Explanation: tumors from both thyroid and kidney can be positive for PAX8.
Question 3
Which of the following statements is true?

A. Metastases to the thyroid are a common finding.
B. Most patients with thyroid metastases have no known primary.
C. Melanoma is a common primary that metastasizes to the thyroid.
D. PAX8 may be positive in both thyroid and renal tumors.
Answer 3
D. PAX8 may be positive in both thyroid and kidney tumors.
Question 4
    Which item is correct regarding sclerosing mucoepidermoid carcinoma with eosinophilia:

    A. Sclerosing mucoepidermoid carcinoma with eosinophilia is not associated with Hashimoto thyroiditis
    B. Lymph nodes metastases, extracapsular spread, vascular invasion and perineural invasion are common
    C. Death due to sclerosing mucoepidermoid carcinoma with eosinophilia is common
    D. Eosinophil infiltration is common, and no keratin pearls and keratin debris are seen
    E. The squamous component is highly malignant
Answer 4
    B. Lymph nodes metastases, extracapsular spread, vascular invasion and perineural invasion are common.

    Death due to disease is uncommon, although lymph nodes metastases, extracapsular spread, vascular invasion and perineural invasion are common.
Question 5
Which of the following features are not required for the diagnosis of poorly differentiated thyroid carcinoma

  1. Absence of conventional nuclear features of papillary thyroid carcinoma
  2. Necrosis / convoluted nuclei / increased mitotic activity
  3. Solid, trabecular or insular growth
  4. Vascular invasion
Answer 5
D. Vascular invasion.

The Turin criteria specify solid / trabecular / insular growth, lack of conventional nuclear features of papillary thyroid carcinoma and one of the following: necrosis, convoluted nuclei or increased mitotic activity (3 or more mitoses/10 HPF). Vascular invasion may be seen in a variety of thyroid carcinomas and is an adverse prognostic factor regardless of histologic subtype or grade.
Question 6
Which antibody is most useful for diagnosing struma ovarii?

A. PAX8
B. Thyroglobulin
C. Calcitonin
D. GATA-3
E. CEA
Answer 6
B. Thyroglobulin
Thyroid follicular cells are positive for thyroglobulin, TTF1 and PAX8. However, ovarian epithelium also shows immunopositivity for PAX8. Therefore, thyroglobulin and TTF1 antibodies are useful for the diagnosis of struma ovarii.
Question 7
Which statement is not true for oncocytic carcinoma?

  1. More aggressive compared to conventional follicular carcinoma
  2. More resistant to radioactive iodine compared to conventional follicular carcinoma
  3. Not only metastases to bone or lung; can also spread to lymph node
  4. Oncocytic appearance is due to accumulation of dysfunctional mitochondria
  5. Risk factors include iodine deficiency and irradiation exposure
Answer 7
E. Risk factors include iodine deficiency and irradiation exposure. There are no known exogenous risk factors for developing oncocytic tumors.
Question 8
Which thyroid FNA cytologic appearance is classified as nondiagnostic / unsatisfactory?

  1. ≥ 6 groups of well visualized follicular cells
  2. Abundant thick colloid
  3. A few cells with cytological atypia
  4. Foamy histiocytes only
  5. Numerous inflammatory cells
Answer 8
D. Foamy histiocytes only

When the aspirated material contains only foamy histiocytes and no follicular epithelium or colloid, it is qualified as nondiagnostic / unsatisfactory. However, in some local reporting systems (e.g. Japanese), these cases are reported as "adequate, cyst fluid only" because their malignancy risk is almost the same as the benign category and lower than the nondiagnostic / unsatisfactory category.

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Question 9
    Which of the following mutations is most commonly associated with NIFTP?

  1. BRAF V600E
  2. PAX8 / PPAR gamma rearrangement
  3. PIK3CA
  4. RAS family
  5. TERT promoter
Answer 9
D. RAS family

NIFTP shares molecular alterations similar to those seen in follicular lesions (follicular adenoma and follicular carcinoma).
Question 10
    Which of the following features differentiates a PTC from a NIFTP?

  1. Follicular growth pattern
  2. Nuclear elongation
  3. Nuclear grooves
  4. Thick colloid
  5. True papillae
Answer 10
E. True papillae

The presence of any true papillae is an exclusion criteria for making a diagnosis of NIFTP. Other exclusion criteria include capsular invasion, increased mitotic rate and tumor necrosis.
Question 11
Which statement is not true for mucoepidermoid carcinoma of thyroid?

  1. Comedo necrosis and psammoma bodies may be seen
  2. Foci of associated papillary thyroid carcinoma are often seen
  3. Lymph nodes metastases, extrathyroidal invasion are common
  4. Mucoepidermoid carcinoma of thyroid is associated with lymphocytic thyroiditis
  5. Similar to sclerosing mucoepidermoid carcinoma with eosinophilia, it cannot have t (11;19) - CRTC1 / MAML2 rearrangement
Answer 11
E. Similar to sclerosing mucoepidermoid carcinoma with eosinophilia, it cannot have t (11;19) - CRTC1 / MAML2 rearrangement

Mucoepidermoid carcinoma can have t (11;19) - CRTC1 / MAML2 rearrangement.
Question 12
Which statement is not true for medullary thyroid carcinoma (MTC)?

  1. Majority of MTC have translocation involving RET proto-oncogene
  2. MTC can be monitored for recurrence with serum CEA levels
  3. MTC has a wide variety of morphology, can mimic any other thyroid malignancies
  4. MTC is most commonly found at the junction of the upper and mid portions of the thyroid lobes
  5. MTC is positive for TTF1, synaptophysin and chromogranin
Answer 12
A. Majority of medullary thyroid carcinoma (MTC) have translocation involving RET proto-oncogene is false. The majority of MTC have gain of function mutations in RET gene. MYH13-RET fusion can be found in rare RET / RAS negative MTC. RET-PTC rearrangement is found in papillary thyroid carcinoma.
Question 13
Which statement is incorrect about hobnail PTC?

A. Rare variant of papillary thyroid carcinoma
B. Relatively aggressive clinical behavior
C. Microscopically characterized by hobnail cells and micropapillary pattern
D. Common BRAF V600E , TP53 and TERT promoter mutations
E. High mortality
Answer 13
E. High mortality

Hobnail papillary thyroid carcinoma is an unusual and aggressive variant of PTC characterized by predominance of cells with a hobnail appearance often arranged in micropapillary pattern. Despite multiple mutations and frequent nodal (up 75%) and distant (up to 40%) metastases, mortality is relatively low – disease specific survival rates are 80+% and 70+% at 5 and 10 years after surgery
Question 14
What proportion of a hobnail-micropapillary pattern in the tumor is required for a diagnosis of PTC hobnail variant

A. 5%
B. 10%
C. 25%
D. 30%
E. 50%
Answer 14
D. 30%

The presence of at least 30% of cells with hobnail-micropapillary features is mandatory to diagnose a tumor as PTC hobnail variant. Nevertheless, a minor hobnail-micropapillary pattern (5% - 30%) has prognostic significance and should be noted in the pathology report.
Question 15
What category of the Bethesda System of Reporting Thyroid Cytopathology corresponds best to FNA smears of hobnail PTC with comet-like cells?

A. I (non-diagnostic)
B. III (AUS/FLUS)
C. IV (FN/SFN)
D. V (suspicious for malignancy)
E. VI (malignant)
Answer 15
E. VI (malignant)

Cases with diagnostic hobnail cells are easily placed into the Bethesda VI category
Question 16
    All of the following statements are true about Graves disease except:

  1. Graves disease is caused by anti-TPO autoantibodies
  2. It is associated with HLA-DR
  3. It is caused due to anti-thyrotropin antibodies
  4. Most commonly affects middle aged women
Answer 16
A. Graves disease may be associated with anti-TPO anti-bodies but it is caused by anti-thyrotropin / TSH receptor auto-antibody that mimic TSH and stimulate hormone synthesis, secretion and thyroid growth. Most commonly affects middle aged women with female to male ratio of 4:1. It is associated with HLA class II molecule HLA-DR (HLA-DRB1*08 and DRB3*0202).
Question 17
    Which statement for thyroid follicular carcinoma is FALSE?

  1. Cannot have necrosis or increased mitotic figures (≥ 3/10 HPF)
  2. Commonly metastases to bone, lung, not lymph node
  3. Detecting RAS mutations and PPAX8-PPAR gamma rearrangements can be used to distinguish follicular carcinoma from adenoma
  4. Nuclear atypia does not indicate malignancy
  5. Risk factors include iodine deficiency and irradiation exposure
Answer 17
C. Detecting RAS mutations and PAX8-PPAR gamma rearrangements can be used to distinguish follicular carcinoma from adenoma. RAS mutations and PAX8-PPAR gamma rearrangements can be found in follicular adenoma.
Question 18
    Which histopathologic feature is not mandatory to report according to the CAP thyroid protocol?

  1. Extranodal extension
  2. Histologic type
  3. Lymphatic invasion
  4. Perineural invasion
  5. Tumor focality
Answer 18
D. Perineural invasion is an optional feature to report, because its clinical significance is not well defined.
Question 19
Which statement regarding endemic goiter is false:

  1. Increases risk for follicular neoplasm
  2. Increases risk for papillary neoplasm
  3. May cause tracheal compression
  4. Most common cause is dietary deficiency of iodine
Answer 19
B. Endemic goiter increases the risk of follicular neoplasm and anaplastic carcinoma. On the contrary, papillary neoplasms occur more in iodine sufficient areas.
Question 20
The main genes involved in regulation of thyroid development are:

  1. BRAF, TP53, TERT
  2. HRas, NRAS, Kras
  3. NKX2-1, FOXE1, PAX8, HHEX
  4. PAX6, ASPM, KATNB1, TUBB5
  5. RET, PPARg, NTRK
Answer 20
C. NKX2-1, FOXE1, PAX8, HHEX
Question 21
Thyroid gland is derived from the following embryonal structures:

  1. One lateral and two medial anlagen
  2. One medial, one lateral and two intermediate anlagen
  3. One medial and one lateral anlagen
  4. One medial and two lateral anlagen
  5. Two lateral anlagen only
Answer 21
D. One medial and two lateral anlagen
Question 22
Dyshormonogenetic goiter is characterized by all of the following except:

  1. Decreased T3, T4 and increased TSH
  2. Family history of hypothyroidism or goiter in 20% cases
  3. Highly atypical pleomorphic and hyperchromatic nuclei in internodular areas
  4. Increased T3, T4 and decreased TSH
  5. Markedly cellular nodules showing a variety of architectural patterns with minimal to absent pale colloid
Answer 22
D. Increased T3, T4 and decreased TSH. Dyshormonogenetic goiter is characterized by thyroid enlargement due to various hereditary defects in thyroid hormone synthesis. It is the second most common cause of congenital hypothyroidism after thyroid agenesis / dysgenesis. Family history of hypothyroidism or goiter is present in 20% of cases. Lack of circulating thyroid hormone activates TSH secretion, which causes overstimulation and hyperplasia of defective thyroid gland. There is diffuse asymmetric enlargement of thyroid gland with multinodular cut surface with absent to minimal pale colloid. Nodular and internodular thyroid parenchyma is markedly hypercellular. Nodular follicular cells are without atypia whereas internodular areas show fibrosis with single highly pleomorphic and hyperchromatic nuclei.
Question 23
Which microscopic feature of dyshormonogenetic goiter mimics thyroid malignancy?

  1. Capsular invasion of the nodules
  2. Highly atypical pleomorphic and hyperchromatic (bizarre) nuclei
  3. Large areas of necrosis
  4. Orphan Annie nuclei
  5. Scattered psammoma bodies
Answer 23
B. Highly atypical pleomorphic and hyperchromatic (bizarre) nuclei. Dyshormonogenetic goiter is a benign thyroid hyperplasia due to hereditary defects in thyroid hormone synthesis. It lacks malignant features common for papillary (Orphan Annie nuclei, psammoma bodies), follicular (capsular invasion) or high grade (necrosis) thyroid cancer. However, internodular tissue in dyshormonogenetic goiter often displays marked nuclear atypia with bizarre nuclei (enlarged, irregularly shaped, pleomorphic, hyperchromatic) similar to those found in radiation thyroiditis and anaplastic carcinoma.
Question 24
Which of the following statements is NOT true about diffuse sclerosing variant of papillary thyroid carcinoma?

A. Aggressive type of papillary thyroid carcinoma
B. Histologically characterized by dense sclerosis, squamous metaplasia, numerous psammoma bodies and background Hashimoto thyroiditis
C. Frequent extrathyroidal extension and lymph node metastasis
D. High mortality rate with low 10 year survival (50%)
E. Patients are younger than those with classic papillary thyroid carcinoma
Answer 24
D. Despite being an aggressive variant of PTC with some adverse prognostic features, mortality rates are similar to those of classic PTC, with 93% disease specific survival at 10 years.
Question 25
What type of sample is evaluated during a rapid on site evaluation of a thyroid fine needle aspiration?

  1. Air dried stained slide
  2. Cell block material
  3. Core biopsy slide
  4. SurePath slide
  5. ThinPrep slide
Answer 25
A. Air dried stained slide – air dried slides are ideal for rapid on site evaluation.

Reference: Thyroid gland - Cytology / fine needle aspiration

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Question 26
Which of the following fine needle aspiration indications would favor using ultrasound guided rather than palpation guided fine needle aspiration?

  1. First biopsy of the specific lesion in question
  2. Patient referred specifically for fine needle aspiration with rapid on site evaluation
  3. Predominantly solid nodule
  4. Superficial thyroid nodule > 1 cm
  5. Thyroid nodule of interest in background of a multinodular goiter
Answer 26
E. Thyroid nodule of interest in background of a multinodular goiter – ultrasound guidance will assist in localizing fine needle aspiration to nodule of interest as opposed to off-target nodules with benign radiographic features. Ultrasound guided fine needle aspiration allows for real time correlation to diagnostic ultrasound images.

Reference: Thyroid gland - Cytology / fine needle aspiration

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Question 27
How are calcium oxalate crystals useful in frozen sections from thyroid and parathyroid?

  1. Differentiate cancer from benign tissue
  2. Distinguishing thyroid from parathyroid tissue
  3. Helps to locate psammoma bodies
  4. Identify age of patient
  5. No practical utility
Answer 27
B. Distinguishing thyroid from parathyroid tissue; calcium oxalate crystals are useful in differentiating thyroid tissue (scattered to abundant crystals) from parathyroid tissue (no crystals) at frozen section
Question 28
What syndrome is associated with cribriform morular variant of thyroid carcinoma?

A. Carney complex
B. Familial adenomatous polyposis
C. Cowden syndrome
D. Gardner syndrome
Answer 28
B. Familial adenomatous polyposis
Familial adenomatous polyposis is a rare condition transmitted in an autosomal dominant pattern related to germline mutation of the tumor suppressor gene APC, which strongly predisposes to colorectal cancer. Thyroid carcinoma rarely coexists with FAP (in just 0.3-1.2% of cases). When it does, it is almost exclusively CMV-PTC.

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Question 29
    Which of the following statements are NOT true of C cell hyperplasia?

  1. C cells are found along the entire longitudinal axis of the thyroid lobe.
  2. Neoplastic C cell hyperplasia can be detected in H & E stains.
  3. Patients with a thyroid mass and hypercalcinemia may have something other than MTC.
  4. Reactive and neoplastic C cell hyperplasia are biologically and morphologically distinct.
  5. RET mutation distinguishes neoplastic from reactive C cell hyperplasia.
Answer 29
A. C cells are NOT found along the entire longitudinal axis of the thyroid lobe, since only the upper two thirds of the thyroid lobes are populated by C cells.
Question 30
What risk of malignancy is associated with benign thyroid cytology?

  1. 0 - 3%
  2. 5 - 10%
  3. 12 - 15%
  4. 20 - 30%
  5. 40 - 50%
Answer 30
A. 0 - 3% Most published studies reported that a benign FNA diagnosis is associated with a very low false negative rate, estimated to be in the range of 0 - 3%. It should be noted that the precise risk of malignancy for cytologically benign nodules is difficult to assess because only a minority of these patients undergo surgery.
Question 31
    Which case belongs to architectural atypia?

  1. A sparsely cellular aspirate comprised of Hürthle cells with minimal colloid
  2. Atypical lymphoid cells
  3. Focally prominent microfollicles with minimal nuclear atypia
  4. Most of the aspirate appears benign but rare cells have irregular nuclear contours
  5. Psammomatous calcifications in the absence of nuclear features of PTC
Answer 31
C. Focally prominent microfollicles with minimal nuclear atypia. Microfollicles are architectural atypia suggesting follicular neoplasm.

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Reference: Atypia of Undetermined Significance / Follicular Lesion of Undetermined Significance (AUS / FLUS)
Question 32

    A 70 year old male underwent FNA for the nodule of the thyroid right lobe. A cytological image of the lesion is shown. Which marker would most likely show positive staining?

  1. PAX8
  2. Calcitonin
  3. GATA3
  4. Thyroglobulin
  5. TTF1
Answer 32
Question 33
Which of the following features are not found in anaplastic thyroid carcinoma?

  1. All are considered high stage (IV) tumor
  2. Can have squamoid / squamous differentiation

  3. Necrosis and increased mitotic figures
  4. PAX8+, thyroglobulin+, TTF1+
  5. Vascular invasion and pleomorphic nucleus
Answer 33
D. PAX8+, thyroglobulin+, TTF1+. 

Anaplastic thyroid carcinoma can be PAX8+ in more than 50% cases; however, this tumor is generally negative for thyroglobulin and TTF1.
Question 34
Which statement about amyloid goiter of the thyroid is false:

  1. Can be seen in renal transplant patients on dialysis
  2. Commonly seen in males
  3. Is associated with medullary thyroid carcinoma
  4. Microscopically shows diffuse deposition of amyloid
  5. Rarely presents with dysphagia, dysphonia or dyspnea
Answer 34
C. Is associated with medullary thyroid carcinoma

Amyloid goiter is not associated with medullary thyroid carcinoma. It is defined as amyloid deposits in thyroid associated with a goiter, but not with a malignant neoplasm.
Question 35
50 year old woman presented with widely invasive follicular thyroid carcinoma penetrating thyroid capsule and strap muscles (confirmed on thyroidectomy) and spinal metastasis (confirmed by imaging and biopsy). What is the clinical stage as per the AJCC / TNM 8th edition?

  1. Stage I
  2. Stage II
  3. Stage III
  4. Stage IVA
  5. Stage IVC
Answer 35
B. Stage II. Despite the advanced disease, this patient is qualified as having stage II because her age is less than 55 years. Age at presentation is a critical prognostic characteristic in well differentiated thyroid carcinoma.

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Question 36
Histopathological examination of total thyroidectomy specimen revealed conventional papillary thyroid carcinoma in the right lobe (1.8 cm), with minimal extrathyroidal extension (perithyroidal fat), microscopically involved posterior resection margin and micrometastasis in the single perithyroidal lymph node (0.2 cm). What are the correct pT and pN categories?

  1. pT1N0
  2. pT1aN1a
  3. pT1bN1a
  4. pT2N1a
  5. pT3N1a
Answer 36
C. pT1bN1a. T1b describes a tumor > 1 cm but ≤ 2 cm in greatest dimension limited to the thyroid. Minimal extrathyroidal extension was removed from the definition of T3 disease in the AJCC / TNM 8th edition and therefore has no impact on T category. Metastasis to the central lymph nodes qualifies as N1a.

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Question 37
Which cytologic appearance of thyroid FNA specimen is classified as adequate?

  1. 3 groups with 10 follicular cells
  2. Abundant thick colloid only
  3. Air dried specimen without any atypical cells
  4. Foamy histiocytes only
  5. Respiratory epithelium only
Answer 37
B. Abundant thick colloid

When the aspirated material contains only abundant thick colloid and no follicular epithelium, it is qualified as adequate. Colloid may have variable appearance. It is important to recognize a substance as a colloid, not blood. 3 groups with 10 benign follicular cells are not sufficient to be qualified as diagnostic per the current criteria.

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Question 38
The following statements about adenolipoma of the thyroid gland are correct, EXCEPT:

  1. Clinical presentation of adenolipoma is usually a slow growing neck mass
  2. Imaging studies of cold thyroid nodule are usually nonspecific with extensive differential diagnosis
  3. Large adenolipoma can cause airway obstruction
  4. Recurrence of adenolipoma after surgical resection is common
Answer 38
D. "Recurrence of adenolipoma after surgical resection is common" is incorrect - surgical resection of thyroid adenolipoma is curative with no recurrence or malignant potential

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